International dental journal · 2025
Causal Links Between Bone Diseases and Temporomandibular Disorders.
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Zhang Ling, Zhang Qinghua, Zhao Dong
Аннотация
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.
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.