Studien, Wissenschaftliche Arbeiten, in Bezug zu Krankheiten

Systemische Erkrankungen

A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Although most medical conditions will eventually involve multiple organs in advanced stage (i.e. Multiple organ dysfunction syndrome), diseases where multiple organ involvement is at presentation or in early stage are considered above.

SCIENTIFIC PAPERS

Addy, M. and P. Renton-Harper (1996). "Local and systemic chemotherapy in the management of periodontal disease: an opinion and review of the concept." J Oral Rehabil 23(4): 219-31.

ABSTRACT: Periodontal disease appears to arise from the interaction of pathogenic bacteria with a susceptible host. The main aims of disease management have been to establish a high standard of oral hygiene and to professionally and thoroughly debride the root surface Chemical agents could be considered for both aspects of management. Chemoprevention using supragingivally delivered agents such as chlorhexidine may be questioned for value in the pre-treatment hygiene phase but have well-established efficacy immediately preoperatively and during the post-operative weeks. Long-term maintenance use of chlorhexidine is problematic due to local side effects. Antiplaque toothpastes show modest benefits to gingivitis but are not proven to prevent recurrence of periodontitis. Chemotherapy may be directed at subgingival plaque, using antimicrobials, or at the host response using anti-inflammatory agents. Antimicrobials can be locally or systemically delivered. In most cases antimicrobial chemotherapy should be considered adjunctive to mechanical debridement. The advantages of local and systemic chemotherapy must be balanced against the disadvantages and potential side effects of agents. Antimicrobial chemotherapy offers little or no benefit to the treatment of most chronic adult periodontitis patients and should be reserved for the more rapid or refractory types of disease, and after the debridement phase. Despite the large number of studies there are insufficient comparative data to support any one local delivery system or systemic regimen as superior to another. Systemic versus local antimicrobials have not been compared to date. Host response modifying drugs such as non-steriodal anti-inflammatory drugs (NSAIDS) offer the potential to reduce breakdown and promote healing, including bone regeneration. However until more data are available, NSAIDs should not be used in the management of chronic periodontal diseases, there being no specific agent(s) or regimen established for use. Chemotherapy has an important place in the management of chronic periodontal diseases but routine use must be considered as an over prescription of these valuable agents.

Alexander, R. E. (2006). "Relationship between periodontal disease and systemic diseases." Tex Dent J123(2): 139; author reply 139.

Amar, S., N. Gokce, et al. (2003). "Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation." Arterioscler Thromb Vasc Biol 23(7): 1245-9.

ABSTRACT: OBJECTIVE: The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown. METHODS AND RESULTS: We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03). CONCLUSIONS: Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation, possibly placing them at increased risk for cardiovascular disease.

Bascones-Martinez, A. and M. Escribano-Bermejo (2005). "[Necrotizing periodontal disease: a manifestation of systemic disorders]." Med Clin (Barc) 125(18): 706-13.

ABSTRACT: Necrotizing periodontal disease (NPD) is an infection characterized by gingival necrosis presenting as "punched-out" papillae, with gingival bleeding, and pain. Prevotella intermedia and spirochetes have been associated with the gingival lesions. Predisposing factors may include emotional stress, immunosuppression, especially secondary to human immunodeficiency virus (HIV) infection, cigarette smoking, poor diet and pre-existing gingivitis. During the last few years, diagnosis of NPD has became more important not only because of its contribution to the appearance of clinical attachment loss and gingival sequelae, but also because it has been revealed as a marker for immune deterioration in HIV-seropositive patients.

Beck, J. D. and S. Offenbacher (2002). "Relationships among clinical measures of periodontal disease and their associations with systemic markers." Ann Periodontol 7(1): 79-89.

ABSTRACT: BACKGROUND: Recent investigations of the relationship between periodontitis and systemic disease require that periodontal disease also must be thought of as a disease process that is an exposure for a systemic disease or condition (outcome), rather than as the outcome itself. When viewing periodontal disease as an exposure, investigators must consider the clinical, microbiological, and inflammatory components of periodontitis that potentially convey risk for the systemic outcome of interest, which may or may not be the same as those associated with the assessments used to define tooth-based disease. Another important consideration is the temporal relationship between the exposure and the outcome of interest. METHODS: To explore which definitions of periodontal disease or clustering of clinical signs are important with regards to systemic exposure to inflammatory stress, we examined the relationship between clinical periodontal disease measures and 2 systemic inflammatory markers of increased risk for cardiovascular disease: serum soluble intercellular adhesion molecule (sICAM), which is a measure of vascular stress and serum C-reactive protein (CRP), which is a measure of hepatic acute-phase response. The Dental Arteriosclerosis Risk in Communities (ARIC) study, a cross-sectional study of the relationship between periodontal disease and cardiovascular disease, forms the basis for the examples used in this investigation. RESULTS: Our findings demonstrated that while attachment loss, probing depth, (PD) and bleeding on probing (BOP) are individually associated with sICAM and CRP, only BOP remains significant for sICAM when all 3 are in the model and, for CRP, only PD remains significant. Both of these clinical parameters were more robust in estimating the degree of systemic inflammation than traditional classifications of mild, moderate, and severe periodontitis or other measures of disease severity such as attachment loss. CONCLUSIONS: When selecting a definition of "systemic periodontitis" (periodontal disease that represents an exposure for a systemic condition), it is helpful to think of periodontal disease as a chronic oral infection with a number of clinical signs, rather than as the dento-centrically defined entity, periodontal disease. Thus, "systemic periodontitis" should be defined predicated upon those clinical signs that best represent the underlying mechanisms and temporal sequence that may affect that systemic outcome.

Beck, J. D. and S. Offenbacher (2005). "Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease." J Periodontol 76(11 Suppl): 2089-100.

ABSTRACT: There have been 42 published studies describing associations between oral conditions and cardiovascular diseases. In the absence of randomized controlled trials, the 16 longitudinal studies represent the highest level of evidence available. However, two databases produced eight of the 16 studies. There also is extensive variability in definitions of the oral exposure that include salivary flow, reported periodontal disease, number of teeth, oral organisms, antibodies to oral organisms, Total Dental Index, Community Periodontal Index of Treatment Needs, plaque scores, probing depth, attachment loss, and bone level. Variability also exists in the cardiovascular outcomes that include atherosclerosis measures and events, such as hospitalization for coronary heart disease (CHD), chronic CHD, fatal CHD, total stroke, ischemic stroke, and revascularization procedures. One of the criticisms of this research is that the exposure has not been represented by measures of infection. To begin to address this concern, we present new data showing that patterns of high and low levels of eight periodontal pathogens and antibody levels against those organisms are related to clinical periodontal disease as well as other characteristics of the individuals, such as age, race, gender, diabetic status, atherosclerosis, and CHD. As others before us, we conclude that the cumulative evidence presented above supports, but does not prove, a causal association between periodontal infection and atherosclerotic cardiovascular disease or its sequelae. A number of legitimate concerns have arisen about the nature of the relationship and, indeed, the appropriate definitions for periodontal disease when it is thought to be an exposure for systemic diseases. There is still much work needed to identify which aspects of the exposure are related to which aspects of the outcome. Principal component analyses illustrate the complexity of the interactions among risk factors, exposures, and outcomes. These analyses provide an initial clustering that describes and suggests the presence of specific syndromes.

Berglundh, T., B. Liljenberg, et al. (1998). "Local and systemic TCR V gene expression in advanced periodontal disease." J Clin Periodontol 25(2): 125-33.

ABSTRACT: The aim of the present investigation was to study the expression of specific alpha/beta T cell receptor (TCR) gene products in relation to some microbiological and immunological features of advanced destructive periodontitis. 21 individuals with advanced periodontal disease (diseased group) and 16 age- and sex-matched healthy subjects (healthy group) were recruited. Following a clinical examination of the diseased group, the 3 deepest interproximal sites in the upper and lower premolar- or molar segments (i.e., 12 sites in each individual) were selected for further analysis. Samples from the subgingival microbiota were obtained from the pocket of the selected sites and were prepared for a microbiological examination. The gingival tissue at one of the selected sites was also biopsied. Each excised soft tissue specimen was divided into 2 equal portions. One portion of the biopsy was prepared for histometric and morphometric analyses. The 2nd portion was snap frozen and prepared for immunohistochemical analysis. A sample of peripheral blood was obtained from each individual of the diseased and the healthy group and prepared for immunohistochemical analysis. The selected sites of the diseased group harbored varying numbers of microorganisms which have been associated with periodontal disease. The excised gingival tissue contained inflammatory lesions with substantial numbers of lymphocytes and plasma cells including T- and B-cells and a TCR V alpha/beta gene repertoire dominated by Vbeta 17. The TCR profile of the lesion, however, differed markedly from that of the circulating blood of the diseased subjects. While only minor differences were observed between the blood samples of the diseased and the healthy subjects regarding the TCR genes, CD5, HLA-DR and CD5+CD19 positive cells occurred in higher proportions in the blood samples of the subjects susceptible to periodontal disease than in healthy controls. It may be suggested that (i) TCR V alpha/Vbeta expression in peripheral blood samples of subjects with periodontal disease does not differ from that of healthy individuals, and (ii) the periodontitis lesion expresses a unique TCR repertoire in which the Vbeta 17 gene dominates.

Campbell, E. (2007). "It's more than the mouth: the effects of periodontal disease on systemic health." Dent Assist 76(3): 26-8, 30-1.

Celenligil-Nazliel, H., E. Kansu, et al. (1999). "Periodontal findings and systemic antibody responses to oral microorganisms in Behcet's disease." J Periodontol 70(12): 1449-56.

ABSTRACT: BACKGROUND: Behcet's disease is a multisystem disorder of unknown etiology, affecting predominantly the oral mucosa, skin, and eyes. Recurrent and painful episodes of oral ulcerations interfere with regular oral hygiene leading to rapid bacterial plaque accumulation. The aims of this study were to evaluate the periodontal status of patients with Behcet's disease and determine serum antibody responses to selected oral microorganisms, including major periodontopathogens in these patients. METHODS: Thirty-three patients with Behcet's disease and 15 healthy subjects were included in the study. Plaque, sulcular bleeding, periodontal index scores, probing depths, and total number of teeth were recorded. Serum IgG antibody levels to a panel of 13 oral microorganisms were determined. RESULTS: Significantly higher values for each of the clinical measures were observed in patients with Behcet's disease compared to healthy subjects (P <0.0001). Antibody levels to selected members of plaque, including Actinomyces viscosus, Streptococcus mutans, Streptococcus sanguis, Streptococcus oralis, Eikenella corrodens, Campylobacter rectus, and Prevotella intermedia were significantly lower in patients with Behcet's disease than in controls (P <0.001-0.05). In contrast, these patients exhibited significantly elevated antibody levels to Actinobacillus actinomycetemcomitans Y4 compared to controls (P <0.01). CONCLUSIONS: Our data indicate that the patients with Behcet's disease generally exhibit clinical findings of established periodontal disease. Decreased antibody responses to early colonizers of both supra- and subgingival plaque were observed along with the elevation in antibody levels to A. actinomycetemcomitans. These results suggest that the bacterial plaque ecology and/or immune responses to these microorganisms may be affected in Behcet's disease which could lead to changes in the expression of periodontal disease.

Chang, K. M., M. E. Ryan, et al. (1996). "Local and systemic factors in periodontal disease increase matrix-degrading enzyme activities in rat gingiva: effect of micocycline therapy." Res Commun Mol Pathol Pharmacol 91(3): 303-18.

ABSTRACT: We previously reported that both local and systemic factors relevant to the pathogenesis of periodontal disease can increase gingival collagenase activity in rats. Since the degradation of extracellular matrix is an essential feature of periodontal disease and this tissue breakdown requires multiple enzyme interactions, the current study was carried out to determine the effects of bacterial endotoxin (LPS) (a local factor) and diabetes (a systemic factor) on a panel of matrix-degrading enzymes (collagenase, gelatinase, elastase, and beta-glucuronidase) in the gingiva of rats. In addition, the effects of therapy with a semisynthetic tetracycline (minocycline) were investigated. Ten male, Sprague-Dawley rats were made diabetic by IV injection of streptozotocin. Four of the ten rats then received minocycline (10 mg/day) by oral gavage on a daily basis for 3 weeks. Nineteen nondiabetic rats served as controls and 9 of them received 10 microliters of E. coli LPS (10 mg/ml) by injection into the labial gingiva every other day during the last week of the study. The other 10 nondiabetic rats were sham injected with saline into the gingiva. At the end of the 3 week experimental period, gingival tissue and skin were dissected from each rat and extracted for enzyme analysis. Our results showed that diabetes markedly increased the four matrix-degrading enzyme activities in both gingiva and skin. In contrast, local LPS injection increased these enzyme activities in the gingiva alone. Systemic therapy with minocycline completely ameliorated these elevated enzyme levels in diabetic rats in both gingiva and skin. Minocycline added in vitro to the enzyme assay systems containing skin extract from diabetic rats also inhibited collagenase and gelatinase activities, but no inhibition was observed for elastase and beta-glucuronidase activities, indicating that the MMPs and other enzymes were inhibited by minocycline, during diabetes, by indirect and indirect mechanisms, respectively.

Craig, R. G., P. Kotanko, et al. (2007). "Periodontal diseases--a modifiable source of systemic inflammation for the end-stage renal disease patient on haemodialysis therapy?" Nephrol Dial Transplant 22(2): 312-5.

Dietrich, T. and R. I. Garcia (2005). "Associations between periodontal disease and systemic disease: evaluating the strength of the evidence." J Periodontol 76(11 Suppl): 2175-84.

ABSTRACT: Much work has been published on the association between periodontal disease and systemic disease, including original reports, narrative reviews, systematic reviews, and meta-analyses. Based on the existent work, one can assign an evidence level and grade, using standard evidence-based criteria, to the data available in the four major categories of medical outcomes studied: cardiovascular/cerebrovascular, pregnancy, pulmonary, and diabetes. We discuss methodologic and conceptual problems in the study of oral-systemic associations, focusing as an example on the association between periodontal disease and cardiovascular/cerebrovascular disease. We argue that the hierarchical ranking of studies by levels of evidence may be misleading. In particular, while randomized controlled trials (RCTs) are needed to determine the efficacy of periodontal treatment to reduce the risk of cardiovascular events, they may be of limited value in determining the etiologic role of periodontal disease on coronary heart disease and stroke. We discuss limitations of RCTs as well as the limitations of currently available data from epidemiologic studies, including study design and confounding and misclassification errors. We conclude that well-designed observational studies into the associations between periodontal disease and systemic disease need to remain an integral component of future research efforts in order to fully understand such associations.

Dumitrescu, A. L. (2006). "Occurrence of self-reported systemic medical conditions in patients with periodontal disease." Rom J Intern Med 44(1): 35-48.

ABSTRACT: OBJECTIVES: The objective of this retrospective study was to investigate the occurrence of self-reported systemic disorders in patients referred to a specialist clinic for periodontal treatment and to determine if an association existed between general health and periodontal disease severity in this population. MATERIAL AND METHODS: The study design was a case-controlled, retrospective chart review. Patient charts (n=1044) were selected from the Department of Periodontology, Carol Davila University of Medicine and Pharmacy. These charts were examined to determine patient's self-reported systemic condition. In addition, the periodontal diagnosis was recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine the periodontal diagnosis. RESULTS: The most frequent disorders in patients with gingivitis were high blood pressure (35.85%), followed by coronary artery disease (15.741%), kidney and urinary tract disorders (15.71%) and allergic reactions (14.28%). 80% of patients with gingivitis had at least one of these disorders. The most frequent disorders in patients with periodontitis were high blood pressure (29.51%) followed by digestive disorders (18.92%), coronary artery disease (16.54%), kidney and urinary tract disorders (16.24%), endocrine disorders (10.58 %), rheumatoid arthritis/rheumatism (9.68%), Hepatitis A (9.38%), diabetes (8.79%) allergic reactions (8.79%), liver and gallbladder disorders (7.30%), sinusitis (6.55%), osteoporosis (5.51%) and respiratory disorders (5.36%). 81.96% of patients with periodontitis had at least one of these disorders. However, only rheumatoid arthritis was found to be more prevalent in periodontitis patients compared with gingivitis affected individuals (p<0.05). Multiple correlations were found between the independent variables. CONCLUSIONS: These findings support the results from previous investigators that a number of systemic conditions are closely associated with periodontal disease.

Fowler, E. B., L. G. Breault, et al. (2001). "Periodontal disease and its association with systemic disease." Mil Med 166(1): 85-9.

ABSTRACT: Periodontal diseases are oral disorders characterized by inflammation of the supporting tissues of the teeth. Usually, periodontitis is a progressively destructive loss of bone and periodontal ligament (loss of the attachment apparatus of the teeth). Periodontitis has documented risk factors, including but not limited to specific plaque bacteria, smoking, and diabetes mellitus. Initially, the link between systemic disease and periodontal diseases was thought to be unidirectional. Currently, there is increasing evidence that the relationship between these entities may be bidirectional. Recent case-control and cross-sectional studies indicate that periodontitis may confer a 7-fold increase in risk for preterm low birth weight infants and a 2-fold increase in risk for cardiovascular disease. These early reports indicate the potential association between systemic and oral health. Additionally, these studies support the central hypothesis that periodontal disease involves both a local and a systemic host inflammatory response. This knowledge of disease interrelationships may prove vital in intervention strategies to reduce patient risks and prevent systemic disease outcomes. Based on the current evidence of the periodontal-systemic disease connection, the purpose of this report is to help establish the groundwork for closer communication between physicians and periodontists in the military health care setting.

Garcia, R. I., M. M. Henshaw, et al. (2001). "Relationship between periodontal disease and systemic health." Periodontol 2000 25: 21-36.

Glurich, I., S. Grossi, et al. (2002). "Systemic inflammation in cardiovascular and periodontal disease: comparative study." Clin Diagn Lab Immunol 9(2): 425-32.

ABSTRACT: Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, alpha(1)-acid-glycoprotein (AAG), alpha(1)-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.

Graves, D. T., Y. Jiang, et al. (2000). "Periodontal disease: bacterial virulence factors, host response and impact on systemic health." Curr Opin Infect Dis 13(3): 227-232.

ABSTRACT: Teeth are coated with a biofilm that contains periodontal pathogens. Pathogens express virulence factors which enable them to invade and replicate within epithelial cells and to invade the underlying connective tissue. This stimulates production of prostaglandins and cytokines that induce tissue loss. In addition, these bacteria have the potential to modulate the course of systemic diseases such as atherosclerosis and to contribute to low birthweight and preterm labor.

Hamilton, J. (2005). "The link between periodontal disease and systemic diseases: state of the evidence 2005." J Calif Dent Assoc 33(1): 29-38.

Hills-Smith, H. and N. J. Schuman (1983). "Antibiotic therapy in pediatric dentistry. II. Treatment of oral infection and management of systemic disease." Pediatr Dent 5(1): 45-50.

Hyman, J. (2006). "The importance of assessing confounding and effect modification in research involving periodontal disease and systemic diseases." J Clin Periodontol 33(2): 102-3.

Jepsen, R. and G. A. Kuchel (2006). "Nutrition and inflammation: the missing link between periodontal disease and systemic health in the frail elderly?" J Clin Periodontol 33(5): 309-11.

Joag, S. V., I. Adany, et al. (1997). "Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS." J Virol 71(5): 4016-23.

ABSTRACT: Chimeric simian/human immunodeficiency virus (SHIV) consists of the env, vpu, tat, and rev genes of human immunodeficiency virus type 1 (HIV-1) on a background of simian immunodeficiency virus (SIV). We derived a SHIV that caused CD4+ cell loss and AIDS in pig-tailed macaques (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L. J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol. 70:3189-3197, 1996) and used a cell-free stock of this virus (SHIV(KU-1)) to inoculate macaques by the intravaginal route. Macaques developed high virus burdens and severe loss of CD4+ cells within 1 month, even when inoculated with only a single animal infectious dose of the virus by the intravaginal route. The infection was characterized by a burst of virus replication that peaked during the first week following intravenous inoculation and a week later in the intravaginally inoculated animals. Intravaginally inoculated animals died within 6 months, with CD4+ counts of <30/microl in peripheral blood, anemia, weight loss, and opportunistic infections (malaria, toxoplasmosis, cryptosporidiosis, and Pneumocystis carinii pneumonia). To evaluate the kinetics of virus spread, we inoculated macaques intravaginally and euthanized them after 2, 4, 7, and 15 days postinoculation. In situ hybridization and immunocytochemistry revealed cells expressing viral RNA and protein in the vagina, uterus, and pelvic and mesenteric lymph nodes in the macaque euthanized on day 2. By day 4, virus-infected cells had disseminated to the spleen and thymus, and by day 15, global elimination of CD4+ T cells was in full progress. Kinetics of viral replication and CD4+ loss were similar in an animal inoculated with pathogenic SHIV orally. This provides a sexual-transmission model of human AIDS that can be used to study the pathogenesis of mucosal infection and to evaluate the efficacy of vaccines and drugs directed against HIV-1.

John, V. and S. J. Kim (2002). "Periodontal disease and systemic disease. Clinical information for the practicing dentist." J Indiana Dent Assoc 81(2): 15-8.

ABSTRACT: The relationship between periodontal and systemic disease, previously called the "focal infection theory" or "focus of infection," has become an exciting area of clinical and laboratory research. Periodontal disease has been reported to influence diabetes mellitus, cardiovascular disease, osteoporosis, and respiratory disease. It also can influence the course and duration of pregnancy. This article reviews some of these associations and proposed mechanisms by which periodontal disease and systemic conditions influence each other. We also discuss clinical implications for our daily practice in dentistry.

Karaarslan, F., I. Coker, et al. (1998). "Disturbed systemic immune balance in periodontal disease." Autoimmunity 27(2): 123-4.

Kim, J. and S. Amar (2006). "Periodontal disease and systemic conditions: a bidirectional relationship." Odontology 94(1): 10-21.

ABSTRACT: For decades, physicians and dentists have paid close attention to their own respective fields, specializing in medicine pertaining to the body and the oral cavity, respectively. However, recent findings have strongly suggested that oral health may be indicative of systemic health. Currently, this gap between allopathic medicine and dental medicine is quickly closing, due to significant findings supporting the association between periodontal disease and systemic conditions such as cardiovascular disease, type 2 diabetes mellitus, adverse pregnancy outcomes, and osteoporosis. Significant effort has brought numerous advances in revealing the etiological and pathological links between this chronic inflammatory dental disease and these other conditions. Therefore, there is reason to hope that the strong evidence from these studies may guide researchers towards greatly improved treatment of periodontal infection that would also ameliorate these systemic illnesses. Hence, researchers must continue not only to uncover more information about the correlations between periodontal and systemic diseases but also to focus on positive associations that may result from treating periodontal disease as a means of ameliorating systemic diseases.

Kimura, I., J. Kuramoto, et al. (1990). "[A co-operative study on prophylactic effect of oral administration of high-dose amphotericin B syrup for systemic fungal infection in patients with hematological neoplasms. Chugoku-Shikoku Study Group of Mycosis with Hematologic Disease]." Gan To Kagaku Ryoho 17(5): 1027-32.

ABSTRACT: The prophylactic effect of the oral administration of high-dose amphotericin B syrup for the systemic fungal infection was studied in 36 patients with hematological neoplasms. Twenty nine patients received 2,400 mg/day of Amphotericin B syrup for during the remission induction therapy. One patient received 1,200 mg/day, 3 received 800 mg/day and 3 received 400 mg/day of Amphotericin B syrup. The prophylactic effect was recognized in 24 of 36 patients, 66.7%. As adverse effects gastrointestinal symptoms such as nausea and vomiting, hypochloremia and hypopotassemia associated with hypochloremia was observed in one patient, respectively, however, they were all controllable. The blood levels of Amphotericin B in patients received 2,400 mg/day was 0.092 +/- 0.055 micrograms/ml (n = 40) on 7th day and 0.110 +/- 0.046 micrograms/ml (n = 21) on 28th day, respectively. The administration of high-dose of Amphotericin B syrup is expected not only for the prophylaxis but also for the treatment of the systemic fungal infection.

Kinane, D. F., D. F. Lappin, et al. (1999). "Humoral immune responses in periodontal disease may have mucosal and systemic immune features." Clin Exp Immunol 115(3): 534-41.

ABSTRACT: The humoral immune response, especially IgG and IgA, is considered to be protective in the pathogenesis of periodontal disease, but the precise mechanisms are still unknown. Immunoglobulins arriving at the periodontal lesion are from both systemic and local tissue sources. In order to understand better the local immunoglobulin production, we examined biopsy tissue from periodontitis lesions for the expression of IgM, IgG, IgA, IgE and in addition the IgG and IgA subclasses and J-chain by in situ hybridization. Tissues examined were superficial inflamed gingiva and the deeper granulation tissue from periodontal sites. These data confirm that IgM, and IgG and IgA subclass proteins and J-chain can be locally produced in the periodontitis tissues. IgG1 mRNA-expressing cells were predominant in the granulation tissues and in the gingiva, constituting approx. 65% of the total IgG-expressing plasma cells. There was a significantly increased proportion of IgA-expressing plasma cells in the gingiva compared with the granulation tissue (P < 0.01). Most of the IgA-expressing plasma cells were IgA1, but a greater proportion expressed IgA2 mRNA and J-chain mRNA in the gingival tissues (30.5% and 7.5%, respectively) than in the periodontal granulation tissues (19% and 0-4%, respectively). The J-chain or dimeric IgA2-expressing plasma cells were located adjacent to the epithelial cells, suggesting that this tissue demonstrates features consistent with a mucosal immune response. Furthermore, we were able to detect the secretory component in gingival and junctional epithelial cells, demonstrating that the periodontal epithelium shares features with mucosal epithelium. In contrast, deeper tissues had more plasma cells that expressed IgM, and less expressing IgA, a response which appears more akin to the systemic immune response. In conclusion, this study suggests that immune mechanisms involved in the pathogenesis of periodontitis may involve features of both the mucosal and systemic immune systems, dependent on tissue location.

Kinane, D. F. and G. J. Marshall (2001). "Periodontal manifestations of systemic disease." Aust Dent J46(1): 2-12.

ABSTRACT: Periodontitis is a chronic bacterial infection of the supporting structures of the teeth. The host response to infection is an important factor in determining the extent and severity of periodontal disease. Systemic factors modify periodontitis principally through their effects on the normal immune and inflammatory mechanisms. Several conditions may give rise to an increased prevalence, incidence or severity of gingivitis and periodontitis. The effects of a significant number of systemic diseases upon periodontitis are unclear and often it is difficult to causally link such diseases to periodontitis. In many cases the literature is insufficient to make definite statements on links between certain systemic factors and periodontitis and for several conditions only case reports exist whereas in other areas an extensive literature is present. A reduction in number or function of polymorphonuclear leukocytes (PMNs) can result in an increased rate and severity of periodontal destruction. Medications such as phenytoin, nifedipine, and cyclosporin predispose to gingival overgrowth in response to plaque and changes in hormone levels may increase severity of plaque-induced gingival inflammation. Immuno-suppressive drug therapy and any disease resulting in suppression of the normal inflammatory and immune mechanisms (such as HIV infection) may predispose the individual to periodontal destruction. There is convincing evidence that smoking has a detrimental effect on periodontal health. The histiocytoses diseases may present as necrotizing ulcerative periodontitis and numerous genetic polymorphisms relevant to inflammatory and immune processes are being evaluated as modifying factors in periodontal disease. Periodontitis severity and prevalence are increased in diabetics and worse in poorly controlled diabetics. Periodontitis may exacerbate diabetes by decreasing glycaemic control. This indicates a degree of synergism between the two diseases. The relative risk of cardiovascular disease is doubled in subjects with periodontal disease. Periodontal and cardiovascular disease share many common risk and socio-economic factors, particularly smoking, which is a powerful risk factor for both diseases. The actual underlying aetiology of both diseases is complex as are the potential mechanisms whereby the diseases may be causally linked. It is thought that the chronic inflammatory and microbial burden in periodontal disease may predispose to cardiovascular disease in ways proposed for other infections such as with Chlamydia pneumoniae. To move from the current association status of both diseases to causality requires much additional evidence. Determining the role a systemic disease plays in the pathogenesis of periodontal disease is very difficult as several obstacles affect the design of the necessary studies. Control groups need to be carefully matched in respect of age, gender, oral hygiene and socio-economic status. Many studies, particularly before the aetiological importance of dental plaque was recognised, failed to include such controls. Longitudinal studies spanning several years are preferable in individuals both with and without systemic disease, due to the time period in which periodontitis will develop.

Krall, E. A. (2001). "The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease." Ann Periodontol 6(1): 209-13.

ABSTRACT: Osteoporosis and osteopenia may influence periodontal disease and tooth loss. Medications such as hormone replacement therapy and nutritional supplements that are used to prevent or treat osteoporosis have been evaluated for beneficial effects on oral health in a small number of human studies. Hormone replacement therapy (HRT), which slows the rate of bone loss at skeletal sites such as the hip and spine, also appears to reduce the rate of alveolar bone loss in postmenopausal women. HRT use is consistently associated with greater tooth retention and a reduced likelihood of edentulism in studies of elderly women. The number of studies on the effects of calcium or vitamin D intake on oral outcomes is limited, but suggest that higher intake levels are associated with reduced prevalence of clinical attachment loss and lower risk of tooth loss. Data from a prospective study of oral health in men show a similar association between higher calcium intake and reduced alveolar bone loss. The number of teeth with progression of alveolar bone loss over a 7-year period was significantly lower among men whose calcium intake was at least 1,000 mg per day, compared to men with a calcium intake below this level. Future studies should confirm these findings and evaluate the oral effects of new medications for osteoporosis. If confirmed, the implications for dental professionals may include an expanded array of medications for the treatment of periodontal disease and a greater emphasis on nutrition education for patients.

Lagervall, M., L. Jansson, et al. (2003). "Systemic disorders in patients with periodontal disease." J Clin Periodontol 30(4): 293-9.

ABSTRACT: BACKGROUND, AIMS: Over the past 10 years several studies have been published pointing towards a relationship between periodontal disease and various systemic disorders or diseases. The purpose of this retrospective study was to investigate the occurrence of self-reported systemic disorders in patients referred to a specialist clinic for periodontal treatment and to explore possible relationships between general health and periodontal disease severity in this population. MATERIAL AND METHODS: Data were collected from the dental records and the health questionnaires of 1006 subjects. Stepwise multiple linear regression analyses were adopted to calculate correlations between systemic disorders as independent variables and number of remaining teeth and the relative frequency of periodontal pockets of 5 mm or more, respectively, as the dependent variable. RESULTS: The number of remaining teeth was significantly and positively correlated to the presence of cardiovascular disease, diabetes and rheumatoid disease after adjustment for age, sex and smoking. The relative frequency of diseased sites, however, was not significantly correlated to any one of the investigated systemic health disorders. CONCLUSION: No significant associations between investigated systemic disorders and periodontal disease severity were found if the relative frequency of deep periodontal pockets was used as the clinical parameter for periodontal disease severity. However, cardiovascular disease, diabetes and rheumatoid disease were found to be significantly correlated to number of lost teeth, which may represent one aspect of periodontal health. This result held true in nonsmokers only.

Lamster, I. B. (2001). "Current concepts and future trends for periodontal disease and periodontal therapy, Part 1: Etiology, risk factors, natural history, and systemic implications." Dent Today 20(1): 50-5.

Lappin, D. F., A. M. McGregor, et al. (2003). "The systemic immune response is more prominent than the mucosal immune response in the pathogenesis of periodontal disease." J Clin Periodontol 30(9): 778-86.

ABSTRACT: BACKGROUND, AIM: The diseased periodontium appears to express features of a systemic and a mucosal immune response. Our aims were to determine differences in immunoglobulin expression between gingivitis and periodontitis lesions and to ascertain whether immune and inflammatory cells were recruited into the diseased periodontium by the mucosal addressin adhesion molecule (MAdCAM-1). METHODS: In situ hybridization and immunohistochemistry were used to detect the expression of chemokines, adhesion molecules and immunoglobulins in tissue sections of gingival and granulation tissues excised from periodontitis-affected sites and of healthy tissue and gingivitis-affected tissue excised during crown-lengthening procedures. RESULTS: Greater numbers of plasma cells were observed in periodontitis gingival/granulation tissue lesions compared with gingivitis lesions. While IgA1 were predominant in all lesions, IgA2 and J-chain expressing plasma cells were present in increased proportions in gingival tissues compared with granulation tissue. Intracellular adhesion molecule-1 (ICAM-1) was higher in periodontitis than in gingivitis and interleukin-8 mRNA was higher in lesions with a pronounced neutrophil infiltrate. Vascular cell adhesion molecule-1 (VCAM-1) localized to the deep connective tissue and indicated the presence of a systemic type of immune response in this region. Periodontal tissues (n=71 biopsies) did not appear to express MAdCAM-1, in positive control sections of small intestine where it was detected. CONCLUSION: Overall, the systemic-type immune response is predominant, and although the mucosal immune response is minor and limited to the superficial tissues it may have an important role in the host defense to periodontal pathogens.

Li, X., K. M. Kolltveit, et al. (2000). "Systemic diseases caused by oral infection." Clin Microbiol Rev 13(4): 547-58.

ABSTRACT: Recently, it has been recognized that oral infection, especially periodontitis, may affect the course and pathogenesis of a number of systemic diseases, such as cardiovascular disease, bacterial pneumonia, diabetes mellitus, and low birth weight. The purpose of this review is to evaluate the current status of oral infections, especially periodontitis, as a causal factor for systemic diseases. Three mechanisms or pathways linking oral infections to secondary systemic effects have been proposed: (i) metastatic spread of infection from the oral cavity as a result of transient bacteremia, (ii) metastatic injury from the effects of circulating oral microbial toxins, and (iii) metastatic inflammation caused by immunological injury induced by oral microorganisms. Periodontitis as a major oral infection may affect the host's susceptibility to systemic disease in three ways: by shared risk factors; subgingival biofilms acting as reservoirs of gram-negative bacteria; and the periodontium acting as a reservoir of inflammatory mediators. Proposed evidence and mechanisms of the above odontogenic systemic diseases are given.

Mohammad, A. R., M. Brunsvold, et al. (1996). "The strength of association between systemic postmenopausal osteoporosis and periodontal disease." Int J Prosthodont 9(5): 479-83.

ABSTRACT: This cross-sectional study examined the strength of association between systemic osteoporosis and periodontal status in postmenopausal non-Hispanic white women. Twenty subjects with low bone density and a spine bone density of 0.753 +/- 0.039 dual-energy x-ray absorptiometry units (g/cm2) and 22 subjects with high bone density and a spine bone density of 1.032 +/- 0.028 dual-energy x-ray absorptiometry units (g/cm2) were randomly selected from a cohort of 565 women. Periodontal assessment included Plaque Index, Gingival Index, pocket depth, gingival recession, and periodontal attachment level. There were no significant differences in Plaque Index, Gingival Index, and probing depth in both groups; however, there were significant differences in gingival recession components of periodontal attachment level in both groups. This study suggests that systemic osteoporosis may contribute to periodontal attachment loss in the form of gingival recession.

Molloy, J., L. F. Wolff, et al. (2004). "The association of periodontal disease parameters with systemic medical conditions and tobacco use." J Clin Periodontol 31(8): 625-32.

ABSTRACT: OBJECTIVES: The objective of this study was to determine if an association existed between periodontal disease and various systemic medical conditions and tobacco use. MATERIAL AND METHODS: The study design was a case-controlled, retrospective chart review. Patient charts (n=2006) were selected from more than 13,000 active patients attending the University of Minnesota dental clinics. These charts were examined to determine patient's self-reported systemic condition and smoking history. In addition, the number of missing teeth and bone loss were recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine bone loss and number of missing teeth. Each examiner was blind to the findings of the other. RESULTS: After adjusting for age, sex, diabetes and smoking (yes/no) status, seven conditions were significantly (p=0.0003-0.04) related to bone loss or number of missing teeth (vascular disease, heart surgery, vascular surgery, heart attack, thyroid problems, arthritis, stomach ulcers). From these conditions, thyroid problems and arthritis had a negative association with bone loss. CONCLUSIONS: These findings support the results from previous investigators that a number of systemic conditions and smoking are closely associated with missing teeth or bone loss.

Montebugnoli, L., D. Servidio, et al. (2005). "Periodontal health improves systemic inflammatory and haemostatic status in subjects with coronary heart disease." J Clin Periodontol 32(2): 188-92.

ABSTRACT: OBJECTIVES: A relationship between poor oral health and coronary heart disease (CHD) and systemic inflammatory and haemostatic factors has been recently documented in an Italian population. The present study was performed to assess whether intensive dental care may produce a periodontal improvement along with a change in systemic inflammatory and haemostatic factors. MATERIAL AND METHODS: The study population consisted of 18 males aged 40-65 years with proven CHD and elevated values of systemic inflammatory and haemostatic factors. A detailed description of their oral status was given by using two different dental indices (clinical periodontal sum score and clinical and radiographic sum score). Blood samples were taken for measurement of the following systemic markers of inflammation [(C-reactive protein (CRP), leucocytes, fibrinogen)] and haemostatic factors [(von Willebrand factor, fibrin D-dimer and oxidized-low density lipoprotein (Ox-LDL)]. All parameters were determined in each subject at baseline, after 4 months as a control and 3 months after an intensive protocol of scaling and root planing. anova for repeated measures was used for the statistical analysis. RESULTS: No statistical difference was found between values at baseline and at the 4-month-control. All oral indexes showed a significant decrease (p< .01) 3 months after periodontal treatment. All systemic inflammatory indexes decreased but only the decrease in CRP reached statistical significance (p< .05). A significant decrease (p< .01) was also found as regards Ox-LDL among haemostatic factors. CONCLUSIONS: Preliminary results from the present study suggest an association between poor oral status and CHD, and provide evidence that the improvement of periodontal status may influence the systemic inflammatory and haemostatic situation.

Nualart Grollmus, Z. C., M. C. Morales Chavez, et al. (2007). "Periodontal disease associated to systemic genetic disorders." Med Oral Patol Oral Cir Bucal 12(3): E211-5.

ABSTRACT: A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role of bacterial plaque is subject to debate. In the presence of qualitative or quantitative cellular immune alterations, periodontal disease may manifest early on a severe localized or generalized basis--in some cases related to the presence of plaque and/or specific bacteria (severe congenital neutropenia or infantile genetic agranulocytosis, Chediak-Higiashi syndrome, Down syndrome and Papillon-Lefevre syndrome). In the presence of humoral immune alterations, periodontal damage may result indirectly as a consequence of alterations in other systems. In connective tissue disorders, bacterial plaque and alterations of the periodontal tissues increase patient susceptibility to gingival inflammation and alveolar resorption (Marfan syndrome and Ehler-Danlos syndrome). The management of periodontal disease focuses on the control of infection and bacterial plaque by means of mechanical and chemical methods. Periodontal surgery and even extraction of the most seriously affected teeth have also been suggested. There are variable degrees of consensus regarding the background systemic disorder, as in the case of Chediak-Higiashi syndrome, where antibiotic treatment proves ineffective; in severe congenital neutropenia or infantile genetic agranulocytosis, where antibiotic prophylaxis is suggested; and in Papillon-Lefevre syndrome, where an established treatment protocol is available.

Offenbacher, S. (1999). "The link between periodontal disease and systemic health: a scientific update. Interview by Phillip Bonner." Dent Today 18(7): 88-9.

Otomo-Corgel, J. and R. L. Merin (2002). "Periodontal disease and systemic health--what you and your patients need to know." J Calif Dent Assoc 30(4): 307-11.

ABSTRACT: For many years, dentists have recognized the importance of dental health to general health. Recent research findings point to possible associations between chronic oral infections such as periodontitis and systemic health problems. This article will review the evidence for some of these associations and explore factors that may underlie oral-systemic disease connections.

Paquette, D. W. (2002). "The periodontal infection-systemic disease link: a review of the truth or myth." J Int Acad Periodontol 4(3): 101-9.

ABSTRACT: Observational studies indicate periodontal infections as a risk factor for systemic conditions like cardiovascular disease and preterm low birth weight. This paper reviews and argues the biological plausibility for a periodontal infection-systemic disease link and reviews the available experimental data from animal models and human intervention trials. Five principal lines of evidence can be used to explain the biological plausibility of a link. First, infection in general has been implicated in the pathogenesis of both atherosclerosis and preterm delivery. Periodontal infection secondly causes transient and low-grade bacteraemias and endotoxaemias in patients. Thirdly, periodontal infection promotes systemic inflammatory and immune responses that may play roles in disease. Periodontal pathogens express specific virulence factors that can affect atherogenic or parturition events. Lastly, periodontal pathogens have also been isolated from non-oral tissues like atheromatous plaques. Experimental data derived from rodent and pig models indicate that infection or bacteraemias with the periodontal pathogen, Porphyromonas gingivalis, can increase atheroma size or reduce litter weights as compared to controls. While human intervention data are lacking for patients at risk for cardiovascular disease, early data indicate that periodontal therapy administered to pregnant mothers with periodontitis can reduce the incidence of preterm low birth weight deliveries. Nevertheless, more and larger intervention trials are needed before we can fully accept periodontal infection as a true risk factor in the causal pathways of cardiovascular disease and preterm low birth weight.

Persson, R. E., L. G. Hollender, et al. (2003). "Assessment of periodontal conditions and systemic disease in older subjects." J Clin Periodontol 30(3): 207-13.

ABSTRACT: BACKGROUND: An increased risk for periodontitis has been associated both with type-1 or insulin dependent diabetes (IDDM) and with type-2 or non-insulin dependent diabetes (NIDDM). AIMS: 1) To describe and analyze periodontal conditions in older low-income ethnic diverse subjects with or without a diagnosis of diabetes. 2) To assess to what extent diabetes mellitus is associated with periodontal status, and 3) how periodontitis ranks as a coexisting disease among other diseases in subjects with diabetes mellitus. MATERIAL AND METHODS: Radiographic signs of alveolar bone loss were studied in 1101 older subjects 60-75 years old (mean age 67.6, SD+/-4.7). The number of periodontal sites and the proportions of teeth with probing depth (PD) > or =5 mm, clinical attachment levels (CAL) > or =4 mm were studied in a subset of 701 of the subjects. RESULTS: IDDM was reported by 2.9% and NIDDM by 9.2% of the subjects. The number of remaining teeth did not differ by diabetic status. The number of sites with PD > or =5 mm and the proportion of PD with > or =5 mm was significantly smaller in the non-diabetic group (chi2=46.8, p<0.01, and chi2=171.1, p<0.001, respectively). Statistical analysis failed to demonstrate group differences for the number and proportions of sites with CAL > or =4 mm and for radiographic findings of alveolar bone loss. Combining all periodontal parameters revealed that the Mantel-Haenszel common odds of having IDDM/NIDDM and periodontitis was 1.8 : 1 (95% CI: 1.1-3.1, p<0.03). The common odds ratio estimate of an association between heart disease and diabetes was 3.6 : 1 (95% CI: 2.1-2.6, p<0.001). CONCLUSIONS: Probing depth differences between IDDM/NIDDM vs. non-diabetic subjects may reflect the presences of pseudo-pockets and not progressive periodontitis in many subjects with diabetes mellitus. Periodontitis is not a predominant coexisting disease in older subjects with diabetes mellitus.

Persson, R. E., L. G. Hollender, et al. (2002). "Assessment of periodontal conditions and systemic disease in older subjects. I. Focus on osteoporosis." J Clin Periodontol 29(9): 796-802.

ABSTRACT: BACKGROUND: Osteoporosis (OPOR) is a common chronic disease, especially in older women. Patients are often unaware of the condition until they experience bone fractures. Studies have suggested that OPOR and periodontitis are associated diseases and exaggerated by cytokine activity. Panoramic radiography (PMX) allows studies of mandibular cortical index (MCI), which is potentially diagnostic for OPOR. AIMS: i). To study the prevalence of self-reported history of OPOR in an older, ethnically diverse population, ii). to assess the agreement between PMX/MCI findings and self-reported OPOR, and iii). to assess the likelihood of having both a self-reported history of OPOR and a diagnosis of periodontitis. MATERIALS AND METHODS: PMX and medical history were obtained from 1084 subjects aged 60-75 (mean age 67.6, SD +/- 4.7). Of the films, 90.3% were useful for analysis. PMXs were studied using MCI. The PMXs were used to grade subjects as not having periodontitis or with one of three grades of periodontitis severity. RESULTS: A positive MCI was found in 38.9% of the subjects, in contrast to 8.2% self-reported OPOR. The intraclass correlation between MCI and self-reported OPOR was 0.20 (P < 0.01). The likelihood of an association between OPOR and MCI was 2.6 (95%CI: 1.6, 4.1, P < 0.001). Subjects with self-reported OPOR and a positive MCI had worse periodontal conditions (P < 0.01). The Mantel-Haentzel odds ratio for OPOR and periodontitis was 1.8 (95%CI: 1.2, 2.5, P < 0.001). CONCLUSIONS: The prevalence of positive MCI was high and consistent with epidemiological studies, but only partly consistent with a self-reported history of osteoporosis with a higher prevalence of positive MCI in Chinese women. Horizontal alveolar bone loss is associated with both positive self-reported OPOR and MCI.

Persson, R. E., L. G. Hollender, et al. (2002). "Assessment of periodontal conditions and systemic disease in older subjects. II. Focus on cardiovascular diseases." J Clin Periodontol 29(9): 803-10.

ABSTRACT: BACKGROUND: Panoramic radiographs (PMX)s may provide information about systemic health conditions. AIMS: i). To study clinical periodontal conditions and collect self-reported health status in a cohort of 1084 older subjects; ii). to study signs of alveolar bone loss and carotid calcification from panoramic radiographs obtained from these subjects; and iii). to study associations between study parameters. MATERIAL AND METHODS: PMXs from 1064 adults aged 60-75 (mean age 67.6, SD +/- 4.7) were studied. Signs of alveolar bone loss, vertical defects, and molar furcation radiolucencies defined periodontal status. Medical health histories were obtained via self-reports. Signs of carotid calcification were identified from panoramic radiographs. RESULTS: The PMX allowed assessment of 53% of the films (Seattle 64.5% and Vancouver 48.4%). A self-reported history of a stroke was reported by 8.1% of men in Seattle and 2.9% of men in Vancouver (P < 0.01). Heart attacks were reported by 12% of men in Seattle and 7.2% in Vancouver (N.S.). PMX evidence of periodontitis was found in 48.5% of the subjects, with carotid calcification in 18.6%. The intraclass correlation score for PMX findings of carotid calcification and stroke was 0.24 (95% CI: 0.10-0.35, P < 0.001). The odds ratio for PMX carotid calcification and periodontitis was 2.1 (95% CI: 1.3-3.2, P < 0.001), and for PMX carotid calcification and stroke 4.2 (95% CI: 1.9-9.1, P < 0.001). The associations disappeared when smoking was accounted for. A history of a heart attack was associated with stroke, gender, age, and PMX scores of alveolar bone loss. CONCLUSIONS: PMXs may provide valuable information about both oral conditions and signs of carotid calcification, data that are consistent with self-reported health conditions. Alveolar bone loss as assessed from PMXs is associated with cardiovascular diseases.

Pucher, J. J. and J. Otomo-Corgel (2002). "Periodontal disease and systemic health--diabetes." J Calif Dent Assoc 30(4): 312-6.

ABSTRACT: This article discusses the biologic basis of periodontal disease and diabetes mellitus. Following is a consideration of the possibility of a link between diabetes and periodontal disease. Mounting evidence suggests that there is, indeed, a connection between periodontal disease and diabetes.

Pussinen, P. J., K. Tuomisto, et al. (2007). "Endotoxemia, immune response to periodontal pathogens, and systemic inflammation associate with incident cardiovascular disease events." Arterioscler Thromb Vasc Biol 27(6): 1433-9.

ABSTRACT: OBJECTIVE: In periodontitis, overgrowth of gram-negative bacteria may cause endotoxemia and systemic inflammation leading to cardiovascular diseases (CVD). We investigated in a prospective study the associations of serum endotoxin, antibodies to periodontal pathogens, and inflammation markers with the risk of incident CVD. METHODS AND RESULTS: The FINRISK 1992 cohort of 6051 individuals was followed up for 10 years. We examined 185 incident CVD events and a control cohort of 320 individuals using a prospective case-cohort design. High antibody response to periodontal pathogens independently predicted incident CVD events with hazard ratios (HR, quartile 4 versus quartiles 1 to 3, 95% CI) of 1.87 (1.13 to 3.08). The subjects with a high antibody response and high CRP or interleukin (IL)-6 had multivariate-adjusted HRs of 3.01 (1.27 to 7.09) and 3.11 (1.42 to 6.83) compared with low-responders, respectively. The corresponding HRs for high endotoxin concentration were 1.82 (1.22 to 2.73, alone), 3.92 (1.99 to 7.74, with CRP), 3.54 (1.78 to 7.03, with IL-6), and 2.26 (1.13 to 4.52, with tumor necrosis factor (TNF)-alpha) after adjusting for age and gender. These associations were abolished after adjusting for serum lipids. High endotoxin/HDL ratio, however, had a multivariate-adjusted HR of 1.92 (1.19 to 3.08) for CVD events. CONCLUSIONS: Our results suggest that the exposure to periodontal pathogens or endotoxin induces systemic inflammation leading to increased risk for CVD.

Rivera-Hidalgo, F. (2001). "Systemic disease and periodontal disease." Tex Dent J 118(10): 944-53.

Roberts, G. L. (1951). "Oral infection in relation to systemic disease with special reference to the crowning of teeth." Med Press 226(25): 602-5.

Rose, L. F., B. J. Steinberg, et al. (2000). "The relationship between periodontal disease and systemic conditions." Compend Contin Educ Dent 21(10A): 870-7; quiz 878.

ABSTRACT: In this year's report of the United States Surgeon General on oral health in America, two major themes evolved: 1) oral health means much more than healthy teeth, and 2) oral health is integral to general health. This article describes how oral diseases, in particular periodontal diseases, are associated with other health problems, including cardiovascular disease, diabetes mellitus, complications of pregnancies, and osteoporosis.

Rudiger, S., G. Petersilka, et al. (1999). "Combined systemic and local antimicrobial therapy of periodontal disease in Papillon-Lefevre syndrome. A report of 4 cases." J Clin Periodontol 26(12): 847-54.

ABSTRACT: 4 patients, 2 pairs of siblings, suffering from Papillon-Lefevre syndrome were treated for periodontal disease. Following extraction of hopeless teeth, the children received scaling and adjunctive systemic antibiotics (metronidazole and amoxicillin for 7 to 10 days). In addition, they performed supragingival pulsated jet irrigation with 0.06% chlorhexidine digluconate 1 x daily. In 2 siblings, A. actinomycetemcomitans was suppressed subgingivally below detectable levels, pocket probing depths were reduced to 4 mm or less, and plaque and bleeding indices were low. No further disease progression was seen over a 3-year-period. Another female patient also showed clinical improvement and suppression of subgingival A. actinomycetemcomitans and B. forsythus up to the 9-month-follow-up, while her sister showed further attachment loss over the course of 4 years. The present case reports indicated that in some patients suffering from Papillon-Lefevre syndrome periodontal disease may be arrested by means of (i) oral hygiene instruction, (ii) extraction of severely diseased teeth, (iii) scaling, (iv) systemic antibiotics and (v) long-term antimicrobial irrigation.

Scannapieco, F. A. (1998). "Position paper of The American Academy of Periodontology: periodontal disease as a potential risk factor for systemic diseases." J Periodontol 69(7): 841-50.

ABSTRACT: This paper on periodontal disease as a potential risk factor for systemic diseases was prepared by the Research, Science and Therapy Committee of The American Academy of Periodontology. It is intended to provide information regarding the role of periodontal disease in systemic diseases, including bacteremia, infective endocarditis, cardiovascular disease and atherosclerosis, prosthetic device infection, diabetes mellitus, respiratory diseases, and adverse pregnancy outcomes.

Scannapieco, F. A. (2004). "Periodontal inflammation: from gingivitis to systemic disease?" Compend Contin Educ Dent 25(7 Suppl 1): 16-25.

ABSTRACT: There has been a resurgence of interest in recent years in the systemic effects of oral infections such as periodontal diseases. The study of the various means by which periodontal infections and inflammation may influence a variety of systemic conditions is collectively referred to as periodontal medicine. The periodontium responds to tooth-borne biofilm (dental plaque) by the process of inflammation. Dental biofilms release a variety of biologically active products, such as bacterial lipopolysaccharides (endotoxins), chemotactic peptides, protein toxins, and organic acids. These molecules stimulate the host to produce a variety of responses, among them the production and release of potent agents known as cytokines. These include interleukin-1 beta, interleukin-8, prostaglandins, and tumor necrosis factor-alpha. There is a spectrum of periodontal response to these molecules, from mild gingivitis to severe destructive periodontitis. These and other host products and responses may influence a variety of important disease pathways, including atherosclerosis, mucosal inflammation, and premature parturition. The purpose of this article is to review the possible biological pathways by which periodontal diseases may influence these disease processes.

Seiler, J. S. and R. W. Herold (2005). "The use of systemic antibiotics in the treatment of aggressive periodontal disease." Gen Dent 53(2): 155-9; quiz 160, 145-6.

ABSTRACT: General dentists frequently encounter patients with aggressive periodontal disease and should be able to diagnose and manage this disease properly. Periodontal care in the absence of a comprehensive treatment plan and proper therapy can result in the rapid progression of the disease and, ultimately, tooth loss. It is important for the general dentist to diagnose, inform, and treat the periodontal patient accurately, using referral and nonsurgical, surgical, and antimicrobial/antibiotic therapy. This article provides a brief history of the classification of aggressive periodontal disease, describes the microorganisms associated with aggressive periodontal disease, discusses the selection and use of systemic antibiotics in therapy, and lists the various antibiotic regimens for treating aggressive periodontal disease.

Slots, J. and M. Ting (2002). "Systemic antibiotics in the treatment of periodontal disease." Periodontol 2000 28: 106-76.

Yamamoto, Y. (2001). "[Periodontal disease and systemic disease]." Clin Calcium 11(3): 315-8.

ABSTRACT: Periodontal diseases are now recognized as bacterial infections among the chronic diseases of humans. The influence of the oral environment on systemic health, especially the periodontium, has long been supported by scientific evidence. However, an evidence base for the influence of periodontal disease on vital organs such as heart, lung has only recently begun to be established. We are hopeful that this information will stimulate new collaborations between physicians and dentist and serve as basis for studies to help improve the total health.

Yeo, B. K., L. P. Lim, et al. (2005). "Periodontal disease -- the emergence of a risk for systemic conditions: pre-term low birth weight." Ann Acad Med Singapore 34(1): 111-6.

ABSTRACT: This paper addresses the problem of adverse pregnancy outcome in relation to periodontal disease. There is compelling evidence that a link exists between pre-term low birth weight (PLBW) and periodontitis. Although 25% to 50% of PLBW deliveries occur without any known aetiology, there is increasing evidence that infection may play a significant role in pre-term delivery. A model explaining the plausible relationship is proposed based upon the concept of infection leading to a cascade of inflammatory reactions associated with pre-term labour and periodontal disease. Current evidence has pointed to an interest in dental intervention studies to control periodontal disease as one of the potential strategies to reduce pre-term labour. This paper reviews the potential association between periodontal infection and adverse pregnancy outcomes.

Kardiovaskuläre Krankheiten

Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). While the term technically refers to any disease that affects the cardiovascular system, it is usually used to refer to those related to atherosclerosis (arterial disease). These conditions have similar causes, mechanisms, and treatments. In practice, cardiovascular disease is treated by cardiologists, thoracic surgeons, vascular surgeons, neurologists, and interventional radiologists, depending on the organ system that is being treated. There is considerable overlap in the specialties, and it is common for certain procedures to be performed by different types of specialists in the same hospital.

Most Western countries face high and increasing rates of cardiovascular disease. Each year, heart disease kills more Americans than cancer. Diseases of the heart alone caused 30% of all deaths, with other diseases of the cardiovascular system causing substantial further death and disability. It is the number 1 cause of death and disability in the United States and most European countries. A large histological study (PDAY) showed vascular injury accumulates from adolescence, making primary prevention efforts necessary from childhood. By the time that heart problems are detected, the underlying cause (atherosclerosis) is usually quite advanced, having progressed for decades. There is therefore increased emphasis on preventing atherosclerosis by modifying risk factors, such as healthy eating, exercise and avoidance of smoking.

SCIENTIFIC PAPERS

(1996). "Periodontal management of patients with cardiovascular diseases. American Academy of Periodontology." J Periodontol 67(6): 627-35.

ABSTRACT: Periodontists are often called upon to provide periodontal therapy for patients with a variety of cardiovascular diseases. Safe and effective periodontal treatment requires a general understanding of the underlying cardiovascular diseases, their medical management, and necessary modifications to dental/periodontal therapy that may be required. In this informational paper more common cardiovascular disorders will be discussed and dental management considerations briefly described. This paper is intended for the use of periodontists and members of the dental profession.

(2002). "Periodontal management of patients with cardiovascular diseases." J Periodontol 73(8): 954-68.

Andrews, P. A. (2005). "Inflammatory periodontal disease as a potential marker of cardiovascular risk." Transplantation 80(1): 1-2.

Armitage, G. C. (2000). "Periodontal infections and cardiovascular disease--how strong is the association?" Oral Dis 6(6): 335-50.

ABSTRACT: In the past decade there has been renewed interest in the old hypothesis that infections increase the risk of developing cardiovascular disease and stroke. There is now a convincing body of evidence that atherosclerosis has a major inflammatory component and is much more than the simple vascular accumulation of lipids. Infectious agents that have been linked to an increased risk of coronary heart disease (CHD) include Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesviruses. The concept has emerged that each of these agents is an independent risk factor for CHD and that common chronic infections are important. In addition, periodontal infections have also been implicated as one of several factors contributing to the development of CHD. Evidence supporting a causative role of chronic infections in CHD is largely circumstantial. However, the evidence is sufficiently strong to warrant further examination of the possible link between chronic infections and CHD. In this review the lines of evidence for a causative role of C. pneumoniae in the development of CHD are summarized and contrasted with the lines of evidence suggesting a periodontal infection--CHD association. If common or widespread chronic infections are truly important risk factors for CHD, it is unlikely that a single infection will be shown to be causative. It is likely that the entire microbial burden of the patient from several simultaneous chronic infections is more important (e.g., H. pylori-caused gastric ulcers + C. pneumoniae-caused bronchitis + periodontitis). Increased cooperation between cardiologists and periodontists will be required to determine if, and what, combinations of common chronic infections are important in the pathogenesis of CHD and stroke.

Beck, J., R. Garcia, et al. (1996). "Periodontal disease and cardiovascular disease." J Periodontol 67(10 Suppl): 1123-37.

ABSTRACT: It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.

Beck, J. D. and S. Offenbacher (2001). "The association between periodontal diseases and cardiovascular diseases: a state-of-the-science review." Ann Periodontol 6(1): 9-15.

ABSTRACT: Early case-control and cross-sectional studies demonstrating associations between chronic periodontitis and cardiovascular disease (CVD) were quickly followed by secondary analyses of data available from existing longitudinal studies, which indicated that individuals with periodontitis, as determined by clinical measures, were at greater risk for CVD events. Many of these studies contained large numbers of subjects and were adjusted for traditional risk factors. Within the last 18 months, one case-control study and one longitudinal study have reported finding positive associations that were not statistically significant. The earlier studies stimulated a number of studies focused on identifying potential biological mechanisms that might underlie this association. While still early in that process, such studies have implicated a systemic role for oral microorganisms and for the quality and quantity of the host inflammatory response as key biologic processes that may underlie the association of CVD with the clinical manifestation of periodontitis. It is a positive development when changes in our knowledge regarding biologic mechanisms result in reevaluation of past studies, and this reevaluation leads to new studies that incorporate the design elements demanded by this new knowledge. In that spirit, we conclude that all longitudinal studies reported to date can be characterized as follows: none were initially designed to actually test the association of interest; almost all were restricted to clinical measures of periodontitis to index the exposure and lacked measures of infectious burden and host response; and they used a variety of cardiovascular clinical events to index the outcome and did not include subclinical measures of atherosclerosis. In addition, the longitudinal studies that failed to show a significant association between periodontitis and CVD used the least sensitive and crudest clinical measures of periodontal disease. Based upon the current state-of-the-science, all previous studies should be viewed as lacking sufficiently sensitive and comprehensive measures of periodontal disease as a systemic exposure. Since the potential health care impact of this relationship might be extensive, it is time to enter the next phase of research by conducting molecular epidemiology studies that are appropriately designed to test our current understanding of the molecular and cellular mechanisms involved.

Beck, J. D. and S. Offenbacher (2005). "Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease." J Periodontol 76(11 Suppl): 2089-100.

Bokhari, S. A. and A. A. Khan (2006). "The relationship of periodontal disease to cardiovascular diseases--review of literature." J Pak Med Assoc 56(4): 177-81.

ABSTRACT: Association of Oral and Systemic diseases has gained importance because the high occurrence of oral diseases is an extremely common source of infection. Epidemiological Studies have presented periodontal diseases as a risk factor for development of cardiovascular diseases. A chronic oral infection such as periodontitis is a constant potential source of infection and has now been considered as a separate risk factor for cardiovascular diseases, cerebrovascular diseases, peripheral arterial disease and respiratory diseases as well as delivery of low-birth-weight infants. The possible pathways linking oral infections to systemic diseases are metastatic infections, bacterial endotoxins, and systemic vascular injury. People with a history of periodontal disease and/or tooth loss were found at higher risk for Peripheral arterial disease (PAD) as compared to those without periodontal disease and/or tooth loss. All studies on the relationship of periodontal diseases to cardiovascular diseases are inconclusive and most of the data is based on epidemiological studies.

Chong, P. H. and B. Kezele (2000). "Periodontal disease and atherosclerotic cardiovascular disease: confounding effects or epiphenomenon?" Pharmacotherapy 20(7): 805-18.

ABSTRACT: Recent evidence suggests that periodontal disease may predispose to atherosclerotic cardiovascular disease. Data support mechanisms of host-derived local and systemic proinflammatory responses similar to atherosclerosis, consisting of monocytic-derived cytokines and other inflammatory mediators, which are induced by periodontal pathogens and its endotoxin, lipopolysaccharide. These mechanisms may contribute to the start of vascular endothelial dysfunction and further sequelae leading to atherosclerosis. Experimental evidence and biologic plausibility appear to support this proposal. However, clinical evidence from a MEDLINE search from January 1966-December 1999 proposed a weak or no correlation primarily due to confounding factors. The aim of care is to reduce vulnerable pathogens from the infected periodontium by standard treatment; however, new approaches appear promising. Increased awareness of a potential link among infective agents, immunoinflammatory processes, and atherosclerosis may clarify clinical implications.

Chow, J. P. (1998). "Periodontal and cardiovascular diseases." J Am Dent Assoc 129(4): 410.

Craig, R. G. (2004). "Inflammation, cardiovascular disease and destructive periodontal diseases. The evolving role of the dental profession." N Y State Dent J 70(5): 22-6.

ABSTRACT: Destructive periodontal diseases have been associated with increased risk of atherosclerotic complications, including myocardial infarction (MI) and stroke. This finding comes at a time when our understanding of atherosclerotic complications are changing from a focus on the occlusion of arteries, due to the buildup of plaque deposits, to an increased awareness of the role of inflammation in plaque rupture and thrombus formation. The role of inflammation can have great significance to the dental profession if inflammatory cells and factors derived from chronic infections, such as destructive periodontal diseases, are shown to contribute to plaque rupture. This "Perspectives" feature will review the role of inflammation in atherosclerotic complications, and the association between destructive periodontal diseases, systemic inflammation and atherosclerotic complications. It will also highlight ongoing research designed to determine whether destructive periodontal diseases contribute to atherosclerotic complications.

Cunha-Cruz, J. and P. Nadanovsky (2003). "[Does periodontal disease cause cardiovascular disease? Analysis of epidemiological evidences]." Cad Saude Publica 19(2): 357-68.

ABSTRACT: This article reports a critical analysis of epidemiologic studies that evaluated periodontal disease as a cause of cardiovascular disease. Thirty-five studies were identified through a manual search of the special abstracts volumes of the Journal of Dental Research, as well as an electronic search on MEDLINE, LILACS, and ISI and inspection of the articles' bibliographies. Inclusion criteria were: articles in any language published between 1989 and 2000 reporting the presence or absence of an association between periodontal and cardiovascular diseases. Available studies are scarce, and interpretations are limited by potential bias and confounding. The studies analyzed (whether separately or jointly) fail to provide convincing epidemiologic evidence for a causal association between periodontal and cardiovascular diseases. Although the possibility that oral diseases can cause cardiovascular diseases cannot be discarded, until better data are available, periodontal disease should not be incriminated as a cause of cardiovascular disease.

Czerniuk, M., K. J. Filipiak, et al. (1999). "[Periodontal state and cardiovascular diseases]." Pol Arch Med Wewn 101(5): 433-6.

D'Aiuto, F., M. Parkar, et al. (2006). "Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial." Am Heart J 151(5): 977-84.

ABSTRACT: BACKGROUND: Chronic infections, such as periodontitis, are associated with increased risk of systemic diseases driven by a persistent low-grade systemic inflammation and metabolic changes. Severity of periodontitis has also been associated with increased systolic blood pressure (BP). However, the issue remains poorly investigated. We aimed to estimate the effect of periodontal therapy on traditional and novel cardiovascular risk factors in systemically healthy individuals who have periodontitis. METHODS: We enrolled 40 otherwise healthy patients with severe chronic generalized periodontitis in a 6-month pilot intervention trial. Individuals were randomized either to a standard course of periodontal therapy (subgingival scaling and root planing) or an intensive one (including the adjunctive use of a locally delivered antimicrobial, IPT). RESULTS: Compared to control, IPT produced significant reductions in a cluster of inflammatory markers at 1 (P = .0406) and 2 (P = .0060) months together with an improvement in lipid markers at 2 (P = .0320) and 6 (P = .0432) months after therapy. Intensive periodontal therapy produced greater reductions in IL-6 at 1 (0.4 +/- 0.2 ng/L difference, 95% CI 0.03-0.9, P = .0284) and 2 months (0.3 +/- 0.2 ng/L difference, 95% CI 0.1-0.8, P = .0284), together with decreases in C-reactive protein (0.4 +/- 0.2 mg/L difference, 95% CI 0.01-0.8, P = .0438) and total cholesterol (0.3 +/- 0.1 mmol/L difference, 95% CI 0.04-0.6, P = .0254). Moreover, a 7 +/- 3-mm Hg decrease in systolic BP was observed at 2 months in the IPT group (95% CI 1-12, P = .0211), and this difference was greater in current smokers (14 +/- 5 mm Hg 95% CI 3-25, P = 0.0124). Intensive periodontal therapy subjects exhibited a 1.53% +/- 1.20% (95% CI 1.05-2.24, P = .0290) and 2.00% +/- 1.42% (95% CI 0.98-4.09, P = .0568) decreases in cardiovascular risk scores (Framingham) at 2 and 6 months, respectively, when compared to those in the standard group. CONCLUSIONS: Our findings suggest that intensive periodontal treatment reduces systemic inflammatory markers and systolic BP, and improves lipid profiles with subsequent changes in cardiovascular risk when compared to standard therapy.

D'Aiuto, F., D. Ready, et al. (2004). "Periodontal disease and C-reactive protein-associated cardiovascular risk." J Periodontal Res 39(4): 236-41.

ABSTRACT: BACKGROUND: Periodontitis has been associated with a moderate systemic inflammatory response. Successful periodontal therapy could decrease serum inflammatory parameters. The aim of this report was to explore the outcomes of periodontal therapy in terms of changes in C-reactive protein (CRP)-associated cardiovascular disease (CVD) risk as defined in a recent American Heart Association (AHA) consensus conference. METHODS: Ninety-four systemically healthy subjects suffering from severe generalized periodontitis received standard non-surgical periodontal therapy. Periodontal parameters and serum inflammatory responses [interleukin-6 (IL-6) and CRP] were monitored 2 and 6 months after therapy. RESULTS: At baseline, subjects with more severe and widespread periodontitis had a higher chance of having high CRP-associated CVD risk (OR 5.6, 95% CI 1.2-27.4). Age and body mass index were also significant in the analysis. After therapy, a significant decrease in number of subjects associated with a medium and high CRP-associated risk was observed (p < 0.001 chi(2)), with 40 of 94 subjects displaying a decrease in their class of risk. Patients who had a better oral response to periodontal therapy were also more likely to have decreased their inflammatory risk category (OR 4.8, 95% CI 1.4-15.8) after correcting for age, gender, ethnicity and cigarette smoking. CONCLUSIONS: This study indicated that periodontitis may add to the inflammatory burden of the individual and may result in increased levels of cardiovascular risk based on serum CRP concentrations. These observations will need to be confirmed in a definitive trial. Given the high prevalence of periodontitis in the population, these data would caution physicians to be aware of the possible oral source of an increased inflammatory burden.

D'Aiuto, F. and M. S. Tonetti (2005). "Contribution of periodontal therapy on individual cardiovascular risk assessment." Arch Intern Med 165(16): 1920-1.

Dave, S., E. L. Batista, Jr., et al. (2004). "Cardiovascular disease and periodontal diseases: commonality and causation." Compend Contin Educ Dent 25(7 Suppl 1): 26-37.

ABSTRACT: Periodontal diseases have long been recognized as a public health problem. Awareness of the destructive nature of periodontal diseases and the importance of a tight control of bacterial plaque are basic concepts of periodontal treatment. In the past decade, there has been a conceptual shift from periodontal diseases as an oral problem to periodontitis having an impact on systemic health. Recent evidence suggests a strong relationship between periodontal inflammatory disease and systemic diseases, such as cardiovascular disease. It is now generally accepted that inflammation plays an important role in atherosclerosis, and factors that systemically amplify inflammation are under close investigation. This article reviews some of the emerging concepts for the inflammatory mechanisms of periodontal diseases and atherosclerosis and examines the potential role of local inflammation in systemic inflammatory disease.

Demmer, R. T. and M. Desvarieux (2006). "Periodontal infections and cardiovascular disease: the heart of the matter." J Am Dent Assoc 137 Suppl: 14S-20S; quiz 38S.

ABSTRACT: BACKGROUND: Oral infection models have emerged as useful tools to study the hypothesis that infection is a cardiovascular disease (CVD) risk factor. Periodontal infections are a leading culprit, with studies reporting associations between periodontal disease and CVD. The results, however, have varied, and it often is unclear what conclusions can be drawn from these data. SUMMARY: An association exists between periodontal disease and CVD. It is unknown, however, whether this relationship is causal or coincidental. Early studies predominantly used nonspecific clinical and radiographic definitions of periodontal disease as surrogates for infectious exposure. While most studies demonstrated positive associations between periodontal disease and CVD, not all studies were positive, and substantial variations in results were evident. More recent studies have enhanced the specificity of infectious exposure definitions by measuring systemic antibodies to selected periodontal pathogens or by directly measuring and quantifying oral microbiota from subgingival dental plaque. Results from these studies have shown positive associations between periodontal disease and CVD. CONCLUSIONS: Evidence continues to support an association among periodontal infections, atherosclerosis and vascular disease. Ongoing observational and focused pilot intervention studies may inform the design of large-scale clinical intervention studies. Recommending periodontal treatment for the prevention of atherosclerotic CVD is not warranted based on scientific evidence. Periodontal treatment must be recommended on the basis of the value of its benefits for the oral health of patients, recognizing that patients are not healthy without good oral health. However, the emergence of periodontal infections as a potential risk factor for CVD is leading to a convergence in oral and medical care that can only benefit the patients and public health.

Dennison, D. K. (1998). "Cardiovascular disease and periodontal disease." J Gt Houst Dent Soc 70(3): 12-7.

Dumitrescu, A. L. (2005). "Influence of periodontal disease on cardiovascular diseases." Rom J Intern Med 43(1-2): 9-21.

ABSTRACT: Periodontal medicine defines a rapidly emerging branch of periodontology focusing on the wealth of new data establishing a strong relationship between periodontal health or disease and systemic health or disease. The aim of this paper is to critically examine the evidence for an association between periodontal infections and cardiovascular disease. MATERIAL AND METHODS: Literature and data on periodontal diseases and their links to cardiovascular disease. Medline and Pub-Med search. Review of relevant information and data. RESULTS: There is increasing evidence that individuals with periodontal disease may be at higher risk for adverse medical outcomes, including cardiovascular disease. A number of studies to date indicate that this increased risk appears to be independent of other known behavioral and medical risk factors and also appears to be related to the severity of periodontal disease. This article evaluates the inflammatory mechanisms of periodontal disease and cardiovascular disease and examines the potential role of local inflammation in systemic inflammatory disease. CONCLUSIONS: Periodontal diseases may be risk factors for cardiovascular diseases.

Genco, R., S. Offenbacher, et al. (2002). "Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms." J Am Dent Assoc 133 Suppl: 14S-22S.

ABSTRACT: BACKGROUND: Many early epidemiologic studies reported an association between periodontal disease and cardiovascular disease. However, other studies found no association or nonsignificant trends. This report summarizes the evidence from epidemiologic studies and studies that focused on potential contributing mechanisms to provide a more complete picture of the association between periodontal and heart disease. TYPES OF STUDIES REVIEWED: The authors summarize the longitudinal studies reported to date, because they represent the highest level of evidence available regarding the connection between periodontal disease and heart disease. The authors also review many of the case-control and cross-sectional studies published, as well as findings from clinical, animal and basic laboratory studies. RESULTS: The evidence suggests a moderate association--but not a causal relationship--between periodontal disease and heart disease. Results of some case-control studies indicate that subgingival periodontal pathogenic infection may be associated with myocardial infarction. Basic laboratory studies point to the biological plausibility of this association, since oral bacteria have been found in carotid atheromas and some oral bacteria may be associated with platelet aggregation, an event important for thrombosis. Animal studies have shown that atheroma formation can be enhanced by exposure to periodontal pathogens. CONCLUSIONS: The accumulation of epidemiologic, in vitro, clinical and animal evidence suggests that periodontal infection may be a contributing risk factor for heart disease. However, legitimate concerns have arisen about the nature of this relationship. These are early investigations. Since even a moderate risk contributed by periodontal disease to heart disease could contribute to significant morbidity and mortality, it is imperative that further studies be conducted to evaluate this relationship. One particularly important study to be carried out is the investigation of a possible clinically meaningful reduction in heart disease resulting from the prevention or treatment of periodontal disease.

Glurich, I., S. Grossi, et al. (2002). "Systemic inflammation in cardiovascular and periodontal disease: comparative study." Clin Diagn Lab Immunol 9(2): 425-32.

Goldie, M. P. (2004). "C-reactive protein, cardiovascular disease, and periodontal disease." Int J Dent Hyg2(3): 139-41.

Golebiewska, M., K. Taraszkiewicz-Sulik, et al. (2006). "Periodontal condition in patients with cardiovascular diseases." Adv Med Sci 51 Suppl 1: 69-72.

ABSTRACT: The cardiovascular system diseases constitute a serious problem for modern medicine. THE AIM: To investigate the potential risk and the connection of periodontal diseases and cardiovascular disorders. MATERIAL: The examination was performed in the group of 104 patients of both sexes, aged 50-90 years. The patients were divided into two groups: group I--patients with hypertension (47 subjects), group II--patients with fresh myocardial infarction, treated with primary coronary angioplasty (57 subjects). METHODS: The OHI index, according to Greene and Vermillion, was used to assess the oral hygiene and periodontal clinical conditions were evaluated according to Russell's PI index, modified by Davies. CPI index was used to estimate the state of periodontium. Teeth loss was classified according to the Eichner's classification. RESULTS: The value of OHI index differs in both groups. Highest value was registered at 5 patients in the I group vs 2 in the II group. Lowest value was recorded in 11 patients in the I group and 4 in the II group. The value 0.0-0.2 PI was recorded at 14 persons in the I group and 11 in the II group. The value 1.6-3.8 of PI index was registered at 2 in the I group and 6 in the II group. Healthy periodontium was stated in 10 patients with hypertension and only 2 with myocardial infarction. The CPI = 2 was shown in 12 patients with hypertension and 11 with myocardial infarction, CPI = 3 was shown in 23 patients with myocardial infarction. CONCLUSION: The studies revealed bad condition of the oral cavities of patients with hypertension, and specifically with fresh myocardial infarction.

Howell, T. H., P. M. Ridker, et al. (2001). "Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians." J Am Coll Cardiol 37(2): 445-50.

ABSTRACT: OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men.

Joshipura, K. J., H. C. Wand, et al. (2004). "Periodontal disease and biomarkers related to cardiovascular disease." J Dent Res 83(2): 151-5.

ABSTRACT: Periodontal disease is a chronic infection of the gums characterized by a loss of attachment between the tooth and bone, and by bone loss. We evaluated cross-sectionally the association between periodontal disease and C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (t-PA), LDL-C, von Willebrand factor, and soluble tumor necrosis factor receptors 1 and 2. The final sample consisted of 468 men (ages 47-80 yrs), participating in the Health Professional Follow-up Study, who provided blood and were free of CVD, diabetes, and cancer. In multivariate regression models controlling for age, cigarette smoking, alcohol intake, physical activity, and aspirin intake, self-reported periodontal disease was associated with significantly higher levels of CRP (30% higher among periodontal cases compared with non-cases), t-PA (11% higher), and LDL-C (11% higher). Based on our data, periodontal disease showed significant associations with biomarkers of endothelial dysfunction and dyslipidemia, which may potentially mediate the association between periodontal and cardiovascular disease.

Katz, J., G. Chaushu, et al. (2001). "On the association between hypercholesterolemia, cardiovascular disease and severe periodontal disease." J Clin Periodontol 28(9): 865-8.

ABSTRACT: BACKGROUND: Premature death in men is known to be significantly associated with coronary heart disease (CHD). More and more studies are pointing toward a possible association between periodontal disease and increased risk of cardiovascular disease. The association of poor oral hygiene and atherosclerosis can be explained by the effect of chronic inflammatory disease on blood rheology. The purpose of the present study was to assess the relationship between CHD and periodontal disease. PATIENTS AND METHODS: The study population included 1094 Israeli army service men aged 26-53 years (mean: 39+/-5 years). The study group comprised 151 subjects classified as having coronary heart disease CHD, i.e., myocardial infarction, and or anginal syndrome with angiographic evidence of significant coronary disease, or suffer from atherosclerotic risk factors, i.e., diabetes (fasting glucose) and HTN according to strict, well-established criteria. Blood levels of cholesterol and triglycerides were also determined. The severity of periodontal disease was assessed by the aid of CPITN. The control group comprised 943 healthy subjects. Statistical analysis was performed with chi2 test. RESULTS: Statistical analysis showed a significant association of CPITN score 4 with hypercholesterolemia and a possible association with CHD. CONCLUSIONS: The generation of higher cholesterol blood levels is proposed as a possible link between chronic periodontal inflammation and atherosclerosis.

Kinane, D. F. (1998). "Periodontal diseases' contributions to cardiovascular disease: an overview of potential mechanisms." Ann Periodontol 3(1): 142-50.

ABSTRACT: Periodontitis and atherosclerosis have complex etiologies, genetic and gender predispositions, and potentially share many risk factors-the most significant of which may be smoking status. These diseases also have many pathogenic mechanisms in common. It is becoming increasingly clear that infections and chronic inflammatory conditions such as periodontitis may influence the atherosclerotic process. The severity and chronicity of periodontal disease provides a rich source of subgingival microbial and host response products and effects over a long time period. The objective of this review is to consider the mechanisms whereby diseases such as periodontitis, which is chronic and Inflammatory In nature and initiated by microbial plaque, can predispose to atherosclerosis. In common with periodontal disease. the pathogenesis of atherosclerosis is not completely understood and both diseases are currently under Intensive investigation. Two main processes in particular are worthy of consideration and may provide the link between these 2 diseases, namely the lipopolysaccharide-related responses and the hyperresponsive monocyte phenomenon. Insufficient experimental evidence exists, however, to further support these hypotheses at present and clearly more research is needed on both of these processes and the interrelationships between both diseases.

Kinane, D. F. and G. D. Lowe (2000). "How periodontal disease may contribute to cardiovascular disease." Periodontol 2000 23: 121-6.

Klinger, A., M. Goldstein, et al. (2002). "[Periodontal disease--an additional risk factor for cardiovascular diseases?]." Refuat Hapeh Vehashinayim 19(2): 67-74, 79.

ABSTRACT: In 1989, a case-control study was published, linking between coronary heart disease and periodontal disease in the studied population. Since then, a number of additional studies, focused the attention to the possible role of dental infections in the pathogenesis of atherosclerosis. Some of these newer cohort studies, are prospective in nature, measuring incidence of the two diseases in large patient populations. The present article reviews these studies, and the proposed mechanisms which might explain the relationships between these two systemically distinct diseases.

Kornman, K. S. and G. W. Duff (2001). "Candidate genes as potential links between periodontal and cardiovascular diseases." Ann Periodontol 6(1): 48-57.

ABSTRACT: Recent epidemiological associations between periodontal disease and cardiovascular disease have led to a search for biological mechanisms that explain the associations. Genetic factors that influence biological processes involved in both diseases represent one of the potential mechanisms that may link periodontitis and cardiovascular disease. At present, several candidate genes have been investigated in one of the diseases but not the other. Although there are limited data to support a specific candidate gene as the explanation for observed associations between the 2 diseases, a few candidates look promising. One candidate that influences inflammation, interleukin-1 gene polymorphisms, has been associated with periodontal disease and cardiovascular disease. This review will consider biological mechanisms and genes that may be reasonable candidates for an etiological mechanism that influences the clinical characteristics of both periodontal disease and cardiovascular disease.

Kuramitsu, H. K., M. Qi, et al. (2001). "Role for periodontal bacteria in cardiovascular diseases." Ann Periodontol 6(1): 41-7.

ABSTRACT: BACKGROUND: Several epidemiological studies as well as a recent animal model approach have suggested a role for periodontal diseases in the development of cardiovascular disease (CVD). This relationship could be mediated by inflammatory responses induced by periodontal pathogens as well as direct interaction of these organisms with cardiac tissue. METHODS: In order to explore these possibilities, the effects of the periodontal pathogen Porphyromonas gingivalis on cellular events proposed to play a role in CVD were investigated. RESULTS: P. gingivalis, as well as its outer membrane vesicles (OMV), was able to induce foam cell formation (an important characteristic of CVD) in the murine macrophage cell line J774 A.1. This property appears to be mediated by the lipopolysaccharide (LPS) fraction of the cells. Several other oral bacteria were also able to induce foam cell formation. Furthermore, since the rupture of the fibrous cap of plaque appears to be an important factor in acute coronary syndrome, it was demonstrated that P. gingivalis 381 degraded fibrous caps isolated from autopsy samples. In addition, it was observed that strain 381 strongly induced matrix metalloproteinase (MMP)-9 protease activity, implicated in plaque rupture, from the J774 A.1 macrophages. Finally, strain 381 was able to enhance monocyte chemoattractant protein-1 (MCP-1) and NADH oxidase expression from endothelial cells. CONCLUSIONS: Therefore, P. gingivalis exhibits several properties which could play a role in CVD as mediators of LDL oxidation, foam cell formation, and rupture of atherosclerotic plaque.

Loesche, W. J. (2000). "Periodontal disease: link to cardiovascular disease." Compend Contin Educ Dent21(6): 463-6, 468, 470 passim; quiz 484.

ABSTRACT: Poor oral hygiene that leads to dental infections could contribute to adverse medical outcomes such as cardiovascular disease. Twelve studies of varying degrees of design rigor have associated dental conditions, such as periodontal disease, missing teeth, and edentulousness, with either coronary heart disease or a cerebral vascular accident. Six of the studies were longitudinal so that the demonstration of the oral health parameters as significant predictors of the cardiovascular event would elevate the dental parameter to the status of a risk factor. Because dental diseases (especially periodontal disease) are treatable, the dental component is a modifiable risk factor; therefore, maintaining good oral health should receive the highest priority for a healthy life.

Loesche, W. J. (2000). "Periodontal infection a risk factor for cardiovascular disease?" Postgrad Med107(5): 17, 20.

Losche, W. (2007). "Periodontitis and cardiovascular disease: periodontal treatment lowers plasma cholesterol." South Med J 100(7): 663-4.

Nesse, W., F. K. Spijkervet, et al. (2006). "[Links between periodontal disease and general health. 1. Pneumonia and cardiovascular disease]." Ned Tijdschr Tandheelkd 113(5): 186-90.

ABSTRACT: The possible link between oral and general health is based on an old concept. This paper summarizes current ideas on the role of translocation of oral pathogens to other parts of the body in the development of systemic disease. It appears that colonisation of the oral cavity by respiratory pathogens is a risk factor in the development of pneumonia in institutionalised elderly and intensive care patients. Using a chloorhexidine oral rinse may reduce the risk of pneumonia. Furthermore, periodontal disease is associated with an increased risk of cardiovascular disease. Translocation of oral microorganisms and an increase in serum concentrations of inflammatory mediators are considered to play a role in the development of cardiovascular disease. Potentially, preventive oral health care and periodontal intervention could play a part in preventing cardiovascular disease.

Paquette, D. W. (2004). "The periodontal-cardiovascular link." Compend Contin Educ Dent 25(9): 681-2, 685-92; quiz 694.

ABSTRACT: Cardiovascular disease (CVD) and periodontitis are common chronic conditions, and the former remains a major contributor to human mortality. Recent attention has focused on a potential link between periodontal disease and CVD. Observational studies consistently indicate that people with destructive periodontitis may be 1.3 to 2 times more likely to have CVD. This association appears to be biologically plausible, and investigations in atherosclerosis animal models demonstrate larger atheroma sizes in animals infected with the periodontal pathogen, Porphyromonas gingivalis, compared with control animals. Although direct intervention data on the effects of periodontal therapy on CVD risk in patients are not currently available, indirect data suggest that mechanical periodontal therapy can decrease surrogate cardiovascular markers such as serum C-reactive protein. After a recent systematic review on the periodontal-cardiovascular link, a consensus panel concluded that patients and clinicians should be informed that periodontal therapy may prevent the onset or progression of CVD.

Paquette, D. W., N. Brodala, et al. (2007). "Cardiovascular disease, inflammation, and periodontal infection." Periodontol 2000 44: 113-26.

Persson, R. E., L. G. Hollender, et al. (2002). "Assessment of periodontal conditions and systemic disease in older subjects. II. Focus on cardiovascular diseases." J Clin Periodontol 29(9): 803-10.

Pinero, J. (1998). "Nd:YAG-assisted periodontal curettage to prevent bacteria before cardiovascular surgery." Dent Today 17(3): 84-7.

Renvert, S. (2003). "Destructive periodontal disease in relation to diabetes mellitus, cardiovascular diseases, osteoporosis and respiratory diseases." Oral Health Prev Dent 1 Suppl 1: 341-57; discussison 358-9.

Scannapieco, F. A., R. B. Bush, et al. (2003). "Associations between periodontal disease and risk for atherosclerosis, cardiovascular disease, and stroke. A systematic review." Ann Periodontol 8(1): 38-53.

ABSTRACT: BACKGROUND: Recent studies implicate exposure to systemic conditions involving chronic inflammation, including chronic periodontitis, in the etiology of atherosclerosis. RATIONALE: A systematic review of the literature was conducted to assess the association between chronic inflammatory periodontal disease and atherosclerosis. FOCUSED QUESTION: Does periodontal disease influence the initiation/progression of atherosclerosis and, therefore, cardiovascular disease (CVD), stroke, and peripheral vascular disease (PVD)? SEARCH PROTOCOL: MEDLINE, pre-MEDLINE, MEDLINE Daily Update, and the Cochrane Controlled Trials Register were searched to identify human studies that related variables associated with atherosclerosis to periodontal disease. Searches were made for papers published from 1966 through March 2002. INCLUSION CRITERIA: Published randomized controlled clinical trials (RCTs), longitudinal, cohort, and case-control studies were included. Study participants included those with atherosclerosis, myocardial infarction (MI), stroke, or PVD. Oral conditions included periodontal disease. EXCLUSION CRITERIA: Only studies on humans were included. DATA COLLECTION AND ANALYSIS: Because the studies used different oral assessment measures, it was not possible to perform a meta-analysis of the data reported. Weighted mean differences, relative risks, or odds ratios were compared for cohort studies. MAIN RESULTS: 1. Of the initial 1,526 studies identified, 31 (including 8 case-control and 18 cross-sectional reports) were included in the analysis. Taken together, most of the literature supports a modest association between periodontal disease and atherosclerosis. However, data reported in several studies do not show this association. 2. The absence of a standard definition and measures for periodontal disease complicates interpretation of results, as do potential confounding risk factors common to both conditions. REVIEWERS' CONCLUSIONS: 1. Periodontal disease may be modestly associated with atherosclerosis, MI, and CVD. 2. Additional large-scale longitudinal epidemiologic and intervention studies are necessary to validate this association and to determine causality.

Stanford, T. W., Jr. (2005). "Periodontal disease and cardiovascular disease: is there an association?" Tex Dent J 122(12): 1198-201.

Stein, H. (1999). "Periodontal disease as a risk factor for cardiovascular disease and myocardial infarction." Ont Dent 76(1): 16-20.

Taylor, B. A. and G. H. Tofler (2002). "Evidence for an association between periodontal disease and cardiovascular disease." Ann R Australas Coll Dent Surg 16: 82-3.

Vettore, M. V. (2004). "Periodontal disease and cardiovascular disease." Evid Based Dent 5(3): 69.

Vilkuna-Rautiainen, T., P. J. Pussinen, et al. (2006). "Serum antibody response to periodontal pathogens and herpes simplex virus in relation to classic risk factors of cardiovascular disease." Int J Epidemiol35(6): 1486-94.

ABSTRACT: BACKGROUND: Increasing evidence links chronic infections, especially burden of several infections, with increased risk for cardiovascular diseases (CVD). We studied joint immune response against two major periodontal pathogens and herpes simplex virus (HSV) in relation to established risk factors of CVD. METHODS: Serum antibody levels to HSV, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by ELISA. The study included 1107 subjects, 734 from Finland and 373 from Russia. RESULTS: Combined antibody response to periodontal pathogens was associated inversely (OR, 95% CI) with high-density lipoprotein (HDL) cholesterol concentration (beta = 0.35; 0.20, 0.60; P < 0.001) and directly with HSV antibody quartiles: compared with the first quartile, ORs (95% CI) for quartiles 2-4 were 1.43 (0.88-2.32), 1.74 (1.07-2.82), and 1.89 (1.18-3.02), respectively (P for trend <0.001), after adjusting for age, gender, area, education, smoking, BMI, alcohol, triglycerides, and number of teeth. In linear regression analysis, the 3-pathogen antibody score (comprising antibody levels against periodontal pathogens and HSV) was inversely associated with HDL cholesterol concentration (beta = -0.067/1 mmol/l; -0.235, -0.018; P < 0.05). CONCLUSIONS: HSV infection may promote infection by periodontal pathogens. Furthermore, the infectious burden comprising HSV and periodontitis may increase the risk for CVD by clearly decreasing HDL cholesterol concentrations.

Willershausen, B., T. Krahwinkel, et al. (2003). "Correlation between inflammatory periodontal diseases and cardiovascular diseases." Eur J Med Res 8(11): 499-504.

ABSTRACT: AIMS: Since cardiovascular diseases can exhibit a possible connection with chronic periodontal diseases, the aim of the present study was to examine the presence of periodontal impairment in patients with coronary heart diseases (CHD). METHODS: For this purpose periodontal charts were raised for 101 patients (78 male, 23 female, mean age 61.8 +/- 10.5 years) with cardiovascular diseases; comparison was drawn between theses charts and those for a control group of 101 healthy patients (59 male, 42 female, mean age 56.6 +/- 9.9 years). Over and above the dental diagnosis (probing depth [mm], vitality, tooth mobility, plaque index (PI), inclination towards sulcus bleeding) each related to 6 characteristic teeth, various habitual aspects (diet, smoke and drink patterns, stress, body weight) were recorded. RESULTS: Within the CHD-group the periodontal chart revealed for all teeth examined a mean probing depth of 3.4 +/- 1.1mm, with the corresponding reading for the control group being 2.8 +/- 0.9 mm. The mean bleeding index (Van-der-Weiden) read 1.1 +/- 0.7 for the CHD-group and 0.7 +/- 0.6 for the control group. The mean plaque index reading was 1.4 +/- 0.9 for the group suffering from heart diseases and 0.7 +/- 0.8 for the control group. Comparison of these periodontal charts showed statistically significant differences (p<= 0.01), whereas mean degrees of tooth mobility did not differ in a statistically significant way. In summary, the results described hint at a correlation between an existent coronary heart disease and the presence of a periodontitis. CONCLUSION: However, also for consideration below are further influential factors, such as diet, individual life conduct, smoking habits, Body-Mass-Index or microbiological aspects.

Wu, T., M. Trevisan, et al. (2000). "Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen." Am J Epidemiol 151(3): 273-82.

ABSTRACT: Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

Thromboserisiko

Prospektive Studien
Seit längerer Zeit ist bekannt, daß eine Verbindung zwischen Parodontitis und einem erhöhten Risiko für koronare Herzkrankheit (KHK) und anderen thromboembolischen Komplikationen besteht. In einer großen prospektiven US-Studie aus den siebziger und achtziger Jahren (Health examination survey) mit 9760 Personen wurde ein um 25% erhöhtes Risiko für KHK bei Patienten mit Parodontitis gefunden. Ebenso war schlechte Mundhygiene, verifiziert durch den Plaqueindex, mit dem KHK-Risiko korreliert.

Die Parodontitis ist unabhängig von den Risikofaktoren, die beiden Erkrankungen zugrundeliegen können, wie z.B. Rauchen oder systemische Erkrankungen (Diabetes), in einigen Studien als statistisch signifikanter Risikofaktor für thromboembolische Komplikationen erkannt worden.

Mittlerweile weisen auch mehrere Studien darauf hin, daß es sich hierbei um eine kausale Beziehung handelt:

Pathogenese

Direkte Wirkung von Endotoxinen der Markerkeime auf Thrombocyten. Die wichtigsten Parodontitis-Markerkeime (Porphyromonas gingivalis, Prevotella intermedia) produzieren im Sulcus Protease 1, ein eiweißzerstörendes Enzym (Trypsin-ähnlich), das ein wichtiger Pathogenitätsfaktor ist (Gewebsinvasivität) und aus dem Taschenepithel in den Blutkreislauf eindringen kann. Diese Protease 1 aktiviert Thrombozyten und entfaltet damit eine Wirkung, die der des Thrombins gleicht. In geringen Konzentrationen führen die Proteasen zu einer Aggregation der Thrombocyten und damit zu thrombotischen bzw. embolischen Komplikationen.

Bakterielles Endotoxin: Zellwandbestandteile gramnegativer Parodontitis-Bakterien (Endotoxin, Lipopolysaccharide) belasten bei chronischer Parodontitis den gesamten Organismus, da sie dauernd in den Blutstrom gelangen. Diese Lipopolysaccharide (LPS) wirken als B-Zell-Mitogen, d.h. die Antikörperproduzierenden Zellen aktivierend und damit Antikörper-induzierend. Außerdem stimulieren sie als allgemeines immunologisches Adjuvans die Abwehrreaktion. Im Tierversuch konnte an Mäusen gezeigt werden, daß die Lipopolysaccharide von Porphyromonas gingivalis sehr potente Induktoren einer raschen Thrombocyten-Aggregation waren.

Die lokale Abwehrreaktion im Sulcus ist durch die lebhafte Produktion von Cytokinen (Immunmediatoren) begleitet, z.B. Interleukin l, Prostaglandin E2, Tumornekrosefaktor. Diese Cytokine initiieren ebenfalls die Atherogenese und begünstigen damit thromboembolische Ereignisse.

Direkte Wirkung von Sulcusbakterien durch Bakteriämie: Streptococcus sanguis, ein benigner Kommensale im Suicus gingivalis, aggregiert menschliche Thrombocyten in vitro. Im Tierversuch wurde gezeigt, daß zirkulierende Streptokokken in Kaninchen eine Aggregation von Thrombocyten hervorrufen, einschließlich der typischen Anlagerung der Aggregate und von Fibrin an endokarditischen Vegetationen.

In summa zeigt die Assoziation von Parodontitis mit koronarer Herzkrankheit Charakteristika, wie sie auch bei anderen Infekten mit transitorischer, jedoch rekurrierender Bakteriämie beschrieben wurden. Die Suche nach gemeinsamen biologischen Mechanismen ist im Gange und wird eventuell Möglichkeiten der gezielten therapeutischen Beeinflussung eröffnen.

Therapeutische Konsequenzen
Bis dahin ist zweifellos das zahnärztliche und patientenseitige Bemühen um eine gute Mundhygiene ein wichtiger Faktor zur Vorbeugung gegen thromboembolische Komplikationen.

Informationen aus dem Umweltmedizinischen Labor München

Atemwegserkrankungen

Diseases of the mammalian Respiratory system are classified physiologically into obstructive (i.e. conditions which impede the rate of flow into and out of the lungs) and restrictive (i.e. conditions which cause a reduction in the functional volume of the lungs).

Anatomically, respiratory disease can be classified into these categories; upper and lower respiratory tract (most commonly used in the context of infectious respiratory disease), parenchymal and vascular lung diseases.

SCIENTIFIC PAPERS

Aida, Y., T. Kukita, et al. (1995). "Lipopolysaccharides from periodontal pathogens prime neutrophils for enhanced respiratory burst: differential effect of a synthetic lipid a precursor IVA (LA-14-PP)." J Periodontal Res 30(2): 116-23.

ABSTRACT: When neutrophils are incubated with bacterial lipopolysaccharide (LPS), they become primed for enhanced release of superoxide anion (O2-) in response to stimulation by FMLP. We investigated the human neutrophil-priming activity of LPS from the periodontal pathogens, Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi) and Actinobacillus actinomycetemcomitans (Aa) in comparison with that of LPS from Escherichia coli (E. coli). The optimum conditions for LPS to prime neutrophils were assessed for every LPS and found to be as follows: Neutrophils were incubated with LPS in the presence of 10% heat-inactivated plasma and 1 mM EDTA at 37 degrees C for 30 min and then stimulated with 1 microM FMLP at 37 degrees C for 7 min. Under these conditions, half-maximum priming was observed at 6.2 ng/ml Pg-LPS, 45 ng/ml Pi-LPS, 1.5 ng/ml Aa-LPS and 1.5 ng/ml E. coli-LPS. The priming activity of each LPS was neutralized by polymyxin B. Anti-CD14 monoclonal antibody inhibited priming by all LPS. The priming by Aa-LPS and E. coli-LPS was inhibited by LA-14-PP, a synthetic lipid A precursor IVA, but that by Pg-LPS and Pi-LPS was not. Priming by tumor necrosis factor alpha was not affected by polymyxin B, anti-CD14 antibody or LA-14-PP. Gelation of Limulus amebocyte lysate occurred at 10 pg/ml Pg-LPS, 30 pg/ml Pi-LPS, 3 pg/ml Aa-LPS and 3 pg/ml E. coli-LPS. Thus LPS from different periodontal pathogens primed neutrophils with different efficacy.

De Toni, S., E. Piva, et al. (1997). "Respiratory burst of neutrophils in diabetic patients with periodontal disease." Ann N Y Acad Sci 832: 363-7.

ABSTRACT: Periodontal disease, a frequent complication of diabetes mellitus, is the major cause of tooth loss. However, studies on neutrophil function in patients with this condition have yielded contradictory findings. The NADPH oxidase activity of 40 diabetic patients with periodontosis who were on metabolic control was evaluated and compared with that in 40 healthy subjects. Superoxide anion production was measured by a photometric method, with NBT reduction at 490 nm in a microplate reader and by a microscopic method, with a percentage of positive PMNs with granules of formazan in the cytoplasm. When the PMN respiratory burst was activated by phorbol myristate acetate (PMA), a protein kinase C (PKC) soluble activator, superoxide production of diabetics (4.31 +/- 1.67 A x 10(-3)/min) and normal subjects (4.25 +/- 1.25 A x 10(-3)/min) was comparable by photometric method, whereas a significantly defective response to opsonized zymosan was observed when the microscopic method was used (58 +/- 17% in diabetics and 66 +/- 18% in controls; p = 0.05). Therefore in patients with diabetes the impact on PMN function is of multifactorial origin, and is probably correlated to the glucose level and to glycation of PMN protein, such as NADPH oxidase or myeloperoxidase. Alternatively, glucose in PMN may be reduced by aldose reductase to polyols, and this pathway requires NADPH, the coenzyme for the respiratory burst. Moreover, we found that superoxide production in response to opsonized zymosan was reduced in diabetic patients. The activation of protein tyrosine kinase (PTK) is an important mechanism underlying transmembrane signaling and, moreover, protein tyrosine phosphorylations, stimulated by zymosan receptor-mediated activation, might be caused by the activation of specific PTK, whereas activation by PMA is probably mediated through another PKC type.

Giaretti, G., P. L. Gatti, et al. (1985). "[Correlation between periodontal disease and upper respiratory system pathology]." Parodontol Stomatol (Nuova) 24(2): 47-8.

Polster, H. and S. Polster (1980). "[Oral hygiene, caries incidence and the periodontal state in children and adolescents and their relation to disease of the throat and respiratory tracts]." Stomatol DDR 30(8): 566-72.

Redman, R. S. (1989). "Respiratory epithelium in an apical periodontal cyst of the mandible." Oral Surg Oral Med Oral Pathol 67(1): 77-80.

ABSTRACT: A cyst attached to the apex of a mandibular canine was partly lined with respiratory epithelium. This is an interesting observation for two reasons: (1) The few well-documented instances of this type of epithelium in apical periodontal cysts have been in the maxilla, where a plausible source for the respiratory epithelium for most of them was a breach in the floor of the maxillary sinus. (2) The mandibular location of the cyst reported here indicates that the respiratory epithelium within it was derived through proliferation and metaplasia of the rests of Malassez.

Scannapieco, F. A. and A. W. Ho (2001). "Potential associations between chronic respiratory disease and periodontal disease: analysis of National Health and Nutrition Examination Survey III." J Periodontol72(1): 50-6.

ABSTRACT: BACKGROUND: Associations between poor oral health and chronic lung disease have recently been reported. The present study evaluated these potential associations by analyzing data from the National Health and Nutrition Examination Survey III (NHANES III), which documents the general health and nutritional status of randomly selected United States subjects from 1988 to 1994. METHODS: This cross-sectional, retrospective study of the NHANES III database included a study population of 13,792 subjects > or = 20 years of age with at least 6 natural teeth. A history of bronchitis and/or emphysema was recorded from the medical questionnaire, and a dichotomized variable combined those with either chronic bronchitis and/or emphysema, together considered as chronic obstructive pulmonary disease (COPD). Subject lung function was estimated by calculating the ratio of forced expiratory volume (FEV) after 1 second (FEV1)/forced vital capacity (FVC). Oral health status was assessed from the DMFS/T index (summary of cumulative caries experience), gingival bleeding, gingival recession, gingival probing depth, and periodontal attachment level. Unweighted analyses were used for initial examination of the data, and a weighted analysis was performed in a final logistic regression model adjusting for age, gender, race and ethnicity, education, income, frequency of dental visits, diabetes mellitus, smoking, and alcohol use. RESULTS: The mean age of all subjects was 44.4 +/- 17.8 years (mean +/- SD): COPD = 51.2 +/- 17.9 years and subjects without COPD = 43.9 +/- 17.7 years. Subjects with a history of COPD had more periodontal attachment loss than subjects without COPD (1.48 +/- 1.35 mm versus 1.17 +/- 1.09 mm, P = 0.0001). Subjects with mean attachment loss (MAL) > or = 3.0 mm had a higher risk of COPD than those having MAL < 3.0 mm (odds ratio, 1.45; 95% CI, 1.02 to 2.05). A trend was noted in that lung function appeared to diminish with increasing periodontal attachment loss. CONCLUSIONS: The findings of the present analysis support recently published reports that suggest an association between periodontal disease and COPD.

Scannapieco, F. A. and M. P. Rethman (2003). "The relationship between periodontal diseases and respiratory diseases." Dent Today 22(8): 79-83.

Wiersbitzky, S., H. Seipelt, et al. (1987). "[Antibiotic therapy and status of dentition (caries and periodontal diseases) in children with chronic nonspecific respiratory tract diseases]." Padiatr Grenzgeb26(3): 215-21.

Diabetes

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia (high blood sugar) and other signs, as distinct from a single illness or condition. The World Health Organization recognizes three main forms of diabetes: type 1, type 2, and gestational diabetes (occurring during pregnancy), which have similar signs, symptoms, and consequences, but different causes and population distributions. Ultimately, all forms are due to the beta cells of the pancreas being unable to produce sufficient insulin to prevent hyperglycemia. Type 1 is usually due to autoimmune destruction of the pancreatic beta cells which produce insulin. Type 2 is characterized by tissue-wide insulin resistance and varies widely; it sometimes progresses to loss of beta cell function. Gestational diabetes is similar to type 2 diabetes, in that it involves insulin resistance; the hormones of pregnancy cause insulin resistance in those women genetically predisposed to developing this condition.

Types 1 and 2 are incurable chronic conditions, but have been treatable since insulin became medically available in 1921, and today are usually managed with a combination of dietary treatment, tablets (in type 2) and, frequently, insulin supplementation. Gestational diabetes typically resolves with delivery.

SCIENTIFIC PAPERS

(2006). "Periodontal disease onset in children with diabetes earlier than thought." J Am Dent Assoc137(4): 446.

(2007). "Diabetes mellitus promotes periodontal destruction in children." Br Dent J 203(2): 99.

ABSTRACT: This study reports significantly increased attachment loss in young diabetic children.

Al-Shammari, K. F., J. M. Al-Ansari, et al. (2006). "Association of periodontal disease severity with diabetes duration and diabetic complications in patients with type 1 diabetes mellitus." J Int Acad Periodontol8(4): 109-14.

ABSTRACT: OBJECTIVES: The association between periodontal disease severity and diabetes complications and duration in patients with type 1 diabetes mellitus (DM) was investigated in this comparative cross-sectional study. MATERIALS AND METHODS: Twenty-nine patients with type 1 DM of < or = 5 years duration were compared with 43 patients with > 5 years duration of DM. Complete medical history and examination and assessments of retinopathy, neuropathy, and nephropathy were performed, followed by assessments of the plaque index (PI), pocket depth (PD), clinical attachment level (CAL), and the number of missing teeth by one examiner masked to the diabetic status of the patients. RESULTS: The number of missing teeth (4 versus 0) and CAL (2.88 vs 2.56 mm) were significantly higher in patients with longer DM duration (p < 0.05). For patients with > or = 5 years DM duration, periodontal disease severity was also greater in patients with one or more DM complications, as assessed by the number of missing teeth (17 vs 0; p < 0.001) and CAL (4.74 vs 2.81 mm; p < 0.01). Stepwise multiple regression analysis associated the presence of > or = 1 DM complications and smoking history with severe attachment loss (CAL > or = 7 mm; p < 0.001). CONCLUSION: Periodontal disease severity is associated with both DM duration and the presence of DM complications in this sample of type 1 DM patients.

Aren, G., E. Sepet, et al. (2003). "Periodontal health, salivary status, and metabolic control in children with type 1 diabetes mellitus." J Periodontol 74(12): 1789-95.

ABSTRACT: BACKGROUND: The aim of this study was to determine whether detectable periodontal destruction and alterations in the salivary status were present with duration of diabetes in children with type 1 insulin-dependent diabetes mellitus (type 1 DM) as compared to healthy controls. METHODS: Sixteen newly diagnosed children with DM (group 1), 16 children with type 1 DM of long duration (group 2), and 16 healthy children (group 3) participated in the study. Periodontal health was assessed by plaque index, gingival index, bleeding on probing, and periodontal probing depths. The flow rate, pH, buffering capacity, and peroxidase activities of stimulated saliva were determined. The data were analyzed by Kruskall-Wallis, Student t test, and Pearson's correlation analysis. RESULTS: The mean values for fasting blood glucose levels for the diabetic groups were significantly higher than for the controls. The mean values for salivary buffering capacities and salivary pH from the diabetic groups were significantly lower than for the controls. The plaque index values for the diabetic groups were significantly higher than for the controls. The mean gingival index value for group 1 was significantly lower than for group 2. The mean periodontal probing depths for group 1 were similar to those of the non-DM controls, but the mean periodontal probing depths for group 2 were significantly greater than for both the non-DM controls and group 1. Group 1 had significantly greater bleeding on probing scores than did the other groups (P < 0.05). CONCLUSION: The glycemic status of the diabetic subjects affects the periodontal probing depths, salivary pH, buffering capacity, and peroxidase activity.

Arrieta-Blanco, J. J., B. Bartolome-Villar, et al. (2003). "Dental problems in patients with diabetes mellitus (II): gingival index and periodontal disease." Med Oral 8(4): 233-47.

ABSTRACT: Among the late complications associated to the diabetes mellitus, periodontal disease has been highlighted, and it can be more severe and refractory to treatment than in healthy subjects. OBJECTIVES: Determine the prevalence of gingivitis and periodontitis as well as the Community Periodontal Index of Need of Treatment (CPITN) in diabetic population compared with a control one. Analyze the histological characteristics in the gingiva of diabetic patients. STUDY DESIGN: The study sample was made up of 74 control subjects and 70 diabetics. We evaluated the following parameters: gingival status according to the Loe and Silness criterion, probe depth, loss of insertion, gingival recession and Community Periodontal Index of Need of Treatment. We also performed gingival biopsies in 42 diabetic patients and 29 controls for histological studies. RESULTS: We found a statistically higher gingivitis index, loss of insertion and gingival recession in diabetic patients compared to the control population, the same not occurring with the probe depth. We did not find significant differences in the CPITN according to the type of diabetes mellitus, metabolic control or disease duration. The biopsy study did not show significant changes in the gingiva of the diabetic patients compared to the control population. CONCLUSIONS: The gingivitis index was higher in the diabetic population. After examination of the treatment needs, we observed how the diabetic patients required more complex treatment.

Campus, G., A. Salem, et al. (2005). "Diabetes and periodontal disease: a case-control study." J Periodontol 76(3): 418-25.

ABSTRACT: BACKGROUND: Periodontitis is often associated with diabetes and might be considered one of the chronic complications of diabetes mellitus, both in Type 1 (T1DM) and Type 2 (T2DM). This case-control study was designed to evaluate the possible association between non-insulin-dependent diabetes (T2DM) and clinical and microbiological periodontal disease among adult Sardinians. METHODS: A total of 212 individuals participated in this study: 71 T2DM patients aged 61.0 +/- 11.0 years and 141 non-diabetic controls in good general health aged 59.1 +/- 9.2 years. All subjects were given a clinical periodontal examination for probing depth, attachment level, presence of calculus, bleeding on probing, and assessment of plaque. Subgingival plaque samples were obtained, and P. gingivalis, P. intermedia, and T. forsythensis were identified using multiplex polymerase chain reaction. RESULTS: T2DM patients showed a significantly lower number of teeth present (P = 0.002); a significant increase in number of probing depths >4 mm, and percent of pocket depths >4 mm (P = 0.04 and P = 0.05, respectively); periodontitis (P = 0.046); bleeding on probing (P = 0.02); and plaque index (P = 0.01). A significant association with diabetes was detected for plaque (X2= 4.46; P <0.05) and bleeding on probing (X2= 3.60; P <0.05). Concerning bacteria prevalence, a positive association was detected for P. gingivalis (X2= 2.80; P <0.05) and T. forsythensis (X2= 3.87; P <0.05). Presence of plaque was positively associated with case status (odds ratio [OR] = 1.3; 95% confidence interval [CI]: 1.2, 3.6) and with prevalence of P. gingivalis and T. forsythensis (OR = 1.2, 95% CI: 1.3, 2.2; and 1.2, 95% CI: 1.2, 1.8, respectively). CONCLUSION: Patients with T2DM undoubtedly have a susceptibility for more severe periodontal disease.

Chee, H. K., L. P. Lim, et al. (2006). "Non-surgical periodontal therapy and serum lipid levels in patients with diabetes mellitus." Ann R Australas Coll Dent Surg 18: 46.

Feng, Z. M., Y. S. Wu, et al. (2007). "[Change of expression of matrix metalloproteinase-2 in the periodontal tissues of diabetes mellitus rats during orthodontic tooth movement]." Hua Xi Kou Qiang Yi Xue Za Zhi 25(2): 118-21.

ABSTRACT: OBJECTIVE: To observe the expression and distribution of matrix mentallproteinase-2 (MMP-2) in the periodontal tissues of diabetes mellitus (DM) rats during tooth movement, and to observe the affection of diabetes mellitus on the collagen metabolism. METHODS: Eighty male Sprague-Dawley rats were used. Mesial force was applied to pull the maxillary first molar. Forty rats were rendered diabetic by injection of streptozotocin. In 3 weeks after the injection, rats were subjected to lateral tooth movement. The animals were sacrificed after 0, 3, 7, 14 and 21 days respectively. Two-step immunohistochemical method was applied to localize and examine the expression of MMP-2 in periodontal tissue of rats. RESULTS: MMP-2 immunohistochemical results indicated that the MMP-2 expression increased and was observed on both sides periodontium of movement tooth, osteoclast, cementoblast, osteocyte, fibroblast and osteoblast appeared positive. According to the immunohistochemistry image analysis, experiment group changes was less obvious than control group. Dynamic changes of OD occured, reaching the minimum on the 7th day and then increasing slowly. IOD increased steadily, up to the peak on the 7th day, and then decreased, which still remained a high level on the 21st day. CONCLUSION: DM alveolar bone collagen metabolism increases. DM alveolar bone reactive potency decreases in orthodontic tooth movement, weak collagen metabolism. MMP-2's activity changes regularly, in close relation to bone remodeling, and plays an important role during the orthodontic tooth movement.

Genco, R. J., S. G. Grossi, et al. (2005). "A proposed model linking inflammation to obesity, diabetes, and periodontal infections." J Periodontol 76(11 Suppl): 2075-84.

ABSTRACT: BACKGROUND: Obesity is an important risk factor for diabetes, cardiovascular disease, and periodontal disease. Adipocytes appear to secrete proinflammatory cytokines which may be the molecules linking the pathogenesis of these diseases. We evaluated the relationship between obesity, periodontal disease, and diabetes mellitus insulin resistance as well as the plasma levels of tumor necrosis factor alpha (TNFalpha) and its soluble receptors (sTNFalpha) to assess the relationship of inflammation to obesity, diabetes, and periodontal infections. METHODS: The relationship between periodontal disease, obesity, and insulin resistance was examined in the Third National Health and Nutrition Examination Survey (NHANES III). In a population of 12,367 non-diabetic subjects, the variable body mass index (BMI) was used as an assessment of obesity and periodontal disease was assessed by mean clinical attachment loss. The plasma levels of TNFalpha and sTNFalpha were assessed in subsets of 1,221 adults from Erie County, New York, who represented the highest and lowest quartile of BMI. These subjects had extensive periodontal and medical evaluations. RESULTS: In the NHANES III portion of the study, BMI was positively related to severity of periodontal attachment loss (P <0.001). Weighted multiple logistic regressions showed that this relationship is likely mediated by insulin resistance, since overweight individuals (with BMI >or=27 kg/m2) with high levels of insulin resistance (IR) exhibited an odds ratio of 1.48 (95% confidence interval 1.13 - 1.93) for severe periodontal disease as compared to overweight subjects with low IR. In the Erie County adult population, the highest levels of TNFalpha and sTNFalpha receptors were found in those individuals in the highest quartile of BMI. A positive correlation of TNFalpha levels with periodontal disease was found only in those in the lowest quartile of BMI. CONCLUSIONS: Obesity is a significant predictor of periodontal disease and insulin resistance appears to mediate this relationship. Furthermore, obesity is associated with high plasma levels of TNFalpha and its soluble receptors, which in turn may lead to a hyperinflammatory state increasing the risk for periodontal disease and also accounting in part for insulin resistance. Further studies of the molecular basis of insulin resistance and its relationship to diabetes, periodontal disease, and obesity are necessary to fully test the hypothesis that adipocyte production of proinflammatory cytokines is a pathogenic factor linking obesity to diabetes and periodontal infections.

Gomes, M. A., F. H. Rodrigues, et al. (2006). "Levels of immunoglobulin A1 and messenger RNA for interferon gamma and tumor necrosis factor alpha in total saliva from patients with diabetes mellitus type 2 with chronic periodontal disease." J Periodontal Res 41(3): 177-83.

ABSTRACT: BACKGROUND: Diabetes mellitus and periodontal disease have high incidence in the general population and are associated with various degrees of dysfunction in the immune system. It has been shown that diabetic patients with severe periodontal disease have more complications of diabetes and less effective metabolic control compared with diabetic patients with healthy gingiva. Patients with diabetes and severe periodontal disease present higher levels of serous immunoglobulin A (IgA). Elevation of the IgA1 isotype is thought to contribute to this phenomenon. Another important event in the diabetes-periodontitis association is the disturbance in local and systemic production of inflammatory cytokines. OBJECTIVE: In this study we tested the hypothesis that type 2 diabetic patients with chronic moderate periodontal disease have differences in salivary IgA1 titers and cytokine expression when compared with the chronic severe periodontal disease cases. METHODS: We utilized a jacalin-IgA capture assay to determine the IgA1 titers in total saliva and reverse transcriptase-polymerase chain reaction to detect mRNA for interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in total saliva samples of 13 patients with chronic moderate periodontal disease and 10 with chronic severe periodontal disease. RESULTS AND CONCLUSIONS: We observed a predominance of IgA1 titers of 64 (45.5%) in saliva samples from chronic severe periodontal disease patients and titers averaging 512 (30.8%) in chronic moderate periodontal disease patients. We detected mRNA for IFN-gamma in six out of 10 chronic severe periodontal disease subjects and in two out of 13 chronic moderate periodontal disease patients. TNF-alpha expression was similar in both groups. Our data suggest that higher levels of IgA1 may exert partial protection of the periodontal tissue in chronic moderate periodontal disease diabetic patients when compared to severe periodontal disease. Despite the small number of patients, IFN-gamma expression had a trend association with severity of periodontitis and TNF-alpha gene expression did not correlate with severity of periodontal disease.

Graves, D. T., H. Al-Mashat, et al. (2004). "Evidence that diabetes mellitus aggravates periodontal diseases and modifies the response to an oral pathogen in animal models." Compend Contin Educ Dent25(7 Suppl 1): 38-45.

ABSTRACT: Bacterial plaque has been shown to initiate periodontal diseases. Most studies indicate that the host response, rather than the direct effect of bacteria, is responsible for much of the destruction associated with periodontitis. Bacteria or their products have an indirect role by stimulating inflammation, which is associated with the excessive production of inflammatory mediators, such as prostaglandins, or cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1. These mediators, in turn, induce the production and activation of enzymes that destroy gingival connective tissue and stimulate the formation of osteoclasts to resorb bone. Based on results in animal models and studies in humans showing that similar responses occur, the initial steps in the breakdown of connective tissue attachment to the tooth surface and bone resorption involve the production of inflammatory cytokines. Moreover, the risk and severity of periodontal diseases is affected by systemic factors, such as diabetes. Diabetes in particular seems to impair the ability to produce new bone formation after bone loss by preventing the formation of new bone that normally occurs after bone is resorbed, a process called coupling. In addition, the cytokines that stimulate loss of tissue, particularly TNF-alpha, may kill the cells that repair damaged connective tissue or bone. In diabetes there may be more TNF-alpha produced, leading to an even more limited capacity to repair tissue. The diminished capacity to form new bone may make it more difficult for diabetics in particular to repair the loss of tissue that occurs in periodontal diseases.

Graves, D. T., R. Liu, et al. (2006). "Diabetes-enhanced inflammation and apoptosis--impact on periodontal pathology." J Dent Res 85(1): 15-21.

ABSTRACT: Diabetes, particularly type 2 diabetes, is a looming health issue with many ramifications. Because diabetes alters the cellular microenvironment in many different types of tissues, it causes myriad untoward effects, collectively referred to as 'diabetic complications'. Two cellular processes affected by diabetes are inflammation and apoptosis. This review discusses how diabetes-enhanced inflammation and apoptosis may affect the oral environment. In particular, dysregulation of tumor necrosis factor and the formation of advanced glycation products, both of which occur at higher levels in diabetic humans and animal models, potentiate inflammatory responses and induce apoptosis of matrix-producing cells. The enhanced loss of fibroblasts and osteoblasts through apoptosis in diabetics could contribute to limited repair of injured tissue, particularly when combined with other known deficits in diabetic wound-healing. These findings may shed light on diabetes-enhanced risk of periodontal diseases.

Guo, Y. H. and B. L. Zhu (2004). "[The effect of initial therapy on periodontal status and saccharified Hb (HbAIc) of patients with type II diabetes mellitus]." Shanghai Kou Qiang Yi Xue 13(2): 150-1.

ABSTRACT: PURPOSE: To investigate the effect of periodontal initial therapy on the level of glycated hemoglobin(HbAIc) and periodontal status in non-insulin dependent diabetes mellitus(NIDDM)patients with periodontitis. METHODS: 33 cases with NIDDM periodontitis were included in the study.The periodontal therapy included oral hygiene instruction,ultrasonic scaling and subgingival scaling.The level of glycosylated hemoglobin and periodontal status before treatment and four weeks after treatment were determined and compared. RESULTS: The percentage of bleeding on probing and probing depth were significantly reduced in all patients after periodontal therapy.The glycosylated hemoglobin level was significantly decreased in patients with advanced periodontitis,while patients with moderate periodontitis showed no changes following therapy. CONCLUSION: The result of periodontal therapy in the diabetic patients was satisfied in short time.It can reduce the level of glycated hemoglobin.

Herring, M. E. and S. K. Shah (2006). "Periodontal disease and control of diabetes mellitus." J Am Osteopath Assoc 106(7): 416-21.

ABSTRACT: Data from the Centers for Disease Control and Prevention indicate that more than 20 million people (approximately 7% of the population) in the United States have diabetes mellitus. Physicians often fail to examine the mouths and teeth of their patients, even though the condition of the mouth and teeth have clinical relevance for the treatment of patients with diabetes mellitus. The authors examine the current state of knowledge regarding periodontal disease and the effect of periodontal disease on worsening of glycemic control. They review several studies investigating how the management of periodontal disease affects the ability of patients to control symptoms of diabetes mellitus. The authors conclude with several recommendations for the treatment of patients with periodontal disease to improve glycemic control.

Jahn, C. (2004). "Diabetes and periodontal health." Dent Assist 73(4): 24-7; quiz 28-9.

Jansson, H., E. Lindholm, et al. (2006). "Type 2 diabetes and risk for periodontal disease: a role for dental health awareness." J Clin Periodontol 33(6): 408-14.

ABSTRACT: BACKGROUND: Several studies have found correlations between diabetes and an increased prevalence of periodontitis. OBJECTIVE: To analyse, in a group of subjects with type 2 diabetes (T2D), (i) the association between medical characteristics and severe periodontal disease and (ii) dental care habits and knowledge of oral health. METHODS: One hundred and ninety-one subjects with T2D were examined. Based on assessment of marginal bone height in panoramic radiographs, two periodontal subgroups were identified: one periodontally diseased (PD+) and one periodontally healthy (PD-) group. All subjects completed a questionnaire about their medical and oral health. RESULTS: Twenty per cent of the subjects were classified as PD+. This was verified by clinical parameters. PD+ individuals had higher haemoglobin A1c (HbA1c) levels (p=0.033) and higher prevalences of cardiovascular complications (p=0.012). They were also less likely to be of Scandinavian origin (p=0.028) and more likely to smoke (p<0.001) than the PD- group. The PD+ group rated their oral health as poor (p<0.0001) and believed that T2D had an influence on their oral status (p<0.0001). CONCLUSION: The best predictor for severe periodontal disease in subjects with T2D is smoking followed by HbA1c levels. T2D subjects should be informed about the increased risk for periodontal disease when suffering from T2D.

Jones, J. A., D. R. Miller, et al. (2007). "Does periodontal care improve glycemic control? The Department of Veterans Affairs Dental Diabetes Study." J Clin Periodontol 34(1): 46-52.

ABSTRACT: OBJECTIVES: Report results of a randomized-clinical trial of the efficacy of periodontal care in the improvement of glycemic control in 165 veterans with poorly controlled diabetes over 4 months. METHODS: Outcomes were change in Haemoglobin A1c (HbA1c) in the Early Treatment versus untreated (Usual Care) groups and percent of participants with decreases in HbA1c. Analyses included simple/multiple variable linear/logistic regressions, adjusted for baseline HbA1c, age, and duration of diabetes. RESULTS: Unadjusted analyses showed no differences between groups. After adjustment for baseline HbA1c, age, and diabetes duration, the mean absolute HbA1c change in the Early Treatment group was -0.65% versus -0.51% in the Usual Care group (p=0.47). Adjusted odds for improvement by 0.5% in the Early Treatment group was 1.67 (95% confidence interval: 0.84, 3.34, p=0.14). Usual Care subjects were twice as likely to increase insulin from baseline to 4 months (20% versus 11%, p=0.12) and less likely to decrease insulin (1% versus 6%, p=0.21) than Early Treatment subjects. Among insulin users at baseline, more increased insulin in the Usual Care group (40% versus 21%, p=0.06). CONCLUSIONS: No significant benefit was found for periodontal therapy after 4 months in this study; trends in some results were in favour of periodontal treatment.

Katz, J., I. Bhattacharyya, et al. (2005). "Expression of the receptor of advanced glycation end products in gingival tissues of type 2 diabetes patients with chronic periodontal disease: a study utilizing immunohistochemistry and RT-PCR." J Clin Periodontol 32(1): 40-4.

ABSTRACT: OBJECTIVES: Relationship between diabetes and periodontal disease is well established. It has been shown that advanced glycation end-products (AGEs) might exert noxious effects on gingival tissues through its receptor. Evidence for the role of receptors of AGE (RAGE) in periodontal disease was verified in a murine model for diabetes. However, the presence of RAGE in human gingival tissues has not been demonstrated previously. In this study we demonstrate the presence of RAGE in human periodontium in patients with chronic periodontitis with and without type 2 diabetes. MATERIAL AND METHODS: Gingival biopsies from eight patients with both type 2 diabetes and chronic periodontitis and 14 healthy control subjects with chronic periodontitis were immunohistochemically stained for RAGE. Five samples from the study groups and four controls were subjected to reverse transcriptase coupled to polymerase chain reaction (RT-PCR) for quantitative determination of mRNA for RAGE. RESULTS: On immunohistochemistry, positive staining for RAGE was seen in the endothelium and the basal and spinous layer of the inflamed gingival epithelium in both type 2 diabetes and non-diabetes tissue with no statistically significant difference between both groups. RT-PCR, however, showed a 50% increase in mRNA for RAGE in the gingiva of diabetic patients when compared with controls (p<0.05). CONCLUSIONS: Although there was no change in the staining intensity for RAGE between both groups, the increase in the mRNA for RAGE in the type 2 diabetes gingival epithelium may indicate a possible involvement of this receptor in the periodontal destruction in type 2 diabetes.

Kiran, M., N. Arpak, et al. (2005). "The effect of improved periodontal health on metabolic control in type 2 diabetes mellitus." J Clin Periodontol 32(3): 266-72.

ABSTRACT: OBJECTIVES: The aim of the present study was to investigate the effect of improved periodontal health on metabolic control in type 2 diabetes mellitus (DM) patients. MATERIAL AND METHODS: Fourty-four patients with type 2 DM were selected. Subjects were randomly assigned into two groups. Data collection: Plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment levels (CALs), gingival recession (GR) and bleeding on probing (BOP) were recorded at baseline at 1st and 3rd months. Fasting plasma glucose (FPG), 2-h post-prandial glucose (PPG), glycated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), HDL-cholesterol, LDL-cholesterol and microalbuminure were analysed at baseline, 3 months following the periodontal therapy. The treatment group received full-mouth scaling and root planing whereas the control group received no periodontal treatment. RESULTS: A statistically significant effect could be demonstrated for PI, GI, PPD, CAL and BOP for the treatment group. HbA1c levels in the treatment group decreased significantly whereas the control group showed a slight but insignificant increase for this parameter. CONCLUSIONS: The results of our study showed that non-surgical periodontal treatment is associated with improved glycaemic control in type 2 patients and could be undertaken along with the standard measures for the diabetic patient care.

Koerber, A., K. E. Peters, et al. (2006). "The views of dentists, nurses and nutritionists on the association between diabetes and periodontal disease: a qualitative study in a Latino community." J Public Health Dent 66(3): 212-5.

ABSTRACT: OBJECTIVE: To interview health professionals in a Latino community about the association between diabetes and periodontitis, and provide a basis to develop interventions for them to promote oral health and good glycemic control among patients with diabetes. METHODS: Five dentists, seven nurses and two nutritionists were interviewed about their practices relevant to oral health and diabetes, knowledge about the association, beliefs about Latinos, recommendations on reaching others in their fields, and barriers. The interviews were audiotaped, transcribed, and analyzed qualitatively. RESULTS: Professionals identified policy, community and practice barriers for promoting diabetic control and oral health. CONCLUSIONS: Producing a resource list, cross-educating professionals about diabetes and oral health, training professionals to better serve Latino patients, developing appropriate protocols for each profession regarding the association between diabetes and periodontitis, and educating the community about diabetic control, oral health and disease prevention were identified as potential strategies to improve oral health among Latino persons with diabetes.

Lalla, E., B. Cheng, et al. (2007). "Diabetes mellitus promotes periodontal destruction in children." J Clin Periodontol 34(4): 294-8.

ABSTRACT: AIM: The association between diabetes mellitus and periodontal attachment and bone loss is well established. Most of the prior literature has focused on adults, and studies in children have mostly reported gingival changes. Our aim was to assess the periodontal status of a large cohort of children and adolescents with diabetes. MATERIAL AND METHODS: We examined 350 children with diabetes (cases) and 350 non-diabetic controls (6-18 years of age). Using three different case definitions for periodontal disease, which incorporated gingival bleeding and/or attachment loss findings, multiple logistic regression analyses adjusting for age, gender, ethnicity, frequency of prior dental visits, dental plaque, and examiner were performed. RESULTS: Subjects with diabetes had increased gingival inflammation and attachment loss compared with controls. Regression analyses revealed statistically significant differences in periodontal destruction between cases and controls across all disease definitions tested (odds ratios ranging from 1.84 to 3.72). The effect of diabetes on periodontal destruction remained significant when we separately analysed 6-11 and 12-18 year old subgroups. CONCLUSIONS: These findings demonstrate an association between diabetes and an increased risk for periodontal destruction even very early in life, and suggest that programmes to address periodontal needs should be the standard of care for diabetic youth.

Lalla, E., B. Cheng, et al. (2007). "Diabetes-related parameters and periodontal conditions in children." J Periodontal Res 42(4): 345-9.

ABSTRACT: Background and Objective: The relationship between diabetes and periodontal diseases is well established. Our aim in this study was to explore the diabetes-related parameters that are associated with accelerated periodontal destruction in diabetic youth. Material and Methods: Three-hundred and fifty 6-18-year-old children with diabetes received a periodontal examination. Data on important diabetes-related variables were collected. Analyses were performed using logistic regression, with gingival/periodontal disease as the dependent variable, for the whole cohort and separately for two subgroups (6-11 and 12-18 years of age). Results: Regression analyses, adjusting for age, gender, ethnicity, frequency of prior dental visits, dental plaque, and dental examiner, revealed a strong positive association between mean hemoglobin A1c over the 2 years prior to inclusion in the study and periodontitis (odds ratio = 1.31, p = 0.030). This association approached significance in the younger subgroup (odds ratio = 1.56, p = 0.052, n = 183). There was no significant relationship between diabetes duration or body mass index-for-age and measures of gingival/periodontal disease in this cohort. Conclusion: These findings suggest that accelerated periodontal destruction in young people with diabetes is related to the level of metabolic control. Good metabolic control may be important in addressing periodontal complications in young patients with diabetes, similarly to what is well established for other systemic complications of this disease.

Lalla, E., B. Cheng, et al. (2006). "Periodontal changes in children and adolescents with diabetes: a case-control study." Diabetes Care 29(2): 295-9.

ABSTRACT: OBJECTIVE: To evaluate the level of oral disease in children and adolescents with diabetes. RESEARCH DESIGN AND METHODS: Dental caries and periodontal disease were clinically assessed in 182 children and adolescents (6-18 years of age) with diabetes and 160 nondiabetic control subjects. RESULTS: There were no differences between case and control subjects with respect to dental caries. Children with diabetes had significantly higher plaque and gingival inflammation levels compared with control subjects. The number of teeth with evidence of attachment loss (the hallmark of periodontal disease) was significantly greater in children with diabetes (5.79 +/- 5.34 vs. 1.53 +/- 3.05 in control subjects, unadjusted P < 0.001). When controlling for age, sex, ethnicity, gingival bleeding, and frequency of dental visits, diabetes remained a highly significant correlate of periodontitis, especially in the 12- to 18-year-old subgroup. In the case group, BMI was significantly correlated with destruction of connective tissue attachment and bone, but duration of diabetes and mean HbA(1c) were not. CONCLUSIONS: Our findings suggest that periodontal destruction can start very early in life in diabetes and becomes more prominent as children become adolescents. Programs designed to promote periodontal disease prevention and treatment should be provided to young patients with diabetes.

Lalla, E., S. Kaplan, et al. (2006). "Periodontal infection profiles in type 1 diabetes." J Clin Periodontol33(12): 855-62.

ABSTRACT: OBJECTIVES: We investigated the levels of subgingival plaque bacteria and serum IgG responses in patients with type 1 diabetes and non-diabetic controls of comparable periodontal status. MATERIAL AND METHODS: Fifty type 1 diabetes patients (mean duration 20.3 years, range 6-41) were age-and gender-matched with 50 non-diabetic individuals with similar levels of periodontal disease. Full-mouth clinical periodontal status was recorded, and eight plaque samples/person were collected and analysed by checkerboard hybridization with respect to 12 species. Homologous serum IgG titres were assessed by checkerboard immunoblotting. In a sub-sample of pairs, serum cytokines and selected markers of cardiovascular risk were assessed using multiplex technology. RESULTS: Among the investigated species, only levels of Eubacterium nodatum were found to be higher in diabetic patients, while none of the IgG titres differed between the groups, both before and after adjustments for microbial load. Patients with diabetes had significantly higher serum levels of soluble E-selectin (p=0.04), vascular cell adhesion molecule-1 (VCAM-1; p=0.0008), adiponectin (p=0.01) and lower levels of plasminogen activator inhibitor-1 (PAI-1; p=0.02). CONCLUSIONS: After controlling for the severity of periodontal disease, patients with type 1 diabetes and non-diabetic controls showed comparable subgingival infection patterns and serum antibody responses.

Lalla, E., S. Kaplan, et al. (2007). "Effects of periodontal therapy on serum C-reactive protein, sE-selectin, and tumor necrosis factor-alpha secretion by peripheral blood-derived macrophages in diabetes. A pilot study." J Periodontal Res 42(3): 274-82.

ABSTRACT: BACKGROUND AND OBJECTIVE: Diabetes is associated with an increased risk for vascular disease and periodontitis. The aim of this study was to assess the effects of periodontal treatment in diabetes with respect to alterations in the pro-inflammatory potential of peripheral blood mononuclear cells. MATERIAL AND METHODS: Ten patients with diabetes and moderate to severe periodontitis received full-mouth subgingival debridement. Blood samples for serum/plasma and mononuclear cell isolation were collected prior to and 4 wk after therapy. Mononuclear cells were analyzed by flow cytometry and stimulated with lipopolysaccharide or ionomycin/phorbol ester to determine the pro-inflammatory capacity of macrophages and lymphocytes, respectively. RESULTS: Following periodontal treatment, all patients demonstrated a significant improvement in clinical periodontal status (p < 0.05), despite only modest reduction in subgingival bacterial load or homologous serum immunoglobulin G titers. CD14(+) blood monocytes decreased by 47% (p < 0.05), and the percentage of macrophages spontaneously releasing tumor necrosis factor-alpha decreased by 78% (p < 0.05). There were no significant changes in the capacity of lymphocytes to secrete interferon-gamma. Among a number of serum inflammatory markers tested, high-sensitivity-C-reactive protein significantly decreased by 37% (p < 0.01) and soluble E-selectin decreased by 16.6% (p < 0.05). CONCLUSION: These data suggest a reduced tendency for monocyte/macrophage-driven inflammation with periodontal therapy and a potential impact on atherosclerosis-related complications in diabetic individuals.

Lim, L. P., F. B. Tay, et al. (2007). "Relationship between markers of metabolic control and inflammation on severity of periodontal disease in patients with diabetes mellitus." J Clin Periodontol 34(2): 118-23.

ABSTRACT: AIM: The aim of this study was to investigate the relationship between markers of metabolic control and inflammation and periodontal disease parameters in patients with diabetes. MATERIAL & METHODS: One hundred and eighty one adult patients with diabetes attending treatment at two diabetes centres were invited to participate in the study. Periodontal examination included full-mouth assessment for probing depths and bleeding on probing (BOP). Blood analyses were carried out for glycated haemoglobin, (HbA1c), high-sensitivity C reactive protein, (hsCRP) and lipid profile comprising total cholesterol, low-density lipoprotein cholesterol (LDL chol), high-density lipoprotein cholesterol (HDL chol) and triglycerides. RESULTS: Upon multivariate analysis, periodontal disease severity in terms of increased percentage of BOP and mean percentage of sites with probing depths > or = 5 mm were found to be associated with inadequate glycaemic control as measured by HbA1c (p<0.01). HsCRP was also found to be a significant predictor for mean percentage of sites with probing depths > or = 5 mm (p<0.05). After controlling for age, gender, smoking habits and number of teeth, positive correlations were found between HbA1c and percentage sites with probing depths > or = 5 mm, percentage sites BOP, total cholesterol, LDL chol and triglycerides (p<0.05). Using the adjusted differences, subjects with acceptable glycaemic control (HbA1c < 8%) showed a lower percentage of sites with BOP and probing depths > or = 5 mm (p<0.05) when compared with those having inadequate glycaemic control. There was also a trend towards lower blood cholesterol in the well-controlled group. CONCLUSION: The level of glycaemic control as measured by HbA1c emerged as the most consistent risk factor associated with the extent and severity of periodontal disease in this study cohort.

Liu, R., H. S. Bal, et al. (2006). "Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation." J Dent Res 85(6): 510-4.

ABSTRACT: Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9-fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells.

Lu, H. K. and P. C. Yang (2004). "Cross-sectional analysis of different variables of patients with non-insulin dependent diabetes and their periodontal status." Int J Periodontics Restorative Dent 24(1): 71-9.

ABSTRACT: The periodontal condition of 72 non-insulin dependent diabetes patients was compared with that of 92 nondiabetic individuals. Plaque Index (PII), Calculus Index (CI), Gingival Index (GI), and attachment loss (AL) were measured on four surfaces of six teeth in each subject. All four parameters were significantly higher in the diabetic group. No significant difference in the frequency of toothbrushing was found between the groups. For all age groups, GI and AL were higher in the diabetic group. In each group, GI was not changed with age, while AL increased with age. Classification of the groups based on PII showed that the diabetic group's GI was higher than the nondiabetic group for low, medium, or high PII values. The diabetic group showed higher AL for only the medium and high PII groups. Classification by CI revealed that the diabetic group's GI and AL were significantly higher than those of the nondiabetic group for subjects with low, medium, or high values of CI. Multiple regression analysis revealed that the main factor affecting GI was the presence or absence of diabetes. PII and CI both showed a significant relationship with GI; age was the second most significant factor. The most significant factors influencing AL were CI and the presence or absence of diabetes; age was the second most significant factor. Patients who had had diabetes for more than 10 years had a higher AL than those who had suffered from diabetes for less than 10 years. Patients with average HbA1c values > or = 10% had more serious mean GI values than those with HbA1c values < 10%. In patients with diabetes, age, plaque accumulation, and calculus formation have more detrimental effects on the periodontal apparatus than in healthy individuals.

Luczaj-Cepowicz, E., G. Marczuk-Kolada, et al. (2006). "Evaluation of periodontal status in young patients with insulin-dependent diabetes mellitus (type 1)." Adv Med Sci 51 Suppl 1: 134-7.

ABSTRACT: PURPOSE: The aim of the study was to value periodontal status in young persons with well-controlled insulin-dependent diabetes mellitus (IDDM). MATERIAL AND METHODS: We examined 50 young people with IDDM (25 girls and 25 boys) and 50 healthy subjects (25 girls and 25 boys). Mean age of examined persons was about 14 years. We investigated gingival indexes: GI (Gingival Index) and PBI (Papillary Bleeding Index) and periodontal indexes: PI (Periodontal Index) and PDI (Periodontal Disease Index). The results were statistically analysed, and significant differences we observed for p < 0.05. RESULTS: The mean scores of Gingival Index and Papillary Bleeding Index were lower in healthy subjects but differences were not statistically significant. Only maximum scores of these indexes were significantly higher in diabetics. The mean and maximum values of Periodontal Index were significantly higher in patients with IDDM. We did not notice differences between mean scores of PDI in both examined groups. Analysis of maximum values of Periodontal Disease Index reveals higher level in diabetic girls than in female controls. CONCLUSIONS: IDDM patients may be at risk of periodontal diseases. Well-controlling insulin-dependent diabetes mellitus may be important for periodontal tissues status and prophylaxis of periodontal diseases.

Mattout, C., D. Bourgeois, et al. (2006). "Type 2 diabetes and periodontal indicators: epidemiology in France 2002-2003." J Periodontal Res 41(4): 253-8.

ABSTRACT: BACKGROUND AND OBJECTIVE: Diabetes and periodontal disease have been associated in the literature. In the present study, the periodontal heath of noninsulin-dependent diabetic adults was compared with that of a general population of nondiabetic patients. MATERIAL AND METHODS: In France, 2144 adults (age: 35-65 years) were examined for life habits (tobacco, alcohol), biological diagnosis (type II diabetes, arterial hypertension), biometry (weight, size) and biochemistry. Dental and periodontal data included plaque index, gingival index, probing depth, and clinical attachment loss. RESULTS: Descriptive and multifactorial analysis evidenced a more severe periodontal disease in diabetic patients. Moreover, when the plaque index was held constant, the gingival index was more elevated in diabetics. In nondiabetics, age, gender, glycemia, alcohol, and tobacco smoking were identified as significant risk factors for periodontal disease. In contrast, in diabetic subjects, only tobacco smoking was a significant risk factor. CONCLUSION: In type II diabetics, the diabetes factor is probably more significant than periodontal risk factors, age, and gender.

Mealey, B. L. and T. W. Oates (2006). "Diabetes mellitus and periodontal diseases." J Periodontol 77(8): 1289-303.

ABSTRACT: BACKGROUND: The purpose of this review is to provide the reader with practical knowledge concerning the relationship between diabetes mellitus and periodontal diseases. Over 200 articles have been published in the English literature over the past 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of diabetes and periodontitis and different clinical criteria applied to prevalence, extent, and severity of periodontal diseases, levels of glycemic control, and complications associated with diabetes. METHODS: This article provides a broad overview of the predominant findings from research published in English over the past 20 years, with reference to certain "classic" articles published prior to that time. RESULTS: This article describes current diagnostic and classification criteria for diabetes and answers the following questions: 1) Does diabetes affect the risk of periodontitis, and does the level of metabolic control of diabetes have an impact on this relationship? 2) Do periodontal diseases affect the pathophysiology of diabetes mellitus or the metabolic control of diabetes? 3) What are the mechanisms by which these two diseases interrelate? and 4) How do people with diabetes and periodontal disease respond to periodontal treatment? CONCLUSIONS: Diabetes increases the risk of periodontal diseases, and biologically plausible mechanisms have been demonstrated in abundance. Less clear is the impact of periodontal diseases on glycemic control of diabetes and the mechanisms through which this occurs. Inflammatory periodontal diseases may increase insulin resistance in a way similar to obesity, thereby aggravating glycemic control. Further research is needed to clarify this aspect of the relationship between periodontal diseases and diabetes.

Mealey, B. L. and G. L. Ocampo (2007). "Diabetes mellitus and periodontal disease." Periodontol 200044: 127-53.

Mealey, B. L. and M. P. Rethman (2003). "Periodontal disease and diabetes mellitus. Bidirectional relationship." Dent Today 22(4): 107-13.

ABSTRACT: Periodontitis is a common problem in patients with diabetes. The relationship between these 2 maladies appears bidirectional--insofar that the presence of one condition tends to promote the other, and that the meticulous management of either may assist treatment of the other. Both diabetes and periodontitis can stimulate the chronic release of proinflammatory cytokines that have a deleterious effect on periodontal tissues. The chronic systemic elevation of proinflammatory cytokines caused by periodontitis may even predispose individuals to the development of type 2 diabetes. Mechanical treatment of periodontitis (scaling and root planing), when combined with short-term administration of therapeutic levels of tetracycline-type antimicrobials, can temporarily improve glycemic control in diabetic patients, especially in those with advanced forms of periodontitis and poor glycemic control before treatment. The biochemical mechanisms suggested by these studies imply that other periodontal procedures designed to rid patients of periodontal pathogens may also improve the management of diabetes. Therefore, the authors suggest that periodontal patients with diabetes be treated in consultation with a periodontist (Figures 3a through 4b).

Moles, D. R. (2006). "Evidence of an association between diabetes and severity of periodontal diseases." Evid Based Dent 7(2): 45.

Nesse, W., F. K. Spijkervat, et al. (2006). "[Links between periodontal disease and general health. 2. Preterm birth, diabetes and autoimmune diseases]." Ned Tijdschr Tandheelkd 113(5): 191-6.

ABSTRACT: The condition of the periodontium may effect people's general health. There is evidence of a correlation between periodontal disease and preterm birth or low birth weight. In pregnant women with periodontal disease, scaling and root planing seems to reduce the risk of preterm birth or low birth weight. Furthermore, periodontal disease appears to have an adverse effect on glycemic control in diabetics. However, periodontal treatment as a means to glycemic control is restricted unless it includes the use of systemic antibiotics. Slowly, a possible correlation between periodontal disease and autoimmune diseases is emerging. Further research into the correlations between periodontal disease and systemic health is desirable and might well result in new therapeutic options.

Nishimura, F., Y. Iwamoto, et al. (2007). "The periodontal host response with diabetes." Periodontol 200043: 245-53.

Promsudthi, A., S. Pimapansri, et al. (2005). "The effect of periodontal therapy on uncontrolled type 2 diabetes mellitus in older subjects." Oral Dis 11(5): 293-8.

ABSTRACT: OBJECTIVE: The purpose of this study was to examine the effect of periodontal therapy on glycemic control in older type 2 diabetic patients. METHODS: Fifty-two diabetic patients, age 55-80 years (mean age = 61 years), with glycated hemoglobin (HbA1c) 7.5-11.0% (mean +/- s.d. = 8.98 +/- 0.88) and severe periodontitis were included in the present study. The treatment group received mechanical periodontal treatment combined with systemic doxycycline, 100 mg day(-1) for 14 days. The control group received neither periodontal treatment nor systemic doxycycline. Clinical periodontal parameters, fasting plasma glucose (FPG), and HbA1c levels were measures at baseline and 3 months. RESULTS: Periodontal treatment significantly improved periodontal status of the treatment group (P < 0.05), however the reduction in the level of FPG and HbA1c did not reach significance. In the control group, no significant changes in clinical periodontal parameters, FPG and HbA1c levels were observed, except for significant increase in attachment loss (P < 0.05). Comparing the two groups, although the 3-month level of HbA1c of the treatment group was lower than that of the control group, the difference did not reach significance. CONCLUSIONS: The results of the present study indicate that the periodontal condition of older Thais with uncontrolled diabetes is: (a) significantly improved 3 months after mechanical periodontal therapy with adjunctive systemic antimicrobial treatment, and (b) rapidly deteriorating without periodontal treatment. The effect of periodontal therapy on the glycemic control of older uncontrolled diabetics will require further studies that will have to include much larger sample sizes.

Pucher, J. and J. Stewart (2004). "Periodontal disease and diabetes mellitus." Curr Diab Rep 4(1): 46-50.

ABSTRACT: Infections of the tissue surrounding the teeth (periodontitis) are usually caused by anaerobic gram-negative microorganisms. This infection causes destruction of the supporting alveolar bone and can lead to tooth loss. Removal of these microorganisms can slow or arrest the progression of periodontitis. Diabetes patients are at greater risk of developing periodontitis, may not respond as well to periodontal therapy as nondiabetic patients, and may require more aggressive treatment to manage periodontitis. Microorganisms that cause periodontitis and the host response to these may increase insulin resistance in diabetic patients. Treatment of periodontitis could improve glycemic control. A model is presented in which periodontal pathogens may cause increases in proinflammatory cytokines that mediate increases in insulin resistance, resulting in an increase in blood glucose. Following periodontal therapy, this process may be reversed.

Rodrigues, D. C., M. J. Taba, et al. (2003). "Effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus." J Periodontol 74(9): 1361-7.

ABSTRACT: BACKGROUND: The literature suggests that an alteration in glucose metabolism occurs as a result of antibacterial periodontal therapy. The objective of this study was to monitor the effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus (DM). METHODS: Thirty type 2 DM subjects with periodontitis were randomly divided into two groups. Group 1 (G1), 15 subjects, received one-stage full-mouth scaling and root planing (FMSRP) plus amoxicillin/clavulanic acid 875 mg; group 2 (G2), 15 patients, received only FMSRP. At baseline and after 3 months, the glycated hemoglobin (HbA1c) values, fasting glucose, and clinical parameters (with computerized probing and individualized acrylic stents) were recorded. Following therapy, the subjects were enrolled in a 2-week interval maintenance program for 3 months. RESULTS: After treatment, both groups showed clinical improvements. A probing depth (PD) reduction of 0.8 +/- 0.6 mm (P < 0.05) occurred in G1 and 0.9 +/- 0.4 mm in G2 (P < 0.05), but there were no significant changes in attachment level. Treatment reduced the HbA1c values after the 3-month observation period in both groups; however, the reduction in HbA1c values for the G2 group was statistically significant, but not for the G1 group. The changes in fasting glucose levels were not significant for either group. CONCLUSIONS: Periodontal therapy improved glycemic control in patients with type 2 DM in both groups; however, the reduction in HbA1c values reached statistical significance only in the group receiving scaling and root planing alone [correction].

Sadzeviciene, R., P. Paipaliene, et al. (2005). "The influence of microvascular complications caused by diabetes mellitus on the inflammatory pathology of periodontal tissues." Stomatologija 7(4): 121-4.

ABSTRACT: The aim of our study was to analyze inflammatory pathology of periodontal tissues in patients with diabetes mellitus, and the relationship of this pathology with other complications caused by diabetes mellitus. In our study, we evaluated 126 people aged 16-53 years (42 males and 84 females) with diabetes mellitus admitted to the Clinic of Endocrinology of the Hospital of Kaunas University of Medicine (HKUM). The condition of periodontal tissues was evaluated according to the World Health organization (WHO) CPITN index. Oral hygiene was evaluated using a simplified oral hygiene index (OHI-S) according to Green-Vermillion. Out of 126 subjects with diabetes mellitus, periodontitis was detected in 96 patients (36 males and 60 females) (CPITN index 2-5). Gingivitis was found in 27 subjects (CPITN index 1). Only 2.4% of the studied patients had healthy periodontal tissues. The study analyzed complications of other organs (neuropathy, and nephropathy and retinopathy) caused by diabetes mellitus. The obtained findings showed that microvascular complications were diagnosed more frequently in the presence of more severe inflammatory pathology of periodontal tissues. Retinopathy was diagnosed in patients with CPITN index 2.8+/-0.1, while patients with CPITN index 1.8+/-0.3 had no retinopathy. Neuropathy was more common among patients whose CPITN index was 2.9+/-0.1, while the condition was absent in cases where the CPITN index was 1.8+/-0.2. Comparable results were yielded by the studies of nephropathies in relation with changes in periodontium. Nephropathy was diagnosed in patients whose CPITN index was 3.0+/-0.1, and was not found in patients with CPITN index 2.1+/-0.2. The generalization of the obtained study data allows for stating that a more detailed analysis of factors causing complications of diabetes mellitus will also allow for a more profound understanding of the etiopathogenetic mechanisms that cause inflammatory pathology of periodontal tissues.

Saremi, A., R. G. Nelson, et al. (2005). "Periodontal disease and mortality in type 2 diabetes." Diabetes Care 28(1): 27-32.

ABSTRACT: OBJECTIVE: Periodontal disease may contribute to the increased mortality associated with diabetes. RESEARCH DESIGN AND METHODS: In a prospective longitudinal study of 628 subjects aged > or =35 years, we examined the effect of periodontal disease on overall and cardiovascular disease mortality in Pima Indians with type 2 diabetes. Periodontal abnormality was classified as no or mild, moderate, and severe, based on panoramic radiographs and clinical dental examinations. RESULTS: During a median follow-up of 11 years (range 0.3-16), 204 subjects died. The age- and sex-adjusted death rates for all natural causes expressed as the number of deaths per 1,000 person-years of follow-up were 3.7 (95% CI 0.7-6.6) for no or mild periodontal disease, 19.6 (10.7-28.5) for moderate periodontal disease, and 28.4 (22.3-34.6) for severe periodontal disease. Periodontal disease predicted deaths from ischemic heart disease (IHD) (P trend = 0.04) and diabetic nephropathy (P trend < 0.01). Death rates from other causes were not associated with periodontal disease. After adjustment for age, sex, duration of diabetes, HbA1c, macroalbuminuria, BMI, serum cholesterol concentration, hypertension, electrocardiographic abnormalities, and current smoking in a proportional hazards model, subjects with severe periodontal disease had 3.2 times the risk (95% CI 1.1-9.3) of cardiorenal mortality (IHD and diabetic nephropathy combined) compared with the reference group (no or mild periodontal disease and moderate periodontal disease combined). CONCLUSIONS: Periodontal disease is a strong predictor of mortality from IHD and diabetic nephropathy in Pima Indians with type 2 diabetes. The effect of periodontal disease is in addition to the effects of traditional risk factors for these diseases.

Schara, R., M. Medvescek, et al. (2006). "Periodontal disease and diabetes metabolic control: a full-mouth disinfection approach." J Int Acad Periodontol 8(2): 61-6.

ABSTRACT: Some studies demonstrated that local mechanical periodontal treatment and systemic antibiotics might improve the level of metabolic control in patients with diabetes. The aim of this clinical pilot trial was to evaluate if type 1 diabetes patients with periodontitis will experience improvement in periodontal status and glycemic control after a full-mouth disinfection treatment. Ten adult patients with poor metabolic control (mean glycated hemoglobin (HbA1c) = 10.7 %) and periodontitis were included in the study. All patients received a full-mouth disinfection in 24 hours as described by Quirynen et al. (1995) at baseline and 6 months later. The periodontal parameters included plaque index (PI), bleeding on probing, probing depth and clinical attachment loss. Metabolic control was measured by the serum level of HbA1c. All measurements were done at baseline and at 3, 6, 9 and 12 months. The results demonstrated a significantly lower PI, less bleeding on probing, reduction in probing depth and gain of clinical attachment at 3 months and 9 months of the study. Similarly, a significant reduction in the serum level of HbA1c was measured three months after full-mouth disinfection but disappeared 6 months later at the 6- and 12-month check points. We conclude that a full-mouth disinfection approach significantly improves periodontal status and metabolic control in type 1 diabetes patients with periodontitis. However, the results of our study imply that a full-mouth disinfection method has to be applied at least every 3 months to control periodontal status and glycemic control in type 1 diabetes patients. Further studies with greater numbers of diabetes patients are needed to confirm the long-term beneficial effects of a full-mouth disinfection approach on diabetic metabolic control.

Skaleric, U., R. Schara, et al. (2004). "Periodontal treatment by Arestin and its effects on glycemic control in type 1 diabetes patients." J Int Acad Periodontol 6(4 Suppl): 160-5.

ABSTRACT: Studies indicate that a dual pathway between diabetes mellitus and periodontal disease exists. Elimination of periodontal infection by using systemic antibiotics in conjunction with scaling and root planing (SRP) improved metabolic control in diabetic patients, as defined by reduction in glycated haemoglobin or reduction in insulin requirements (Grossi and Genco, 1998). The aim of this randomised pilot clinical trial was to determine if type 1 diabetes patients with periodontitis will experience a reduction in HbA1c levels when treated with locally delivered minocycline microspheres (Arestin) as an adjunct to scaling and root planing. Twenty adult patients with poorly controlled diabetes (HbA1c 7.5%) and adult periodontitis, as determined by the presence of four teeth with 5 mm periodontal pockets, two of which had 6-9 mm pockets and bleeding on probing, were included in the study. All patients received full mouth SRP at baseline. Arestin was administered to all pockets > or => or = 5 mm at baseline and again at 12 weeks in the test group. Probing depth (PD), clinical attachment level (CAL), plaque index (PI), gingival index (GI), and HbA1c were evaluated at baseline and at weeks 6, 12, 18 and 24. The results demonstrated that local administration of Arestin as an adjunct to scaling and root planing is significantly more effective in reducing probing depths and providing a gain in clinical attachment levels than scaling and root planing alone in type 1 diabetic patients. Hb1Ac was reduced in all patients; however the difference between the test and control groups was not significant.

Tan, W. C., F. B. Tay, et al. (2006). "Diabetes as a risk factor for periodontal disease: current status and future considerations." Ann Acad Med Singapore 35(8): 571-81.

ABSTRACT: INTRODUCTION: Over the past decade, there has been an emerging interest in the interrelationship between systemic conditions and oral health. Diabetes is perhaps one of the best documented conditions that have been closely linked with periodontal disease. This paper reviews the role of diabetes as a risk factor in periodontal disease. The treatment implications in the management of periodontal disease as an integral component of diabetes care is also discussed in light of the current understanding of the pathogenesis of these 2 chronic conditions. MATERIALS AND METHODS: Epidemiological, clinical and laboratory studies examining the relationship between diabetes and periodontal diseases were selected from both medical and dental journals. RESULTS: The severity of periodontal destruction has been shown to be related to the direct and indirect effects of glycaemic control, with other factors also being implicated. Although some studies have pointed towards a bi-directional relationship between glycaemic control and periodontal health, it is still not clear if improvement in periodontal health could lead to improved metabolic control. CONCLUSION: Diabetes and periodontal disease are closely related in many ways, though the effect of periodontal disease on diabetes control remain to be determined, with larger intervention studies. In light of the increasing evidence of the relationship between diabetes and periodontal disease, management of oral health should form an integral part of diabetes management.

Taylor, G. W., M. C. Manz, et al. (2004). "Diabetes, periodontal diseases, dental caries, and tooth loss: a review of the literature." Compend Contin Educ Dent 25(3): 179-84, 186-8, 190; quiz 192.

ABSTRACT: Diabetes mellitus, is a common chronic disease, and its prevalence in the United States, particularly type 2 diabetes, is increasing. Complications associated with diabetes impose a heavy burden on many people, especially among certain minority populations. Periodontal diseases, dental caries, and tooth loss also are common conditions in the United States, but their prevalence is generally decreasing. Nevertheless, among important subgroups of the population, particularly certain minority and economically disadvantaged groups, there is a disproportionately higher burden of periodontal diseases, dental caries, and tooth loss. This article reviews the post-1960 English-language literature on the relationship between diabetes and oral health, specifically focusing on periodontal disease, dental caries, and tooth loss. Substantial evidence exists to support the role of diabetes and poorer glycemic control as important risk factors for periodontal disease. Additionally, the evidence provides support for viewing the relationship between diabetes and periodontal diseases as bidirectional. However, additional research is necessary to firmly establish that treating periodontal infections can contribute to glycemic control management and possibly to the reduction of type 2 diabetes complications. The literature does not describe a consistent relationship between type 2 diabetes and dental caries. It reports increased, decreased, and similar caries experiences between those with and without diabetes. This review suggests that currently there is insufficient evidence to determine whether a relationship between diabetes and risk for coronal or root caries exists. Most of the reviewed studies reported greater tooth loss in people with diabetes. However, the differences were slight and not significant in several of the reports. Furthermore, this review of the association between diabetes and tooth loss reveals that valid population-based evidence generalizable to the US population is sparse. Further investigations of the association of diabetes with dental caries and tooth loss are warranted. If adverse effects of diabetes on dental caries and/or tooth loss are substantiated, the results of such studies would help design intervention studies to prevent or reduce the occurrence of dental caries and tooth loss in people with diabetes. These results also may affect existing clinical practice protocols and promote new public policy related to diabetes.

Varela-Centelles, P. I., M. Fortunez Rodriguez, et al. (2002). "[Nursing, diabetes, and periodontal disease]." Rev Enferm 25(7-8): 18-21.

ABSTRACT: In primary health care, the specific contribution nurses make to the community they serve manifests itself clearly when treating individuals suffering from chronic illnesses, with whom nurses basically fulfill an educational role. In the control of diabetics, a nurse plays a fundamental role in their periodical check-ups and their education about diabetes. Nonetheless, it is not a common practice to provide an adequate treatment for these pathologies nor oral hygiene self methods during these office visits, when the time requirements are not extensive and when the information available highlights the need to contemplate oral hygiene in both educational aspects and check-ups for diabetics, regardless of his/her age or the degree of metabolic control.

Verma, S. and K. M. Bhat (2004). "Diabetes mellitus--a modifier of periodontal disease expression." J Int Acad Periodontol 6(1): 13-20.

ABSTRACT: The understanding of causes and progression of periodontal disease has increased considerably in recent years making it all the more important to gain knowledge about diabetes and its interrelationship with periodontal disease so as to be able to assess their impact on one another more accurately. Strong evidence exists to support the fact that diabetic patients are at an increased risk for periodontitis. A number of underlying factors are known to contribute to enhanced periodontal destruction in diabetics. There has been intensive research to characterise the mechanisms responsible for the pathogenesis of both microvascular and macrovascular complications. It is also known that there is variability in the rate of development and severity of these complications with some diabetics experiencing none of them. Many of the host response traits that confer susceptibility to periodontitis in otherwise healthy individuals are exaggerated in diabetics. These diabetes associated susceptibility traits include neutrophil dysfunction, abnormal cross-linking and glycosylation of collagen, defective secretion of growth factors and subsequent impaired healing. However it is uncertain which of the hypothesised mechanisms or combinations of mechanisms is directly responsible for the pathogenesis of the complications or whether different mechanisms are operative in different tissues.

Xiong, X., P. Buekens, et al. (2006). "Periodontal disease and gestational diabetes mellitus." Am J Obstet Gynecol 195(4): 1086-9.

ABSTRACT: OBJECTIVE: We examined the relationship between periodontal disease and different types of diabetes in pregnant and nonpregnant women. STUDY DESIGN: This study was based on the data from the third National Health and Nutrition Examination Survey (NHANES III), including 256 pregnant and 4234 nonpregnant women. Women were classified into those with gestational diabetes mellitus (GDM) in current pregnancy, with GDM in previous pregnancy, and with type 1 or 2 diabetes. RESULTS: In pregnant women, the prevalence of periodontitis was 44.8% in women with GDM and 13.2% in nondiabetic women, with adjusted odds ratio (aOR) of 9.11 (95% confidence interval [CI] 1.11-74.9). In nonpregnant women, the prevalence of periodontitis was 40.3% in women with type 1 or 2 diabetes, 25.0% in women with previous history of GDM, and 13.9% in nondiabetic women, with aOR of 2.76 (1.03-7.35) for women with type 1 or 2 diabetes. CONCLUSION: We found an association between periodontal disease and GDM.

Yang, P. S., Y. Wang, et al. (2003). "[The effect of periodontal initial therapy on circulating TNF-alpha and HbA1C in type 2 diabetes patients with periodontitis]." Zhonghua Kou Qiang Yi Xue Za Zhi 38(5): 364-6.

ABSTRACT: OBJECTIVE: To investigate the effect and mechanism of periodontal initial therapy on type 2 diabetes patients with periodontitis. METHODS: 15 type 2 diabetes patients with periodontitis were selected. Their body mass index (BMI), sulcus bleeding index (SBI), probing depth (PD), circulating tumor necrosis factor-alpha (TNF-alpha) concentration, and the value of glycosylated hemoglobin (HbA1C), triglycerides (TG) and cholesterol (CHOL) were assessed respectively before and 4-6 weeks after periodontal initial therapy. RESULTS: After initial therapy, SBI, PD, circulating TNF-alpha concentration, and the value of HbA1C and TG were reduced significantly (P<0.05), while there were no significant differences in BMI and CHOL value (P>0.05). CONCLUSIONS: Periodontal initial therapy can effectively reduce HbA1C value in type 2 diabetes patients with periodontitis, possibly through the reduction of circulating TNF-alpha concentration.

Neurodegenerative Krankheiten

Neurodegenerative disease is a condition in which cells of the brain and spinal cord are lost. The brain and spinal cord are composed of neurons that do different functions such as controlling movements, processing sensory information, and making decisions. Aside from a small number of neural stem cells that are created daily, cells of the brain and spinal cord are not readily regenerated en mass, so excessive damage can be devastating. Neurodegenerative diseases result from deterioration of neurons which over time will lead to neurodegeneration and disabilities resulting from this. They are crudely divided into two groups according to phenotypic effects, although these are not mutually exclusive:

conditions causing problems with movements, such as ataxia
conditions affecting memory and conditions related to dementia

Neurodegenerative diseases can result from stroke, heat stress, head and spinal cord trauma (blunt or infectious pathology), and bleeding that occurs in the brain, the pressure from which eventually causes the death of one or more neurons.

Many times neuronal death begins long before the patient will ever experience any symptoms. It can be months or years before any effect is felt. Symptoms are noticed when lots of cells have died and certain parts of the brain have been weakened to the point that they can no longer function properly.

SCIENTIFIC PAPERS

Dirks, S. J., E. D. Paunovich, et al. (2003). "The patient with Parkinson's disease." Quintessence Int 34(5): 379-93.

ABSTRACT: Parkinson's disease is an idiopathic, slowly progressive disorder of the central nervous system characterized by resting tremor, muscular rigidity, slow and decreased movement (bradykinesia), and postural instability. In the United States, Parkinson's disease is the fourth most common neurodegenerative disorder in the elderly, affecting an estimated half a million people. Oral health care providers can expect to be called upon to care for patients with this progressively debilitating disease. To provide competent care to patients with Parkinson's disease, clinicians must understand the disease, its treatment, and its impact on the patient's ability to undergo and respond to dental care.

Meske, V., F. Albert, et al. (1999). "Culture of autopsy-derived fibroblasts as a tool to study systemic alterations in human neurodegenerative disorders such as Alzheimer's disease--methodological investigations." J Neural Transm 106(5-6): 537-48.

ABSTRACT: The present study was undertaken in order to analyse the possibility of culturing post mortem derived human fibroblasts. The combination of post mortem fibroblasts with the autopsy proven and histopathologically staged brain will allow the correlative investigation of dynamic biochemical processes which are systemically underlying or accompanying a neurological and/or psychiatric disorder. These studies are limited in autopsy brain or are uncertain when the neuropathological status is lacking, i.e. when fibroblasts were obtained from living patients. Our examinations of human autopsy fibroblast and those under experimentally controlled post mortem conditions with rats clearly demonstrate that autopsy-derived fibroblasts can be reliably cultured. The cells grown displayed typical morphological and staining characteristics as well as pharmacological responsiveness. Even cells obtained from a 99 years old individual or an individual with a post mortem delay of 48 hours grew in our culture system.

Perry, V. H. (2004). "The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease." Brain Behav Immun 18(5): 407-13.

ABSTRACT: Systemic inflammation is associated with sickness behaviour and signals pass from the blood to the brain via macrophage populations associated with the brain, the perivascular macrophages and the microglia. The amplitude, or gain, of this transduction process is critically dependent on the state of activation of these macrophages. In chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, or prion disease the pathology is associated with a highly atypical inflammatory response, characterised by the activation of the macrophage populations in the brain: the cells are primed. Recent evidence suggests that systemic inflammation may impact on local inflammation in the diseased brain leading to exaggerated synthesis of inflammatory cytokines and other mediators in the brain, which may in turn influence behaviour. These interactions suggest that systemic infections, or indeed any systemic challenge that promotes a systemic inflammatory response, may contribute to the outcome or progression of chronic neurodegenerative disease.

Perry, V. H., T. A. Newman, et al. (2003). "The impact of systemic infection on the progression of neurodegenerative disease." Nat Rev Neurosci 4(2): 103-12.

Smith, T. S. and J. P. Bennett, Jr. (1997). "Mitochondrial toxins in models of neurodegenerative diseases. I: In vivo brain hydroxyl radical production during systemic MPTP treatment or following microdialysis infusion of methylpyridinium or azide ions." Brain Res 765(2): 183-8.

ABSTRACT: Mitochondrial electron transport chain (ETC) function is selectively reduced in multiple tissues, including brain, from patients with Parkinson's disease (PD) and Alzheimer's disease (AD). The ETC defects are specific to each illness, involve complex I in PD and complex IV in AD, are transferable with mitochondrial DNA (mtDNA) and lead to increased production of reactive oxygen species (ROS) in mtDNA-deficient clonal neuronal cells hybridized with mtDNA ('cybrids') from PD or AD patients. C57BL/6 mice treated with MPTP developed elevated tissue hydroxyl radical ('OH) levels in striatum and ventral midbrain but not cerebellum. In brain microdialysis in awake rats, striatal 'OH output increased 3-5-fold after infusion of methylpyridinium ion (MPP+), a complex I inhibitor, or sodium azide, a complex IV inhibitor. Elevated 'OH after MPP+ was blocked stereospecifically by infusion of the nitric oxide synthase (NOS) inhibitor nitro-L-arginine or by the NMDA channel blocker MK801. Neither NOS inhibition nor NMDA blockade altered azide-induced 'OH production. ETC inhibition in vivo increases production of toxic 'OH, but the underlying mechanisms vary as a function of which ETC complex is inhibited. These results support the concept of developing oxygen free radical scavengers for both AD and PD and further suggest that inhibition of NOS and blockade of NMDA receptor function may alter progression of idiopathic PD.

Tanke, H. J. (2007). "Genomics and proteomics: the potential role of oral diagnostics." Ann N Y Acad Sci1098: 330-4.

ABSTRACT: Advances in genomics and proteomics increasingly contribute to the understanding of signal transduction pathways that control growth, differentiation, and death of cells. Since defects in these processes may result in the expression of inherited and or acquired disease, the identification of candidate disease genes and modifier genes by parallel use of genotyping together with an integrated study of gene expression and metabolite levels is instrumental for future health care. This approach, called systems biology, aims to recognize early onset of disease, institute preventive treatment, and identify new molecular targets for novel drugs in cancer, cardiovascular and metabolomic disease (e.g., diabetes), and neurodegenerative disorders. Gene interaction networks have recently been demonstrated, in which hub genes, that is, genes that show the highest level of interactions with other genes, play a special role. Hub genes, often chromatin regulators, may act as modifier genes (genes that modify the effect of other genes) in multiple mechanistically unrelated genetic diseases in humans. In addition, it has been shown that small metabolites such as hormones and cytokines, or proteins/enzymes such as C reactive protein (C-RP) and matrix metaloproteinase (MMP), reflect disease status in case of oral cancer, asthma, or periodontal and cardiac disease. Many of these molecular targets, as well as pathogen-specific DNA and RNA sequences, can be measured in oral fluids, providing a unique opportunity to develop novel noninvasive diagnostic tests. Efforts so far concentrate on the use of lab-on-a-chip technology in combination with novel reporters and microsensor arrays to measure multianalytes in oral fluids. Handheld devices that perform sensitive detection of multiple analytes in oral fluid will be obtainable in the near future.

Van Den Heuvel, A. G., J. Van der Grond, et al. (1997). "Differentiation between portal-systemic encephalopathy and neurodegenerative disorders in patients with Wilson disease: H-1 MR spectroscopy." Radiology 203(2): 539-43.

ABSTRACT: PURPOSE: To investigate the extent to which neurodegeneration and metabolic changes caused by portosystemic shunting occur in Wilson disease. MATERIALS AND METHODS: Twenty-two adult patients with biochemically proved Wilson disease underwent magnetic resonance (MR) imaging, hydrogen-1 MR spectroscopy, neurologic and psychometric testing, and ultrasound evaluation of the liver. In addition, 13 age-matched adult control subjects underwent MR imaging and H-1 MR spectroscopy. For MR spectroscopy, the authors used a single-voxel technique with a repetition time of 2,000 msec and an echo time of 31 msec. The volume of interest included the right and left globi pallidus, which are the most common sites of lesions in Wilson disease. RESULTS: N-acetylaspartate-creatine and choline-creatine ratios were decreased in patients with Wilson disease versus control subjects (P < .001 for N-acetylaspartate-creatine ratio, P < .05 for choline-creatine ratio). Also, patients with Wilson disease and portosystemic shunting had lower myo-inositol-creatine ratios than did patients with Wilson disease and no portosystemic shunting (P < .05). CONCLUSION: Reductions in N-acetylaspartate indicate neuronal loss consistent with the neurodegenerative pattern associated with Wilson disease. In addition, H-1 MR spectroscopy shows metabolic abnormality in the brain, as decreased myoinositol, caused by portosystemic shunting.

Widera, D., W. D. Grimm, et al. (2007). "Highly efficient neural differentiation of human somatic stem cells, isolated by minimally invasive periodontal surgery." Stem Cells Dev 16(3): 447-60.

ABSTRACT: Neural stem cells (NSCs) are potential sources for cell therapy of neurodegenerative diseases and for drug screening. Despite their potential benefits, ethical and practical considerations limit the application of NSCs derived from human embryonic stem cells (ES) or adult brain tissue. Thus, alternative sources are required to satisfy the criteria of ready accessibility, rapid expansion in chemically defined media and reliable induction to a neuronal fate. We isolated somatic stem cells from the human periodontium that were collected during minimally invasive periodontal access flap surgery as part of guided tissue regeneration therapy. These cells could be propagated as neurospheres in serum-free medium, which underscores their cranial neural crest cell origin. Culture in the presence of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) under serum-free conditions resulted in large numbers of nestin-positive/Sox-2-positive NSCs. These periodontium-derived (pd) NSCs are highly proliferative and migrate in response to chemokines that have been described as inducing NSC migration. We used immunocytochemical techniques and RT-PCR analysis to assess neural differentiation after treatment of the expanded cells with a novel induction medium. Adherence to substrate, growth factor deprivation, and retinoic acid treatment led to the acquisition of neuronal morphology and stable expression of markers of neuronal differentiation by more than 90% of the cells. Thus, our novel method might provide nearly limitless numbers of neuronal precursors from a readily accessible autologous adult human source, which could be used as a platform for further experimental studies and has potential therapeutic implications.

Osteoporose

Researchers have suggested that a link between osteoporosis and bone loss in the jaw. Studies suggest that osteoporosis may lead to tooth loss because the density of the bone that supports the teeth may be decreased, which means the teeth no longer have a solid foundation.

However, hormone replacement therapy may offer some protection. A study published in the August 1999 Journal of Periodontology concludes that estrogen supplementation in women within five years of menopause slows the progression of periodontal disease. Researchers have suspected that estrogen deficiency and osteopenia/osteoporosis speed the progression of oral bone loss following menopause, which could lead to tooth loss. The study concluded that estrogen supplementation may lower gingival inflammation and the rate of attachment loss (destruction of the fibers and bone that support the teeth) in women with signs of osteoporosis, thus helping to protect the teeth.

Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. Osteoporotic bones are more at risk of fracture. Osteoporosis is defined by the World Health Organization (WHO) in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old sex-matched healthy person average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture. While treatment modalities are becoming available (such as the bisphosphonates), prevention is still considered the most important way to reduce fracture. Due to its hormonal component, more women, particularly after menopause, suffer from osteoporosis than men. In addition it may be caused by various hormonal conditions, smoking and medications (specifically glucocorticoids) as well as many chronic diseases.

SCIENTIFIC PAPERS

Bollen, A. M. (2006). "Female osteoporosis may be associated with composite endpoint of periodontal disease." J Evid Based Dent Pract 6(4): 289-90.

Dmitrieva, L. A., V. G. Atrushkevich, et al. (2006). "[Periodontal tissues state in patients with systemic osteoporosis]." Stomatologiia (Mosk) 85(5): 17-9.

ABSTRACT: The results of the study of periodontal tissues in patients with systemic osteoporosis in rheumatoid arthritis are presented. The reduction of bone density in the region of interalveolar septa, insignificant bone tissue loss of the horizontal type and pathological teeth mobility were reported.

Evio, S., L. Tarkkila, et al. (2006). "Effects of alendronate and hormone replacement therapy, alone and in combination, on saliva, periodontal conditions and gingival crevicular fluid matrix metalloproteinase-8 levels in women with osteoporosis." Oral Dis 12(2): 187-93.

ABSTRACT OBJECTIVE: To compare the effects of hormone replacement therapy (HRT), alendronate and their combination on oral health of elderly postmenopausal women with osteoporosis. MATERIALS AND METHODS: Sixty patients, aged 65-80 years (mean 71 years), with a T-score of bone mineral density of -2.5 s.d. or less at either the lumbar spine or the femoral neck, were randomized to receive 2 mg of estradiol plus 1 mg norethisterone acetate (HRT) (n = 20), 10 mg of alendronate (n = 18), or their combination (n = 22) for 2 years. Periodontal and oral status and mouth symptoms were recorded, and salivary analyses made at the beginning and at the end of the study. Gingival crevicular fluid (GCF) matrix metalloproteinase (MMP-8) levels were determined to address destructive events in periodontal tissue. RESULTS: Resting salivary flow rate decreased by 19% (P < 0.05), and GCF MMP-8 tended to increase in the alendronate group. None of the regimens affected subjective feelings of dry or burning mouth. There were no significant changes in dental or periodontal status, stimulated flow rate or composition of saliva during the study. CONCLUSIONS: Alendronate decreased resting salivary flow rate but otherwise HRT or alendronate separately or in combination had no effect on oral health in elderly women with osteoporosis.

Gera, I. (2002). "[Osteoporosis: a risk factor for periodontal disease (literature review)]." Fogorv Sz 95(2): 49-54.

ABSTRACT Osteoporosis is a major public health problem all over the world. Caucasian women have the highest risk. Osteoporosis affects about 10% of the total population but the prevalence among postmenopausal women is more than 30%. It had long been stated that general osteoporosis played no role in the etiology of destructive periodontitis with inflammatory nature. Nevertheless a substantial number of publications in recent years indicated just an opposite relationship. It has been shown that total body calcium and bone density was closely associated with mandibular bone density and several studies have demonstrated close relationship between edentulism and systemic osteopenia. Certain data showed clear relationship between osteoporosis and periodontal disease, and osteoporosis is considered as one of the risk factors for periodontal bone loss. Both osteoporosis and periodontal disease are chronic multifactorial diseases with many genetic and behavioral risk factors and determinants. Both diseases can be successfully controlled by eliminating several risk factors. Estrogen replacement therapy can be protective against both postmenopausal osteoporosis and severe periodontitis in postmenopausal women. Tobacco smoking and diet are also important risk factors for both diseases and genetic factors have also been identified as important risk factors in the etiology of both diseases. Recent epidemiological and clinical data provides limited but convincing evidence suggesting an association between osteoporosis and periodontal disease, and many common risk factors could have been detected in the etiology of both diseases.

Geurs, N. C. (2007). "Osteoporosis and periodontal disease." Periodontol 2000 44: 29-43.

Geurs, N. C., C. E. Lewis, et al. (2003). "Osteoporosis and periodontal disease progression." Periodontol 2000 32: 105-10.

Groen, J. J. (1972). "[Alveolar osteoporosis and atrophy as a cause of periodontal disease]." Ned Tijdschr Tandheelkd 79(11): 409-15.

Groen, J. J., J. Menczel, et al. (1968). "Chronic destructive periodontal disease in patients with presenile osteoporosis." J Periodontol 39(1): 19-23.

Hayward, M. and C. Fiedler-Nagy (1987). "Mechanisms of bone loss: rheumatoid arthritis, periodontal disease and osteoporosis." Agents Actions 22(3-4): 251-4.

Inagaki, K., Y. Kurosu, et al. (2006). "[Osteoporosis and periodontal disease in postmenopausal women: association and mechanisms]." Clin Calcium 16(2): 269-77.

ABSTRACT Many studies have attempted to define the relationship between postmenopausal osteoporosis and periodontal disease. Most studies support a positive association between these common diseases; however, many are cross-sectional in nature, include relatively small sample sizes, and have inadequate control of potential confounding factors, such as age, gender, hormone intake, race, and smoking, limiting our understanding of the nature of the relationship between these diseases. Clinical conditions causing low estrogen environments in postmenopausal women allow T- and B-cell abnormalities, increased local production of the bone-active cytokines (i.e., Interleukin-1, -6 and -8, tumor necrosis factor [TNF]-alpha) and a rise in prostaglandin E(2), resulting in the progression of periodontitis.

Inagaki, K., Y. Kurosu, et al. (2003). "[Osteoporosis and periodontal disease in postmenopausal women]." Clin Calcium 13(5): 556-64.

ABSTRACT Many studies have attempted to define the relationship between postmenopausal osteoporosis and periodontal disease. Most studies support a positive association between these common diseases; however, many are cross-sectional in nature, include relatively small sample sizes, and have inadequate control of potential confounding factors, such as age, gender, hormone intake, race, and smoking, limiting our understanding of the nature of the relationship between these diseases. Clinical conditions causing low estrogen environments in postmenopausal women allow increased local production of the bone-active cytokine and the progression of periodontal disease. Prospective studies are needed to confirm or refute a causal relation.

Inagaki, K. and T. Noguchi (2002). "[Osteoporosis: a risk factor in periodontal disease]." Clin Calcium12(7): 978-86.

ABSTRACT Many studies have attempted to define the relationship between osteoporosis and periodontal disease. Most studies support a positive association between these common diseases; however, many are cross-sectional in nature, include relatively small sample sizes, and have inadequate control of potential confounding factors, such as age, gender, hormone intake, race, and smoking, limiting our understanding of the nature of the relationship between these diseases. Prospective studies are needed to confirm or refute a causal relation.

Jagelaviciene, E. and R. Kubilius (2006). "The relationship between general osteoporosis of the organism and periodontal diseases." Medicina (Kaunas) 42(8): 613-8.

ABSTRACT Osteoporosis and periodontitis are very prevalent diseases and are most common in middle-aged and elderly women. These diseases are related as both damage bone tissue and share common risk factors. Discussions about the association between these two bone-damaging diseases began in 1960. A hypothesis was raised that systemic imbalance in bone resorption and deposition might manifest itself in the alveolar bone earlier than in other bones. When analyzing systemic and local changes in bone density, a number of issues were investigated and attempted to answer the question of whether dental osteopenia is a local manifestation of osteoporosis having similar etiology and risk factors, or it is an independent process depending primarily on factors that cause periodontal disease. Histomorphometric and microradiographic studies showed that increasing porosity of the cortical layer in mandible resulted in the decrease in bone mass. Bone strength is best expressed through bone mineral density, and it can be called a diagnostic criterion of osteoporosis. The examination of bone mineral density is called densitometry and may be performed using dual-energy x-ray absorptiometry. Orthopantomography is a method that is widely applied in odontological practice and is also informative in determining the bone density of the mandible. It can be applied when performing orthopantomographic and vertical linear measurements, as well as in determining indices in the studies of osteoporotic changes. Since many patients attend odontological clinics, nearly all of them undergo orthopantomography. This is a good possibility to investigate osteoporotic changes in the mandible, to select individuals for further studies, and to ensure clinical benefit and good treatment results.

Jeffcoat, M. K. (2000). "Preterm birth, osteoporosis, and periodontal disease." Compend Contin Educ Dent Suppl(30): 5-11; quiz 65.

ABSTRACT The purpose of this two-part article is to review two major events in the life span of a woman. These include the putative relationship between oral health, pregnancy, and postmenopausal osteoporosis. Current knowledge about risk factors for preterm birth and for osteoporosis are discussed. The newest studies that address the relationship between oral and systemic health are also reviewed.

Jeffcoat, M. K., N. C. Geurs, et al. (2003). "Osteoporosis and periodontal bone loss." Clin Calcium 13(5): 577-81.

ABSTRACT Osteoporosis and osteopenia are characterized by reductions in bone mass, and may lead to skeletal fragility and fracture. Until the advent and widespread use of such methodology to measure bone density, such as dual energy X-ray absorption (DXA), the definition of osteoporosis was usually made using the clinical signs of a fracture. In 1994 the World Health Organization defined osteoporosis as a bone mineral density level more than 2.5 standard deviations below the mean of young normal women (WHO, 1994). The potential inter-relationship of the two diseases will be discussed in this paper.

Khokhlova, E., A. I. Volozhin, et al. (1995). "[The periodontal status of patients with hypoestrogenemia in relation to the severity of systemic osteoporosis]." Stomatologiia (Mosk) 74(2): 31-3.

ABSTRACT Changes in the periodontium progress in the patients with hypoestrogenemia, this progress being the slowest in patients with amenorrhea, intermediate in those subjected to oophorectomy, and the most rapid in those in the postmenopausal period. A conclusion was made that reduction of mineralisation of the bones enhances pathologic changes in the periodontium.

Krall, E. A. (2001). "The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease." Ann Periodontol 6(1): 209-13.

ABSTRACT Osteoporosis and osteopenia may influence periodontal disease and tooth loss. Medications such as hormone replacement therapy and nutritional supplements that are used to prevent or treat osteoporosis have been evaluated for beneficial effects on oral health in a small number of human studies. Hormone replacement therapy (HRT), which slows the rate of bone loss at skeletal sites such as the hip and spine, also appears to reduce the rate of alveolar bone loss in postmenopausal women. HRT use is consistently associated with greater tooth retention and a reduced likelihood of edentulism in studies of elderly women. The number of studies on the effects of calcium or vitamin D intake on oral outcomes is limited, but suggest that higher intake levels are associated with reduced prevalence of clinical attachment loss and lower risk of tooth loss. Data from a prospective study of oral health in men show a similar association between higher calcium intake and reduced alveolar bone loss. The number of teeth with progression of alveolar bone loss over a 7-year period was significantly lower among men whose calcium intake was at least 1,000 mg per day, compared to men with a calcium intake below this level. Future studies should confirm these findings and evaluate the oral effects of new medications for osteoporosis. If confirmed, the implications for dental professionals may include an expanded array of medications for the treatment of periodontal disease and a greater emphasis on nutrition education for patients.

Krejci, C. B. (1996). "Osteoporosis and periodontal disease: is there a relationship?" J West Soc Periodontol Periodontal Abstr 44(2): 37-42.

ABSTRACT Osteoporosis, by definition, is a generalized progressive reduction in both bone mineral and bone matrix which results in bone of normal composition but decreased mass. Functionally, osteoporotic bone is characterized by greater fragility and an increased propensity to fracture. It ranks as the most common metabolic bone disease and the most common skeletal disorder in the world. As such, it constitutes a major public health problem. Due to the extent of the disease, many have questioned its relevance to the maxilla and mandible and its possible relationship to periodontitis. The purpose of this paper is to review both osteoporosis and periodontitis and to present the research completed to date which has investigated the possible interrelationships between the two diseases.

Krook, L., J. P. Whalen, et al. (1972). "Human periodontal disease and osteoporosis." Cornell Vet 62(3): 371-91.

Lai, Y. L. (2004). "Osteoporosis and periodontal disease." J Chin Med Assoc 67(8): 387-8.

Lerner, U. H. (2006). "Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis." J Dent Res 85(7): 596-607.

ABSTRACT During physiological conditions, the skeleton is remodeled in so-called bone multi-cellular units. Such units have been estimated to exist at 1-2 x 10(6) sites in the adult skeleton. The number and activities of these units are regulated by a variety of hormones and cytokines. In post-menopausal osteoporosis, lack of estrogen leads to increased numbers of bone multi-cellular units and to uncoupling of bone formation and bone resorption, resulting in too little bone laid down by osteoblasts compared with the amount of bone resorbed by osteoclasts. Inflammatory processes in the vicinity of the skeleton, e.g., marginal and apical periodontitis, will affect the remodeling of the nearby bone tissue in such a way that, in most patients, the amount of bone resorbed exceeds that being formed, resulting in net bone loss (inflammation-induced osteolysis). In some patients, however, inflammation-induced bone formation exceeds resorption, and a sclerotic lesion will develop. The cellular and molecular pathogenetic mechanisms in inflammation-induced osteolysis and sclerosis are discussed in the present review. The cytokines believed to be involved in inflammation-induced remodeling are very similar to those suggested to play crucial roles in post-menopausal osteoporosis. In patients with periodontal disease and concomitant post-menopausal osteoporosis, the possibility exists that the lack of estrogen influences the activities of bone cells and immune cells in such a way that the progression of alveolar bone loss will be enhanced. In the present paper, the evidence for and against this hypothesis is presented.

Lundstrom, A., J. Jendle, et al. (2001). "Periodontal conditions in 70-year-old women with osteoporosis." Swed Dent J 25(3): 89-96.

ABSTRACT The aim of the present study was to examine the periodontal conditions in an age cohort of 70-year-old women and compare an osteoporosis group with a control group with normal bone mineral density. 210 women 70 years old and randomly sampled from the population register of the community of Linkoping were examined. Bone mineral density (BMD) of the hip was measured by dual energy X-ray absorptiometry. 19 women were diagnosed with osteoporosis (BMD below 0.640 g/cm2 in total hip). 15 of them accepted to participate in the study. As a control group 21 women with normal bone mineral density (BMD exceeding 0.881 g/cm2) were randomly selected from the initial population. The clinical examination included registration of the number of remaining teeth, dental plaque and periodontal conditions. The radiographic examination included a dental panorama and vertical bite-wing radiographs. The subjects also answered a questionnaire about their general health, age at menopause, concurrent medication, smoking and oral hygiene habits. The results from this study showed no statistically significant differences in gingival bleeding, probing pocket depths, gingival recession and marginal bone level between the women with osteoporosis and the women with normal bone mineral density. In conclusion, the present randomly selected and controlled study of osteoporotic and non-osteoporotic women, showed no statistically significant differences in periodontal conditions or marginal bone level. As periodontitis as well as osteoporosis are associated with age, our study of a well-defined age cohort is of interest, but the results should be interpreted with caution since the compared groups are small.

Maksimovskii Iu, M., A. I. Moshchil, et al. (1991). "[Periodontal status in generalized osteoporosis in women with ovarian functional insufficiency]." Stomatologiia (Mosk) 70(1): 24-6.

ABSTRACT Enhanced atrophic processes in periodontal tissues were revealed in women with inadequate ovarian function (primary amenorrhea, ovariectomy, climax), examined by clinical methods and by determining their periodontal inflammation index, hygienic index, gingival fluid level, and by x-ray methods. The findings correspond to generalized osteoporosis signs; this condition was detected by single-photon absorptiometry and ultrasonic osteometry.

Mohammad, A. R., M. Brunsvold, et al. (1996). "The strength of association between systemic postmenopausal osteoporosis and periodontal disease." Int J Prosthodont 9(5): 479-83.

ABSTRACT This cross-sectional study examined the strength of association between systemic osteoporosis and periodontal status in postmenopausal non-Hispanic white women. Twenty subjects with low bone density and a spine bone density of 0.753 +/- 0.039 dual-energy x-ray absorptiometry units (g/cm2) and 22 subjects with high bone density and a spine bone density of 1.032 +/- 0.028 dual-energy x-ray absorptiometry units (g/cm2) were randomly selected from a cohort of 565 women. Periodontal assessment included Plaque Index, Gingival Index, pocket depth, gingival recession, and periodontal attachment level. There were no significant differences in Plaque Index, Gingival Index, and probing depth in both groups; however, there were significant differences in gingival recession components of periodontal attachment level in both groups. This study suggests that systemic osteoporosis may contribute to periodontal attachment loss in the form of gingival recession.

Mohammad, A. R., J. D. Jones, et al. (1994). "Osteoporosis and periodontal disease: a review." J Calif Dent Assoc 22(3): 69-75.

ABSTRACT A review of the literature on the relationship between osteoporosis and periodontal disease is presented. Osteoporosis, a metabolic disease, and periodontal disease, which is infectious, are both major health problems with multifactorial etiologies. There is histologic and radiographic evidence from animals and humans that osteoporosis does affect alveolar bone by decreasing bone mass and trabeculation. The literature reviewed in this paper suggests, but does not yet provide conclusive evidence for, a direct relationship between osteoporosis and periodontal disease.

Ortega, R. M., A. M. Requejo, et al. (1998). "[Implication of calcium deficiency in the progress of periodontal diseases and osteoporosis]." Nutr Hosp 13(6): 316-9.

ABSTRACT Several authors have established a relationship between osteoporosis and periodontal disease. The ageing process is associated with a loss of both oral and total bone mass. It has been shown that a reduction of bone mineralization aggravates pathological periodontal changes, resulting in less support for the teeth. The present study investigates the nutritional influences that may condition the appearance of both pathological process. Insufficient dietary calcium and a reduction in the calcium: phosphorous ratio may favour the appearance of both these conditions by promoting bone reabsorption. Bone loss affects the following in descending order: jaw bones (especially alveolar bone), cranial bones, ribs, vertebrae and long bones. Alveolar bone which has the highest rate of renewal, is affected first and consequently is the most severely affected in the long term. The role of calcium in the etiology of osteoporosis is a controversial issue. Nevertheless, its implication has been proven in numerous investigations. The effect of adequate calcium intake on dental health has formed the basis of several recent studies. These investigations have demonstrated that increased calcium intake improves the suffering of inflammatory processes and tooth mobility in patients suffering from gingivitis with haemorrhaging. Based on the results of studies which link dietary calcium and phosphorous to the risk of osteoporosis and periodontal disease, and bearing in mind that in a large proportion of the Spanish population calcium intake is below that recommended, there is a need for a general improvement of the diet. It may be of special interest to increase the calcium intake of patients suffering periodontal disease. It may also help in the prevention of osteoporosis.

Otogoto, J. and N. Ota (2003). "[Correlation between periodontal disease and osteoporosis using panoramic radiographic parameters for diagnosed osteoporosis in dental clinic]." Clin Calcium 13(5): 582-6.

ABSTRACT The correlation between periodontal disease and osteoporosis was evaluated by comparing age, panoramic radiographic and clinical parameters of periodontal disease. Diagnosis of osteoporosis in periodontal diseased patients was evaluated by panoramic radiographic parameters (mandibular cortical width:MCW). Subjects which had more than 20 teeth and examined by panoramic radiography were untreated adults with periodontal disease who were free of other systemic disease. The following parameters were examined on panoramic X-ray film:alveolar bone loss (ABL), mandibular bone mass with the use of mandibular cortical width (MCW). ABL was significantly higher and MCW significantly lower in the postmenopausal group (>6 years after menopause). The number of teeth was significantly lower and CAL significantly higher in the postmenopausal group (>11 years after menopause). Age and ABL correlated positively in men and women. Years after menopause and ABL and MCW and CAL in the postmenopausal group were correlated positively. Women whose MCW was less than mean - 2 SD should be diagnosed with osteoporosis. Our results demonstrated that periodontal disease correlates with osteoporosis, and MCW could be useful in detecting of osteoporosis in women with periodontal disease.

Palomo, L., N. Bissada, et al. (2006). "Bisphosphonate therapy for bone loss in patients with osteoporosis and periodontal disease: clinical perspectives and review of the literature." Quintessence Int 37(2): 103-7.

ABSTRACT As the baby boomer generation in the United States ages, more patients are using bisphosphonates for systemic bone diseases like osteoporosis. Because of their ability to inhibit bone resorption and osteoclastic activity, bisphosphonates may also be beneficial in modulating host response for periodontal disease management. This literature review examines the mechanism of action for bisphosphonates and their uses in treating periodontal disease. The dental profession should continue to evaluate this class of drugs and to closely monitor patients who are on bisphosphonate therapy.

Persson, R. E., L. G. Hollender, et al. (2002). "Assessment of periodontal conditions and systemic disease in older subjects. I. Focus on osteoporosis." J Clin Periodontol 29(9): 796-802.

ABSTRACT BACKGROUND: Osteoporosis (OPOR) is a common chronic disease, especially in older women. Patients are often unaware of the condition until they experience bone fractures. Studies have suggested that OPOR and periodontitis are associated diseases and exaggerated by cytokine activity. Panoramic radiography (PMX) allows studies of mandibular cortical index (MCI), which is potentially diagnostic for OPOR. AIMS: i). To study the prevalence of self-reported history of OPOR in an older, ethnically diverse population, ii). to assess the agreement between PMX/MCI findings and self-reported OPOR, and iii). to assess the likelihood of having both a self-reported history of OPOR and a diagnosis of periodontitis. MATERIALS AND METHODS: PMX and medical history were obtained from 1084 subjects aged 60-75 (mean age 67.6, SD +/- 4.7). Of the films, 90.3% were useful for analysis. PMXs were studied using MCI. The PMXs were used to grade subjects as not having periodontitis or with one of three grades of periodontitis severity. RESULTS: A positive MCI was found in 38.9% of the subjects, in contrast to 8.2% self-reported OPOR. The intraclass correlation between MCI and self-reported OPOR was 0.20 (P < 0.01). The likelihood of an association between OPOR and MCI was 2.6 (95%CI: 1.6, 4.1, P < 0.001). Subjects with self-reported OPOR and a positive MCI had worse periodontal conditions (P < 0.01). The Mantel-Haentzel odds ratio for OPOR and periodontitis was 1.8 (95%CI: 1.2, 2.5, P < 0.001). CONCLUSIONS: The prevalence of positive MCI was high and consistent with epidemiological studies, but only partly consistent with a self-reported history of osteoporosis with a higher prevalence of positive MCI in Chinese women. Horizontal alveolar bone loss is associated with both positive self-reported OPOR and MCI.

Reisel, J. H. (1972). "[Clinical osteoporosis and periodontal disease. II]." Ned Tijdschr Tandheelkd 79(3): 100-2.

Serhan, C. N. (2004). "Clues for new therapeutics in osteoporosis and periodontal disease: new roles for lipoxygenases?" Expert Opin Ther Targets 8(6): 643-52.

ABSTRACT Lipoxygenase (LOX) pathways are well appreciated for their ability to regulate key events contributing to the cardinal signs of inflammation. Recent evidence indicates that LOX genes are associated with osteoporosis. Also, overexpression of the 15-LOX Type 1 in transgenic rabbits leads to a reduced inflammatory phenotype and protection from periodontal disease, as well as atherosclerosis. Osteoporosis and inflammation-associated bone degradation, such as periodontitis, affect many individuals worldwide and are known to have pathogenesis that involves local mediators via communication between osteoclasts and osteoblasts during osteogenesis. Evidence has emerged indicating that LOX gene expression is associated with reduced bone strength in murine models of osteoporosis. Overexpression of the 15-LOX gene and its products, such as lipoxins, confers endogenous anti-inflammation. This article discusses the recent findings that may link aberrant LOX pathway expression in these diseases, suggesting new avenues for therapeutic approaches via activation of endogenous pathways for resolution of local inflammation.

Shen, E. C., C. H. Gau, et al. (2004). "Periodontal status in post-menopausal osteoporosis: a preliminary clinical study in Taiwanese women." J Chin Med Assoc 67(8): 389-93.

ABSTRACT BACKGROUND: Osteoporosis and periodontitis are common diseases affecting post-menopausal women; however, the exact relationship between the diseases is still uncertain. The purposes of this study were to examine the periodontal status in a group of type I post-menopausal women with and without osteoporosis and to elucidate the possible role of the osteoporosis in the pathogenesis of periodontal disease. METHODS: Thirty-four patients (18 in the osteoporotic and 16 in the non-osteoporotic group) were selected from 329 post-menopausal Taiwanese women who had completed radiographic measurements of spinal bone mineral density and received full-mouth periodontal examination. Periodontal measurements, including O'Leary plaque index, probing depths, clinical attachment level, and gingival recession, on 6 sites of each tooth of full mouth were examined and recorded by 1 examiner. RESULTS: Significantly greater probing depth was noted at the interproximal, but not at the facio-lingual, osteoporotic sites if compared to those non-osteoporotic sites. The depth was also significantly influenced by the examining factors of plaque accumulation, tooth location, and jaws. By individual jaw, increased attachment loss accompanied by greater probing depth and gingival recession was found at the osteoporotic sites on mandible if compared to non-osteoporotic sites. On maxilla, however, less gingival recession and attachment loss were observed at the osteoporotic sites. CONCLUSIONS: In the present study, increased attachment loss accompanied by greater probing depth and gingival recession was found at the osteoporotic sites on mandible. However, the parameters were also influenced by the examining factors of plaque accumulation, tooth location, and jaws. Therefore, we suggest that post-menopausal osteoporosis may play a role in the pathogenesis of periodontal disease, especially on the mandible, although the etiology of periodontal disease is still multi-factorial.

Takemura, A. and M. Nishida (2006). "[Application of dietary supplement to periodontal disease and osteoporosis]." Clin Calcium 16(2): 354- 58.

ABSTRACT It is known that there is a relationship between various systemic diseases, life style and periodontal disease. In such a situation, it is becoming clear a relationship between the systemic bone density and the mandibular bone, alveolar bone density and clinical periodontal parameters. And it is also cleared that to lower common risk factors related to these conditions might be useful to prevent osteoporosis and periodontal disease. As it is reported that medical treatment such as hormone replacement therapy (HRT) is effective not only preventing lowering skeletal bone density but also maintaining mandibular and alveolar bones, it is also considered that continuing supplementation of some nutritions such as calcium and isoflavone is also expected to have preventive effects.

von Wowern, N., B. Klausen, et al. (1994). "Osteoporosis: a risk factor in periodontal disease." J Periodontol 65(12): 1134-8.

ABSTRACT Osteoporosis is suspected as a risk factor in periodontal disease, but previous studies have failed to establish a relationship. Possible explanations for this could be lack of precise methods for assessment of osteoporosis in the jaws and confounding of the result by other factors such as age, gender, or smoking. In the present study 12 female patients with osteoporotic fractures (Group O) and 14 normal women (Group N) were examined clinically for plaque (VPI), gingival bleeding (GBI), and loss of attachment on the 6 Ramfjord index teeth. Bone mineral content (BMC) of the mandible and forearm was determined by dual photon scanning. Results were presented as arithmetic means +/- standard error, and differences between groups were tested by 2-sample t-test. The two groups were comparable with respect to age (O: 68.3 +/- 1.8 years, N: 68.1 +/- 1.5 years), menopausal age (O: 47.5 +/- 1.8 years, N: 47.2 +/- 1.3 years), and smoking habits (O: 4 smokers, N: 3 smokers). The osteoporotic women had significantly lower BMC values than controls in the mandible (O: 0.63 +/- 0.04 in U/cm2; N: 0.78 +/- 0.02 in U/cm2, P < 0.01) and forearm (O: 1.05 +/- 0.05 in U/cm; N: 1.28 +/- 0.05 in U/cm, P < 0.01). No significant differences were found with respect to plaque (O: 46.67 +/- 10.00%, N: 36.67 +/- 6.67%) and gingival bleeding (O: 46.67 +/- 11.67%, N: 43.33 +/- 10.00%), whereas significantly greater loss of attachment was seen in osteoporotic women (O: 3.65 +/- 0.18 mm, N: 2.86 +/- 0.19 mm, P < 0.01).

Wactawski-Wende, J. (2001). "Periodontal diseases and osteoporosis: association and mechanisms." Ann Periodontol 6(1): 197-208.

ABSTRACT There is increasing evidence that osteoporosis, and the underlying loss of bone mass characteristic of this disease, is associated with periodontal disease and tooth loss. Periodontitis has long been defined as an infection-mediated destruction of the alveolar bone and soft tissue attachment to the tooth, responsible for most tooth loss in adult populations. Current evidence including several prospective studies supports an association of osteoporosis with the onset and progression of periodontal disease in humans. The majority of studies have shown low bone mass to be independently associated with loss of alveolar crestal height and tooth loss. However studies that focus on the relation of clinical attachment loss and osteoporosis are less consistent. To date, the majority of studies on the relationship between periodontal disease and osteoporosis have been hindered by small sample sizes, limited control of other potential confounding factors, varying definitions of both periodontal disease and osteoporosis, and few prospective studies where the temporality of the association can be established. Potential mechanisms by which host factors may influence onset and progression of periodontal disease directly or indirectly include underlying low bone density in the oral cavity, bone loss as an inflammatory response to infection, genetic susceptibility, and shared exposure to risk factors. Systemic loss of bone density in osteoporosis, including that of the oral cavity, may provide a host system that is increasingly susceptible to infectious destruction of periodontal tissue. Studies have provided evidence that hormones, heredity, and other host factors influence periodontal disease incidence and severity. Both periodontal disease and osteoporosis are serious public-health concerns in the United States. Prevalence of both osteoporosis and tooth loss increase with advancing age in both women and men. Understanding the association between these common diseases and the mechanisms underlying those associations will aid health professionals to provide improved means to prevent, diagnose, and treat these very common diseases. This paper reviews the current evidence on the association between periodontal disease and osteoporosis.

Weber, R. L., M. J. Wiesen, et al. (1997). "Osteoporosis: a risk factor for dental implants and in the prognosis of periodontal therapy." Periodontal Clin Investig 19(2): 5-8.

ABSTRACT Two patients were referred to the Graduate Periodontal Clinic, one for placement of dental implants, the other for treatment of advanced periodontal disease. It was determined from an analysis of the Hounsfield scales of bone density from a CT scan that the patient requesting dental implants had severe osteoporotic changes and was, therefore, not a good candidate for the procedure. The second patient's medical history revealed multiple fractures occurring over the years that suggested the presence of osteoporosis. This diagnosis was subsequently confirmed by referral of the patient to an osteoporosis clinic.

Whalen, J. P. and L. Krook (1996). "Periodontal disease as the early manifestation of osteoporosis." Nutrition 12(1): 53-4.

Yamada, F. (1972). "[Epidemiological studies on the relationship between periodontal diseases and osteoporosis among the farm and fishing villagers in North-East Japan]." Koku Eisei Gakkai Zasshi 22(2): 197-202.

Yoshinari, N., H. Kawase, et al. (2006). "[The relationship between periodontal disease and osteoporosis in animals]." Clin Calcium 16(2): 279-86.

ABSTRACT Osteoporosis is suspected as a potential risk factor in periodontal disease. However, the detailed relationship between these diseases is unclear. The particular models of laboratory animals for the both diseases are needed to clarify the interactive influence route. In this article, we introduce the animal models for both diseases, review the relationship between osteoporosis and periodontal disease in animals and report our laboratory study. The purpose of our study was to investigate the effect of an ovariectomy on the progression of experimental periodontitis in rats. Thirty female Sprague-Dawley rats as control, 30 sham-operated rats and 30 ovariectomized rats (OVX group) were included. In the maxillary molars of every rat, a nylon thread was ligated to induce experimental periodontitis. The results were as follows : at 6 and 12 weeks in the OVX group, the levels of bone mineral density (BMD) had decreased more significantly. The periodontal tissues in the OVX group showed a severer inflammation and alveolar bone resorption. From these results, it is suggested that the osteoporotic conditions may affect the progression of periodontal lesions in rats. It will be necessary to clarify with a molecular mechanism with the establishment of animal models in both diseases in the future.

Pankreaserkrankungen

Pancreatic cancer is a malignant tumour within the pancreatic gland. Each year about 32,000 individuals in the United States are diagnosed with this condition, and more than 60,000 in Europe. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with few victims still alive 5 years after diagnosis, and complete remission still extremely rare.

About 95 percent of pancreatic tumors are adenocarcinomas . The remaining 5 percent include other tumors of the exocrine pancreas (e.g. serous cystadenomas), acinar cell cancers, and pancreatic neuroendocrine tumors (such as insulinomas). These tumors have a completely different diagnostic and therapeutic profile, and generally a more favorable prognosis.

SCIENTIFIC PAPERS

(2007). "Pancreatic cancer: new studies, new treatments. "Periodontal disease,", "gemcitabine" and "adjuvant therapy" are the new buzzwords." Health News 13(6): 8-9.

Michaud, D. S., K. Joshipura, et al. (2007). "A prospective study of periodontal disease and pancreatic cancer in US male health professionals." J Natl Cancer Inst 99(2): 171-5.

ABSTRACT: Two previous cohort studies reported positive associations between tooth loss or periodontitis and pancreatic cancer risk. Data on periodontal disease were obtained at baseline and every other year thereafter in a cohort of 51,529 male health professionals aged 40-75 years. A total of 216 patients were diagnosed with incident pancreatic cancer during 16 years of follow-up. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models controlling for potential confounders, including detailed smoking history. All statistical tests were two-sided. Compared with no periodontal disease, history of periodontal disease was associated with increased pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26; P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude incidence rates: 61 versus 19 per 100,000 person-years). In contrast, baseline number of natural teeth and cumulative tooth loss during follow-up were not strongly associated with pancreatic cancer. The association between periodontal disease and increased risk of pancreatic cancer may occur through plausible biologic mechanisms, but confirmation of this association is necessary.

Taguchi, A. (2007). "Re: A prospective study of periodontal disease and pancreatic cancer in US male health professionals." J Natl Cancer Inst 99(9): 738-9; author reply 739.

Frühgeburten

Low birth weight, defined as birth weight less than 2,500 g, continues to be a significant public health issue in both developed and developing countries. This obstetric complication is usually a direct result of preterm labour, in which case it is referred to as preterm delivery of low-birthweight infants (PLBW). Introduction of neonatal intensive care methods during the 1960s and the subsequent development of surfactant therapy in the 1980s resulted in improvements in the survival rates of PLBW neonates. However, compared with infants of normal birth weight, PLBW infants are still 40 times more likely to die during the neonatal period.12 PLBW births represent approximately 10% of all live births in North America, and medical care for these infants is estimated to exceed $5 billion US annually.

For a long time we've known that risk factors such as smoking, alcohol use, and drug use contribute to mothers having babies that are born prematurely at a low birth weight.

Now evidence is mounting that suggests a new risk factor – periodontal disease. Pregnant women who have periodontal disease may be seven times more likely to have a baby that is born too early and too small.

More research is needed to confirm how periodontal disease may affect pregnancy outcomes. It appears that periodontal disease triggers increased levels of biological fluids that induce labor. Furthermore, data suggests that women whose periodontal condition worsens during pregnancy have an even higher risk of having a premature baby.

All infections are cause for concern among pregnant women because they pose a risk to the health of the baby. The Academy recommends that women considering pregnancy have a periodontal evaluation.

SCIENTIFIC PAPERS

Alves, R. T. and R. A. Ribeiro (2006). "Relationship between maternal periodontal disease and birth of preterm low weight babies." Pesqui Odontol Bras 20(4): 318-23.

ABSTRACT: It has been recently suggested that periodontal disease is an associated factor for prematurity and low birth weight. The aim of this work was to assess the periodontal status of puerperae and determine its possible relationship with preterm low birth weight (PLBW) delivery. The sample included 59 women seen at two maternity hospitals in Juiz de Fora, MG, Brazil. Nineteen mothers had premature and low birth weight babies (gestational age below 37 weeks and birth weight below 2,500 g--group I), and 40 had mature, normal weight babies (gestational age over 37 weeks and birth weight over 2,500 g--group II). The mothers' data were obtained from medical files, interview, and periodontal clinical examination carried out up to 48 hours after delivery. The Periodontal Screening and Recording (PSR) was used for periodontal assessment. The association between periodontal disease and PLBW was expressed as odds ratio (OR). There was a higher rate of periodontal disease in group I (84.21% - 16/19) as compared with group II (37.5% - 15/40). The data also showed a significant association between periodontal disease and PLBW (OR = 8.9 - 95% CI: 2.22-35.65--p = 0.001). It was concluded that maternal periodontal disease was an associated factor for prematurity and low birth weight in this sample.

Barnes, C. M. (2007). "Treatment of periodontal disease and the risk of preterm birth." Pract Proced Aesthet Dent 19(2): 118.

Dasanayake, A. P., S. Russell, et al. (2003). "Preterm low birth weight and periodontal disease among African Americans." Dent Clin North Am 47(1): 115-25, x-xi.

ABSTRACT: African Americans consistently experience higher rates of preterm and low birth weight (LBW) deliveries than do whites. LBW and preterm infants are more likely to die before their first birthday and survivors may suffer from a number of health problems. Therefore, identification of modifiable risk factors for preterm deliveries and LBW has considerable public health significance. Pregnant women's poor periodontal healtlh is emerging as one such factor. Maternal clinical periodontal status and bacteriologic and immunologic profiles related to periodontal disease have been associateted with risk of fetal growth and preterm LBW, and periodontal treatment during pregnancy has reduced the incidence of preterm deliveries. This article reviews the literature on the above association and presents data from a previously published prospective study of predominantly African Americans to show that preterm LBW deliveries are associated with higher midtrimester maternal serum antibody levels against Porphyromonas gingivalis.

Davenport, E. S., C. E. Williams, et al. (2002). "Maternal periodontal disease and preterm low birthweight: case-control study." J Dent Res 81(5): 313-8.

ABSTRACT: Periodontal disease has been suggested to be an important risk factor for preterm low birthweight (PLBW). Here we report a case-control study of 236 cases (infants < 37 wks and weighing < 2499 g) and a daily random sample of 507 controls (> or = 38 wks and weighing > or = 2500 g). Clinical periodontal indices were measured on the labor wards. Associated risk factors for periodontal disease and PLBW were ascertained by means of a structured questionnaire and maternity notes. The risk for PLBW decreased with increasing pocket depth (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.68 to 1.00). After adjustment for maternal age, ethnicity, maternal education, smoking, alcohol consumption, infections, and hypertension during pregnancy, this decreased further (OR 0.78, 95% CI 0.64 to 0.99). We found no evidence for an association between PLBW and periodontal disease. Our results do not support a specific drive to improve periodontal health of pregnant women as a means of improving pregnancy outcomes.

Davenport, E. S., C. E. Williams, et al. (1998). "The East London Study of Maternal Chronic Periodontal Disease and Preterm Low Birth Weight Infants: study design and prevalence data." Ann Periodontol 3(1): 213-21.

ABSTRACT: The influence of subject-based and environmental factors on the balance between the subgingival microbial challenge and the host response in periodontal diseases illustrates the intimate link between oral and systemic health. From this stems the hypothesis that the persistent Gram-negative challenge and associated inflammatory sequelae in periodontal disease may have consequences extending beyond the periodontal tissues themselves. This paper addresses the design of a case-control study to examine the relationship between preterm low birth weight (PLBW) and maternal periodontal disease. We present preliminary data on the prevalence of these 2 conditions in a group of mothers at the Royal Hospitals Trust, London, U.K. Cases are defined as mothers delivering an infant weighing less than 2,500g before 37 weeks gestation and controls as mothers delivering an infant of more than 2,500g after 38 weeks. We estimated that a study involving 800 mothers (1:3 case:control) should have sufficient power to detect an association with a minimum odds ration of 3 at the 5% significance level. Demographic details of 177 subjects demonstrated that they were representative of the local population, and the prevalence of PLBW was within the expected range. However, the extent and severity of periodontal disease were higher than predicted and may have reflected elevations in gingival inflammation associated with pregnancy. The final outcome of the study should help determine the need for further interventionist studies to demonstrate a causal relationship between periodontal disease and PLBW, as well as provide information on the prevalence of periodontal diseases in this study population.

Garvin, J. (2006). "Periodontal treatment does not reduce the risk of preterm delivery, study finds." J Am Dent Assoc 137(12): 1642-3.

Gazolla, C. M., A. Ribeiro, et al. (2007). "Evaluation of the incidence of preterm low birth weight in patients undergoing periodontal therapy." J Periodontol 78(5): 842-8.

ABSTRACT: BACKGROUND: Preterm low birth weight was reported to be related to periodontal infections that might influence the fetus-placenta complex. The aim of this study was to provide periodontal treatment for pregnant women and to evaluate if this treatment can interfere with pregnancy duration and weight of the newborn. METHODS: The sample consisted of 450 pregnant women who were under prenatal care at a polyclinic in Tres Coracoes, Brazil. Women with risk factors, such as systemic alterations (ischemic cardiopathy, hypertension, tuberculosis, diabetes, cancer, anemia, seizure, psychopathology, urinary tract infection, sexually transmitted diseases, asthma, and human immunodeficiency virus), and/or users of alcohol, tobacco, and drugs were excluded from the study. Data related to age, socioeconomic level, race, marital status, number of previous pregnancies, and previous preterm delivery also were evaluated. Initially, the sample was divided into two groups: 122 healthy patients (group 1) and 328 patients with periodontal disease (group 2). In group 2, 266 patients underwent treatment and 62 patients dropped out. After mothers gave birth, pregnancy duration and the weight of all infants were analyzed and recorded. RESULTS: There was no statistical difference between the healthy and treated groups. However, there was a difference in the non-treated group, with a 79% incidence of preterm low birth weight. Educational level, previous preterm birth, and periodontal disease were related significantly to preterm delivery (P <0.001). CONCLUSION: Periodontal disease was related significantly to preterm low birth weight.

Goepfert, A. R., M. K. Jeffcoat, et al. (2004). "Periodontal disease and upper genital tract inflammation in early spontaneous preterm birth." Obstet Gynecol 104(4): 777-83.

ABSTRACT: OBJECTIVE: To estimate the relationship between maternal periodontal disease and both early spontaneous preterm birth and selected markers of upper genital tract inflammation. METHODS: In this case-control study, periodontal assessment was performed in 59 women who experienced an early spontaneous preterm birth at less than 32 weeks of gestation, in a control population of 36 women who experienced an early indicated preterm birth at less than 32 weeks of gestation, and in 44 women with an uncomplicated birth at term (>or = 37 weeks). Periodontal disease was defined by the degree of attachment loss. Cultures of the placenta and umbilical cord blood, cord interleukin-6 levels, and histopathologic examination of the placenta were performed for all women. RESULTS: Severe periodontal disease was more common in the spontaneous preterm birth group (49%) than in the indicated preterm (25%, P =.02) and term control groups (30%, P =.045). Multivariable analyses, controlling for possible confounders, supported the association between severe periodontal disease and spontaneous preterm birth (odds ratio 3.4, 95% confidence interval 1.5-7.7). Neither histologic chorioamnionitis, a positive placental culture, nor an elevated cord plasma interleukin-6 level was significantly associated with periodontal disease (80% power to detect a 50% difference in rate of histological chorioamnionitis, alpha = 0.05). CONCLUSION: Women with early spontaneous preterm birth were more likely to have severe periodontal disease than women with indicated preterm birth or term birth. Periodontal disease was not associated with selected markers of upper genital tract inflammation. LEVEL OF EVIDENCE: II-2

Goldenberg, R. L. and J. F. Culhane (2006). "Preterm birth and periodontal disease." N Engl J Med355(18): 1925-7.

Hefti, A. F. (2006). "Periodontal therapy and preterm birth." Int J Dent Hyg 4 Suppl 1: 39-42; discussion 50-2.

Holbrook, W. P., A. Oskarsdottir, et al. (2004). "No link between low-grade periodontal disease and preterm birth: a pilot study in a healthy Caucasian population." Acta Odontol Scand 62(3): 177-9.

Hubbard, S. and A. Shanks (2004). "Relationship between periodontal disease and preterm low birth weight infants." Tenn Med 97(2): 81.

Jarjoura, K., P. C. Devine, et al. (2005). "Markers of periodontal infection and preterm birth." Am J Obstet Gynecol 192(2): 513-9.

ABSTRACT: OBJECTIVE: This study was undertaken to explore the relationship between clinical, microbiologic, and serologic markers of periodontitis and preterm birth (PTB). STUDY DESIGN: We compared women with a singleton gestation giving birth before the 37th week (cases, n = 83) with term delivery controls (n = 120). Periodontal examination and collection of dental plaque and blood samples were performed within 48 hours after delivery. Microbial levels and maternal immunoglobulin G titers to oral bacteria were analyzed. Multivariate regression models were fitted controlling for common covariates. RESULTS: Cases showed greater mean attachment loss (1.7 vs 1.5 mm, P = .003) and higher prevalence of periodontitis (30.1% vs 17.5%, P = .027). No differences in microbial or serum antibody levels were detected between the groups. Logistic regression revealed that PTB was associated with attachment loss (adjusted odds ratio: 2.75, 95% CI: 1.01-7.54). Linear regression indicated a significant ( P = .04) association between attachment loss and low birth weight (LBW). CONCLUSION: The data support the notion that periodontitis is independently associated with PTB and LBW.

Jeffcoat, M. K. (2000). "Preterm birth, osteoporosis, and periodontal disease." Compend Contin Educ Dent Suppl(30): 5-11; quiz 65.

ABSTRACT: The purpose of this two-part article is to review two major events in the life span of a woman. These include the putative relationship between oral health, pregnancy, and postmenopausal osteoporosis. Current knowledge about risk factors for preterm birth and for osteoporosis are discussed. The newest studies that address the relationship between oral and systemic health are also reviewed.

Jeffcoat, M. K., N. C. Geurs, et al. (2001). "Periodontal infection and preterm birth: results of a prospective study." J Am Dent Assoc 132(7): 875-80.

ABSTRACT: BACKGROUND: Previous studies have suggested that chronic periodontal infection may be associated with preterm births. The authors conducted a prospective study to test for this association. METHODS: A total of 1,313 pregnant women were recruited from the Perinatal Emphasis Research Center at the University of Alabama at Birmingham. Complete periodontal, medical and behavioral assessments were made between 21 and 24 weeks gestation. After delivery, medical records were consulted to determine each infant's gestational age at birth. From these data, the authors calculated relationships between periodontal disease and preterm birth, while adjusting for smoking, parity (the state or fact of having born offspring), race and maternal age. Results were expressed as odds ratios and 95 percent confidence intervals, or CIs. RESULTS: Patients with severe or generalized periodontal disease had adjusted odds ratios (95 percent CI) of 4.45 (2.16-9.18) for preterm delivery (that is, before 37 weeks gestational age). The adjusted odds ratio increased with increasing prematurity to 5.28 (2.05-13.60) before 35 weeks' gestational age and to 7.07 (1.70-27.4) before 32 weeks' gestational age. CONCLUSIONS: The authors' data show an association between the presence of periodontitis at 21 to 24 weeks' gestation and subsequent preterm birth. Further studies are needed to determine whether periodontitis is the cause. CLINICAL IMPLICATIONS: While this large prospective study has shown a significant association between preterm birth and periodontitis at 21 to 24 weeks' gestation, neither it nor other studies to date were designed to determine whether treatment of periodontitis will reduce the risk of preterm birth. Pending an answer to this important question, it remains appropriate to advise expectant mothers about the importance of good oral health.

Jeffcoat, M. K., N. C. Geurs, et al. (2001). "Current evidence regarding periodontal disease as a risk factor in preterm birth." Ann Periodontol 6(1): 183-8.

ABSTRACT: Preterm birth, resulting in babies born too little and too soon, is a major cause of morbidity. Evidence indicates that infections can be major risk factors in preterm birth. Case-control studies point to an association between periodontal infection and increased rates of preterm birth. This paper summarizes evidence to date and the strategies that ongoing intervention studies are using to answer the fundamental clinical question: can periodontal therapy reduce the risk of preterm birth?

Jeffcoat, M. K., J. C. Hauth, et al. (2003). "Periodontal disease and preterm birth: results of a pilot intervention study." J Periodontol 74(8): 1214-8.

ABSTRACT: BACKGROUND: Previous case-control and prospective studies have shown an association between the presence of periodontitis and the risk of preterm birth (PTB). The goal of this pilot trial was to determine the feasibility of conducting a trial to determine whether treatment of periodontitis reduces the risk of spontaneous preterm birth (SPTB). METHODS: Three hundred sixty-six (366) women with periodontitis between 21 and 25 weeks' gestation were recruited and randomized to one of three treatment groups with stratification on the following two factors: 1) previous SPTB at <35 weeks and 2) body mass index <19.8 or bacterial vaginosis as assessed by Gram stain. The treatment groups consisted of: 1) dental prophylaxis plus placebo capsule; 2) scaling and root planing (SRP) plus placebo capsule; and 3) SRP plus metronidazole capsule (250 mg t.i.d. for one week). An additional group of 723 pregnant women meeting the same criteria for periodontitis and enrolled in a prospective study served as an untreated reference group. RESULTS: The rate of PTB at <35 weeks was 4.9% in the prophylaxis group, compared to 3.3% in the SRP plus metronidazole group and 0.8% in the SRP plus placebo group (P = 0.75 and 0.12, respectively). The rate of PTB at <35 weeks was 6.3% in the reference group. CONCLUSIONS: This trial indicates that performing SRP in pregnant women with periodontitis may reduce PTB in this population. Adjunctive metronidazole therapy did not improve pregnancy outcome. Larger trials will be needed to achieve statistical significance, especially at less than 35 weeks gestational age.

Khader, Y. S. and Q. Ta'ani (2005). "Periodontal diseases and the risk of preterm birth and low birth weight: a meta-analysis." J Periodontol 76(2): 161-5.

ABSTRACT: BACKGROUND: This meta-analysis of periodontal disease in relation to the risk of preterm birth/low birth weight (PTB/ LBW) is based on two case-control studies and three prospective cohort studies that met pre-stated inclusion criteria. METHODS: Information on the designs of the studies, characteristics of the study population, exposure and outcome measures, control for confounders, and risk estimates were abstracted independently by two investigators using a standard protocol. RESULTS: Pregnant women with periodontal disease had an overall adjusted risk of preterm birth that was 4.28 (95% confidence interval [CI], 2.62 to 6.99; P <0.005) times that risk for healthy subjects. The overall adjusted odds ratio of preterm low birth weight was 5.28 (95% CI, 2.21 to 12.62; P <0.005), while the overall adjusted odds ratio of a delivery of either PTB or LBW was 2.30 (95% CI, 1.21 to 4.38; P <0.005). CONCLUSIONS: Our findings indicate that periodontal diseases in the pregnant mother significantly increase the risk of subsequent preterm birth or low birth weight. While it remains important to promote good oral hygiene during routine prenatal visits, there is no convincing evidence, on the basis of existing case control and prospective studies, that treatment of periodontal disease will reduce the risk of preterm birth. Consequently, large randomized, placebo-controlled, masked clinical trials are required.

Konopka, T., M. Rutkowska, et al. (2003). "The secretion of prostaglandin E2 and interleukin 1-beta in women with periodontal diseases and preterm low-birth-weight." Bull Group Int Rech Sci Stomatol Odontol 45(1): 18-28.

ABSTRACT: Prematurity is of one of the main causes of neonatal morbidity and mortality. Clinical observations show, that periodontitis in pregnant women can be a direct risk factor for preterm labor, with a greater influence rate compared to other risk factors. The aim of the study was to asses the relationship between periodontal diseases and PLBW in the population of women from the Lower Silesian Region (Poland), and the evaluation of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) levels in gingival cervicular (GCF) and blood serum in women with PLBW and women giving birth on time as well as secretion of these proinflammatory mediators in whole blood after bacterial lipopolysaccharide stimulation. The study group consisted of 84 women with PLBW (39.2% primiparous), aged 17-41 (mean 27.57). The controls were 44 women (47.7% primiparous) aged 16-38 (mean 26.36) who gave birth on time to a normal birthweight baby. PGE2 and IL-1 beta concentrations in serum and GCF were determined by means of immunoenzymatic method (EIA). In the studied population women over 28 years and exposed to medical risk factors had more frequent PLBW occurrence probability. In primiparous over 28 there is 4 times greater probability of preterm labor, and in case of the severe and generalized periodontitis presence there is 3.9 times higher possibility of PLBW compared to women with healthy periodontium. In all women with PLBW there is a significantly higher PGE2 and IL-1 beta concentration in GCF, and in primiparous also PGE2 level in blood serum, compared to controls.

Li, X. J., Y. Q. Sha, et al. (2004). "[Advances research of periodontal disease and preterm low birth weight deliveries]." Zhonghua Kou Qiang Yi Xue Za Zhi 39(4): 341-3.

Lin, D., K. Moss, et al. (2007). "Persistently high levels of periodontal pathogens associated with preterm pregnancy outcome." J Periodontol 78(5): 833-41.

ABSTRACT: BACKGROUND: Few studies examining the association between periodontal diseases and preterm birth have explored the underlying microbial and antibody responses associated with oral infection. METHODS: A nested case-control study was performed using data from a recent interventional trial following the delayed-treatment control group of 31 subjects with periodontal diseases. The levels of eight oral bacteria and the maternal immunoglobulin G (IgG) responses in serum to these bacteria were measured at antepartum and postpartum visits to determine the relationship to cases (preterm delivery <37 weeks' gestation) and controls (term delivery). RESULTS: Antepartum, the levels of periodontal pathogens tended to be higher in the preterm (case group) deliveries compared to the term deliveries (control group). Maternal anti-Porphyromonas gingivalis IgG was significantly lower in the preterm group compared to the term group (P = 0.028). Postpartum, levels of P. gingivalis, Tannerella forsythia, Prevotella intermedia, and Prevotella nigrescens were statistically significantly higher in preterm births compared to term deliveries, adjusting for baseline levels. The joint effects of red and orange microbial clusters were significantly higher in the preterm group compared to the term group. CONCLUSIONS: High levels of periodontal pathogens and low maternal IgG antibody response to periodontal bacteria during pregnancy are associated with an increased risk for preterm delivery. Further studies elucidating the role of the microbial load and maternal immune response as related to pregnancy outcome seem merited.

Lopez, N. J., I. Da Silva, et al. (2005). "Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis." J Periodontol 76(11 Suppl): 2144-53.

ABSTRACT: BACKGROUND: One hypothesis to explain the association between periodontal disease (PD) preterm/low birth weight (PT/LBW) is that PT/LBW may be indirectly mediated through translocation of bacteria or bacterial products in the systemic circulation. Transient bacteremias occur in subjects with marginal periodontitis or with gingivitis, and it is possible that bacteria and their products may reach the placental membranes hematogenously and provide the inflammatory effect to induce preterm labor. The effect of gingivitis as a potential risk factor for PT/LBW has still not been studied. A randomized controlled trial was undertaken to determine the effect of routine plaque control and scaling on the pregnancy outcomes in women with gingivitis. METHODS: Eight hundred seventy (870) pregnant women with gingivitis, aged 18 to 42, were enrolled while receiving prenatal care in Santiago, Chile. Women were randomly assigned in a two-to-one fashion to either a treatment group (N = 580), receiving periodontal treatment before 28 weeks of gestation or to a control group (N = 290), receiving periodontal treatment after delivery. Periodontal therapy consisted of plaque control, scaling, and daily rinsing with 0.12% clorhexidine. Maintenance therapy was provided every 2 to 3 weeks until delivery, and consisted of oral hygiene instruction and supragingival plaque removal by instrumentation, as needed. The primary outcomes assessed were delivery at less than 37 weeks of gestation or an infant weighing less than 2,500 g. RESULTS: Of the 870 women enrolled, 36 women (27 in the treatment group and nine in the control group) were excluded from the analyses for different reasons. The incidence of PT/LBW in the treatment group was 2.14% (12/560) and in the control group, 6.71% (19/283) (odds ratio [OR] 3.26; 95% confidence interval [CI] 1.56 to 6.83; P = 0.0009). Multivariate logistic regression analysis showed that, after adjusting for several known risk factors for PT/LBW, women with gingivitis were at a higher risk of PT/LBW than women who received periodontal treatment (OR 2.76; 95%CI 1.29 to 5.88; P = 0.008). CONCLUSIONS: Periodontal treatment significantly reduced the PT/LBW rate in this population of women with pregnancy-associated gingivitis. Within the limitations of this study, we conclude that gingivitis appears to be an independent risk factor for PT/LBW for this population.

Lopez, N. J., P. C. Smith, et al. (2002). "Higher risk of preterm birth and low birth weight in women with periodontal disease." J Dent Res 81(1): 58-63.

ABSTRACT: Pregnant women with periodontal disease (PD) may be at increased risk for having preterm low-birth-weight (PLBW) children. We investigated whether the maintenance of the mothers' periodontal health after 28 weeks' gestation reduces the risk of PLBW. Of the 639 women studied, 406 had gingivitis and received treatment before 28 weeks' gestation, and 233 had PD and were treated after delivery. Data about previous and current pregnancies and known risk factors were obtained from patients' medical records. Primary outcomes were delivery before 37 weeks' gestation or an infant with birth weight below 2500 g. The incidence of PLBW was 2.5% in periodontally healthy women, and 8.6% in women with PD (p = 0.0004, relative risk = 3.5, 95% CI, 1.7 to 7.3). Risk factors significantly associated with PLBW were previous PLBW, PD, fewer than 6 pre-natal visits, and low maternal weight gain. PD was associated with both preterm birth and low birth weight, independent of other risk factors.

Lopez, N. J., P. C. Smith, et al. (2002). "Periodontal therapy may reduce the risk of preterm low birth weight in women with periodontal disease: a randomized controlled trial." J Periodontol 73(8): 911-24.

ABSTRACT: BACKGROUND: Recent studies have suggested that periodontal disease is a risk factor for preterm low birth weight (PLBW). A randomized controlled trial was undertaken to help further evaluate the proposed association between periodontal disease and PLBW. METHODS: Four hundred pregnant women with periodontal disease, aged 18 to 35, were enrolled while receiving prenatal care in Santiago, Chile. Women were randomly assigned to either an experimental group (n = 200), which received periodontal treatment before 28 weeks of gestation or to a control group (n = 200) which received periodontal treatment after delivery. Previous and current pregnancies and known risk factors were obtained from patient medical records and interviews. The primary outcome assessed was the delivery at less than 37 weeks of gestation or an infant weighing less than 2,500 g. RESULTS: Of the 400 women enrolled, 49 were excluded from the analyses for different reasons. The incidence of PLBW in the treatment group was 1.84% (3/163) and in the control group was 10.11% (19/188), (odds ratio [OR] 5.49, 95% confidence interval [CI] 1.65 to 18.22, P= 0.001). Multivariate logistic regression analysis showed that periodontal disease was the strongest factor related to PLBW (OR 4.70, 95% CI 1.29 to 17.13). Other factors significantly associated with such deliveries were: previous PLBW (OR 3.98, 95% CI 1.11 to 14.21), less than 6 prenatal visits (OR 3.70, 95% Cl 1.46 to 9.38), and maternal low weight gain (OR 3.42, 95% CI 1.16 to 10.03). Conclusions: Periodontal disease appears to be an independent risk factor for PLBW. Periodontal therapy significantly reduces the rates of PLBW in this population of women with periodontal disease.

Lopez, R. (2005). "Periodontal disease, preterm birth and low birthweight." Evid Based Dent 6(4): 90-1.

Lopez, R. (2007). "Periodontal treatment in pregnant women improves periodontal disease but does not alter rates of preterm birth." Evid Based Dent 8(2): 38.

ABSTRACT: DesignThis was a multicentre randomised controlled trial (RCT).InterventionPregnant women were divided into two groups. Those to whom dental treatment was given had up to four visits of periodontal scaling and root planing using ultrasonic and hand instruments, with local anaesthesia as needed. Treatment recipients were also given instruction in oral hygiene and monthly tooth polishing and re-instruction in oral hygiene, with scaling and planing as needed. Control patients received only a brief oral examination at monthly follow-ups but attended the same number of visits as the treatment group. Patients in the control group were offered the same periodontal therapy after delivery.Outcome measureThe primary outcome was gestational age at delivery. Secondary outcomes included birth weight, the proportion of infants who were small for gestational age, Apgar scores, and admissions to a neonatal intensive care unit.ResultsPreterm birth (before 37 weeks of gestation) occurred in 49 out of 407 women (12.0%) in the treatment group (resulting in 44 live births) and in 52 out of 405 women (12.8%) in the control group (resulting in 38 live births). Although periodontal treatment improved periodontitis measures (P<0.001), it did not significantly alter the risk of preterm delivery [P 0.70; hazard ratio for treatment group versus control group, 0.93; 95% confidence interval (CI), 0.63-1.37]. There were no significant differences between the treatment and control groups in mean babies' birth weights (3239 g versus 3258 g; P 0.64) or in the rate of delivery of infants who were small for gestational age (12.7% versus 12.3%; odds ratio, 1.04; 95% CI, 0.68-1.58). There were five spontaneous abortions or stillbirths in the treatment group, compared with 14 in the control group (P 0.08).ConclusionsTreatment of periodontitis in pregnant women improves periodontal disease and is safe but does not significantly alter rates of preterm birth, low birth weight or foetal growth restriction.Evidence-Based Dentistry (2007) 8, 5-6. doi:10.1038/sj.ebd.6400486.

McGaw, T. (2002). "Periodontal disease and preterm delivery of low-birth-weight infants." J Can Dent Assoc 68(3): 165-9.

ABSTRACT: Preterm delivery of low-birth-weight infants (PLBW) remains a significant public health issue and a leading cause of neonatal death and long-term neurodevelopmental disturbances and health problems. Recent epidemiological and microbiological immunological studies have suggested that periodontal disease may be an independent risk factor for PLBW. Postulated mechanisms include translocation of periodontal pathogens to the fetoplacental unit and action of a periodontal reservoir of lipopolysaccharides or inflammatory mediators. However, non-causal explanations for the correlation between periodontitis and PLBW can also be offered. Prospective studies, and eventually interventional studies, will be necessary before periodontitis can be considered as a causal factor for PLBW.

Michalowicz, B. S. and R. Durand (2007). "Maternal periodontal disease and spontaneous preterm birth." Periodontol 2000 44: 103-12.

Michalowicz, B. S., J. S. Hodges, et al. (2006). "Treatment of periodontal disease and the risk of preterm birth." N Engl J Med 355(18): 1885-94.

ABSTRACT: BACKGROUND: Maternal periodontal disease has been associated with an increased risk of preterm birth and low birth weight. We studied the effect of nonsurgical periodontal treatment on preterm birth. METHODS: We randomly assigned women between 13 and 17 weeks of gestation to undergo scaling and root planing either before 21 weeks (413 patients in the treatment group) or after delivery (410 patients in the control group). Patients in the treatment group also underwent monthly tooth polishing and received instruction in oral hygiene. The gestational age at the end of pregnancy was the prespecified primary outcome. Secondary outcomes were birth weight and the proportion of infants who were small for gestational age. RESULTS: In the follow-up analysis, preterm birth (before 37 weeks of gestation) occurred in 49 of 407 women (12.0%) in the treatment group (resulting in 44 live births) and in 52 of 405 women (12.8%) in the control group (resulting in 38 live births). Although periodontal treatment improved periodontitis measures (P<0.001), it did not significantly alter the risk of preterm delivery (P=0.70; hazard ratio for treatment group vs. control group, 0.93; 95% confidence interval [CI], 0.63 to 1.37). There were no significant differences between the treatment and control groups in birth weight (3239 g vs. 3258 g, P=0.64) or in the rate of delivery of infants that were small for gestational age (12.7% vs. 12.3%; odds ratio, 1.04; 95% CI, 0.68 to 1.58). There were 5 spontaneous abortions or stillbirths in the treatment group, as compared with 14 in the control group (P=0.08). CONCLUSIONS: Treatment of periodontitis in pregnant women improves periodontal disease and is safe but does not significantly alter rates of preterm birth, low birth weight, or fetal growth restriction. (ClinicalTrials.gov number, NCT00066131 [ClinicalTrials.gov].).

Moore, S., M. Ide, et al. (2004). "An investigation into the association among preterm birth, cytokine gene polymorphisms and periodontal disease." Bjog 111(2): 125-32.

ABSTRACT: OBJECTIVE: To investigate a putative relationship between preterm delivery and the carriage of polymorphic genes that code for the cytokines interleukin-1beta (IL-1beta) at codon +3953 and tumour necrosis factor-alpha (TNF-alpha) at codon -308 in a group of postpartum women and to elucidate if the concurrent presence of periodontal disease increased the risk of preterm delivery in this group. DESIGN: Case-control study SETTING: Postnatal wards at Guy's and St Thomas' Hospital Trust. POPULATION: Postpartum women from southeast London, UK. METHODS: Case subjects were defined as those who experienced a birth at less than 37 weeks of gestation. Control subjects gave birth at term. Demographic data were collected and a periodontal examination was performed. Blood samples were collected and analysed by restriction fragment length polymerase techniques for the presence of each of the allelic variants. MAIN OUTCOME MEASURES: The level of periodontal disease and the carriage of allelic variants of IL-1beta+3953 and TNF-alpha-308 genes. RESULTS: Forty-eight case subjects and 82 control subjects were assessed. There was no statistically significant difference in the carriage of the IL-1beta+3953 allelic variant between cases and controls (29%versus 18%, P= 0.112). However, 23 (48%) of the case subjects and 24 (29%) of controls were heterozygous or homozygous for the variant TNF-alpha-308 gene (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.0-5.0, P= 0.026). There was no association between the carriage of either the polymorphic IL-1beta+3953 or TNF-alpha-308 variant and the severity of periodontal disease. The combination of periodontal disease and the allelic variant did not increase the risk of preterm delivery. CONCLUSIONS: In this study, a higher proportion of women who delivered preterm carried the polymorphic TNF-alpha-308 gene. There did not appear to be any interaction between either of the genotypes and periodontal disease with preterm delivery as has been reported for bacterial vaginosis and the TNF-alpha-308 polymorphic gene.

Nesse, W., F. K. Spijkervat, et al. (2006). "[Links between periodontal disease and general health. 2. Preterm birth, diabetes and autoimmune diseases]." Ned Tijdschr Tandheelkd 113(5): 191-6.

Noack, B., J. Klingenberg, et al. (2005). "Periodontal status and preterm low birth weight: a case control study." J Periodontal Res 40(4): 339-45.

ABSTRACT: BACKGROUND: Previous studies have suggested that periodontal disease may be an important risk factor for preterm low birth weight. However, the link between periodontal health status of pregnant women and preterm low birth weight is contentious, as recent studies found no association between periodontitis and pregnancy outcome. OBJECTIVE: The aim of this study was to investigate this potential link in a German Caucasian population. METHODS: Fifty-nine pregnant women with a high risk for a preterm low birth weight infant (suffering from preterm contractions, cases, group 1) as well as 42 control women with no preterm contractions during pregnancy and having an infant appropriate for date and weight (>or= 37 weeks gestation, >or= 2500 g, group 2) were examined. Clinical periodontal status was recorded on a full mouth basis. Subgingival plaque samples were taken and periodontal pathogens were identified by polymerase chain reaction. Additionally, interleukin-1 beta level in gingival crevicular fluid was analysed. RESULTS: The mean percentage of sites showing moderate to advanced attachment loss (>or=3 mm) was low in all study groups (group 1: 9.9 +/- 11.2%; group 2:10.6 +/- 14.1%, respectively). No significant differences between the groups in any aspects of the studied periodontitis parameters could be detected. Using a logistic regression model controlling for known preterm low birth weight risk factors, no periodontitis-associated factors increased risk for preterm contractions or preterm low birth weight. The odds ratio (OR) was 1.19 for preterm contractions, the 95% confidence interval (CI) 0.46; 3.11 and 0.73 for preterm low birth weight; 95% CI: 0.13; 4.19, respectively. CONCLUSION: In this population, periodontitis was not a detectable risk factor for preterm low birth weight in pregnant women.

Oertling, K. M. and R. Barsley (2003). "The relationship between periodontal disease and preterm low birth weight and a new Medicaid dental program intervention for pregnant women." Lda J 62(4): 10-3.

Offenbacher, S., K. A. Boggess, et al. (2006). "Progressive periodontal disease and risk of very preterm delivery." Obstet Gynecol 107(1): 29-36.

ABSTRACT: OBJECTIVE: The goal was to estimate whether maternal periodontal disease was predictive of preterm (less than 37 weeks) or very preterm (less than 32 weeks) births. METHODS: A prospective study of obstetric outcomes, entitled Oral Conditions and Pregnancy (OCAP), was conducted with 1,020 pregnant women who received both an antepartum and postpartum periodontal examination. Predictive models were developed to estimate whether maternal exposure to either periodontal disease at enrollment (less than 26 weeks) and/or periodontal disease progression during pregnancy, as determined by comparing postpartum with antepartum status, were predictive of preterm or very preterm births, adjusting for risk factors including previous preterm delivery, race, smoking, social domain variables, and other infections. RESULTS: Incidence of preterm birth was 11.2% among periodontally healthy women, compared with 28.6% in women with moderate-severe periodontal disease (adjusted risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1-2.3). Antepartum moderate-severe periodontal disease was associated with an increased incidence of spontaneous preterm births (15.2% versus 24.9%, adjusted RR 2.0, 95% CI 1.2-3.2). Similarly, the unadjusted rate of very preterm delivery was 6.4% among women with periodontal disease progression, significantly higher than the 1.8% rate among women without disease progression (adjusted RR 2.4, 95% CI 1.1-5.2). CONCLUSION: The OCAP study demonstrates that maternal periodontal disease increases relative risk for preterm or spontaneous preterm births. Furthermore, periodontal disease progression during pregnancy was a predictor of the more severe adverse pregnancy outcome of very preterm birth, independently of traditional obstetric, periodontal, and social domain risk factors. LEVEL OF EVIDENCE: II-2.

Offenbacher, S., V. Katz, et al. (1996). "Periodontal infection as a possible risk factor for preterm low birth weight." J Periodontol 67(10 Suppl): 1103-13.

ABSTRACT: Peridontal diseases are gram-negative anaerobic infections that can occur in women of childbearing age (18 to 34 years). In the present investigation we sought to determine whether the prevalence of maternal periodontal infection could be associated with preterm low birth weight (PLBW), controlling for known risk factors and potential covariates. A case-control study of 124 pregnant or postpartum mothers was performed. PLBW cases were defined as a mother with a birth of less than 2,500 g and one or more of the following: gestational age < 37 weeks, preterm labor (PTL), or premature rupture of membranes (PROM). Controls were normal birth weight infants (NBW). Assessments included a broad range of known obstetric risk factors, such as tobacco use, drug use, alcohol consumption, level of prenatal care, parity, genitourinary infections, and nutrition. Each subject received a periodontal examination to determine clinical attachment level. PLBW cases and primiparous PLBW cases (n = 93) had significantly worse periodontal disease than the respective NBW controls. Multivariate logistic regression models, controlling for other risk factors and covariates, demonstrated that periodontal disease is a statistically significant risk factor for PLBW with adjusted odds ratios of 7.9 and 7.5 for all PLBW cases and primiparous PLBW cases, respectively. These data indicate that periodontal diseases represent a previously unrecognized and clinically significant risk factor for preterm low birth weight as a consequence of either PTL or preterm PROM.

Peretz, B. (2005). "Preterm low birthweight (PLBW) and maternal periodontal disease: a debate in the literature." Refuat Hapeh Vehashinayim 22(1): 88.

Pretorius, C., A. Jagatt, et al. (2007). "The relationship between periodontal disease, bacterial vaginosis, and preterm birth." J Perinat Med 35(2): 93-9.

ABSTRACT: Spontaneous preterm labor leading to preterm birth is a major cause of perinatal mortality and morbidity worldwide. The etiology of spontaneous preterm labor is multifactoral but there is overwhelming evidence to implicate infection in up to 40% of cases. Historically, this infective link has focused on the associations between abnormal genital tract flora in pregnancy (diagnosed by the presence of bacterial vaginosis) and preterm birth. Recently, another condition related to abnormal flora (periodontal disease) has been linked with preterm birth. There are microbiological similarities between the oral cavity and the female genital tract giving rise to a possible common pathophysiology. This review records the interrelationship between periodontal disease, bacterial vaginosis, and preterm birth. We postulate on the mechanism linking the three conditions, particularly through microbiology and gene-environmental interactions. Periodontal disease and bacterial vaginosis may be risk factors in their own rights or may be interrelated. We speculate on whether periodontitisis a marker for an immune hyperresponse to abnormal flora which in the oral cavity results in periodontitis and in the case of bacterial vaginosis might result in preterm birth. We also postulate on the risk of preterm birth by periodontitis alone, bacterial vaginosis alone, or both.

Radnai, M. and I. Gorzo (2002). "[Periodontal disease as a potential risk factor for preterm birth and low birth weight (Literature review)]." Fogorv Sz 95(6): 241-4.

ABSTRACT: In Hungary the number of low birth-weight new-born babies is about 8200 in a year, while the frequency of for preterm birth is 8.2%. The infant mortality among the low birth-weight babies is higher, than among the normal weight babies. Every efforts are used to decrease the number of preterm births. Researches have been carried out since decades on finding its possible risk factors. A possible risk factor for low birth-weight babies may be the chronic periodontal infection. The publication provides a review of recently published evidences of the potential association between periodontal infection and preterm low birth-weight.

Radnai, M., I. Gorzo, et al. (2006). "Possible association between mother's periodontal status and preterm delivery." J Clin Periodontol 33(11): 791-6.

ABSTRACT: BACKGROUND: A case-control study was undertaken to detect whether initial chronic localized periodontitis could be a risk factor for preterm birth (PB) and foetal growth restriction. METHODS: A PB case was defined if a patient had a threatening premature event during pregnancy pre-term premature rupture of membranes, or spontaneous pre-term delivery, before the 37th week of pregnancy, and/or the weight of the newborn was <2500 g. Into the PB (case) group, 77 women were allocated, while 84 were included in the control group, all of whom had delivery after the 37th gestational week and with a newborn weighing >or=2500 g. RESULTS: A significant association was found between PB and initial chronic localized periodontitis, the criteria being bleeding at >or=50% of the examined teeth and having at least at one site at >or=4 mm probing depth (p=0.0001). The adjusted odds ratio for initial chronic localized periodontitis was 3.32, 95% CI: 1.64-6.69. The average weight of newborns of mothers with periodontitis was significantly less than that of the women without periodontitis (p=0.002). CONCLUSIONS: The results support the hypothesis that initial chronic localized periodontitis of pregnant women could lead to PB, and birth-weight reduction.

Riche, E. L., K. A. Boggess, et al. (2002). "Periodontal disease increases the risk of preterm delivery among preeclamptic women." Ann Periodontol 7(1): 95-101.

ABSTRACT: BACKGROUND: Preterm births are a major cause of neonatal morbidity and mortality, and represent an important public health issue. About 30% of preterm births are due to medical conditions of the mother or the fetus, among "which preeclampsia plays a major role. We have previously reported that maternal periodontal disease enhances the risk for preterm delivery and preeclampsia. Our current objective was to determine whether maternal periodontal disease increases the risk for preterm delivery among preeclamptic women. METHODS: Women were enrolled prior to their twenty-sixth week of gestation. Periodontal status was assessed at baseline and defined as healthy, mild, or moderate/severe. Repeat examinations were performed at delivery to assess changes in periodontal status. RESULTS: A cohort of 1,020 women was studied, 47 of whom had preeclampsia. A strong association between periodontal disease status at enrollment and rate of premature delivery was observed among preeclamptic women after adjusting for the major risk factors for preterm delivery, including maternal race; age; marital status; WIC (women, infants, children program) or food stamps; insurance; previous preterm delivery; and chorioamnionitis. Among preeclamptic women, 49.3% with mild periodontal disease and 82.6% with moderate to severe disease delivered preterm (hazard ratios [HR] 4.11 and 11.0, respectively). Periodontal disease worsening during pregnancy in preeclamptic women was also associated with an increased risk of preterm births (HR 8.44). CONCLUSION: These results suggest that mothers with preeclampsia may be at greater risk for preterm delivery if periodontal disease is present early in pregnancy or progresses during pregnancy.

Russell, S. and A. P. Dasanayake (2006). "Maternal periodontal disease is related to preterm low birth weight delivery in a group of Brazilian women." J Evid Based Dent Pract 6(3): 236-7.

Russell, S. and A. P. Dasanayake (2006). "Periodontal status is unrelated to preterm low birth weight in a group of Caucasian German women." J Evid Based Dent Pract 6(3): 240-1.

Sanchez, A. R., S. Bagniewski, et al. (2007). "Correlations between maternal periodontal conditions and preterm low birth weight infants." J Int Acad Periodontol 9(2): 34-41.

ABSTRACT: OBJECTIVE: The goal of this cross-sectional study was to assess the correlation between periodontal conditions of pregnant women and characteristics of the infant at birth. METHODS: One hundred thirteen pregnant patients received a thorough dental and periodontal examination and questionnaire. Probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and calculus index (CI) were recorded. Patients were classified as to whether they had periodontitis (presence of 2 or more teeth with 1 or more sites experiencing CAL > or = 3 mm and PD > or = 4 mm at the same site), gingivitis (> or = 25% of sites with BOP), or healthy periodontium. Patients were followed to ascertain information on pregnancy-related complications, gestational age, and birth weight. Miscarriages and infants born as single births at < 37 weeks or weighing < 5.5 pounds were classified as preterm low birth weight (PT/LBW) infants. The periodontal clinical parameters were compared between groups using the Kruskal-Wallis test and the Wilcoxon rank sum test. Spearman rank correlation coefficients were calculated to estimate the correlations. RESULTS: Of the 113 pregnant patients, outcome data were available on 111 patients. In addition, data from one patient who delivered twins and two patients who had miscarriages were not considered in the correlation analyses. The prevalence of periodontitis and gingivitis in this population was 23.9% and 54%, while the prevalence of PT/LBW infants was 19%, 7%, and 13% among the patients with periodontitis, gingivitis, and healthy periodontium, respectively. Given the small number of patients with PT/LBW infants, we were unable to identify any statistically significant associations between the periodontal clinical parameters and PT/LBW, although the data suggested the trend that patients with PT/LBW infants were more likely to have poorer probing depths (median number of sites with PD > or = 4mm, 13 vs. 6; p = 0.19). Among the 108 single births, birth weight was negatively correlated with maternal mean PD in the periodontitis group (r = -0.37, p = 0.055), and the percentage of sites with BOP in the mandible (r = -0.32, p = 0.014), total CL (r = -0.31, p = 0.01 7) and maxillary arch CI (r = -0.29, p = 0.025) in the gingivitis group. CONCLUSION: Infant birth weight showed moderate relationships with maternal periodontal conditions in subjects with periodontal diseases.

Sanchez, A. R., L. I. Kupp, et al. (2004). "Maternal chronic infection as a risk factor in preterm low birth weight infants: the link with periodontal infection." J Int Acad Periodontol 6(3): 89-94.

ABSTRACT: In the past decade, there has been mounting scientific evidence suggesting that periodontal disease may play an important role as a risk factor for adverse pregnancy outcomes. This article focuses on the definition, incidence, risk factors associated with preterm low birthweight infants (PLBW), the evidence linking chronic infections and PLBW, and the scientific evidence linking periodontal infections with adverse pregnancy outcomes. Additionally, this review summarizes the current epidemiological studies on the PLBW/infection relation and makes conclusions based on these results. Data from a limited number of studies available support the hypothesis that periodontal disease may act as a risk factor for PLBW infants. The fetal exposure to different periodontal pathogens needs to be confirmed, the mechanisms associated with the potential passage of periodontal bacteria across the placental barrier, and the efficacy of different periodontal treatments in reducing the risk for PLBW need to be studied further.

Stamilio, D. M., J. J. Chang, et al. (2007). "Periodontal disease and preterm birth: do the data have enough teeth to recommend screening and preventive treatment?" Am J Obstet Gynecol 196(2): 93-4.

Vergnes, J. N. and M. Sixou (2007). "Preterm low birth weight and maternal periodontal status: a meta-analysis." Am J Obstet Gynecol 196(2): 135 e1-7.

ABSTRACT: OBJECTIVE: This study was undertaken to assess the effect of maternal periodontal disease on preterm delivery and/or birth of low-weight infants. STUDY DESIGN: We conducted a meta-analytic review of 5 medical databases (MEDLINE, EMBASE, LILACS, BIOSIS and PASCAL) for human observational studies linking preterm delivery and/or birth of low-weight infants to maternal periodontal disease. The MOOSE guidelines for meta-analysis of observational studies were followed. RESULTS: The literature search revealed 17 articles that met the inclusion criteria. Seven thousand one hundred fifty-one women participated in the studies, 1056 of whom delivered a preterm and/or low birthweight infant. The overall odds ratio was 2.83 (95% CI: 1.95-4.10, P < .0001). This pooled value needed to be interpreted cautiously because there appeared to be a clear trend for the better quality studies to be of lower association strength. CONCLUSION: These findings indicate a likely association, but it needs to be confirmed by large, well-designed, multicenter trials.

Watts, T. (2002). "Maternal periodontal disease and preterm low birthweight: case-control study." Br Dent J 193(5): 267.

Wood, S., A. Frydman, et al. (2006). "Periodontal disease and spontaneous preterm birth: a case control study." BMC Pregnancy Childbirth 6: 24.

ABSTRACT: BACKGROUND: Several studies have suggested an association between periodontal disease and prematurity but this finding has not been consistently observed. METHODS: Case control study. Cases (n = 50) were women who had delivered after spontaneous preterm labor at <35 weeks gestation. Two groups of controls (n = 101) were recruited: women who were undelivered but at a preterm gestation and women who delivered at term. A standard, clinical, periodontal examination was performed and gingival crevicular fluid was obtained from standardized locations and tested for neutrophil elastase along with the bacterial enzymes gingipain and dipeptidylpeptidase. Data were analyzed with Fisher's exact tests, ANOVA and multivariate logistic regression. RESULTS: There was no difference in the proportion of sites with significant attachment loss (> or =3 mm): Cases-3.2%, Controls-2.2% p = 0.21. The gingival crevicular fluid concentrations of elastase and gingipain were elevated in cases vs. controls 238.8 uU/ul vs. 159.6 uU/ul p = .007 and 2.70 uU/ul vs. 1.56 uU/ul p = .001. On multivariate analysis, the mean log concentration of elastase, but not of gingipain, remained a significant predictor of preterm labor p = .0.015. CONCLUSION: We found no evidence that clinical periodontal disease is associated with spontaneous preterm birth. Elevated gingival crevicular fluid levels of elastase were associated with preterm birth but further research is needed before this can be assumed to be a causal relationship.

Zachariasen, R. D. and D. K. Dennison (1998). "Periodontal disease and preterm low birth weight deliveries." J Gt Houst Dent Soc 70(4): 16-9.

Zadeh-Modarres, S., B. Amooian, et al. (2007). "Periodontal health in mothers of preterm and term infants." Taiwan J Obstet Gynecol 46(2): 157-61.

ABSTRACT: OBJECTIVE: Recent studies have suggested that chronic periodontitis may induce an inflammatory response which can cause premature delivery. This study was designed to assess the association between periodontal health and preterm labor in Iranian female population. MATERIALS AND METHODS: In this case-control study, 201 pregnant women without systemic disease or other risk factors for preterm labor were chosen. The control group (n = 99) had term labor (infants > or =37 weeks) and the case group (n = 102) had preterm labor (infants < 37 weeks). Bleeding index, pocket depth and debris index were measured. RESULTS: The data of bleeding index (cases, 0.64 +/- 0.38; controls, 0.57 +/- 0.35), probing depth (cases, 2.80 +/- 0.30; controls, 1.63 +/- 0.23) and debris index (cases, 1.38 +/- 0.67; controls, 0.81 +/- 0.38) revealed a statistically significant difference between the two groups (p < 0.05). CONCLUSION: According to the findings of this study, there is a noticeable relationship between periodontal health and duration of pregnancy; periodontal disease could be a risk factor for preterm labor. Oral hygiene is strongly recommended to be included in prenatal care.