Exploring the Links Between Rheumatoid Arthritis and Pulpal-Periapical Diseases: Insights from Meta-Analysis and Two-Sample Mendelian Randomization.

INTRODUCTION

Several clinical trials have investigated the relationship between rheumatoid arthritis (RA) and periapical periodontitis (AP), yielding inconsistent results. Our study aimed to synthesize clinical evidence through a meta-analysis and evaluate potential association using two-sample Mendelian randomization (TSM), which leverages genetic information for a more comprehensive perspective.

METHODS

A systematic literature search was executed across PubMed, Web of Science, Scopus, and gray literature sources until February 20, 2025. Studies comparing radiolucent periapical lesions in RA patients with controls were qualified for this meta-analysis. Genetic data from genome-wide association studies of European populations with RA were used to scrutinize the relationships with diseases of pulp and periapical tissues, particularly chronic periapical periodontitis and pulpitis, employing a TSMR approach. Our primary estimates used the radial inverse-variance weighted method complemented by a series of sensitivity analyses to ensure robustness. MR-Egger intercept, Cochran's Q statistical analysis, and I2 were used to assess the potential heterogeneity and pleiotropy.

RESULTS

The meta-analysis included 1,206 participants across 5 selected studies. No significant correlation was found between radiographically diagnosed AP and RA at the patient level (odds ratio [OR] = 1.56, 95% confidence interval [CI] = 0.91-2.67, P = .10). However, AP prevalence was 1.67 times higher in RA patients compared to healthy individuals at the tooth level (OR = 1.67, 95% CI = 1.18-2.35, P < .01). Genetically, RA was correlated with an elevated risk of diseases of pulp and periapical tissues (OR = 1.05; 95% CI = 1.03-1.07; P < .0000), chronic periapical periodontitis (OR = 1.05; 95% CI = 1.02-1.08; P = .0006) and pulpitis (OR = 1.01; 95% CI = 1.00-1.02; P = .0175), respectively.

CONCLUSIONS

Evidence from both the meta-analysis and the TSMR study moderately corroborates the associations between RA and pulpal-periapical diseases. Further research employing both human and animal models are recommended to confirm this link and elucidate potential underlying mechanisms.