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1.  Periodontal Disease as a Risk Factor for Bisphosphonate-Related Osteonecrosis of the Jaw 
Journal of periodontology  2013;85(2):226-233.
Background
Previous case reports and animal studies suggest periodontitis is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). We conducted a case-control study to evaluate the association between clinical and radiographic measures of periodontal disease and BRONJ.
Methods
25 BRONJ patients were matched with 48 controls. Trained examiners measured probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) on all teeth except third molars, and gingival and plaque indices on six index teeth. Alveolar bone height was measured from orthopantomograms. Most BRONJ cases were using antibiotics (48%) or a chlorhexidine mouthrinse (84%) at enrollment. Adjusted comparisons of cases vs. controls used multiple linear regression.
Results
The average number of BP infusions was significantly higher in BRONJ cases compared to controls (38.4 vs 18.8, p=0.0001). In unadjusted analyses, BRONJ cases had more missing teeth (7.8 vs 3.1, p=0.002) and high average CAL (2.18 vs 1.56 mm, p=0.047) and percent of sites with CAL ≥3 mm (39.0 vs 23.3, p=0.039) than controls. Also, BRONJ cases had lower average bone height (as a fraction of tooth length, 0.59 vs 0.62, p=0.004) and more teeth with bone height under half of tooth length (20% vs 6%, p=0.001). These differences remained significant after adjusting for age, sex, smoking, and number of bisphosphonate infusions.
Conclusions
BRONJ patients have fewer teeth, greater CAL, and less alveolar bone support compared to controls after adjusting for number of bisphosphonate infusions. Group differences in antibiotics and chlorhexidine rinse usage may have masked differences in the other clinical measures.
doi:10.1902/jop.2013.130017
PMCID: PMC3972496  PMID: 23786404
Bisphosphonates; Periodontitis; Periodontal Disease; Alveolar Bone Loss; Osteonecrosis; Bisphosphonate-related osteonecrosis of the jaw
2.  The Influence of Anti-Infective Periodontal Treatment on C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials 
PLoS ONE  2013;8(10):e77441.
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.
doi:10.1371/journal.pone.0077441
PMCID: PMC3796504  PMID: 24155956
3.  Periodontal Disease, Tooth Loss and Incident Rheumatoid Arthritis: Results from the First National Health and Nutrition Examination Survey and its Epidemiologic Follow-up Study 
Journal of Clinical Periodontology  2011;38(11):998-1006.
Aims
Infection may be a rheumatoid arthritis (RA) risk factor. We examined whether signs of periodontal infection were associated with RA development in NHANES I & NHEFS.
Materials and Methods
In 1971–1974, 9,702 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 (vs. 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 (vs. 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 2–4 fold higher among participants with periodontitis or missing ≥9 teeth (vs. healthy participants).
Conclusions
Although participants with periodontal disease or≥5 missing teeth experienced higher odds of prevalent/incident RA, most ORs were nonstatistically significant and lacked dose-responsiveness. Differential RA ascertainment bias complicated the interpretation of these data.
doi:10.1111/j.1600-051X.2011.01776.x
PMCID: PMC3403745  PMID: 22092471
Rheumatoid Arthritis; Periodontal; Infections; Cohort Studies; Bias
4.  Maternal Periodontitis Treatment and Child Neurodevelopment at 24 to 28 Months of Age 
Pediatrics  2011;127(5):e1212-e1220.
BACKGROUND:
Some maternal infections are associated with impaired infant cognitive and motor performance. Periodontitis results in frequent bacteremia and elevated serum inflammatory mediators.
OBJECTIVE:
The purpose of this study was to determine if periodontitis treatment in pregnant women affects infant cognitive, motor, or language development.
METHODS:
Children born to women who had participated in a previous trial were assessed between 24 and 28 months of age by using the Bayley Scales of Infant and Toddler Development (Third Edition) and the Preschool Language Scale (Fourth Edition). Information about the pregnancy, neonatal period, and home environment was obtained through chart abstractions, laboratory test results, and questionnaires. We compared infants born to women treated for periodontitis before 21 weeks' gestation (treatment group) or after delivery (controls). In unadjusted and adjusted analyses, associations between change in maternal periodontal condition during pregnancy and neurodevelopment scores were tested by using Student's t tests and linear regression.
RESULTS:
A total of 411 of 791 eligible mother/caregiver-child pairs participated. Thirty-seven participating children (9.0%) were born at <37 weeks' gestation. Infants in the treatment and control groups did not differ significantly for adjusted mean cognitive (90.7 vs 91.4), motor (96.8 vs 97.2), or language (92.2 vs 92.1) scores (all P > .5). Results were similar in adjusted analyses. Children of women who experienced greater improvements in periodontal health had significantly higher motor and cognitive scores (P = .01 and .02, respectively), although the effect was small (∼1-point increase for each SD increase in the periodontal measure).
CONCLUSION:
Nonsurgical periodontitis treatment in pregnant women was not associated with cognitive, motor, or language development in these study children.
doi:10.1542/peds.2010-3129
PMCID: PMC3081189  PMID: 21482606
child neurodevelopment; periodontitis; pregnancy; treatment
5.  Serum Inflammatory Mediators in Pregnancy: Changes Following Periodontal Treatment and Association with Pregnancy Outcomes 
Journal of periodontology  2009;80(11):1731-1741.
Objective
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
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 weeks and 16 weeks 6 days (study baseline) and 29–32 weeks gestation was analyzed for C-reactive protein, prostaglandin E2, matrix metalloproteinase-9, fibrinogen, endotoxin, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α. Cox regression, multiple linear regression, t-tests, chi-square and Fisher’s exact tests were used to examine associations between the biomarkers, periodontal treatment, and gestational age at delivery and birthweight.
Results
796 women had baseline serum data; 620 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 change from baseline in any biomarker was significantly associated with preterm birth or infant birthweight (P>0.05). In treatment subjects, change in endotoxin was negatively associated with 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 13–17 weeks and 29–32 weeks gestation were not associated with risk for preterm birth or with infant birthweight.
doi:10.1902/jop.2009.090236
PMCID: PMC2922720  PMID: 19905943
Pregnancy; preterm birth; periodontitis; inflammation; cytokines
6.  Poor oral hygiene as a risk factor for infective endocarditis–related bacteremia 
Background
Infective endocarditis (IE) often is caused by bacteria that colonize teeth. The authors conducted a study to determine if poor oral hygiene or dental disease are risk factors for developing bacteremia after toothbrushing or single-tooth extraction.
Methods
One hundred ninety-four participants in a study were in either a toothbrushing group or a single-tooth extraction with placebo group. The authors assessed the participants’ oral hygiene, gingivitis and periodontitis statuses. They assayed blood samples obtained before, during and after the toothbrushing or extraction interventions for IE-associated bacteria.
Results
The authors found that oral hygiene and gingival disease indexes were associated significantly with IE-related bacteremia after toothbrushing. Participants with mean plaque and calculus scores of 2 or greater were at a 3.78- and 4.43-fold increased risk of developing bacteremia, respectively. The presence of generalized bleeding after toothbrushing was associated with an almost eightfold increase in risk of developing bacteremia. There was no significant association between any of the measures of periodontal disease and the incidence of bacteremia after toothbrushing. The oral hygiene or disease status of a tooth was not significantly associated with bacteremia after its extraction.
Conclusion
Bacteremia after toothbrushing is associated with poor oral hygiene and gingival bleeding after toothbrushing.
Clinical Implications
Improvements in oral hygiene may reduce the risk of developing IE.
PMCID: PMC2770162  PMID: 19797553
Bacteremia; bacteria; infective endocarditis; heart valves; risk factors
7.  Change in Periodontitis during Pregnancy and Risk of Preterm Birth and Low Birthweight 
Aim
Determine if periodontitis progression during pregnancy is associated with adverse birth outcomes.
Materials and Methods
We used clinical data and birth outcomes from the OPT Study, which randomized women to receive periodontal treatment before 21 weeks 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 ≥ 3mm 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 grams, 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 percent 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 study’s limitations, disease progression was not associated with increased risk for delivering a preterm or low birthweight infant.
Clinical Relevance
Scientific Rationale
Maternal periodontitis and disease progression during pregnancy have been associated with elevated risk for preterm birth. We used data from a recent clinical trial to explore possible associations between progressive periodontitis and birth outcomes.
Principal Findings
The distribution of gestational age at delivery and mean birthweights did not differ significantly between women who experienced progressive periodontitis and those who did not.
Clinical Implication
While it is important to treat dental diseases, including periodontitis, during pregnancy, women whose periodontal condition worsens during pregnancy are not at elevated risk for adverse pregnancy outcomes.
doi:10.1111/j.1600-051X.2009.01385.x
PMCID: PMC2741139  PMID: 19426177
preterm birth; low birthweight; periodontal disease; pregnancy; disease progression

Results 1-7 (7)