Bolland MJ, et al. - In this systematic review, random-effects meta-analysis, and trial sequential analysis, researchers examined the impact of vitamin D supplementation on fractures, falls, and bone mineral density. An evaluation of 81 trials exhibited no impact of vitamin D supplementation (including higher and lower doses) on fractures, falls, and bone density. They reported that there is little validation for using vitamin D supplements to preserve or improve musculoskeletal health, and this outcome ought to be reflected in clinical guidelines.

Methods

• In this investigation, researchers used findings from literature searches in previously published meta-analyses.
• Using the search term “vitamin D” and additional keywords, without any language restrictions, they updated these findings by searching PubMed, Embase, and Cochrane Central on September 14, 2017 and February 26, 2018.
• Randomized controlled trials of adults (>18 years) assessing vitamin D vs untreated controls, placebo, or lower-dose vitamin D supplements were evaluated.
• If the study groups differed only by use of vitamin D, trials with multiple interventions (eg, co-administered calcium and vitamin D) were eligible.
• Trials of hydroxylated vitamin D analogues were excluded.
• Outcome data for total or hip fractures, falls, or bone mineral density measured at the lumbar spine, total hip, femoral neck, total body, or forearm were included in eligible studies.
• Data were extracted about participant characteristics, study design, interventions, outcomes, funding sources, and conflicts of interest.
• Participants with at least one fracture, at least one hip fracture, or at least one fall were the co-primary endpoints; relative risks with an intention-to-treat analysis using all available data were used to compare data for fractures and falls.
• The percentage change in bone mineral density from baseline at lumbar spine, total hip, femoral neck, total body, and forearm were the secondary endpoints.

Results

• Eighty-one randomized controlled trials (n=53,537 participants) that reported fracture (n=42), falls (n=37), or bone mineral density (n=41), were identified.
• Vitamin D had no impact on total fracture (36 trials; n=44,790, relative risk 1.00, 95% CI 0.93–1.07), hip fracture (20 trials; n=36,655, 1.11, 0.97–1.26), or falls (37 trials; n=34,144, 0.97, 0.93–1.02) in pooled analyses.
• Outcomes were comparable in randomized controlled trials of high-dose vs low-dose vitamin D and in subgroup analyses of randomized controlled trials using doses greater than 800 IU per day.
• No clinically relevant between-group differences were found in bone mineral density at any site (range −0.16% to 0.76% over 1–5 years) in pooled analyses.
• The effect estimate lay within the futility boundary for relative risks of 15%, 10%, 7.5%, and 5% (total fracture only) for total fracture and falls, implying that vitamin D supplementation did not decrease fractures or falls by these amounts.
• For hip fracture, at a 15% relative risk, the effect estimate lay between the futility boundary and the inferior boundary; this means there is credible proof that vitamin D supplementation did not decrease hip fractures by this amount, but whether it might increase hip fractures is still not certain.
• Data reported that the effect estimate lay within the futility boundary at thresholds of 0.5% for total hip, forearm, and total body bone mineral density, and 1.0% for lumbar spine and femoral neck, giving reliable proof that vitamin D did not change these results by these amounts.