A Mendelian randomization study on the association of bone mineral density with periodontitis.

OBJECTIVE: Observational studies indicated that individuals with osteoporosis could be at an increased risk of periodontitis. This study aimed to investigate whether there is a causal association of bone mineral density (BMD) with periodontitis using Mendelian randomization (MR). MATERIALS AND METHODS: Summary statistics were sourced from genome-wide association study on BMD measured at different skeletal sites, including estimated heel BMD (eBMD, N = 426,824), forearm BMD (FA-BMD, N = 8143), femoral neck BMD (FN-BMD, N = 32,735), and lumbar spine BMD (LS-BMD, N = 28,498). Genetic variants of periodontitis (N = 45,563) and loose teeth (N = 461,031) were used as outcome surrogates. Inverse variance weighted meta-analysis (IVW) was adopted as main analyses. Other sensitivity MR approaches were used to boost power and account for pleiotropy. RESULTS: IVW results suggested no evidence for a causal association of any phenotypes of BMD with periodontitis (eBMD, odds ratio [OR] = 0.984, 95% confidence interval [CI] = 0.885-1.083; FA-BMD, OR = 1.028, 95%CI = 0.864-1.193; FN-BMD, OR = 1.033, 95%CI = 0.896-1.169; LS-BMD, OR = 0.991, 95%CI =0.878-1.103; all P > 0.65). Such null associations were consistent through other sensitivity MR approaches. Similarly, no significant causal effects of BMD on loose teeth were found. CONCLUSIONS: Within the limitation of the study, our MR estimates suggested that a decreased BMD is unlikely to substantially increase the risk of periodontitis.

Mendelian randomization highlights the causal association of obesity with periodontal diseases.

AIM: The underlying mechanisms connecting obesity and periodontal diseases remain unclear. This study investigates the potential causal association of obesity with periodontal diseases using Mendelian randomization (MR). MATERIALS AND METHODS: Single-nucleotide polymorphisms of obesity traits including body mass index (BMI), waist circumference (WC), and WC adjusted for BMI (WCadjBMI) from large-scale genome-wide association studies were screened for instrumental variables. The single trait periodontitis and the combined trait comprising periodontitis and loose teeth were adopted as surrogates for periodontal diseases. Inverse-variance weighted (IVW), series of sensitivity analyses and multivariable MR were employed to determine the association of obesity with periodontal diseases. RESULTS: IVW results showed that per 1-SD increment in BMI (odds ratio, OR = 1.115; 95% confidence interval [CI] = 1.064-1.169; p < .001) and WC (OR = 1.117; 95% CI = 1.052-1.185; p < .001), but not WCadjBMI, were significantly associated with an increased risk of periodontitis/loose teeth. Moreover, the MR estimates were consistent across other MR sensitivity analyses and multivariable MR. However, a causal association of obesity with the single trait periodontitis was not identified. CONCLUSIONS: The presented evidence supports previous epidemiological findings by showing a potential causal association of genetic liability to obesity with periodontal diseases. The biological mechanisms underlying this association warrant further investigation.

Cascade Reactions Catalyzed by Gold Hybrid Nanoparticles Generate CO Gas Against Periodontitis in Diabetes.

The treatment of diabetic periodontitis poses a significant challenge due to the presence of local inflammation characterized by excessive glucose concentration, bacterial infection, and high oxidative stress. Herein, mesoporous silica nanoparticles (MSN) are embellished with gold nanoparticles (Au NPs) and loaded with manganese carbonyl to prepare a carbon monoxide (CO) enhanced multienzyme cooperative hybrid nanoplatform (MSN-Au@CO). The Glucose-like oxidase activity of Au NPs catalyzes the oxidation of glucose to hydrogen peroxide (H2O2) and gluconic acid，and then converts H2O2 to hydroxyl radicals (•OH) by peroxidase-like activity to destroy bacteria. Moreover, CO production in response to H2O2, together with Au NPs exhibited a synergistic anti-inflammatory effect in macrophages challenged by lipopolysaccharides. The underlying mechanism can be the induction of nuclear factor erythroid 2-related factor 2 to reduce reactive oxygen species, and inhibition of nuclear factor kappa-B signaling to diminish inflammatory response. Importantly, the antibacterial and anti-inflammation effects of MSN-Au@CO are validated in diabetic rats with ligature-induced periodontitis by showing decreased periodontal bone loss with good biocompatibility. To summarize, MSN-Au@CO is fabricate to utilize glucose-activated cascade reaction to eliminate bacteria, and synergize with gas therapy to regulate the immune microenvironment, offering a potential direction for the treatment of diabetic periodontitis.

Mendelian randomization supports the causal role of fasting glucose on periodontitis.

Purpose: The effect of hyperglycemia on periodontitis is mainly based on observational studies, and inconsistent results were found whether periodontal treatment favors glycemic control. The two-way relationship between periodontitis and hyperglycemia needs to be further elucidated. This study aims to evaluate the causal association of periodontitis with glycemic traits using bi-directional Mendelian randomization (MR) approach. Methods: Summary statistics were sourced from large-scale genome-wide association study conducted for fasting glucose (N = 133,010), HbA1c (N = 123,665), type 2 diabetes (T2D, N = 659,316), and periodontitis (N = 506,594) among European ancestry. The causal relationship was estimated using the inverse-variance weighted (IVW) model and further validated through extensive complementary and sensitivity analyses. Results: Overall, IVW showed that a genetically higher level of fasting glucose was significantly associated with periodontitis (OR = 1.119; 95% CI = 1.045-1.197; PFDR= 0.007) after removing the outlying instruments. Such association was robust and consistent through other MR models. Limited evidence was found suggesting the association of HbA1C with periodontitis after excluding the outliers (IVW OR = 1.123; 95% CI = 1.026-1.229; PFDR= 0.048). These linkages remained statistically significant in multivariate MR analyses, after adjusting for body mass index. The reverse direction MR analyses did not exhibit the causal association of genetic liability to periodontitis with any of the glycemic trait tested. Conclusions: Our MR study reaffirms previous findings and extends evidence to substantiate the causal effect of hyperglycemia on periodontitis. Future studies with robust genetic instruments are needed to confirm the causal association of periodontitis with glycemic traits.