Association between periodontitis and peripheral artery disease: a systematic review and meta-analysis.

BACKGROUND: Inflammation is a common feature of both peripheral arterial disease (PAD) and periodontitis. Some studies have evaluated the association between PAD and periodontitis. However, there is still no specialized meta-analysis that has quantitatively assessed the strength of the association. Thus, we conducted this meta-analysis to critically assess the strength of the association between PAD and periodontitis. METHODS: PubMed, Embase, and the Cochrane Library were searched for observational studies of the association between periodontitis and PAD in February 2018. Risk ratios (RRs) and their 95% confidence intervals (CIs) from included studies were pooled to evaluate the strength of the association between periodontitis and PAD. Weighted mean differences (WMDs) and their 95% CIs were pooled to compare the difference in periodontal-related parameters between PAD and non-PAD patients. RESULTS: Seven studies including a total of 4307 participants were included in the meta-analysis. The pooled analysis showed that there was a significant difference in the risk of periodontitis between PAD patients and non-PAD participants (RR = 1.70, 95% CI = 1.25-2.29, P = 0.01). There was also a significant difference in number of missing teeth between PAD patients and non-PAD participants (WMD = 3.75, 95% CI = 1.31-6.19, P = 0.003). No significant difference was found in clinical attachment loss between PAD patients and non-PAD participants (WMD = - 0.05, 95% CI = - 0.03-0.19, P = 0.686). CONCLUSION: In conclusion, the results of this meta-analysis revealed a significant relationship between periodontitis and PAD. Moreover, our study indicated that PAD patients had more missing teeth than control subjects did. Further high-quality and well-designed studies with specific inclusion and exclusion criteria are required to strengthen the conclusions of this study.

Evaluation of the associations between immunoglobulin E levels and the number of natural teeth.

BACKGROUND/PURPOSE: The purpose of the study was to evaluate the association between the number of natural teeth and the total serum immunoglobulin E (IgE), allergen-specific IgE against Dermatophagoides farina, allergen-specific IgE against cockroaches, or allergen-specific IgE against dogs with nationally representative data using the Korean National Health and Nutrition Examination Survey (KNHANES). METHODS: This study involved a cross-sectional analysis using KNHANES data from 2010. A total of 1916 participants were eligible for this study. Multiple regression analyses were used to evaluate the risk of tooth loss in relation to IgE levels. The model was adjusted for age, sex, body mass index, smoking habits, drinking habits, exercise habits, vitamin D levels, metabolic syndrome, allergic rhinitis, asthma, atopic dermatitis, and tooth-brushing frequency. RESULTS: The number of natural teeth of the first quartile to the fourth quartile of total serum IgE were 25.9 ± 0.2, 25.9 ± 0.2, 25.1 ± 0.2, and 25.4 ± 0.2, respectively, showing an inverse association (P < 0.05). The number of natural teeth of the first quartile to the fourth quartile of allergen-specific IgE against Dermatophagoides farina and allergen-specific IgE against dogs farina both showed an inverse association with statistical significance (P < 0.05). CONCLUSION: This study clearly showed the inverse association between total serum IgE and number of natural teeth after adjustments, especially regarding participants without systemic diseases, including diabetes mellitus, hypertension, metabolic diseases, and obesity.

C-reactive protein levels and the association of carotid artery calcification with tooth loss.

OBJECTIVES: The relationship between carotid artery calcification (CAC) and tooth loss was investigated and its association with inflammatory mediator levels was evaluated. SUBJECTS AND METHODS: Ninety-two participants were examined for health and periodontal status. Panoramic radiographs were obtained for CAC identification. C-reactive protein (CRP), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were measured. RESULTS: Fifteen participants (16.3%) had CAC, 12 (80.0%) of whom were female. Mean age of participants with CAC was 55.3 ± 12.2 years, while that of participants without CAC was 48.9 ± 9.4 years. Median number of tooth loss in participants with CAC was 11, whereas that of individuals without CAC was 3 (P = 0.008). Age and presence of CAC were associated with the number of tooth loss, independent of health status (ß = 0.452, P = <0.001 and ß = 0.257, P = 0.005). Based on CRP levels, 10 participants (71.4%) were at intermediate risk of coronary heart disease (range, 1.0-2.3 µg ml-1 ), while four participants (28.6%) were at low risk (<1.0 µg ml-1 ). CRP, ICAM-1, or VCAM-1 levels were not significantly related to the presence of CAC or tooth loss. CONCLUSIONS: Patients with higher tooth loss have a greater prevalence of CAC. Patients with CAC should be referred for medical consultation.

Tooth loss early in life accelerates age-related bone deterioration in mice.

Both osteoporosis and tooth loss are health concerns that affect many older people. Osteoporosis is a common skeletal disease of the elderly, characterized by low bone mass and microstructural deterioration of bone tissue. Chronic mild stress is a risk factor for osteoporosis. Many studies showed that tooth loss induced neurological alterations through activation of a stress hormone, corticosterone, in mice. In this study, we tested the hypothesis that tooth loss early in life may accelerate age-related bone deterioration using a mouse model. Male senescence-accelerated mouse strain P8 (SAMP8) mice were randomly divided into control and toothless groups. Removal of the upper molar teeth was performed at one month of age. Bone response was evaluated at 2, 5 and 9 months of age. Tooth loss early in life caused a significant increase in circulating corticosterone level with age. Osteoblast bone formation was suppressed and osteoclast bone resorption was activated in the toothless mice. Trabecular bone volume fraction of the vertebra and femur was decreased in the toothless mice with age. The bone quality was reduced in the toothless mice at 5 and 9 months of age, compared with the age-matched control mice. These findings indicate that tooth loss early in life impairs the dynamic homeostasis of the bone formation and bone resorption, leading to reduced bone strength with age. Long-term tooth loss may have a cumulative detrimental effect on bone health. It is important to take appropriate measures to treat tooth loss in older people for preventing and/or treating senile osteoporosis.

Serum albumin levels and 10-year tooth loss in a 70-year-old population.

Serum albumin levels are a practical marker of general health status in the elderly and have been used to determine the severity of underlying diseases and the risk for death. This longitudinal study evaluated the relationship between serum albumin concentrations and tooth loss over 10 years in elderly subjects, after controlling for confounding factors. A sample of 554 dentate subjects among enrolled subjects (n = 600) was involved in this planned longitudinal study with follow-up examinations after 5 and 10 years. At the 5-year follow-up, 373 (67·3%), subjects were available for re-examination. In addition, 331 (59·7%) were available at the 10-year follow-up. Multiple Poisson regression analysis was conducted to evaluate the relationship between the number of missing teeth over 5 or 10 years and serum albumin levels at baseline after adjusting for 10 variables: gender, serum markers levels at baseline, dental status, smoking habits and educational years and oral health behaviour. The number of missing teeth over 5 or 10 years was significantly negatively associated with serum albumin levels at baseline [incidence rate ratios (IRR) = 0·373, P < 0·0001 for 5 years; IRR = 0·570, P < 0·0001 for 10 years]. We conclude that elderly subjects with hypoalbuminemia are at high risk for 5- and 10-year tooth loss.

Association between the insulin-like growth factor axis in serum and periodontitis in the Study of Health in Pomerania: an exploratory study.

AIM: To evaluate the association of Insulin-like Growth Factor (IGF) I-related variables with periodontitis in the population-based Study of Health in Pomerania (SHIP). MATERIAL AND METHODS: From the cross-sectional SHIP, 2293 subjects with clinical attachment loss (CAL) data and 2398 subjects with tooth count data aged 20-59 years were analysed. Serum IGF-I and IGF-binding protein (BP)-3 levels were determined by chemiluminescence immunoassays. Linear and logistic regressions with fractional polynomials were used to study associations between IGF-related variables and mean CAL or high tooth loss. For non-linear relations between IGFBP-3 and mean CAL, graphical presentations of fractional polynomials were used to deduce knots for linear splines. RESULTS: In fully adjusted models, for serum IGFBP-3 values ≤1200 ng/ml, mean CAL increased significantly for decreasing serum IGFBP-3 levels [B = -0.027 (95% CI, -0.049; -0.005), p = 0.02]. The odds for high tooth loss decreased significantly for high serum IGFBP-3 values [OR = 0.97 (0.95; 0.99), p = 0.02]. Serum IGF-I levels and the IGF-I/IGFBP-3 ratio were not related to mean CAL or tooth loss after full adjustment. CONCLUSIONS: Low serum IGFBP-3 levels might be associated with higher levels of periodontal disease. Neither serum IGF-I nor IGF-I/IGFBP-3 ratios were associated with periodontitis.

Oral health and longitudinal changes in fasting glucose levels: A nationwide cohort study.

We investigated the association between oral hygiene indicators of periodontitis, tooth loss, and tooth brushing on the longitudinal fasting glucose level in non-diabetic subjects. Using a nationwide health screening database in Korea, we included non-diabetic individuals who received a health screening program with oral health check in 2009-2010. We constructed a linear mixed model for the longitudinal data of fasting glucose from the baseline to 2015. During the 4.84-year of median follow-up, 91,963 individuals (mean age 56.2 at baseline) underwent 392,780 health examinations with fasting glucose level (mmol/L). The presence of periodontitis was 39.3%. In the multivariate linear mixed analysis, periodontitis was related with increased fasting glucose levels (ß = 0.0084, standard error = 0.0035, p = 0.018). Similarly, tooth loss was associated with increased level of fasting glucose (ß = 0.0246, standard error = 0.0038, p < 0.001). Compared with tooth brushing ≤2 times/day, tooth brushing ≥3 times/day was associated with decreased fasting glucose levels (ß = -0.0207, standard error = 0.0033, p < 0.001). Our data showed that periodontitis and tooth loss were associated with increased fasting glucose levels in non-diabetic individuals. The study findings imply that frequent tooth brushing may reduce fasting glucose levels. Further research is needed to determine the effect of periodontal intervention on glycemic control.

Levels of C-reactive protein and protein C in periodontitis patients with and without cardiovascular disease.

Since periodontitis is a chronic and inflammatory disease, a number of hypotheses have proposed that it has an etiological or modulating role in cardiovascular disease (CVD). This study aimed to ascertain the changes in the plasma levels of C-reactive protein (CRP) and protein C (PC), a natural anticoagulant also having an anti-inflammatory effect, in patients who have mild-to-severe periodontitis with or without CVD. The test group consisted of 26 patients with CVD and chronic periodontitis and the control group consisted of 26 patients with chronic periodontitis and no systemic disease. In both groups Community Periodontal Index of Treatment Needs scores were recorded and blood samples were collected. CRP levels were significantly high and PC activity was significantly low in the test group compared to the control group (p < 0.001). There was a negative correlation between tooth loss and PC and between CRP and PC. How PC is affected by the inflammatory events and its association with CRP is an active area of investigation.

Periodontitis and Tooth Loss Have Negative Systemic Impact on Circulating Progenitor Cell Levels: A Clinical Study.

The aim of the present study was to investigate the association and impact of periodontitis and tooth loss on a subtype of endothelial progenitor cell (EPC) levels (CD133+/KDR+). Furthermore, the objective was to determine if the periodontal status influenced CD133+/KDR+ levels. In all, 88 patients with periodontitis and 79 healthy controls (HCs) were enrolled in the study. Enrolled patients were examined and characterized by clinical and blood sample analysis. Spearman's correlation test was applied in order to assess the interdependence between CD133+/KDR+ levels and all periodontal parameters. In order to estimate a statistically significant trend (p-trend) for ordered CD133++/KDR+ quartiles, the Jonckheere-Terpstra test was applied for all variables. Patients in the periodontitis group presented significantly lower CD133+/KDR+ levels (66.4 (45.5-269.6 cells/µL)) compared to the HC group (76.7 (24.3-313.2 cells/µL), p < 0.001). Lower CD133+/KDR+ levels negatively correlated with C-reactive protein (CRP), with the number of teeth, and with all periodontal parameters (p < 0.001). Moreover, there was a proportional increase in CD133+/KDR+ levels with a progressive increase in number of teeth (p-trend < 0.001), while there was a proportional decrease in CD133+/KDR+ levels with a proportional increase in clinical attachment level (CAL, p-trend = 0.003), probing depth (PD, p-trend = 0.007), and bleeding sites (bleeding on probing (BOP), p-trend < 0.001) as an extent measure of periodontitis. This study demonstrated that patients with periodontitis presented significantly lower CD133+/KDR+ levels compared to HCs. Moreover, all patients presented an increase in the CD133+/KDR+ EPC levels with an extended level of periodontitis and tooth loss.

Self-reported gingivitis and tooth loss poorly predict C-reactive protein levels: a study among Finnish young adults.

OBJECTIVES: Our aim in this cross-sectional study was to investigate whether self-reported gingivitis and tooth loss were associated with elevated levels of C-reactive protein (CRP) using the same study population where these dental conditions have earlier been associated with prevalent angina pectoris. MATERIAL AND METHODS: The study population consisted of those Northern Finland birth cohort 1966 members who lived in Northern Finland or in the Helsinki region (n=8463) at the time of the survey (1996-1997). The participation rate in a health examination was 71% (n=6033). Gingivitis and tooth loss were determined on the basis of self-reported questions. Prevalence proportion ratios (PPR) and 95% confidence intervals (CI) were estimated using multivariate regression models. RESULTS: The results showed that self-reported gingivitis and tooth loss were weakly associated with elevated levels of CRP (>3 mg/l): adjusted PPR 1.1, CI 1.0-1.3 and PPR 1.1, CI 0.7-1.7, respectively. The proportion of variation in CRP explained by self-reported gingivitis and tooth loss was small, being <1%. CONCLUSION: The results suggest that self-reported gingivitis and tooth loss have a miniscule effect on CRP levels among a general population of young adults.

Persistently raised C-reactive protein levels are associated with advanced periodontal disease.

OBJECTIVE: The aim was to investigate whether there was an association between periodontitis or tooth loss in a homogeneous group of 60-70-year-old Western European men and either a sustained high or low level of C-reactive protein (CRP). MATERIAL AND METHODS: Men enrolled in a cohort study of cardiovascular disease in Northern Ireland were screened in 1990-1994 and rescreened in 2001-2004, when a periodontal examination was completed. High-sensitivity CRP was measured from fasting blood samples. There were 806 men with six or more teeth who had either a high level (>3 mg/l) or a lower level of CRP at both time points. Multivariate analysis was carried out using logistic regression with adjustment for possible confounders. Models were constructed with the CRP level as the outcome variable and various measures of periodontal status (low and high threshold periodontitis) or tooth loss as predictor variables. Confounders included in the analysis were known cardiovascular risk factors of age, smoking, diabetes, BMI and socioeconomic status. RESULTS: There were 67 men who had a high value of CRP (>3 mg/l) and 739 men who had a CRP value

Endotoxin levels are associated with high-density lipoprotein, triglycerides, and troponin in patients with acute coronary syndrome and angina: possible contributions from periodontal sources.

BACKGROUND: Recent studies have reported an association between poor dental health and acute coronary syndrome (ACS). The purpose of this study was to correlate the presence of periodontitis with serum endotoxin/lipopolysaccharides (LPS), lipid profiles, troponin, and immunoglobulin G (IgG) antibody to Porphyromonas gingivalis in control patients or patients with ACS or angina at the time of hospital admission. METHODS: Blood samples from 194 subjects presenting with ACS, angina, or non-cardiac chest pain were analyzed for endotoxin/LPS (Limulus amebocyte lysate assay), lipid profile, troponin, and IgG antibody to P. gingivalis. Data were collected from hospital charts and dental records, and health questionnaire responses. RESULTS: Subjects with ACS or angina were more likely to have poor oral care, fewer remaining teeth, and increased alveolar radiographic bone loss compared to subjects with chest pain. In all subjects, endotoxin/LPS and IgG antibody to P. gingivalis tended to increase in association with increased radiographic bone loss. Endotoxin/LPS increased directly with triglyceride and troponin levels (P = 0.04 and P = 0.006, respectively) and inversely with high-density lipoprotein (HDL) levels (P = 0.002). IgG antibody to P. gingivalis levels was directly correlated with very low-density lipoprotein (P = 0.03) and triglycerides (P = 0.06) and inversely with low-density lipoprotein (P = 0.01). CONCLUSIONS: Results showed more alveolar bone loss in patients with cardiac disease than in patients without cardiac disease, but there was no difference between the groups in the serum levels of endotoxin/LPS or IgG antibody to P. gingivalis. However, there were associations between endotoxin/LPS and levels of serum triglycerides, troponin, and HDL.

Number of teeth and serum lipid peroxide in 85-year-olds.

OBJECTIVES: To investigate influence of dental status on systemic oxidative stress, we evaluated the association between number of teeth and serum lipid peroxide, an oxidative stress index, in 85-years old residents of Japan. METHODS: In October 2003, 207 subjects 85-years old agreed to participate in the present follow-up study after five years from the 8020 Data Bank Survey of Fukuoka prefecture in 1998. Dental health condition including number of teeth was examined by dentists. Data from 204 subjects (88 male, 116 female) who completed nonfasting venous blood examination including lipid peroxide and blood chemistry were analyzed. The examination included a medical questionnaire regarding smoking history, physical activity, alcohol consumption, educational duration, and regular dental care, anthropometric and manometric measurements. RESULTS: Albumin, lipids, and lipid peroxide in serum all were within the normal range. Number of teeth correlated positively with height and white blood cell count, and correlated negatively with lipid peroxide. In a multiple regression analysis to adjust for confounding factors, tooth number retained this correlation with lipid peroxide. By analysis of variance with a Bonferroni-Dunn correction, edentulous subjects showed significantly higher lipid peroxide than those retaining 20 teeth or more. CONCLUSION: The negative association between number of teeth and lipid peroxide links more teeth remaining with less oxidative stress in an 85-year-old population; this may decrease risk of atherosclerotic complications.

Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease.

BACKGROUND: Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss- a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial. METHODS AND RESULTS: Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively. After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14-1.29), interleukin 6 1.14 (1.10-1.18), lipoprotein-associated phospholipase A2 activity 1.05 (1.03-1.06), growth differentiation factor 15 1.11 (1.08-1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11-1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98-1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact. CONCLUSIONS: A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov; NCT00799903.

Total tooth loss and prevalent cardiovascular disease in men and women: possible roles of citrus fruit consumption, vitamin C, and inflammatory and thrombotic variables.

BACKGROUND AND OBJECTIVE: Tooth loss has been associated with cardiovascular disease (CVD), but the mechanisms are unclear. We evaluated the association of total tooth loss with prevalent CVD in men and women; as well as with citrus fruit consumption, plasma vitamin C, and inflammatory and thrombotic variables. METHODS: We used an age-and sex-stratified population survey, of men and women aged 25-74 years, in North Glasgow. RESULTS: Thirty-eight percent of women and 29% of men were edentulous. Total tooth loss was associated with prevalent CVD in both sexes. After adjustment for major potential confounders (age, sex, smoking, and social class), the odds ratio (95% CI) for prevalent CVD was 1.55 (1.13, 2.13) in the edentulous. Total tooth loss was also associated with low citrus fruit consumption and low plasma vitamin C levels, increased plasma C-reactive protein in men, and with increased plasma interleukin-6, fibrinogen, and factor VIII levels in women. CONCLUSION: Prevalent CVD is associated with total tooth loss. Possible mechanisms include low intake of citrus fruit, and hence, low plasma vitamin C levels, and a predisposition to low-grade inflammation and thrombosis. It may be prudent to ensure adequate vitamin C intake in people with no teeth.

Acute-phase inflammatory response to periodontal disease in the US population.

Moderate elevation of serum C-reactive protein (CRP) is a risk factor for cardiovascular disease among apparently healthy individuals, although factors that create this inflammatory response in the absence of systemic illness have not been clarified. This study aimed to: (1) evaluate associations among periodontal disease, established risk factors for elevated CRP, and CRP levels within the US population; and (2) determine whether total tooth loss is associated with reduced CRP. Data were obtained from the third National Health and Nutrition Examination Survey. A random sample of the US population was interviewed in their homes and examined at mobile examination centers. CRP was quantified from peripheral blood samples and analyzed as a continuous variable and as the prevalence of elevated CRP (> or = 10 mg/L). Some 12,949 people aged 18+ years who had periodontal examinations and an additional 1,817 edentulous people aged 18+ years were included in the analysis. Dentate people with extensive periodontal disease (> 10% of sites with periodontal pockets 4+ mm) had an increase of approximately one-third in mean CRP and a doubling in prevalence of elevated CRP compared with periodontally healthy people. Raised CRP levels among people with extensive periodontal disease persisted in multivariate analyses (P < 0.01), with established risk factors for elevated CRP (diabetes, arthritis, emphysema, smoking, and anti-inflammatory medications) and sociodemographic factors controlled for. However, CRP levels were similarly raised in edentulous people. Furthermore, the established risk factors for elevated CRP modified relationships between oral status and CRP levels. Periodontal disease and edentulism were associated with systemic inflammatory response in the US population, most notably among people who had no established risk factors for elevated CRP.

Prospective Study of Serum 25-hydroxy Vitamin D and Tooth Loss.

Vitamin D deficiency and oral diseases (periodontitis, caries, and tooth loss) are highly prevalent in Germany. Previous studies suggested that vitamin D might be a modifiable and protective factor for periodontitis, caries, and tooth loss. However, prospective studies investigating such associations are limited. We explored the association between the concentration of serum 25-hydroxy vitamin D (25OHD) and incidence of tooth loss, progression of clinical attachment loss (CAL) ≥ 3 mm, and progression of restorative and caries status in a population-based longitudinal study. We analyzed data from 1,904 participants from the Study of Health in Pomerania with a five-year follow-up. Generalized estimating equation models were applied to evaluate tooth-specific associations between serum 25OHD and incidence of tooth loss, progression of CAL ≥ 3 mm, and progression of restorative and caries status. Age, sex, education, smoking status, alcohol drinking, waist circumference, dental visit frequency, reasons of dental visit, vitamin D or calcium supplements, and season of blood draw were considered as confounders. Serum 25OHD was inversely associated with incidence of tooth loss. A significant dose-response relationship (p = .0022) was observed across the quintiles of serum 25OHD. After adjusting for multiple confounders, each 10-µg/L increase of serum 25OHD was associated with a 13% decreased risk of tooth loss (risk ratio: 0.87; 95% confidence interval: 0.79, 0.96). The association was attenuated for changes of CAL ≥ 3 mm when adjusting for multiple confounders. No significant association was found between serum 25OHD and caries progression. Vitamin D might be a protective factor for tooth loss. The effect might partially be mediated by its effect on periodontitis.

Cumulative lead exposure and tooth loss in men: the normative aging study.

BACKGROUND: Individuals previously exposed to lead remain at risk because of endogenous release of lead stored in their skeletal compartments. However, it is not known if long-term cumulative lead exposure is a risk factor for tooth loss. OBJECTIVES: We examined the association of bone lead concentrations with loss of natural teeth. METHODS: We examined 333 men enrolled in the Veterans Affairs Normative Aging Study. We used a validated K-shell X-ray fluorescence (KXRF) method to measure lead concentrations in the tibial midshaft and patella. A dentist recorded the number of teeth remaining, and tooth loss was categorized as 0, 1-8 or > or = 9 missing teeth. We used proportional odds models to estimate the association of bone lead biomarkers with tooth loss, adjusting for age, smoking, diabetes, and other putative confounders. RESULTS: Participants with > or = 9 missing teeth had significantly higher bone lead concentrations than those who had not experienced tooth loss. In multivariable-adjusted analyses, men in the highest tertile of tibia lead (> 23 microg/g) and patella lead (> 36 microg/g) had approximately three times the odds of having experienced an elevated degree of tooth loss (> or = 9 vs. 0-8 missing teeth or > or = 1 vs. 0 missing teeth) as those in the lowest tertile [prevalence odds ratio (OR) = 3.03; 95% confidence interval (CI), 1.60-5.76 and OR = 2.41; 95% CI, 1.30-4.49, respectively]. Associations between bone lead biomarkers and tooth loss were similar in magnitude to the increased odds observed in participants who were current smokers. CONCLUSION: Long-term cumulative lead exposure is associated with increased odds of tooth loss.