Calcium and vitamin D supplementation and incident rheumatoid arthritis: The Women's Health Initiative Calcium plus Vitamin D trial

To determine whether calcium plus vitamin D supplementation (CaD) aVects incidence of rheumatoid arthritis (RA). Participants enrolled in the Women's Health Initiative CaD trial (n = 36,282) were randomized to 1,000 mg calcium carbonate plus 400 IU of vitamin D3 daily or to placebo. Incident RA cases were identiWed via self-report and validated rheumatic medication use. Cox proportional hazards models were used to compare RA incidence in the treatment versus placebo groups. The analysis included 32,435 women without the history of RA, of which 163 incident RA cases were identiWed over an average of 5.1 years. No significant diVerences in demographics, total personal vitamin D intake [P = 0.36], or solar irradiance [P = 0.68] were seen between the groups. In intention-to-treat analyses, no diVerences were observed in RA incidence [HR 1.04, 95% CI 0.76, 1.41]. No significant modifying eVects were seen for stratum of age, solar irradiance, or total vitamin D intake, overall or when adjusted for adherence. Significant eVect modifications were seen between CaD and total vitamin D intake and CaD and solar irradiance that suggest increased RA incidence with high vitamin D exposure. CaD supplementation did not demonstrate a significant eVect on RA incidence in postmenopausal women. Modifying eVects between CaD and both solar irradiance and dietary vitamin D intake are suggestive that multiple high vitamin D exposures may increase RA incidence. Further research is needed to fully explore the beneWts and possible adverse eVects of vitamin D supplementation on RA.