Rheumatoid arthritis and osteoporosis: a bi-directional Mendelian randomization study

Abstract

Many observation studies have demonstrated a close relationship between rheumatoid arthritis (RA) and osteoporosis (OP). However, the causal genetic correlation between RA and OP remains unclear. In this study, we performed bi-directional Mendelian randomization (MR) analyses to explore causal inference between these two traits. The instrumental variables for RA were selected from a large-scale genome-wide association study (GWAS) (1,523 cases and 461,487 controls). Bone mineral density (BMD) at five different sites (heel (n=265,627), forearm (FA) (n=8,143), femoral neck (FN) (n=32,735), lumbar spine (LS) (n=28,498), and total body (n=28,498)) were used as phenotypes for OP. The inverse variance weighted (IVW) method did not detect any causal effect of BMDs on RA except heel BMD (beta = -7.57 × 10-4, p = 0.02). However, other methods (MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS) showed no causal association between heel BMD and RA. Likewise, we did not find a causal effect of RA on BMD at any sites. In conclusion, we found no evidence that RA is causally associated with OP/BMD, or vice versa. We suggested that the associations found in previous observational studies between RA and OP/BMD are possibly related to secondary effects such as antirheumatic treatment and reduced physical activity.

Anti-osteoporosis effects and regulatory mechanism of Lindera aggregata based on network pharmacology and experimental validation

“…59 Furthermore, OP is one of the most severe comorbidities of RA. 60 The KEGG results in this study also illustrated that the RA signaling pathway is the core pharmacological mechanism of RLA against OP and four OP-related genes were regulated by RLA. Further qRT-PCR analysis results of the four genes including opg , rankl , ctsk , and acp5a also demonstrated that the regulation of the RA signaling pathway maybe one of the anti-OP mechanisms of RLA.…”

Efficacy Evaluation of Modified Siwu Decoction to Treat Osteoporosis in Patients with Poststroke Hemiplegia by Using the Magnetic Resonance Imaging Features

“…e results indicated that the Siwu Decoction formula can effectively improve the BMD of patients with poststroke hemiplegia osteoporosis, improve bone strength, and help patients recover more [21]. 25-OH-VD is the main form of vitamin D in the human body, which is mainly synthesized by human skin after ultraviolet radiation.…”

Is osteoporosis associated with arthritis? The United States national health and nutrition examination survey 2005–2020(pre-pandemic)

“…The correlation between RA and osteoporosis is also inconclusive. The latest two-way Mendelian randomization study shows that there is no obvious causal relationship between RA and osteoporosis (23). However, data from the British Clinical Practice Research Data Link (CPRD) showed that the incidence of OP in RA patients who did not take glucocorticoids was 7.5‰, which was much higher than that in healthy controls.…”