A pooled analysis of vitamin D dose requirements for fracture prevention

Approximately 75% of fractures occur in people 65 years of age or older.1 By 2050, the worldwide incidence of hip fractures is expected to increase by 240% among women and 310% among men.2 One strategy to prevent fractures in this population might be universal vitamin D supplementation. However, the results of several study level meta-analyses and one pooled participant-level analysis do not agree. Although one trial-level meta-analysis of double-blind, randomized, controlled trials suggested an 18% reduction in the incidence of hip fracture and a 20% reduction in the incidence of any nonvertebral fracture at a received dose of no less than 482 IU of vitamin D per day,3 three study-level meta-analyses4-6 and one pooled analysis of participant-level data7 from open-design and blinded trials suggested that vitamin D may have no effect on total fractures4 or may reduce hip fracture by 7 to 16%, if combined with calcium supplementation, regardless of the dose of vitamin D.4-7 The discordant findings may be explained, in part, by differences in the criteria for including trials in the analyses, with respect to blinding, vitamin D formulation (oral vs. injectable), or accommodations for nonadherence. Our analysis was designed to estimate the effects of vitamin D supplementation according to the actual intake of each participant, rather than simply the dose to which the participant was randomly assigned