Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX

Summary: The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®. Introduction: RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX. Methods: The resource comprised 1,909,896 men and women, aged 20–116 years, from 29 prospective cohorts in which the prevalence of RA was 3% or less (primary analysis) and an additional 17 cohorts with a prevalence greater than 3% (supplementary analysis). The association between RA and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture (MOF), and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. Results: In the primary analysis, RA was reported in 1.3% of individuals. During 15,683,133 person-years of follow-up, 139,002 fractures occurred, of which 27,518 were hip fractures. RA was associated with an increased risk of any clinical fracture (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.35–1.65). The HRs were of similar magnitude for osteoporotic fracture and MOF but higher for hip fracture (HR = 2.23; 95% CI 1.85–2.69). For hip fracture, there was a significant interaction with age with higher HRs at younger ages. HRs did not differ between men and women and were independent of exposure to glucocorticoids and femoral neck BMD. Lower HRs were observed in the supplementary analysis cohorts, particularly in those with a high apparent prevalence of RA, possibly from conflation of RA with osteoarthritis. Conclusions: A diagnosis of RA confers an increased risk of fracture that is largely independent of BMD, sex, and corticosteroids. RA should be retained as a risk factor in future iterations of FRAX with updated risk functions to improve fracture risk prediction.