Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review
Abstract
BACKGROUND: The growing number of systematic reviews/meta-analyses (SR/MAs) on the role of vitamin D in fracture prevention has led to conflicting results and contradictory guidelines.
METHODS: This umbrella review evaluated SR/MAs of randomized controlled trials that compare the effect of vitamin D (±calcium) to placebo/control on fracture risk in adults, as identified from 4 databases (2010-2020). We assessed the quality of SR/MAs using the latest quality tool, AMSTAR-2. We compared their results and investigated reasons for discordance using matrices and sub-group analyses (PROSPERO registration: CRD42019129540).
FINDINGS: We included 25 SR/MAs, 21 were of critically low quality, one of low quality, and three were of moderate quality (2 were on fall-related fracture). Vitamin D combined with calcium (Ca/D) reduced the risk of hip fractures in 8/12 SR/MAs (relative risk (RR) 0.61-0.84), and the risk of any fracture in 7/11 SR/MAs (RR 0.74-0.95), on pooled analyses. Important sources of discordance in results between SR/MAs were identified. These stem from inclusion of different trials, search periods, eligibility criteria, and differences in methodology. There was a trend for sub-group effect by residency, age and vitamin D status, but none reached statistical significance. All 19 SR/MAs on vitamin D alone compared to placebo/control reported no benefit.
INTERPRETATION: Ca/D reduces the risk of hip and any fractures, results that seem driven by findings in…
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