Exercise prevents RA development, but link not causal

Engaging in higher levels of physical activity (PA) seems to protect against the risk of developing rheumatoid arthritis (RA), although this relationship is not causal, according to a Mendelian randomization (MR) analysis.

Researchers used genetic instruments identified from a genome-wide association study of self-reported and accelerometer-based PA traits to conduct a two-sample MR analysis exploring the causal relationship between PA and RA.

A total of four studies met the eligibility criteria, all of which assessed leisure-time/recreational PA and identified PA exposure via self-reported or interviewer-administered questionnaires. Three studies involved older women and one included adult women. Three studies were conducted in the US and the rest in Sweden.

There were 4,213 RA patients among 255,365 participants in total. The quality scores of the studies ranged from 10 to 13, according to the Newcastle-Ottawa Quality Assessment Scale.

PA was found to have an inverse relationship with RA risk. The highest versus lowest PA level reduced the risk by 21 percent (relative risk [RR], 0.79, 95 percent confidence interval [CI], 0.72–0.87), while any PA versus inactivity or occasional exercise conferred a 15-percent protection (RR, 0.85, 95 percent CI, 0.79–0.92).

However, the genetic data yielded no convincing evidence to support a causal role for genetically predicted accelerometer-measured PA (odds ratio [OR] per 1-SD unit increment, 0.97, 95 percent CI, 0.88–1.08), genetically predicted moderate-to-vigorous PA (OR per 1-SD unit increment, 1.08, 95 percent CI, 0.49–2.39), or genetically predicted vigorous PA ≥3 days/week (OR, 2.63, 95 percent CI, 0.05–130.96) in RA risk.

More studies with larger sample sizes and different ethnic populations are required to replicate the present findings.