Context
The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (±calcium) for fracture prevention has led to contradictory guidelines. This umbrella review aims to assess the quality and explore the reasons for discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults.
Evidence Acquisition
We searched 4 databases (2010-2020), Epistemonikos, and references of included SR/MAs, and we contacted experts in the field. We used AMSTAR-2 for quality assessment. We compared results and investigated reasons for discordance using matrices and sub-group analyses (PROSPERO registration: CRD42019129540).
Evidence Synthesis
We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control. Only 2 from 10 SR/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8/12 SR/MAs (relative risk (RR) 0.61-0.84), and any fractures in 7/11 SR/MAs (RR 0.74-0.95). No risk reduction was noted in SR/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SR/MAs stems from inclusion of different trials, related to search periods and eligibility criteria, and varying methodology (using intention to treat, per-protocol, or complete case analysis from individual trials). Vitamin D alone has no protective effect on fracture risk.
Conclusions
Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized subjects. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up period, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.
Toward better risk stratification of asymptomatic Brugada syndrome patients? high-risk BrS patients compared to asymptomatic patients. Whether these findings can be leveraged to better risk stratify asymptomatic BrS patients need to be investigated in future larger prospective cohorts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.