Marginal analysis of multiple outcomes with informative cluster size.

In surveillance studies of periodontal disease, the relationship between disease and other health and socioeconomic conditions is of key interest. To determine whether a patient has periodontal disease, multiple clinical measurements (eg, clinical attachment loss, alveolar bone loss, and tooth mobility) are taken at the tooth-level. Researchers often create a composite outcome from these measurements or analyze each outcome separately. Moreover, patients have varying number of teeth, with those who are more prone to the disease having fewer teeth compared to those with good oral health. Such dependence between the outcome of interest and cluster size (number of teeth) is called informative cluster size and results obtained from fitting conventional marginal models can be biased. We propose a novel method to jointly analyze multiple correlated binary outcomes for clustered data with informative cluster size using the class of generalized estimating equations (GEE) with cluster-specific weights. We compare our proposed multivariate outcome cluster-weighted GEE results to those from the convectional GEE using the baseline data from Veterans Affairs Dental Longitudinal Study. In an extensive simulation study, we show that our proposed method yields estimates with minimal relative biases and excellent coverage probabilities.

Metacarpal Cortical Bone Area Predicts Tooth Loss in Men.

The relationship between bone mineral density and tooth loss in men is unclear. The aim of this retrospective cohort study was to determine if relative metacarpal bone area (MCA) predicts tooth loss in a cohort of 273 male participants in the Dental Longitudinal Study and Normative Aging Study of the Department of Veterans Affairs. Outer and inner cortical bone widths of the middle metacarpal of the nondominant hand were measured on anteroposterior hand radiographs approximately 11 y apart. Baseline MCA was computed and categorized into quartiles. The men were followed from 1971 to 2015. Incident tooth loss during 2 intervals was examined: concurrent with the MCA measurements and long term over the total follow-up (17 ± 7 y). Radiographic alveolar bone loss (ABL) was measured on periapical radiographs as a percentage of the distance from the cementoenamel junction to root apex, and the number of teeth with ABL >40% was computed. Negative binomial generalized linear regression models estimated the mean number of teeth with ABL >40% and the number lost (concurrent and total), controlling for age, smoking, number of teeth at baseline, percentage teeth with ≥1 decayed/filled surface, and years of follow-up. At baseline, MCA was inversely related to number of teeth with >40% ABL. Men in the lowest MCA quartile (Q1) lost the most teeth, both concurrent with MCA measurements and long term, but the association differed by caries level (≤55% or >55% decayed/filled teeth). At the low caries level, the numbers lost in Q1 were 29% greater than in the highest MCA quartile (Q4). At the high caries level, the numbers lost in Q1 were more than twice those in Q4. Associations were attenuated when further controlled for number of teeth with ABL>40%. These findings suggest that systemic bone status plays a role in tooth loss and that the association may be mediated by alveolar bone loss. Knowledge Transfer Statement: Low relative metacarpal bone area was related to loss of alveolar bone and incident tooth loss in men. This information extends previous research, primarily studies of women, showing that osteoporosis adversely affects oral health. Knowledge of a patient's systemic bone status may be important for managing his or her periodontal disease. Tooth loss in the absence of periodontal inflammation may signify systemic bone loss. Interprofessional communication is central to maintaining optimal oral and bone health.

Metabolic Syndrome and Periodontal Disease Progression in Men.

Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study's aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (≥5 mm), clinical attachment loss (≥5 mm), mobility (≥0.5 mm), and alveolar bone loss (≥40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth ≥5 mm (1.37; 1.14 to 1.65), clinical attachment loss ≥5 mm (1.19; 1.00 to 1.41), alveolar bone loss ≥40% (1.25; 1.00 to 1.56), and tooth mobility ≥0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that comprise the metabolic syndrome may play a role in the development or worsening of periodontitis.

Retained asymptomatic third molars and risk for second molar pathology.

Prophylactic extraction of unerupted asymptomatic third molars is the most common oral surgery procedure in the United States. However, limited evidence exists to justify its costs and associated morbidity. We analyzed data collected over 25 years from 416 adult men enrolled in the Veterans Affairs Dental Longitudinal Study to evaluate the association of retained asymptomatic third molars with risk of adjacent second molar pathology (caries and/or periodontitis), based on third molar status (i.e., absent, erupted, or unerupted). Unerupted molars were further categorized as either "soft tissue" or "bony" impacted. We found that the lowest prevalence and incidence of second molar pathology occurred when the adjacent third molar was absent. The presence of a third molar that was soft tissue impacted increased the risk of incident second molar pathology 4.88-fold (95% confidence interval: 2.62, 9.08). Having an erupted or "bony" impacted third molar increased the risk of incident second molar pathology by 1.74 (95% confidence interval: 1.34, 2.25) and 2.16 (95% confidence interval: 1.56, 2.99), respectively. The retention of third molars is associated with increased risk of second molar pathology in middle-aged and older adult men.

Vitamin D and periodontal health in older men.

Vitamin D, an anti-inflammatory mediator, has potential benefits for physical and oral health. Although it is produced endogenously, some individuals have a greater need for dietary and supplemental sources. This repeated-measures cross-sectional study assessed associations between total vitamin D intake and periodontal health in older men. Participants were 562 members of the Department of Veterans Affairs Dental Longitudinal Study, mean age 62.9 years, who were examined 1 to 4 times between 1986 and 1998. A calibrated examiner measured probing pocket depth (PPD) and attachment loss (AL) on each tooth. Alveolar bone loss (ABL) was determined from radiographs. Severe periodontal disease was defined as PPD ≥ 5 mm on ≥ 1 tooth and AL ≥ 6 mm at ≥ 2 sites (not on same tooth), and moderate-to-severe alveolar bone loss as ABL ≥ 40% at ≥ 3 sites. Generalized estimating equations were used to compute the odds ratios (OR) and 95% confidence intervals (95% CI) of having periodontal disease by level of vitamin D intake. Total vitamin D intake ≥ 800 IU was associated with lower odds of severe periodontal disease (OR = 0.67, 95% CI = 0.55-0.81) and moderate-to-severe ABL (OR = 0.54, 95% CI = 0.30-0.96) relative to intake < 400 IU/day. Vitamin D intake may protect against periodontal disease progression.

Changes in body weight and adiposity predict periodontitis progression in men.

Most studies linking obesity and periodontal disease have been cross-sectional in design. We examined whether gains in body weight, waist circumference, and arm fat area are associated with periodontitis progression in 893 non-diabetic men followed for up to four decades in the prospective VA Dental Longitudinal Study. Probing pocket depth (PPD) was measured by calibrated examiners. Repeated-measures generalized linear models estimated the mean cumulative numbers of teeth with PPD events (PPD > 3 mm) at each dental examination and the slopes associated with increasing numbers of affected teeth over time. Means were adjusted for baseline PPD, education, and cigarette pack-years, and time-dependent values of age, mean plaque score, cigarette packs/day, brushing, and flossing. Men who were overweight at baseline and gained weight most rapidly (> 0.19 kg/yr or ~15 lb during follow-up) had significantly more PPD events than men in the lowest tertile of weight gain (≤ -0.05 kg/yr). Overweight men whose waist circumference increased > 0.14-0.39 or > 0.39 cm/yr experienced more PPD events than men in the lowest tertile (≤ 0.14 cm/yr). Increase in arm fat area was associated with disease progression in normal-weight men. These results suggest that tracking adiposity changes with easily obtained anthropometric measures may help predict risk of periodontitis progression.