Bryan S. Michalowicz

Genetic and Heritable Risk Factors in Periodontal Disease

The purpose of this paper is to review current knowledge of genetic risk factors for the periodontal diseases and to present updated and additional data from the Minnesota Twin Periodontal Study. Family studies suggest that susceptibility to the early onset forms of disease, particularly prepubertal and juvenile periodontitis, is, at least in part, influenced by host genotype. Inherited phagocytic cell deficiencies appear to confer risk for prepubertal periodontitis. The prevalence and distribution of juvenile periodontitis in affected families are most consistent with an autosomal recessive mode of inheritance. However, considerable etiologic as well as genetic heterogeneity within these clinically-defined diseases is evident. Whether or not genetic factors influence the more common adult chronic periodontitis is less clear. Although results from family studies suggest that environmental factors appear to be the major determinants of variance in adult periodontitis, data from our twin studies indicate that both genetic and environmental factors influence disease. Furthermore, comparisons between reared-together and reared-apart adult monozygous twins indicate that early family environment has no appreciable influence on probing depth and attachment loss measures in adults. J Periodontol 1994;65:479-488.

Bisphosphonate-Related Osteonecrosis of the Jaw: Clinical Features, Risk Factors, Management, and Treatment Outcomes of 26 Patients

PURPOSE To report the clinical features, risk factors, management, and treatment outcomes of nitrogen-containing bisphosphonate (n-BIS)-related osteonecrosis of the jaw (BRONJ). PATIENTS AND METHODS Patients with suspected BRONJ were referred to the School of Dentistry for evaluation and treatment. RESULTS A total of 26 patients (9 men and 17 women, mean age 64 years) were diagnosed with BRONJ. Of the 26 patients, 23 had received n-BIS therapy for cancer and 3 for osteoporosis. BRONJ lesions were noted more frequently in the mandible and in the posterior sextants. Of the 26 patients, 16 had developed BRONJ after dentoalveolar procedures, and 10 had developed it spontaneously. The mean interval to development of BRONJ was shorter in the patients with cancer receiving intravenous n-BIS than in the patients with osteoporosis receiving oral n-BIS (37.1 versus 77.7 months, P = .02). Using the American Association of Oral and Maxillofacial Surgeons staging system, 2 patients were diagnosed with stage I lesions, 19 with stage II, and 5 with stage III lesions. The initial management of BRONJ was nonsurgical, with debridement performed at subsequent visits, if needed. The BRONJ lesions healed completely in 4 patients, healed partially in 8, remained stable in 7, and progressed in 7. The spontaneous lesions responded favorably to BRONJ management compared with lesions that developed after dentoalveolar procedures (P = .01). No significant difference was found in response to BRONJ management between patients who had continued or discontinued n-BIS therapy after the BRONJ diagnosis (P = .54). CONCLUSIONS Long-term n-BIS therapy and recent dental procedures are consistent findings in patients with BRONJ. Spontaneous BRONJ lesions respond favorably to current BRONJ treatment strategies.

The effect of nonsurgical periodontal therapy on hemoglobin a1c levels in persons with type 2 diabetes and chronic periodontitis a randomized clinical trial

IMPORTANCE Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. OBJECTIVE To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis. DESIGN, SETTING, AND PARTICIPANTS The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers. INTERVENTIONS The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months. MAIN OUTCOMES AND MEASURES Difference in change in HbA1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. RESULTS Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all). CONCLUSIONS AND RELEVANCE Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00997178.

Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study.

AIMS Infection may be a rheumatoid arthritis (RA) risk factor. We examined whether signs of periodontal infection were associated with RA development in the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. MATERIAL AND METHODS In 1971-1974, 9702 men and women aged 25-74 were enrolled and surveyed longitudinally (1982, 1986, 1987, 1992). Periodontal infection was defined by baseline tooth loss or clinical evidence of periodontal disease. Baseline (n = 138) and incident (n = 433) RA cases were defined via self-report physician diagnosis, joint pain/swelling, ICD-9 codes (714.0-714.9), death certificates and/or RA hospitalization. RESULTS Adjusted odds ratios (ORs) (95% CI) for prevalent RA in gingivitis and periodontitis (versus healthy) were 1.09 (0.57, 2.10) and 1.85 (0.95, 3.63); incident RA ORs were 1.32 (0.85, 2.06) and 1.00 (0.68, 1.48). The ORs for prevalent RA among participants missing 5-8, 9-14, 15-31 or 32 teeth (versus 0-4 teeth) were 1.74 (1.03, 2.95), 1.82 (0.81, 4.10), 1.45 (0.62, 3.41) and 1.30 (0.48, 3.53); ORs for incident RA were 1.12 (0.77, 1.64), 1.67 (1.12, 2.48), 1.40 (0.85, 2.33) and 1.22 (0.75, 2.00). Dose-responsiveness was enhanced among never smokers. The rate of death or loss-to-follow-up after 1982 was two- to fourfold higher among participants with periodontitis or missing ≥9 teeth (versus healthy participants). CONCLUSIONS Although participants with periodontal disease or ≥5 missing teeth experienced higher odds of prevalent/incident RA, most ORs were non-statistically significant and lacked dose-responsiveness. Differential RA ascertainment bias complicated the interpretation of these data.

Systematic review and meta-analysis on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts.

BACKGROUND Conduct a systematic review and meta-analysis on nonsurgical treatment of patients with chronic periodontitis by means of scaling and root planing (SRP) with or without adjuncts. METHODS A panel of experts convened by the American Dental Association Council on Scientific Affairs conducted a search of PubMed (MEDLINE) and Embase for randomized controlled trials of SRP with or without the use of adjuncts with clinical attachment level (CAL) outcomes in trials at least 6 months in duration and published in English through July 2014. The authors assessed individual study bias by using the Cochrane Risk of Bias Tool and conducted meta-analyses to obtain the summary effect estimates and their precision and to assess heterogeneity. The authors used funnel plots and Egger tests to assess publication bias when there were more than 10 studies. The authors used a modified version of the US Preventive Services Task Force methods to assess the overall level of certainty in the evidence. RESULTS The panel included 72 articles on the effectiveness of SRP with or without the following: systemic antimicrobials, a systemic host modulator (subantimicrobial-dose doxycycline), locally delivered antimicrobials (chlorhexidine chips, doxycycline hyclate gel, and minocycline microspheres), and a variety of nonsurgical lasers (photodynamic therapy with a diode laser, a diode laser, neodymium:yttrium-aluminum-garnet lasers, and erbium lasers). CONCLUSIONS AND PRACTICAL IMPLICATIONS With a moderate level of certainty, the panel found approximately a 0.5-millimeter average improvement in CAL with SRP. Combinations of SRP with assorted adjuncts resulted in a range of average CAL improvements between 0.2 and 0.6 mm over SRP alone. The panel judged the following 4 adjunctive therapies as beneficial with a moderate level of certainty: systemic subantimicrobial-dose doxycycline, systemic antimicrobials, chlorhexidine chips, and photodynamic therapy with a diode laser. There was a low level of certainty in the benefits of the other included adjunctive therapies. The panel provides clinical recommendations in the associated clinical practice guideline.

Change in periodontitis during pregnancy and the risk of pre-term birth and low birthweight.

AIM Determine whether periodontitis progression during pregnancy is associated with adverse birth outcomes. METHODS We used clinical data and birth outcomes from the Obstetrics and Periodontal Therapy Study, in which randomly selected women received periodontal treatment before 21 weeks of gestation (N=413) or after delivery (410). Birth outcomes were available for 812 women and follow-up periodontal data for 722, including 75 whose pregnancies ended <37 weeks. Periodontitis progression was defined as >or=3 mm loss of clinical attachment. Birth outcomes were compared between non-progressing and progressing groups using the log rank and t tests, separately in all women and in untreated controls. RESULTS The distribution of gestational age at the end of pregnancy (p>0.1) and mean birthweight (3295 versus 3184 g, p=0.11) did not differ significantly between women with and without disease progression. Gestational age and birthweight were not associated with change from baseline in percentage of tooth sites with bleeding on probing or between those who did versus did not progress according to a published definition of disease progression (p>0.05). CONCLUSIONS In these women with periodontitis and within this studys limitations, disease progression was not associated with an increased risk for delivering a pre-term or a low birthweight infant.

Serum Inflammatory Mediators in Pregnancy: Changes After Periodontal Treatment and Association With Pregnancy Outcomes

BACKGROUND The purposes of this study were to determine: 1) if periodontal treatment in pregnant women before 21 weeks of gestation alters levels of inflammatory mediators in serum; and 2) if changes in these mediators are associated with birth outcomes. METHODS A total of 823 pregnant women with periodontitis were randomly assigned to receive scaling and root planing before 21 weeks of gestation or after delivery. Serum obtained between 13 and 16 weeks, 6 days (study baseline) and 29 to 32 weeks of gestation was analyzed for C-reactive protein; prostaglandin E(2); matrix metalloproteinase-9; fibrinogen; endotoxin; interleukin (IL)-1 beta, -6, and -8, and tumor necrosis factor-alpha. Cox regression, multiple linear regression, and the t, chi(2), and Fisher exact tests were used to examine associations among the biomarkers, periodontal treatment, and gestational age at delivery and birth weight. RESULTS A total of 796 women had baseline serum data, and 620 women had baseline and follow-up serum and birth data. Periodontal treatment did not significantly alter the level of any biomarker (P >0.05). Neither baseline levels nor the change from baseline in any biomarker were significantly associated with preterm birth or infant birth weight (P >0.05). In treatment subjects, the change in endotoxin was negatively associated with the change in probing depth (P <0.05). CONCLUSIONS Non-surgical mechanical periodontal treatment in pregnant women, delivered before 21 weeks of gestation, did not reduce systemic (serum) markers of inflammation. In pregnant women with periodontitis, levels of these markers at 13 to 17 weeks and 29 to 32 weeks of gestation were not associated with infant birth weight or a risk for preterm birth.

The Influence of Anti-Infective Periodontal Treatment on C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Periodontal infections are hypothesized to increase the risk of adverse systemic outcomes through inflammatory mechanisms. The magnitude of effect, if any, of anti-infective periodontal treatment on systemic inflammation is unknown, as are the patient populations most likely to benefit. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to test the hypothesis that anti-infective periodontal treatment reduces systemic c-reactive protein (CRP). Methods and Findings MEDLINE, EMBASE, CENTRAL and CINAHL databases were searched using sensitivity-enhancing search terms. Eligible RCTs enrolled patients with periodontal infection, compared a clearly defined anti-infective periodontal intervention (experimental group) to an “inactive control” (no periodontal intervention) or to an “active control” (lower treatment intensity than the experimental group). Mean differences in final CRP values at the earliest post-treatment time point (typically 1-3 months) between experimental and control groups were analyzed using random-effects regression. Among 2,753 possible studies 20 were selected, which included 2,561 randomized patients(median=57). Baseline CRP values were >3.0 mg/L in 40% of trials. Among studies with a control group receiving no treatment, the mean difference in CRP final values among experimental treatment vs. control groups was -0.37 mg/L [95%CI=-0.64, -0.11], (P=0.005), favoring experimental treatment. Trials for which the experimental group received antibiotics had stronger effects (P for interaction=0.03) and the mean difference in CRP final values among experimental treatment vs. control was -0.75 mg/L [95%CI=-1.17,-0.33]. No treatment effect was observed among studies using an active treatment comparator. Treatment effects were stronger for studies that included patients with co-morbidities vs. studies that included “systemically healthy” patients, although the interaction was not significant (P=0.48). Conclusions Anti-infective periodontal treatment results in short-term modest reductions in systemic CRP.

Systemic Immune Responses in Pregnancy and Periodontitis: Relationship to Pregnancy Outcomes in the Obstetrics and Periodontal Therapy (OPT) Study

BACKGROUND Our previous studies reported on the obstetric, periodontal, and microbiologic outcomes of women participating in the Obstetrics and Periodontal Therapy (OPT) Study. This article describes the systemic antibody responses to selected periodontal bacteria in the same patients. METHODS Serum samples, obtained from pregnant women at baseline (13 to 16 weeks; 6 days of gestation) and 29 to 32 weeks, were analyzed by enzyme-linked immunosorbent assay for serum immunoglobulin G (IgG) antibody to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia (previously T. forsythensis), and Treponema denticola. RESULTS At baseline, women who delivered live preterm infants had significantly lower total serum levels of IgG antibody to the panel of periodontal pathogens (P = 0.0018), to P. gingivalis (P = 0.0013), and to F. nucleatum (P = 0.0200) than women who delivered at term. These differences were not significant at 29 to 32 weeks. Changes in IgG levels between baseline and 29 to 32 weeks were not associated with preterm birth when adjusted for treatment group, clinical center, race, or age. In addition, delivery of low birth weight infants was not associated with levels of antibody at baseline or with antibody changes during pregnancy. CONCLUSIONS Live preterm birth is associated with decreased levels of IgG antibody to periodontal pathogens in women with periodontitis when assessed during the second trimester. Changes in IgG antibody during pregnancy are not associated with birth outcomes.

A Pilot Study of Glycosylated Hemoglobin Levels in Periodontitis Cases and Healthy Controls

BACKGROUND Periodontitis is associated with glycemic control in patients with diabetes. The purpose of this study was to determine if glycosylated hemoglobin is elevated in patients with periodontitis who have not been diagnosed with diabetes. METHODS Glycosylated hemoglobin (HbA1c) was assessed using a chairside test in 59 adults without diabetes but with periodontitis (having at least five teeth with probing depth [PD] > or =5 mm, bleeding on probing [BOP], and clinical attachment or radiographic bone loss) and 53 healthy controls (PDs < or =4 mm and BOP < or =15%). Groups were compared using the t test and linear regression. Patients with HbA1c levels > or =6% were compared using the Fisher exact test and logistic regression. RESULTS Periodontitis cases were more likely than controls to be male (68% versus 38%; P = 0.002) and current or former smokers (P = 0.002). Cases had significantly higher body mass index (BMI) than controls (27.6 kg/m(2) versus 25.5 kg/m(2); P = 0.018) but were of similar age (51.3 years versus 50.9 years; P = 0.89). Unadjusted mean HbA1c levels did not differ significantly between cases and controls (5.66% +/- 0.56% versus 5.51% +/- 0.44%; P = 0.12). After adjustments for age, gender, BMI, and current smoking, mean HbA1c was significantly higher in cases (between-group difference, 0.21%; P = 0.046). A higher proportion of cases (27.3%) than controls (13.2%) had HbA1c values > or =6%, although this difference was not statistically significant (P >0.1). CONCLUSIONS Periodontitis is associated with a slight elevation in glycosylated hemoglobin. The clinical significance of this difference remains to be determined. This preliminary finding is consistent with earlier reports that periodontitis is associated with elevated blood glucose in adults without diabetes and may increase ones risk for type 2 diabetes.