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. 2022 Feb 17;107(3):882-898.
doi: 10.1210/clinem/dgab742.

Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review of Meta-Analyses of Controlled Trials

Marlene Chakhtoura  1 , Dania S Bacha  1 , Charbel Gharios  1 , Sara Ajjour  1 , Mariam Assaad  1 , Yara Jabbour  1 , Francesca Kahale  1 , Aya Bassatne  1 , Stephanie Antoun  1 , Elie A Akl  2   3 , Roger Bouillon  4 , Paul Lips  5 , Peter R Ebeling  6 , Ghada El-Hajj Fuleihan  1
Affiliations

Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review of Meta-Analyses of Controlled Trials

Marlene Chakhtoura et al. J Clin Endocrinol Metab. .

Abstract

Context: The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (± calcium) for fracture prevention has led to contradictory guidelines.

Objective: This umbrella review aims to assess the quality and explore the reasons for the discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults.

Methods: We searched 4 databases (2010-2020), Epistemonikos, and references of included SRs/MAs, and we contacted experts in the field. We used A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) for quality assessment. We compared results and investigated reasons for discordance using matrices and subgroup analyses (PROSPERO registration: CRD42019129540). We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control.

Results: Only 2 from 10 SRs/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8 of 12 SRs/MAs (relative risk [RR] 0.61-0.84), and any fractures in 7 of 11 SR/MAs (RR 0.74-0.95). No fracture risk reduction was noted in SRs/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SRs/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).

Conclusion: Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized individuals. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up periods, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.

Keywords: adults; fractures; umbrella review; vitamin D.

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Figures

Figure 1.
Figure 1.
Flow diagram of the included studies. aList of excluded articles is available on request. bThese will be included in separate manuscripts.
Figure 2.
Figure 2.
Effect size estimates and 95% CI for A, hip, and B, any fracture risk with vitamin D and calcium supplementation vs placebo/control. Quality assessment using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) tool described between parenthesis: A, moderate quality; B, low quality; and C, critically low quality. aHR, hazard ratio; OR, odds ratio; RR, risk ratio. bMeta-analyses that included institutionalized trials. cNetwork meta-analyses. dNot available.
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