Sjögren's Disease and Oral Health: A Genetic Instrumental Variable Analysis.

Epidemiological studies have consistently shown that Sjögren's disease (SjD) increases the risk of dental caries. Despite similar evidence indicating an elevated risk of periodontitis, SjD remains a disputed risk factor for this disease. The risk of bias in observational research is a major impediment to confirming this link. Within an instrumental variable framework, genetic variants associated with a risk factor can be used to proxy its effect on an outcome while avoiding common sources of observational study bias. In this study, we leveraged an instrumental variable approach to investigate whether SjD affects the risk of caries and periodontitis. A total of 57 genetic variants strongly associated with SjD were identified from a genome-wide association study of 2,247 European descent cases and 332,115 controls. We tested for associations of these genetic instruments with caries (measured as the number of decayed, missing, and filled surfaces in 26,792 individuals) and periodontitis (17,353 clinical periodontitis cases and 28,210 European controls). Several sensitivity analyses were used to further validate the primary inverse variance weighted (IVW) estimate. IVW analysis revealed an adverse effect of SjD on caries (ß = 0.039, P = 6.3e-16) and periodontitis (odds ratio = 1.033, P = 2.3e-05). Sensitivity analyses, conducted to assess the robustness to potential violations of instrumental variable assumptions, further support these findings. Our results showed that SjD has a detrimental effect on caries and also suggest that SjD promotes periodontitis.

Development and External Validation of a Multivariable Prediction Model to Identify Nondiabetic Hyperglycemia and Undiagnosed Type 2 Diabetes: Diabetes Risk Assessment in Dentistry Score (DDS).

The aim of this study was to develop and externally validate a score for use in dental settings to identify those at risk of undiagnosed nondiabetic hyperglycemia (NDH) or type 2 diabetes (T2D). The Studies of Health in Pomerania (SHIP) project comprises 2 representative population-based cohort studies conducted in northeast Germany. SHIP-TREND-0, 2008 to 2012 (the development data set) had 3,339 eligible participants, with 329 having undiagnosed NDH or T2D. Missing data were replaced using multiple imputation. Potential covariates were selected for inclusion in the model using backward elimination. Heuristic shrinkage was used to reduce overfitting, and the final model was adjusted for optimism. We report the full model and a simplified paper-based point-score system. External validation of the model and score employed an independent data set comprising 2,359 participants with 357 events. Predictive performance, discrimination, calibration, and clinical utility were assessed. The final model included age, sex, body mass index, smoking status, first-degree relative with diabetes, presence of a dental prosthesis, presence of mobile teeth, history of periodontal treatment, and probing pocket depths ≥5 mm as well as prespecified interaction terms. In SHIP-TREND-0, the model area under the curve (AUC) was 0.72 (95% confidence interval [CI] 0.69, 0.75), calibration in the large was -0.025. The point score AUC was 0.69 (95% CI 0.65, 0.72), with sensitivity of 77.0 (95% CI 76.8, 77.2), specificity of 51.5 (95% CI 51.4, 51.7), negative predictive value of 94.5 (95% CI 94.5, 94.6), and positive predictive value of 17.0 (95% CI 17.0, 17.1). External validation of the point score gave an AUC of 0.69 (95% CI 0.66, 0.71), sensitivity of 79.2 (95% CI 79.0, 79.4), specificity of 49.9 (95% CI 49.8, 50.00), negative predictive value 91.5 (95% CI 91.5, 91.6), and positive predictive value of 25.9 (95% CI 25.8, 26.0). A validated prediction model involving dental variables can identify NDH or undiagnosed T2DM. Further studies are required to validate the model for different European populations.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Repeated exposure of the oral mucosa over 12 months with cold plasma is not carcinogenic in mice.

Peri-implantitis may result in the loss of dental implants. Cold atmospheric pressure plasma (CAP) was suggested to promote re-osseointegration, decrease antimicrobial burden, and support wound healing. However, the long-term risk assessment of CAP treatment in the oral cavity has not been addressed. Treatment with two different CAP devices was compared against UV radiation, carcinogen administration, and untreated conditions over 12 months. Histological analysis of 406 animals revealed that repeated CAP exposure did not foster non-invasive lesions or squamous cell carcinoma (SCCs). Carcinogen administration promoted non-invasive lesions and SCCs. Molecular analysis by a qPCR screening of 144 transcripts revealed distinct inflammatory profiles associated with each treatment regimen. Interestingly, CAP treatment of carcinogen-challenged mucosa did not promote but instead left unchanged or reduced the proportion of non-invasive lesions and SCC formation. In conclusion, repeated CAP exposure of murine oral mucosa was well tolerated, and carcinogenic effects did not occur, motivating CAP applications in patients for dental and implant treatments in the future.

Ten-year trends in DMF-S and DMF-T in a northeast German adult population.

OBJECTIVE: The aim of this study was to assess 10-year trends in coronal caries in adults aged 20-83 years using data from the two-representative population-based Studies of Health in Pomerania (SHIP-0/SHIP-Trend-0). METHODS: Repeated cross-sectional data from 4,286 SHIP-0 and 3,913 SHIP-Trend-0 participants were analysed. Carious, filled and missing teeth/surfaces were recorded in a half-mouth design and the DMF-T/S scores and sound surfaces/teeth were calculated according to WHO criteria. Trends in DMF-T/S scores and its single components were presented stratified by age group and sex. RESULTS: A statistically significant decline in coronal caries experience (DMF-T and DMF-S) in adults aged 20 to 83 years as well as for D-T/S components was observed. The proportion of edentulous participants was almost halved from 8.7% (SHIP-0) to 5.1% (SHIP-Trend-0), while the number of M-T declined from 4.4 to 3.5 revealing an overall clear shift to a higher retention rate of teeth. In younger adults (25-34 years) 3.8 more sound teeth (17.2 sound surfaces) were found in average in the mouth and in elderly (65-74 years) a clear shift from extracted to filled teeth was observed (M-T reduced by 5.4, while F-T increased by 4). Regarding sex differences, females had consistently on average higher MF-T/S values, but lower D-T/S values than males. CONCLUSION: A clinically relevant drop in the severity of coronal caries experience in all adult age groups in Northeast Germany shows that not only reductions in caries experience in adolescence translated into adulthood but also later improvements led to long-term oral health.

Association, prediction, generalizability: Cross-center validity of predicting tooth loss in periodontitis patients.

OBJECTIVES: To predict patients' tooth loss during supportive periodontal therapy across four German university centers. METHODS: Tooth loss in 897 patients in four centers (Kiel (KI) n = 391; Greifswald (GW) n = 282; Heidelberg (HD) n = 175; Frankfurt/Main (F) n = 49) during supportive periodontal therapy (SPT) was assessed. Our outcome was annualized tooth loss per patient. Multivariable linear regression models were built on data of 75 % of patients from one center and used for predictions on the remaining 25 % of this center and 100 % of data from the other three centers. The prediction error was assessed as root-mean-squared-error (RMSE), i.e., the deviation of predicted from actually lost teeth per patient and year. RESULTS: Annualized tooth loss/patient differed significantly between centers (between median 0.00 (interquartile interval: 0.00, 0.17) in GW and 0.09 (0.00, 0.19) in F, p = 0.001). Age, smoking status and number of teeth before SPT were significantly associated with tooth loss (p < 0.03). Prediction within centers showed RMSE of 0.14-0.30, and cross-center RMSE was 0.15-0.31. Predictions were more accurate in F and KI than in HD and GW, while the center on which the model was trained had a less consistent impact. No model showed useful predictive values. CONCLUSION: While covariates were significantly associated with tooth loss in linear regression models, a clinically useful prediction was not possible with any of the models and generalizability was not given. Predictions were more accurate for certain centers. CLINICAL RELEVANCE: Association should not be confused with predictive value: Despite significant associations of covariates with tooth loss, none of our models was useful for prediction. Usually, model accuracy was even lower when tested across centers, indicating low generalizability.

Periodontitis Is Related to Exercise Capacity: Two Cross-sectional Studies.

Although a potential link between periodontitis and cardiorespiratory fitness might provide a reasonable explanation for effects of tooth-related alterations seen on cardiometabolic diseases, evidence is currently limited. Thus, we investigated the association between clinically assessed periodontitis and cardiopulmonary exercise testing (CPET). Data from 2 independent cross-sectional population-based studies (5-y follow-up of the Study of Health in Pomerania [SHIP-1; N = 1,639] and SHIP-Trend-0 [N = 2,439]) were analyzed. Participants received a half-mouth periodontal examination, and teeth were counted. CPET was based on symptom limited-exercise tests on a bicycle ergometer. Associations of periodontitis parameters with CPET parameters were analyzed by confounder-adjusted multivariable linear regression. In the total sample, mean pocket probing depth (PPD), mean clinical attachment levels, and number of teeth were consistently associated with peak oxygen uptake (peakVO2) and exercise duration in both studies, even after restriction to cardiorespiratory healthy participants. Statistically significant associations with oxygen uptake at anaerobic threshold (VO2@AT), slope of the efficiency of ventilation in removing carbon dioxide, and peak oxygen pulse (VÉ/VCO2 slope) occurred. Further, interactions with age were identified, such that mainly older individuals with higher levels of periodontal disease severity were associated with lower peakVO2. Restricted to never smokers, associations with mean clinical attachment levels and the number of teeth mostly diminished, while associations of mean PPD with peakVO2, VO2@AT, VÉ/VCO2 slope, and exercise duration in SHIP-1 and SHIP-Trend-0 were confirmed. In SHIP-1, mean peakVO2 was 1,895 mL/min in participants with a mean PPD of 1.6 mm and 1,809 mL/min in participants with a mean PPD of 3.7 mm. To conclude, only mean PPD reflecting current disease severity was consistently linked to cardiorespiratory fitness in 2 cross-sectional samples of the general population. If confirmed in well-designed large-scale longitudinal studies, the association between periodontitis and cardiorespiratory fitness might provide a biologically plausible mechanism linking periodontitis with cardiometabolic diseases.

Is Continuous Eruption Related to Periodontal Changes? A 16-Year Follow-up.

The aims of this study were to 1) determine if continuous eruption occurs in the maxillary teeth, 2) assess the magnitude of the continuous eruption, and 3) evaluate the effects of continuous eruption on the different periodontal parameters by using data from the population-based cohort of the Study of Health in Pomerania (SHIP). The jaw casts of 140 participants from the baseline (SHIP-0) and 16-y follow-up (SHIP-3) were digitized as 3-dimensional models. Robust reference points were set to match the tooth eruption stage at SHIP-0 and SHIP-3. Reference points were set on the occlusal surface of the contralateral premolar and molar teeth, the palatal fossa of an incisor, and the rugae of the hard palate. Reference points were combined to represent 3 virtual occlusal planes. Continuous eruption was measured as the mean height difference between the 3 planes and rugae fix points at SHIP-0 and SHIP-3. Probing depth, clinical attachment levels, gingiva above the cementoenamel junction (gingival height), and number of missing teeth were clinically assessed in the maxilla. Changes in periodontal variables were regressed onto changes in continuous eruption after adjustment for age, sex, number of filled teeth, and education or tooth wear. Continuous tooth eruption >1 mm over the 16 y was found in 4 of 140 adults and averaged to 0.33 mm, equaling 0.021 mm/y. In the total sample, an increase in continuous eruption was significantly associated with decreases in mean gingival height (B = -0.34; 95% CI, -0.65 to -0.03). In a subsample of participants without tooth loss, continuous eruption was negatively associated with PD. This study confirmed that continuous eruption is clearly detectable and may contribute to lower gingival heights in the maxilla.

Impact of Powered Toothbrush Use and Interdental Cleaning on Oral Health.

The long-term effectiveness of powered toothbrushes (PTBs) and interdental cleaning aids (IDAs) on a population level is unproven. We evaluated to what extent changes in PTB and IDA use may explain changes in periodontitis, caries, and tooth loss over the course of 17 y using data for adults (35 to 44 y) and seniors (65 to 74 y) from 3 independent cross-sectional surveys of the German Oral Health Studies (DMS). Oaxaca decomposition analyses assessed to what extent changes in mean probing depth (PD), number of caries-free surfaces, and number of teeth between 1) DMS III and DMS V and 2) DMS IV and DMS V could be explained by changes in PTB and IDA use. Between DMS III and V, PTB (adults: 33.5%; seniors: 28.5%) and IDA use (adults: 32.5%; seniors: 41.4%) increased along with an increase in mean PD, number of caries-free surfaces, and number of teeth. Among adults, IDA use contributed toward increased number of teeth between DMS III and V as well as DMS IV and V. In general, the estimates for adults were of lower magnitude. Among seniors between DMS III and V, PTB and IDA use explained a significant amount of explained change in the number of caries-free surfaces (1.72 and 5.80 out of 8.44, respectively) and the number of teeth (0.49 and 1.25 out of 2.19, respectively). Between DMS IV and V, PTB and IDA use contributed most of the explained change in caries-free surfaces (0.85 and 1.61 out of 2.72, respectively) and the number of teeth (0.25 and 0.46 out of 0.94, respectively) among seniors. In contrast to reported results from short-term clinical studies, in the long run, both PTB and IDA use contributed to increased number of caries-free healthy surfaces and teeth in both adults and seniors.

Long-term tooth retention in periodontitis patients in four German university centres.

OBJECTIVES: In this retrospective study, we compared tooth loss between patients receiving periodontal therapy (PT) in four German university centres, stratified according to periodontal treatment phase. MATERIALS AND METHODS: Overall, 896 patients (Kiel (KI) n = 391; Greifswald (GW) n = 282; Heidelberg (HD) n = 174; Frankfurt a.M. (F) n = 49) were examined initially (T0), after active periodontal therapy (APT, T1) and after supportive periodontal therapy (SPT, T2). Descriptive analyses and multivariable negative binomial regression models were performed. RESULTS: Follow-up periods differed significantly between the centres, ranging between 6.7 ±â€¯3.0 (GW) and 18.2 ±â€¯5.5 (KI) years (p < 0.001). At T0, age, gender, smoking and diabetes showed notable regional distinctions (p < 0.001). However, the number of teeth per patient was similar (between 24.0 ±â€¯4.6 (F) and 24.5 ±â€¯4.1 (HD); p = 0.27). During PT, the number of extracted teeth differed significantly between centres, with greater differences during SPT (0.9 ±â€¯1.8 (GW) to 2.3 ±â€¯2.8 (KI), p < 0.001) compared to APT (0.4 ±â€¯0.9 (F) to 1.0 ±â€¯2.1 (KI), p = 0.02). Annual tooth loss during SPT remained low in all centres (between 0.10 ±â€¯0.14 (F) to 0.15 ±â€¯0.30 (HD), p < 0.001). CONCLUSION: Within the limitation of the study, PT leads to a low risk of tooth loss in all university centres irrespective of patients' baseline characteristics. CLINICAL RELEVANCE: Within the limitations of this retrospective investigation, long-term tooth retention seems to be feasible for most patients, as long as a systematic and structured treatment approach is applied.

Evaluating Modeling and Validation Strategies for Tooth Loss.

Prediction models learn patterns from available data (training) and are then validated on new data (testing). Prediction modeling is increasingly common in dental research. We aimed to evaluate how different model development and validation steps affect the predictive performance of tooth loss prediction models of patients with periodontitis. Two independent cohorts (627 patients, 11,651 teeth) were followed over a mean ± SD 18.2 ± 5.6 y (Kiel cohort) and 6.6 ± 2.9 y (Greifswald cohort). Tooth loss and 10 patient- and tooth-level predictors were recorded. The impact of different model development and validation steps was evaluated: 1) model complexity (logistic regression, recursive partitioning, random forest, extreme gradient boosting), 2) sample size (full data set or 10%, 25%, or 75% of cases dropped at random), 3) prediction periods (maximum 10, 15, or 20 y or uncensored), and 4) validation schemes (internal or external by centers/time). Tooth loss was generally a rare event (880 teeth were lost). All models showed limited sensitivity but high specificity. Patients' age and tooth loss at baseline as well as probing pocket depths showed high variable importance. More complex models (random forest, extreme gradient boosting) had no consistent advantages over simpler ones (logistic regression, recursive partitioning). Internal validation (in sample) overestimated the predictive power (area under the curve up to 0.90), while external validation (out of sample) found lower areas under the curve (range 0.62 to 0.82). Reducing the sample size decreased the predictive power, particularly for more complex models. Censoring the prediction period had only limited impact. When the model was trained in one period and tested in another, model outcomes were similar to the base case, indicating temporal validation as a valid option. No model showed higher accuracy than the no-information rate. In conclusion, none of the developed models would be useful in a clinical setting, despite high accuracy. During modeling, rigorous development and external validation should be applied and reported accordingly.

The Saliva Metabolome in Association to Oral Health Status.

Periodontitis is one of the most prevalent oral diseases worldwide and is caused by multifactorial interactions between host and oral bacteria. Altered cellular metabolism of host and microbes releases a number of intermediary end products known as metabolites. There is an increasing interest in identifying metabolites from oral fluids such as saliva to widen the understanding of the complex pathogenesis of periodontitis. It is believed that some metabolites might serve as indicators toward early detection and screening of periodontitis and perhaps even for monitoring its prognosis in the future. Because contemporary periodontal screening methods are deficient, there is an urgent need for novel approaches in periodontal screening procedures. To this end, we associated oral parameters (clinical attachment level, periodontal probing depth, supragingival plaque, supragingival calculus, number of missing teeth, and removable denture) with a large set of salivary metabolites ( n = 284) obtained by mass spectrometry among a subsample ( n = 909) of nondiabetic participants from the Study of Health in Pomerania (SHIP-Trend-0). Linear regression analyses were performed in age-stratified groups and adjusted for potential confounders. A multifaceted image of associated metabolites ( n = 107) was revealed with considerable differences according to age groups. In the young (20 to 39 y) and middle-aged (40 to 59 y) groups, metabolites were predominantly associated with periodontal variables, whereas among the older subjects (≥60 y), tooth loss was strongly associated with metabolite levels. Metabolites associated with periodontal variables were clearly linked to tissue destruction, host defense mechanisms, and bacterial metabolism. Across all age groups, the bacterial metabolite phenylacetate was significantly associated with periodontal variables. Our results revealed alterations of the salivary metabolome in association with age and oral health status. Among our comprehensive panel of metabolites, periodontitis was significantly associated with the bacterial metabolite phenylacetate, a promising substance for further biomarker research.

Effect of Periodontal Treatment on HbA1c among Patients with Prediabetes.

Evidence is limited regarding whether periodontal treatment improves hemoglobin A1c (HbA1c) among people with prediabetes and periodontal disease, and it is unknown whether improvement of metabolic status persists >3 mo. In an exploratory post hoc analysis of the multicenter randomized controlled trial "Antibiotika und Parodontitis" (Antibiotics and Periodontitis)-a prospective, stratified, double-blind study-we assessed whether nonsurgical periodontal treatment with or without an adjunctive systemic antibiotic treatment affects HbA1c and high-sensitivity C-reactive protein (hsCRP) levels among periodontitis patients with normal HbA1c (≤5.7%, n = 218), prediabetes (5.7% < HbA1c < 6.5%, n = 101), or unknown diabetes (HbA1c ≥ 6.5%, n = 8) over a period of 27.5 mo. Nonsurgical periodontal treatment reduced mean pocket probing depth by >1 mm in both groups. In the normal HbA1c group, HbA1c values remained unchanged at 5.0% (95% CI, 4.9% to 6.1%) during the observation period. Among periodontitis patients with prediabetes, HbA1c decreased from 5.9% (95% CI, 5.9% to 6.0%) to 5.4% (95% CI, 5.3% to 5.5%) at 15.5 mo and increased to 5.6% (95% CI, 5.4% to 5.7%) after 27.5 mo. At 27.5 mo, 46% of periodontitis patients with prediabetes had normal HbA1c levels, whereas 47.9% remained unchanged and 6.3% progressed to diabetes. Median hsCRP values were reduced in the normal HbA1c and prediabetes groups from 1.2 and 1.4 mg/L to 0.7 and 0.7 mg/L, respectively. Nonsurgical periodontal treatment may improve blood glucose values among periodontitis patients with prediabetes (ClinicalTrials.gov NCT00707369).

Does periodontitis affect diabetes incidence and haemoglobin A1c change? An 11-year follow-up study.

AIM: As periodontitis may contribute to the pathogenesis of diabetes, the effects of periodontitis on diabetes incidence and HbA1c change was quantified in a prospective cohort. METHODS: Data from an 11-year follow-up of the Study of Health in Pomerania were analyzed to evaluate the effects of periodontitis on incident diabetes and long-term HbA1c changes in 2047 subjects aged 20-81years. Diabetes was based on self-reported physician diagnoses, antidiabetic medication use, or HbA1c≥6.5% or non-fasting blood glucose levels ≥11.1mmol/L. To assess periodontal status, periodontal pockets were probed, and their depth and clinical attachment levels measured. For both measures, means and percentages of sites≥3mm were calculated. In addition, all probing depths≥4mm were summed (cumulative probing depth). Modified Poisson and multivariable linear models were applied, adjusted for age, gender, highest level of general education, marital status, waist circumference, physical activity, smoking status and follow-up time. RESULTS: Over a mean follow-up period of 11.1years, 207 subjects developed diabetes. Baseline mean clinical attachment levels (CAL) and probing depths (PPD) were not significantly associated with either diabetes incidence [mean CALs, fourth quartile, incidence rate ratio=0.819, 95% confidence interval (CI): 0.489-1.370; P=0.446] or long-term changes in HbA1c (mean CAL, fourth quartile, ß=-0.086, 95% CI: -0.187, -0.016; P=0.098). Sensitivity analyses using alternative exposure definitions confirmed these results. CONCLUSION: Contrary to the currently available literature, no convincing evidence was found of any potential association between periodontitis and diabetes incidence or HbA1c change.

Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study.

An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, <30%, ≥30%) with probing pocket depth (PD) ≥4 mm, and NAFLD status was determined using liver ultrasound assessment. Serum CRP levels were assayed at a central laboratory, and single-nucleotide polymorphisms previously identified through genome-wide association studies as robustly associated with serum CRP were combined into a weighted genetic CRP score (wGSCRP). Logistic regression models estimated the association between periodontitis and NAFLD within strata of serum CRP and separately within strata of the wGSCRP. The prevalence of NAFLD was 26.4% (95% confidence interval [CI], 24.6, 28.1) while 17.8% (95% CI, 16.0-19.6) had ≥30% of sites with PD ≥4 mm. Whereas the wGSCRP was not a modifier ( Pinteraction = 0.8) on the multiplicative scale, serum CRP modified the relationship between periodontitis and NAFLD ( Pinteraction = 0.01). The covariate-adjusted prevalence odds ratio of NAFLD comparing participants with ≥30% of sites with PD ≥4 mm to those with no site affected was 2.39 (95% CI, 1.32-4.31) among participants with serum CRP <1 mg/L. The corresponding estimate was 0.97 (95% CI, 0.57-1.66) for participants with serum CRP levels of 1 to 3 mg/L and 1.12 (95% CI, 0.65-1.93) for participants with serum CRP >3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.

Exome Variant Analysis of Chronic Periodontitis in 2 Large Cohort Studies.

Periodontitis is characterized by inflammation of the gingival tissue. The main risk factors are socioeconomic factors, sex, age, smoking, and diabetes, but periodontal disease has also a genetic background. Previous genome-wide association studies failed to reveal genome-wide significant associations of single common single-nucleotide polymorphisms with chronic periodontitis. Using the Illumina ExomeChip data of 6,576 participants of the German population-based cohort studies Study of Health in Pomerania (SHIP) and SHIP-Trend, the authors performed single variant and also gene-based association studies of rare and common exonic variations on different periodontal case definitions. Although our study comprised the largest sample size to date to assess genetic predisposition for chronic periodontitis, the authors found no significant association. This study emphasizes that for chronic periodontitis, large sample sizes will be necessary to find genetic associations, even when examining rare genetic variants.

Association of Periodontal Destruction and Diabetes with Mortality.

Current evidence indicates the effects of periodontitis on diabetes as well as mortality, for which diabetes itself represents a risk factor. However, the possible interaction of these 2 chronic conditions regarding mortality has not yet been investigated. Therefore, the purpose of this study was to evaluate whether periodontal destruction interacts with diabetes on all-cause and cardiovascular disease (CVD) mortality or if diabetes serves as a mediator in this association. The study sample comprised 3,327 participants aged 20 to 81 y from the Study of Health in Pomerania. Periodontal destruction was assessed via clinical attachment level (CAL) and the number of missing teeth. Information on mortality (date and ICD-10 code) was ascertained from death certificates. Directed acyclic graphs were used to identify potential confounders, and Cox proportional hazard models were applied. In 36,701 person-years of follow-up, 263 study participants deceased, 89 due to CVD. Fully adjusted main effect models resulted in hazard ratios of 1.01 (95% confidence interval [95% CI]: 1.002 to 1.01) for extent of CAL ≥3 mm, 1.10 (95% CI: 1.03 to 1.18) for mean CAL, and 1.03 (95% CI: 1.01 to 1.04) for the number of missing teeth regarding all-cause mortality. Analogous results were obtained for CVD mortality, with hazard ratios of 1.01 (95% CI: 0.99 to 1.02), 1.10 (95% CI: 0.98 to 1.23), and 1.02 (95% CI: 0.99 to 1.05) for extent of CAL, mean CAL, and the number of missing teeth, respectively. Findings did not indicate additive interaction of periodontal destruction and diabetes regarding all-cause and CVD mortality. Similarly, no substantial evidence was found to demonstrate the presence of multiplicative interaction or mediation. Besides adjustment for baseline covariates, time-varying covariates were also considered and led to comparable results. In summary, despite their reciprocal relationship, periodontal destruction and diabetes may be independent risk factors for all-cause and CVD mortality.

Reduced Bone Stiffness in Women Is Associated with Clinical Attachment and Tooth Loss: The Study of Health in Pomerania.

The authors evaluated the association of reduced bone stiffness of the calcaneus with clinical attachment loss (CAL) and tooth loss. The authors analyzed data from 4,678 subjects (2,384 women), aged 20 to 88 y, from the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) and the baseline examination of the SHIP-Trend cohort. Bone stiffness, characterized by the stiffness index (SI) and the osteoporotic fracture risk (OFR), was assessed by quantitative ultrasound of the heel. SI and OFR were significantly associated with the mean CAL in women. While 1) the SI showed a significant association with the mean CAL and 2) the OFR with the median number of teeth in just the postmenopausal women, the OFR showed a significant association with mean CAL for both pre- and postmenopausal women. In postmenopausal women, a 10-unit increase in the SI was associated with a decrease in the mean CAL of 0.05 mm (95% confidence interval [CI]: -0.10 to 0.00; P = 0.046). Moreover, the adjusted median number of teeth was 21.4 (95% CI: 20.9 to 21.9) among the postmenopausal women with a low OFR, while it was 19.1 (95% CI: 17.8 to 20.3; P = 0.001) among the postmenopausal women with a high OFR. For the premenopausal women with a low OFR, the mean CAL was 1.60 mm (95% CI: 1.53 to 1.66), while for the premenopausal women with a high OFR, it was 2.24 mm (95% CI: 1.78 to 2.69; P = 0.006). Reduced bone stiffness was associated with clinical attachment and tooth loss in women but not in men.

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.

Sex Differences of Tooth Loss and Obesity on Systemic Markers of Inflammation.

Sex-specific differences in the incidence of periodontitis and tooth loss may be related to different phenotypes of obesity and their associations with low-grade inflammation. The aim of this study was to evaluate associations of adiposity and low-grade inflammation with tooth loss in men and women. Follow-up data of 2,714 participants from the cohort of Study of Health in Pomerania were analyzed for anthropometric measures, periodontitis, tooth loss, C-reactive protein (CRP), and interleukin 6. Regression analyses were used to estimate the effect of obesity on tooth loss within sex strata. During the follow-up period, men lost more teeth in relation to their obesity status than did women. In contrast, there was a steeper increase in CRP levels across obesity levels in women as compared to men. Incidence rate ratio (IRR) of tooth loss associated with elevated CRP, however, was higher in men (IRR = 1.50; 95% confidence interval [CI]: 1.27, 1.77) than women (IRR = 1.18; 95% CI: 1.02, 1.37). Negative binomial regression with number of lost teeth as outcome revealed dose-response dependencies on body mass index and waist-to-hip ratio. Adjusted for covariates, the IRR of tooth loss associated with the third tertile of waist-to-hip ratio was 1.37 (95% CI: 1.04, 1.80) and 1.53 (95% CI: 1.14, 2.05) in men and women, respectively. Tooth loss related to CRP cutoff of 2 mg/L was significant in men (IRR = 1.33; 95% CI: 1.07, 1.66; p = .006) but not in women (IRR = 0.92; 95% CI: 0.73, 1.17; p = .689). This study suggests that both adiposity and subclinical inflammation affect tooth loss, with distinct differences between men and women. Obesity as a risk factor of tooth loss is particularly related to CRP in men but not in women.