Periodontal disease associates with higher brain amyloid load in normal elderly.

The accumulation of amyloid-ß (Aß) plaques is a central feature of Alzheimer's disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory and/or infectious conditions in humans can promote Aß brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Thirty-eight cognitively normal, healthy, and community-residing elderly (mean age, 61 and 68% female) were examined in an Alzheimer's Disease Research Center and a University-Based Dental School. Linear regression models (adjusted for age, apolipoprotein E, and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aß load using (11)C-Pittsburgh compound B (PIB) positron emission tomography imaging. After adjusting for confounders, clinical attachment loss (≥3 mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased PIB uptake in Aß vulnerable brain regions (p = 0.002). We show for the first time in humans an association between periodontal disease and brain Aß load. These data are consistent with the previous animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aß accumulations.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with three dental Practice-based Research Networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95%CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased four-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment > 2 years; suppuration and dental extractions were independent risk factors for ONJ.

Predicting risk for bisphosphonate-related osteonecrosis of the jaws: CTX versus radiographic markers.

BACKGROUND AND OBJECTIVE: The most common risk factor for bisphosphonate-related osteonecrosis of the jaws (BRONJ) is dentoalveolar surgery. It has been suggested that reduced serum C-terminal telopeptide (CTX) can determine the degree of osteoclast suppression and may predict the development of BRONJ after dentoalveolar surgery. Although there are many radiographic appearances associated with BRONJ, there are little data that describes changes preceding dentoalveolar surgery. The objective of this retrospective study was: 1) to investigate if reduced serum CTX values (i.e., <150 pg/mL) were associated with BRONJ after dentoalveolar surgery; and 2) to determine if specific radiographic changes are associated with teeth that develop BRONJ after extraction. STUDY DESIGN: A retrospective review of radiographic and/or serum CTX data was performed for 68 patients with a history of bisphosphonate therapy who either underwent dental extraction or were diagnosed with BRONJ in the Department of Oral and Maxillofacial Surgery during the period 2007-2009. Postoperative healing was assessed for 26 patients with reduced serum CTX levels (<150 pg/mL) who either underwent dental extraction or treatment for BRONJ. Preoperative radiographs were evaluated for 55 patients who either healed normally or developed BRONJ after dental extraction. RESULTS: All 26 patients (100%) who had serum CTX levels <150 pg/mL healed successfully after dentoalveolar surgery (20 patients) or after treatment for BRONJ (6 patients). Among the 55 patients who underwent radiographic evaluation, 24 patients (83%) with BRONJ exhibited periodontal ligament (PDL) widening associated with extracted teeth, whereas only 3 patients (11%) who healed normally demonstrated PDL widening. CONCLUSION: These data suggest that radiographic PDL widening may be a more sensitive indicator than CTX testing in predicting risk of BRONJ. Current guidelines that recommend minimal surgical intervention may need to be revised to include alternative strategies for the elimination or management of this pathology.

TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects.

The associations of inflammation/immune responses with clinical presentations of Alzheimer's disease (AD) remain unclear. We hypothesized that TNF-alpha and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-alpha classification of clinical AD and NL. This study shows that TNF-alpha and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.

Periodontal disease adversely affects the survival of patients with end-stage renal disease.

Periodontal disease is associated with cardiovascular disease and is thought to accelerate systemic atherosclerosis. Here we examined the relationship between periodontitis and cardiovascular disease mortality in outpatients on hemodialysis using a retrospective analysis of 168 adult patients in New York City and North Carolina. During 18 months of follow-up, cardiovascular disease and all-cause mortality were determined from a centralized dialysis registry. One hundred patients had mild or no periodontal disease but the remaining 68 had moderate-to-severe disease defined as 2 or more teeth with at least 6 mm of inter-proximal attachment loss. At baseline, the proportion of males was significantly lower in the moderate-to-severe group. Compared with mild or no periodontal disease, moderate-to-severe disease was significantly associated with death from cardiovascular causes. Adjustment for age, gender, center and dialysis vintage, smoking status, and history of diabetes mellitus or hypertension did not diminish the strength of this association. Our findings suggest a need for larger studies to confirm this connection, along with intervention trials to determine if treating periodontitis reduces cardiovascular disease mortality in dialysis patients.

Severe periodontitis is associated with low serum albumin among patients on maintenance hemodialysis therapy.

The relationship between periodontitis and two measures of systemic inflammation, serum albumin and C-reactive protein (CRP), were examined among patients who were receiving chronic outpatient hemodialysis. Adult patients at two locations, North Carolina and New York City, were evaluated by dentist examiners. Six sites per tooth (up to 32 teeth per patient) were examined. A periodontitis case was defined as > or = 60% of sites with attachment level > or = 4 mm. Multivariable logistic regression was used to determine the association of periodontitis with low serum albumin, defined as < 3.5 mg/dl, and with high CRP, defined as > 3.0 mg/dl. A total of 154 patients completed the study. The mean age was 54.6 yr (SD 13.3), and average duration of dialysis was 4.0 yr (3 mo to 16 yr). Eighty-six (54.6%) were men, and 89 (58.2%) were black. Common causes of end-stage kidney disease were hypertension (12.3%), diabetes (22.1%), glomerulonephritis (7.1%), and other (58.4%). The average number of teeth was 20.3 (SD 8.4). Thirty-five (23%) patients were periodontitis cases. Severe periodontitis was associated with low serum albumin (odds ratio 8.20; 95% confidence interval 1.61 to 41.82; P = 0.01) compared with individuals without severe periodontitis disease after adjustment for age, gender, race, diabetes, hypertension, body mass index, smoking, study site, total cholesterol, serum calcium, serum phosphorus, and normalized protein catabolic rate. There was no observed association of severe periodontitis with CRP. Investigation of the potential contribution of periodontitis to serum albumin and possibly to morbidity and mortality among patients with end-stage kidney disease seems warranted.

Relationship of destructive periodontal disease to the acute-phase response.

BACKGROUND: Destructive periodontal diseases have been associated with an increased risk of atherosclerotic complications; however, the potential mechanisms are yet to be defined. Inflammation plays a central role in atherosclerosis since C-reactive protein (CRP), an acute-phase protein monitored as a marker of inflammatory status, has been identified as a major risk factor for atherosclerotic complications. Recent reports that destructive periodontal diseases can increase CRP values present the possibility that the acute-phase response may link these 2 disease processes. The objective of the present investigation was to determine the effect of destructive periodontal disease status, severity, and progression on components of the acute-phase response in an urban minority population. METHODS: Clinical measurements recorded included probing depth, attachment level, gingival erythema, bleeding upon probing, suppuration, and plaque. Disease progression was defined as a >2 mm loss of attachment 2 months post-baseline. Serum antibody was measured by enzyme-linked immunosorbent assay. CRP was measured using a high-sensitivity CRP (hsCRP) assay. A commercial laboratory measured serum glucose (non-fasting), albumin, cholesterol, high-density lipoprotein (HDL), triglycerides, low-density lipoprotein (LDL), and iron. RESULTS: Increased serum IgG antibody to Porphyromonas gingivalis, but not to 5 other species, was associated with periodontal disease status, increased severity, and progression as were age, male gender, and smoking. Cholesterol and LDL were increased in disease, and HDL and iron were increased in health. hsCRP, glucose, and cholesterol increased with disease progression. By regression analysis, IgG antibody to P. gingivalis correlated with age, probing depth, and hsCRP, and negatively correlated with albumin and iron. By logistic regression, subjects who experienced multiple sites of disease progression and elevated antibody to P. gingivalis increased the odds ratio of hsCRP>2.08 mg/l by 14.1 and 5.6, respectively. CONCLUSION: These results suggest that destructive periodontal disease and disease progression are associated with changes in serum components consistent with an acute-phase response.

Progression of destructive periodontal diseases in three urban minority populations: role of clinical and demographic factors.

BACKGROUND, AIMS: Differences in prevalence, severity and risk factors for destructive periodontal diseases have been reported for ethnic/racial groups. However, it is not certain whether this disparity is due to ethnicity/race or factors associated with ethnicity/race. Therefore, the present study addressed whether the rates of disease progression and clinical and demographic factors associated with disease progression varied among three ethnic/racial groups. METHODS: The study population consisted of 53 Asian-, 69 African- and 62 Hispanic-Americans. Clinical measurements included probing depth, attachment level, gingival erythema, bleeding upon probing, suppuration and plaque. Disease progression was defined as a > 2 mm loss of attachment 2 months post baseline. The demographic variables examined included occupational status, report of a private dentist, years resident in the United States and smoking history. RESULTS: The rate of attachment loss for the entire population was 0.04 mm or 0.24 mm/year. No significant differences were found among the three ethnic/racial groups. Variables associated with subsequent attachment loss for the entire population were age, male gender, mean whole-mouth plaque, erythema, bleeding upon probing, suppuration, attachment loss and probing depth, and belonging to the "unskilled" occupational group. No differences in risk profiles were found among the 3 ethnic/racial groups. Using stepwise logistic regression analysis, a model was developed to relate the clinical and demographic variables examined with subsequent attachment loss. The model indicated that prior attachment loss, gingival erythema, suppuration, being a current smoker and belonging to the "unskilled" occupational group conferred high risk of > 1 site of attachment loss of > 2 mm. CONCLUSIONS: The results of this study suggest that variables associated with ethnicity/race, such as occupational status, are largely responsible for the observed disparity in destructive periodontal disease progression in these populations.