Analysis of the Relationship between Rheumatoid Arthritis and Osteoporosis Based on Mendelian Randomization

Abstract

Background: As the global population ages, the World Health Organization has found a yearly increase in the incidence of rheumatoid arthritis and osteoporosis. This trend poses a challenge to public health and healthcare and calls for the implementation of more preventive and treatment measures to address these health issues. Objective: This study aims to investigate the causal relationship between rheumatoid arthritis (RA) and osteoporosis (OP) using the Mendelian randomization (MR) method. Method: OP diagnosis was based on the gold standard of bone mineral density (BMD). Single nucleotide polymorphisms (SNPs) were identified from the genome-wide association research database formed by RA and BMD, with a parameter setting of P < 5×10-8, chain imbalance r2<0.01, and kb = 10,000. Five complementary MR methods, including inverse variance weighted (IVW), MR-Egger regression, weighted median, simple mode estimation based on mode, and weighted estimation based on mode, were used to evaluate the causal relationship between RA and OP/BMD using odds ratio (OR) values and 95% confidence intervals (CI). Sensitivity analyses were performed using heterogeneity tests, horizontal pleiotropy, and individual rejection tests. Results: A total of 78 instrumental variables were identified that were closely related to both RA and BMD in mixed populations, while 14 instrumental variables were identified in the European population and 38 instrumental variables were identified in the Asian population. Using IVW as the main analysis method, the MR analysis results of RA and BMD showed the following: mixed population OR = 0.96, 95%CI: 0.93-1.00; European population OR = 0.55, 95%CI: 0.27-1.12; and Asian population OR = 0.95, 95%CI: 0.90-1.01. Sensitivity analyses showed that the MR results were robust. Conclusion: The study found insufficient evidence of a causal relationship between RA and OP/BMD, suggesting that RA may not have a direct effect on OP/BMD.