Calcium, vitamin D, or combined supplementation to prevent fractures and falls: systematic review and meta-analysis

OBJECTIVE: To assess the effect of calcium, vitamin D, or combined supplementation on fractures and falls in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Trials included in systematic reviews from 2014, three databases (Medline, Embase, CENTRAL) to 19 February 2025, clinical trial registries, abstracts from scientific meetings, and references from included studies. ELIGIBILITY CRITERIA: Randomised controlled trials comparing calcium, vitamin D, or combined supplementation with placebo or no treatment in adults (≥18 years) not receiving drug treatment for osteoporosis. DATA EXTRACTION AND SYNTHESIS: The primary outcome was the risk of any fracture. Secondary outcomes included the risk of hip fracture, non-vertebral fracture, vertebral fracture, and falling, as well as the total number of falls. Pairs of reviewers independently screened trials, extracted data, and assessed risk of bias using the second version of Cochrane's risk of bias tool. Findings were synthesised using random effects meta-analyses and appraised using Grading of Recommendations Assessment, Development and Evaluation, with application of thresholds for absolute effects considered important. RESULTS: This review included 69 trials involving 153 902 participants. Participants in most of the trials were community dwelling (87%) and not at high risk of fractures or falls (73%). For the primary outcome of any fracture, little to no effect was found from use of calcium supplements (11 trials, 9067 participants; risk ratio 0.91, 95% confidence interval 0.81 to 1.01; moderate certainty), vitamin D supplements (36 trials, 92 045 participants; 1.00, 0.95 to 1.06; high certainty), or combined supplementation (15 trials, 51 126 participants; 0.91, 0.84 to 0.99; high certainty). Calcium, vitamin D, or combined supplementation appeared to have little to no effect on other fracture and fall outcomes, based largely on moderate to high certainty of evidence. The findings remained robust after an extensive exploration of heterogeneity across multiple subgroup analyses. Evidence for high risk patients or those requiring residential care was limited for many outcomes for calcium monotherapy and for combined supplementation. CONCLUSION: Based on absolute risk reductions and thresholds considered clinically meaningful, this review found little to no benefits from use of calcium, vitamin D, or combined supplementation on the prevention of fractures and falls. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023483915.