Causal Links Between Bone Diseases and Temporomandibular Disorders

Introduction and Aims

Epidemiological observational studies have explored the link between bone joint-related diseases and temporomandibular disorders (TMD), but inconsistent conclusions have emerged due to various limitations. This study aims to investigate the causal relationship between bone joint-related diseases and TMD using Mendelian randomization (MR).

Methods

We utilized a two-sample MR design, applying pooled genome-wide association study (GWAS) data from six subtypes of bone and joint diseases and TMD. Primary analysis was conducted using the inverse-variance weighted (IVW) method, complemented by weighted median (WM), weighted mode, and MR-Egger regression to assess causal relationships. Additionally, we performed reverse causality analyses and applied sensitivity analyses, including MR-PRESSO, MR-Egger, Cochran's Q, and leave-one-out methods to evaluate result robustness, explore heterogeneity, and identify potential biases.

Results

MR genetic prediction analyses indicated that bone and joint-related diseases increase the risk of TMD, with specific odds ratios (OR) for ankylosing spondylitis (AS: OR 1.36, 95% CI: 1.04-1.77, P = .026), rheumatoid arthritis (RA: OR 1.08, 95% CI: 1.03-1.13, P = .001), and osteoporosis (OR 1.0751, 95% CI: 1.0047-1.1505, P = .036). Conversely, reverse MR analysis revealed a positive genetic link from TMD to RA (RA: OR 1.12, 95% CI: 1.02-1.23, P = .018). MR-Egger regression showed no influence of horizontal pleiotropy, and MR-PRESSO detected no outliers. The leave-one-out analysis confirmed the results' stability.

Conclusions

The findings demonstrate a positive, causal association between TMD risk and AS, RA, and osteoporosis. Moreover, TMD patients exhibit an increased risk of developing RA.

Clinical Relevance

Understanding these relationships aids in better diagnosis and management of TMD and its association with bone joint diseases, potentially guiding clinical interventions.