Serum lipoprotein subfractions are associated with the periodontal status: Results from the population-based cohort SHIP-TREND.

AIM: To investigate the medium-term associations of serum protein subfractions derived from proton nuclear magnetic resonance (1 H-NMR) spectroscopy with periodontitis and tooth loss. MATERIALS AND METHODS: A total of 3031 participants of the cohort Study of Health in Pomerania (SHIP-TREND) were included. In addition to conventional serum testing, serum lipoprotein contents and subfractions were analysed by 1 H-NMR spectroscopy. Confounder-adjusted associations of lipoprotein variables with periodontitis and the number of missing teeth variables were analysed using mixed-effects models with random intercepts for time across individuals, accounting for multiple testing. RESULTS: While only spurious associations between lipoprotein levels from conventional blood tests were found-that is, triglycerides were associated with mean clinical attachment level (CAL) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with the number of missing teeth - several associations emerged from serum lipoprotein subfractions derived from 1 H-NMR analysis. Specifically, elevated LDL triglycerides were associated with higher levels of mean probing depth (PD), mean CALs, and increased odds of having <20 teeth. HDL-4 cholesterol levels were inversely associated with mean PD. Systemic inflammation (C-reactive protein) might mediate the effects of LDL and HDL triglyceride contents on periodontitis severity. CONCLUSIONS: Several associations between serum lipoprotein subfractions and periodontitis were observed. As the underlying biochemical mechanisms remain unclear, further research is needed.

Periodontitis and systemic inflammation as independent and interacting risk factors for mortality: evidence from a prospective cohort study.

BACKGROUND: Recent studies have highlighted the role of low-grade systemic inflammation in linking periodontitis to cardiovascular disease (CVD) outcomes, but many aspects remain unclear. This study examines the independent and reciprocal associations of periodontitis and low-grade systemic inflammation with all-cause and CVD mortality in a large-scale cohort. METHODS: A total of 3047 participants from the prospective, population-based Study of Health in Pomerania (SHIP-START) were followed for a period of 13.0 ± 2.4 years. For the association between various inflammation/periodontitis measures and mortality, hazard ratios (HRs) were obtained from covariate-adjusted Cox proportional hazards models. Interactions were analysed in joint models: on the multiplicative scale, HRs were reported and on the additive scale, relative excess risks due to interaction (RERI) were calculated. Subject and variable-specific interval records were used to account for time-varying exposures and covariates. RESULTS: During the observation period, 380 (12.5%) individuals died from CVD (n = 125) or other causes (n = 255). All markers of periodontitis and inflammation showed apparent associations with all-cause mortality (HRs per SD-increase: mean PPD: 1.068 (95% confidence interval (CI): 0.988-1.155), mean CAL: 1.205 (95% CI: 1.097-1.323), missing teeth: 1.180 (95% CI: 1.065-1.307), periodontitis score: 1.394 (95% CI: 1.202-1.616), leukocytes: 1.264 (95% CI: 1.163-1.374), fibrinogen: 1.120 (95% CI: 1.030-1.218), CRP: 1.231 (95% CI: 1.109-1.366), inflammation score: 1.358 (95% CI: 1.210-1.523)). For CVD mortality, all PPD related variables showed significant associations. Interaction modelling revealed some variation with respect to mortality type and exposure combinations. On the additive scale, RERIs for periodontitis score and inflammation score implied 18.9% and 27.8% excess mortality risk for all-cause and CVD mortality, respectively. On the multiplicative scale, the HRs for interaction were marginal. CONCLUSIONS: Both periodontitis and inflammation were significantly associated with all-cause mortality and CVD mortality. On the additive scale, a substantial excess risk was observed due to the interaction of periodontitis and inflammation, suggesting that the greatest treatment benefit may be achieved in patients with both periodontitis and high systemic inflammation. As periodontal therapy has been reported to also reduce systemic inflammation, the possibility of a reduction in CVD mortality risk by anti-inflammatory treatments, including periodontal interventions, seems worthy of further investigation.

Association between bone turnover markers and periodontitis: A population-based cross-sectional study.

AIM: To examine the associations between bone turnover markers and periodontitis in two cross-sectional population-based studies. MATERIALS AND METHODS: We used data from two independent adult samples (N = 4993), collected within the Study of Health in Pomerania project, to analyse cross-sectional associations of N-procollagen type 1 amino-terminal propeptide (P1NP), C-terminal cross-linking telopeptide, osteocalcin, bone-specific alkaline phosphatase (BAP), fibroblast growth factor 23, wingless-type mouse mammary tumour virus integration site family member 5a (WNT5A), and sclerostin values with periodontitis. Confounder-adjusted gamma and fractional response regression models were applied. RESULTS: Positive associations were found for P1NP with mean pocket probing depth (PPD; eß=1.008 ; 95% confidence interval [CI]: 1.001-1.015), mean clinical attachment loss (mean CAL; eß=1.027 ; 95% CI: 1.011-1.044), and proportion of sites with bleeding on probing (%BOP; eß=1.055 ; 95% CI: 1.005-1.109). Similar associations were seen for BAP with %BOP ( eß=1.121 ; 95% CI: 1.042-1.205), proportion of sites with PPD ≥4 mm (%PPD4) ( eß=1.080 ; 95% CI: 1.005-1.161), and sclerostin with %BOP ( eß=1.308 ; 95% CI: 1.005-1.704). WNT5A was inversely associated with mean PPD ( eß=0.956 ; 95% CI: 0.920-0.993) and %PPD4 ( eß=0.794 ; 95% CI: 0.642-0.982). CONCLUSIONS: This study revealed scattered associations of P1NP, BAP, WNT5A, and sclerostin with periodontitis, but the results are contradictory in the overall context. Associations reported in previous studies could not be confirmed.

Salivary metabolites associated with a 5-year tooth loss identified in a population-based setting.

BACKGROUND: Periodontitis is among the most common chronic diseases worldwide, and it is one of the main reasons for tooth loss. Comprehensive profiling of the metabolite content of the saliva can enable the identification of novel pathways associated with periodontitis and highlight non-invasive markers to facilitate time and cost-effective screening efforts for the presence of periodontitis and the prediction of tooth loss. METHODS: We first investigated cross-sectional associations of 13 oral health variables with saliva levels of 562 metabolites, measured by untargeted mass spectrometry among a sub-sample (n = 938) of the Study of Health in Pomerania (SHIP-2) using linear regression models adjusting for common confounders. We took forward any candidate metabolite associated with at least two oral variables, to test for an association with a 5-year tooth loss over and above baseline oral health status using negative binomial regression models. RESULTS: We identified 84 saliva metabolites that were associated with at least one oral variable cross-sectionally, for a subset of which we observed robust replication in an independent study. Out of 34 metabolites associated with more than two oral variables, baseline saliva levels of nine metabolites were positively associated with a 5-year tooth loss. Across all analyses, the metabolites 2-pyrrolidineacetic acid and butyrylputrescine were the most consistent candidate metabolites, likely reflecting oral dysbiosis. Other candidate metabolites likely reflected tissue destruction and cell proliferation. CONCLUSIONS: Untargeted metabolic profiling of saliva replicated metabolic signatures of periodontal status and revealed novel metabolites associated with periodontitis and future tooth loss.

Competing interplay between systemic and periodontal inflammation: obesity overrides the impact of oral periphery.

OBJECTIVES: We aimed at investigating whether the interaction between the local inflammation, periodontitis, and obesity is independently associated with systemic inflammation. METHODS: From the population-based Study of Health in Pomerania, 3366 participants, without (2366) and with (1000) obesity, were studied for the association of periodontitis, measured as probing depth (PD) and plaque together with body mass index (BMI) on C-reactive protein (CRP). Quantile regression was used to evaluate the association between periodontal, anthropometric, and inflammatory variables (outcomes). RESULTS: The overall prevalence of obesity in this adult population was 31.4% in men and 28.1% in women. Both PD and plaque were positively associated with CRP, revealing an increasing impact across the CRP concentration distribution. Adjusting the regression of CRP or fibrinogen on PD for waist circumference attenuated but did not abolish the PD coefficients. Dental plaque was similarly associated with these interrelations. Association between PD and a dental plaque was different among participants with low-, medium-, or high-risk CRP concentrations. CONCLUSION: Local and systemic sources of inflammation contribute to blood levels of inflammatory markers. The respective contributions depend on the relative rate in each of the inflammation-inducing risks and are dominated by adiposity. CLINICAL RELEVANCE: Keeping systemic inflammation low in order to prevent age-related disease sequelae.

Long-term Association of Periodontitis With Decreased Kidney Function.

RATIONALE & OBJECTIVE: Previous studies have yielded inconclusive findings regarding the relationship between periodontitis and kidney function. We sought to investigate whether periodontitis is associated with subsequent decreases in kidney function (reductions in estimated glomerular filtration rate [eGFR] and increased urinary albumin-creatinine ratio [UACR]) in the general population. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: We used baseline and 11-year follow-up data from 2,297 and 1,512 adult participants, respectively, in the Study of Health in Pomerania (SHIP). Age range was limited to 20 to 59 years to avoid the potential influence of tooth loss. EXPOSURES: Periodontal status defined by periodontal pocket probing depth (PPD) and clinical attachment level. Mean levels and the percentage of sites ≥ 3mm was determined for either all sites (PPD) or interproximal sites (clinical attachment level). All PPDs≥4mm were summed to calculate the total PPD. OUTCOMES: GFR estimated from serum creatinine and serum cystatin C (eGFRcr-cys). Moderately increased albuminuria defined as UACR>30mg/g. ANALYTICAL APPROACH: Adjusted linear and logistic mixed regression models. RESULTS: At baseline and follow-up, average eGFRcr-cys was 118.3 and 105.0mL/min/1.73m2, respectively. Using mixed models, no consistently significant associations between periodontitis variables and eGFRcr-cys were detected. Long-term changes in UACR were inconsistently associated with periodontitis measures. After imputation of missing data, associations were either attenuated or no longer detectable. LIMITATIONS: Because periodontal assessments were performed using a partial recording protocol, periodontal disease severity estimates might have been underestimated, resulting in attenuated effect estimates. CONCLUSIONS: We found no consistent evidence for an association between periodontitis and decreased kidney function. In contrast to previous studies, these results do not support the hypothesis that periodontitis is an important risk factor for chronic kidney disease.

Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes.

BACKGROUND: Measuring the glucose concentration in whole blood samples is critical due to unsatisfactory glycolysis inhibition. Previous studies showed that Terumo tubes were superior, but they were taken off the European market in 2016 and alternatives were required. This initiated the present evaluation of glucose stability in five available tube types. METHODS: Venous blood samples were collected from 61 healthy volunteers to test tubes supplied by Terumo (two sets), Greiner FC-Mix, BD FX-Mixture and BD serum. After sampling, the contents were thoroughly mixed and centrifuged within an hour. The glucose concentrations were determined and the samples resuspended except for BD serum tubes (gel barrier). The first 30 samples were stored at room temperature and the remaining 31 at 4°C. After 24, 48, 72 and 96 h, all tubes were (re)centrifuged, and glucose concentration measurements were repeated. RESULTS: Changes in glucose concentrations over time differed significantly between the investigated tube types and to a certain extent between the two storing conditions. Glycolysis was most evident in the BD FX-mixture tubes. Good glucose stability was observed in samples retrieved form BD serum and Greiner tubes. The stability in both Terumo tubes was comparable to that in other studies. Although Greiner and both Terumo tubes are supposed to contain the same glycolysis inhibitor, glucose stability differed between these tubes. CONCLUSIONS: We showed that Greiner is an acceptable alternative to Terumo and that glucose in serum that was rapidly separated from corpuscles by a gel barrier is stable for an extended time.

Prospective association of sex steroid concentrations with periodontal progression and incident tooth loss.

AIM: The aim of this study was to determine the prospective association between sex steroid concentrations with periodontal progression and incident tooth loss in men and women. METHODS: We used data from 1465 women and 1838 men (age 20-81 years) with completed five-year-follow-up from the Study-of-Health-in-Pomerania, a population-based longitudinal cohort. Serum levels of total testosterone (TT) and other sex steroids were measured. Mean clinical attachment loss (CAL) and the number of teeth were assessed. Generalized regression models were implemented for cross-sectional and longitudinal analyses, adjusting for age, education, smoking, waist circumference, diabetes, physical activity, blood sampling time and time between baseline and follow-up. RESULTS: Fully adjusted models revealed no consistent associations between TT and mean CAL, neither in cross-sectional [men: ß = -0.0004 (-0.023;0.022), p = 0.97; women: ß = -0.033 (-0.057; -0.009), p = 0.006] nor in longitudinal analyses [men: ß = -0.033 (-0.100;0.034), p = 0.33; women: ß = -0.023 (-0.086;0.040), p = 0.47]. For tooth loss, neither cross-sectional nor longitudinal associations with any of the sex steroid concentrations were found. CONCLUSIONS: No consistent associations of sexual steroids with periodontal progression or tooth loss were found. Further cohort studies are necessary to evaluate possible associations between endocrinological parameters, like supra- or subphysiologic testosterone concentrations, and periodontal progression or tooth loss.

Longitudinal effects of systemic inflammation markers on periodontitis.

AIM: Systemic low-grade inflammation represents a central hallmark of chronic diseases and has been proposed as the underlying mechanism linking factors like obesity or diabetes with periodontitis. However, the impact of inflammatory markers on periodontitis has not yet been investigated. MATERIALS AND METHODS: The study population comprised 1784 subjects from the Study of Health in Pomerania with complete 11-year follow-up. Fibrinogen and white blood cell (WBC) counts were measured as markers of inflammation. Periodontitis was assessed by probing depth (PD), clinical attachment loss (CAL) and the CDC/AAP case definition. RESULTS: Multilevel regression analyses revealed significant coefficients for the impact of both inflammation markers on the percentage of sites with PD/CAL ≥ 3 mm. Increases in fibrinogen about 1 g/l were associated with 3.0% and 2.7% more sites with PD/CAL ≥ 3 mm respectively. Consistent associations were found using mean values of PD/CAL but not using missing teeth or caries. Regarding the CDC/AAP case definition, 11-year changes in fibrinogen and WBC counts were significantly associated with ≥1 category progression (OR: 1.36 and 1.11). CONCLUSIONS: Fibrinogen levels and WBC counts showed consistent long-term associations with PD, CAL and the CDC/AAP case definition. Results indicate that systemic low-grade inflammation might indeed represent one possible pathway for effects of obesity, diabetes or other chronic inflammatory conditions on periodontitis.

Genome-wide association study of chronic periodontitis in a general German population.

AIM: To identify loci associated with chronic periodontitis through a genome-wide association study (GWAS). MATERIALS AND METHODS: A GWAS was performed in 4032 individuals of two independent cross-sectional studies of West Pomerania (SHIP n = 3365 and SHIP-TREND n = 667) with different periodontal case definitions. Samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 or the Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000 Genome-based autosomal and X-chromosomal genotypes and short insertions and deletions (INDELs) was performed in both cohorts. Finally, more than 17 million SNPs and short INDELs were analysed. RESULTS: No genome-wide significant associations were found for any periodontitis case definition, regardless of whether individuals aged >60 years where excluded or not. Despite no single SNP association reached genome-wide significance, the proportion of variance explained by additive effects of all common SNPs was around 23% for mean proximal attachment loss. Excluding subjects aged >60 years increased the explained variance to 34%. CONCLUSIONS: No single SNPs were found to be genome-wide significantly associated with chronic periodontitis in this study.

The relationship between cortisol awakening response and trait resilience in two patient cohorts and one population-based cohort.

OBJECTIVES: We examined (1) the proportion of cortisol awakening non-responders, (2) the association between cortisol awakening response (CAR) and trait resilience, and (3) the association between CAR increase and trait resilience in two patient cohorts (depression and myocardial infarction [CVD]) and one population-based cohort. METHODS: Eight hundred and eighty study participants delivered CAR scores (response and increase) based on three self-collected saliva samples and a trait resilience score. Descriptive data of CAR non-responders were reported and calculated. Associations between CAR response/increase and trait resilience, sociodemographic and compliance variables were evaluated using multiple logistic and multiple linear regression analyses stratified by cohort. RESULTS: The proportion of CAR non-responders was high in all cohorts (57% depression cohort, 53.4% CVD cohort, 51.6% control cohort). In the depression cohort age was associated with CAR response and increase. In the CVD cohort salivary collection on a weekday was associated with CAR response and awakening time with CAR increase. In the control cohort age was associated with CAR response and sex with CAR increase. CONCLUSIONS: We observed many CAR non-responders and significant associations between CAR response and CAR increase with single sociodemographic and compliance variables. We did not find significant relationships between CAR response or increase and trait resilience.

Cortisol and periodontitis: Prospective observational and Mendelian randomization studies.

Purpose: Cortisol has obesogenic, hyperglycemic and immunomodulating effects. Preclinical and observational research suggested that it is associated with periodontitis but the evidence for potential causality in humans is sparse. We triangulated results from prospective observational and Mendelian randomization (MR) analyses to further explore this. Methods: Using pooled data from 3,388 participants of two population cohort studies embedded in the Study of Health in Pomerania (SHIP) project, we associated serum cortisol levels with periodontal outcomes measured after a median follow-up time of 6.9 years, adjusting for confounding and selection bias using propensity score weighting and multiple imputation. We further examined the effect of genetically proxied plasma morning cortisol levels on periodontitis using two-sample MR of 17,353 cases and 28,210 controls. Results: In SHIP, we found that cortisol levels were positively associated with follow-up levels of mean clinical attachment level (CAL), deep interdental CAL and bleeding on probing but were unrelated to mean probing pocket depth and deep periodontal pockets. In MR analysis, cortisol was not associated with periodontitis. Conclusion: The observational study revealed a prospective association of spot cortisol with makers of periodontitis. Contrary to observational studies, genetically instrumented, long-term cortisol was unrelated to periodontitis. Our results find no univocal evidence that cortisol plays a role in periodontitis pathology, casting doubt on cortisol-related pathways.

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.

Individual predisposition and the intricate interplay between systemic biomarkers and periodontal risk in a general population.

BACKGROUND: Increasing age is associated with systemic diseases as well as with periodontal diseases. We wondered whether a biological age score constructed exclusively from systemic biomarkers would reflect periodontal risk factors at baseline and tooth loss as well as periodontal outcome during 10 years follow-up. METHODS: From the Study of Health in Pomerania (SHIP) 2256 participants (1072 male, 1184 female) were studied for the relationship of the systemic biomarkers glycated hemoglobin (HbA1c), low density lipoprotein cholesterol (LDL), fibrinogen, white blood cell count, blood pressure, and waist circumference to their age. Construction of a biological age (BA) score allowed its comparison with the participants' actual chronological age (CA) and their predisposition to periodontal disease. RESULTS: Though nearly identical in CA, participants appearing younger than their true age had a significantly reduced burden of periodontal risk factors. If BA > CA, then risk factors were more frequent including smoking, oral hygiene, dental visits, education, and income. After 10 years, in participants with identical CA, tooth loss followed their BA calculated at baseline, that is, with BA > CA fewer teeth were preserved. Similarly, periodontal measures varied according to BA; sex differences were obvious. Most significant were BA-related differences in inflammatory and anthropometry parameters. CONCLUSIONS: The results support the assumption that risk profiles aggregated in BA constitute a characteristic susceptibility pattern unique to each individual, common to both systemic and periodontal diseases. Although BA was constructed exclusively from systemic measures at baseline, BA reflects the oral conditions at follow-up.

Increased Sphingosine-1-Phosphate Serum Concentrations in Subjects with Periodontitis: A Matter of Inflammation.

PURPOSE: Periodontitis is an inflammatory disease of the oral cavity with an alarmingly high prevalence within the adult population. The signaling lipid sphingosine-1-phosphate (S1P) plays a crucial role in inflammatory and immunomodulatory responses. In addition to cardiovascular disease, sepsis and tumor entities, S1P has been recently identified as both mediator and biomarker in osteoporosis. We hypothesized that S1P may play a role in periodontitis as an inflammation-prone bone destructive disorder. The goal of our study was to evaluate associations between periodontitis and S1P serum concentrations in the Study of Health in Pomerania (SHIP)-Trend cohort. In addition, we investigated the expression of S1P metabolizing enzymes in inflamed gingival tissue. PATIENTS AND METHODS: We analyzed data from 3371 participants (51.6% women) of the SHIP-Trend cohort. Periodontal parameters and baseline characteristics were assessed. Serum S1P was measured by liquid chromatography tandem mass spectrometry. The expression of S1P metabolizing enzymes was determined by immunofluorescence staining of human gingival tissue. RESULTS: S1P serum concentrations were significantly increased in subjects with both moderate and severe periodontitis, assessed as probing depth and clinical attachment loss. In contrast, no significant association of S1P was seen with caries variables (number and percentage of decayed or filled surfaces). S1P concentrations significantly increased with increasing high-sensitivity C-reactive protein (hs-CRP) levels. Interestingly, inflamed compared to normal human gingival tissue exhibited elevated expression levels of the S1P-generating enzyme sphingosine kinase 1 (SphK1). CONCLUSION: We report an intriguingly significant association of various periodontal parameters with serum levels of the inflammatory lipid mediator S1P. Our data point towards a key role of S1P during periodontitis pathology. Modulation of local S1P levels or its signaling properties may represent a potential future therapeutic strategy to prevent or to retard periodontitis progression and possibly reduce periodontitis-related tooth loss.

Association between type 1 and type 2 diabetes with periodontal disease and tooth loss.

AIM: The aim of this study was to determine whether both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) are associated with increased prevalence and extent of periodontal disease and tooth loss compared with non-diabetic subjects within a homogeneous adult study population. MATERIAL AND METHODS: T1DM, T2DM and non-diabetic subjects were recruited from the population-based Study of Health in Pomerania. Additionally, T1DM subjects were retrieved from a Diabetes Centre. The total study population comprised 145 T1DM and 2647 non-diabetic subjects aged 20-59 years, and 182 T2DM and 1314 non-diabetic subjects aged 50-81 years. Periodontal disease was assessed by attachment loss (AL) and the number of missing teeth. RESULTS: Multivariable regression revealed an association between T1DM (p<0.001) and T2DM (p<0.01) with mean AL after full adjustment. After age stratification (p=0.04 for interaction), the effect of T2DM was only statistically significant in the 60-69-year-old subjects (B=0.90 (95% confidence intervals [95% CI]; 0.49, 1.31). T1DM was positively associated with tooth loss (adjusted, p<0.001). The association between T2DM and tooth loss was statistically significant only for females (odds ratios=1.60 [95% CI: 1.10, 2.33]). CONCLUSIONS: Our study confirmed an association between both T1DM and T2DM with periodontitis and tooth loss. Therefore, oral health education should be promoted in diabetic subjects.

Women are periodontally healthier than men, but why don't they have more teeth than men?

OBJECTIVE: Periodontal diseases are more prevalent in men than in women. However, in a population-based epidemiological study, we found that, on average, women have fewer teeth than men. The aim of this study was to test different hypotheses that could explain this obvious paradox. DESIGN: In 4,290 randomly selected participants from the normal population (Study of Health in Pomerania), we determined diagnostic periodontal parameters, attachment loss, and number of teeth. Behavioral and environmental risk factors were assessed by interviews and questionnaires. Use of estrogens was assessed, and urinary excretion of collagen cross-links was determined. RESULTS: Multiple regression analyses adjusted for caries and periodontitis revealed that in the women of this population, there is an inverse association between the number of children born and the number of teeth (P < 0.01). This relationship depends on socioeconomic status, bone metabolism, and the use of estrogens. In the group of the youngest (20-40 years), the bone turnover rate is positively related to the number of children born (P < 0.01). In postmenopausal women treated with estrogens, the number of teeth was higher than in men of the same age group. Only in women without hormone treatment were there fewer teeth. CONCLUSION: The apparent paradox of having fewer teeth despite better periodontal health in women compared with men is related to an increased bone turnover rate and socioeconomic conditions such as low education and low social status. Periodontal health is even worse if these factors are combined.

Mortality is associated with inflammation, anemia, specific diseases and treatments, and molecular markers.

Lifespan is a complex trait, and longitudinal data for humans are naturally scarce. We report the results of Cox regression and Pearson correlation analyses using data of the Study of Health in Pomerania (SHIP), with mortality data of 1518 participants (113 of which died), over a time span of more than 10 years. We found that in the Cox regression model based on the Bayesian information criterion, apart from chronological age of the participant, six baseline variables were considerably associated with higher mortality rates: smoking, mean attachment loss (i.e. loss of tooth supporting tissue), fibrinogen concentration, albumin/creatinine ratio, treated gastritis, and medication during the last 7 days. Except for smoking, the causative contribution of these variables to mortality was deemed inconclusive. In turn, four variables were found to be associated with decreased mortality rates: treatment of benign prostatic hypertrophy, treatment of dyslipidemia, IGF-1 and being female. Here, being female was an undisputed causative variable, the causal role of IFG-1 was deemed inconclusive, and the treatment effects were deemed protective to the degree that treated subjects feature better survival than respective controls. Using Cox modeling based on the Akaike information criterion, diabetes, mean corpuscular hemoglobin concentration, red blood cell count and serum calcium were also associated with mortality. The latter two, together with albumin and fibrinogen, aligned with an"integrated albunemia" model of aging proposed recently.

Tooth loss, periodontitis, and statins in a population-based follow-up study.

BACKGROUND: Statins, frequently prescribed in lipid-lowering therapies, seem to have additional beneficial effects on periodontitis and tooth loss. If this is true, then chronic treatment with statins should also result in diminished tooth loss as a long-term response. METHODS: A 5-year population-based follow-up study of tooth loss was performed comparing participants treated with statins (n = 134) with those not on the drugs (Study of Health in Pomerania). Negative binomial regression models were used to analyze the count variable of the outcome, including risk factors for tooth loss and measures of cholesterol metabolism. RESULTS: When adjusted for age and sex, statins were associated with reduced tooth loss during the follow-up period (incidence risk ratio [IRR] = 0.70, 95% confidence interval [CI] = 0.50 to 0.99, P = 0.04). When additionally adjusted for risk factors of periodontal breakdown, IRR was 0.72 (95% CI = 0.52 to 1.01). There was significant interaction with low-density lipoprotein cholesterol (LDL-c) at baseline. After stratification by LDL-c, statins were associated with reduced tooth loss, resulting in IRR = 0.89 (95% CI = 0.44 to 1.83) and 0.64 (95% CI = 0.43 to 0.95), P = 0.03, at LDL-c concentrations ≤100 mg/dL and >100 mg/dL (2.58 mmol/L), respectively. The data also showed reduced tooth loss associated with the 5-year reduction in LDL-c levels on a mmol/L basis and independently of statins (IRR = 0.87, 95% CI = 0.80 to 0.96, P = 0.004). CONCLUSION: Long-term treatment with systemically administered statins may have the beneficial effect of protecting against tooth loss.

Abdominal obesity modifies long-term associations between periodontitis and markers of systemic inflammation.

OBJECTIVE: Periodontitis is considered to promote atherosclerosis and cardiovascular diseases through increased low-grade systemic inflammation. However, there is no information on the long-term impact of periodontitis on systemic inflammation from cohort studies. Thus, this study aims to assess the impact of periodontitis on systemic inflammation (fibrinogen and white blood cells (WBC)) in a population-based longitudinal survey in north-eastern Germany. METHODS: The study sample comprised 2622 subjects from the Study of Health in Pomerania with complete 5- and 11-year follow-ups. Periodontitis was assessed by probing depth and clinical attachment level. Multilevel regression analyses were applied to evaluate associations between periodontitis measures and i) fibrinogen/WBC count using 11-year follow-up data and ii) respective z-scores of fibrinogen/WBC count using 5- and 11-year follow-up data. We adjusted for common cardiovascular risk factors and stratified analyses by abdominal obesity (P for interaction <0.10). RESULTS: In lean subjects, beta-coefficients of mean probing depth were B = 0.13 (0.08-0.019; P < 0.001) for fibrinogen and B = 0.50 (0.37-0.64; P < 0.001) for WBC count using 11-year follow-up data only. For lean subjects, models using z-scores confirmed that increased mean probing depths were associated with increased fibrinogen z-scores (B = 0.14 (0.09-0.18; P < 0.001)) and increased WBC z-scores (B = 0.16 (0.11-0.20; P < 0.001)). Consistent results were found for mean clinical attachment levels. For abdominally obese subjects, relations between periodontitis measures and levels of inflammation markers were less pronounced or non-significant. CONCLUSION: Modified by abdominal obesity, periodontitis affected systemic inflammation in a significant dose-dependent manner. Results contribute to the discussion on how periodontitis is linked to atherosclerosis and cardiovascular diseases.