By David Fiore, MD
Professor of Family Medicine, University of Nevada, Reno
Dr. Fiore reports no financial relationships relevant to this field of study.
SYNOPSIS: After conducting an extensive investigation, researchers did not find that vitamin D prevents falls or fractures.
SOURCE: Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: A systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol 2018; Oct 4. pii: S2213-8587(18)30265-1. doi: 10.1016/S2213-8587(18)30265-1. [Epub ahead of print].
Falls are a common and devastating risk for elderly patients. More than one-third of people older than age 70 fall annually.1 Often, these falls cause fractures (most commonly in the hip), with more than a quarter of a million hip fractures occurring in the United States annually (most commonly in elderly women).2 The role, if any, vitamin D and calcium play in preventing fractures has been an area of intense interest for years, with evidence for and against supplementation. Bolland et al attempted to address the issue of vitamin D supplementation and musculoskeletal health using a meta-analysis with “trial sequential analysis” (TSA). Sequential analysis is a statistical technique developed during World War II to expedite materials and weapons production while maintaining quality through sequential testing rather than predetermined sampling, which requires more samples. In medical studies, this technique allows investigators to assess outcomes periodically throughout a trial to predetermine thresholds for significance at various points in the trial rather than setting a large sample size a priori before the trial starts. Recently, this technique has been modified for use in meta-analyses as a tool to assess the statistical reliability as more studies with varying size and quality are added.3
Bolland et al found 81 trials with 55,537 participants that concerned the effect of vitamin D and/or calcium on several outcomes. The coprimary endpoints for this trial were at least one fracture, at least one hip fracture, and at least one fall. The authors presented multiple comparisons and subgroup analyses without finding a benefit of vitamin D or calcium supplementation, including high-dose vs. low-dose supplementation. The use of TSA allowed the authors to assess the effect at predefined estimates of potential benefit (or “futility boundaries”) of 15%, 10%, and 5%. They did not find that there was benefit at any of these levels.
This meta-analysis is in agreement with the U.S. Preventive Services Task Force (USPSTF) guideline on vitamin D and calcium supplementation for primary prevention of fractures in community-dwelling adults as well as with a Cochrane Review on this subject.4,5 Both the USPSTF guideline and the Cochrane Review failed to find evidence for a benefit of vitamin D or calcium for the prevention of fractures in those who have not sustained a prior osteoporotic fracture. Unfortunately, Bolland et al did not assess the efficacy of supplementation as secondary prevention for those who have already sustained a fracture.
In light of this extensive review of the literature on vitamin D supplementation, which revealed no evidence of benefit for preventing falls or fractures, and its agreement with other studies and guidelines, it is time to move away from testing average-risk elderly patients for “vitamin D deficiency” and recommending supplementation (notably, even the Endocrine Society recommends against routine screening and supplementation).6 Patients should be advised to eat foods rich in vitamin D and calcium. Further, patients should safely expose themselves to adequate sunlight and engage in regular weight-bearing exercise as part of a healthy lifestyle, which will help protect them from future fractures.
- World Health Organization. WHO Global Report on Falls Prevention in Older Age, 2007. Available at: . Accessed Oct. 17, 2018.
- Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB. Incidence and mortality of hip fractures in the United States. JAMA 2009;302:1573-1579.
- Copenhagen Trial Unit. Trial Sequential Analysis. Available at: . Accessed Oct. 17, 2018.
- US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK. Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults: US Preventive Services Task Force Recommendation Statement. JAMA 2018;319:1592-1599.
- Avenell A, Mak JC, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev 2014;4:CD000227. doi: 10.1002/14651858.CD000227.pub4.
- Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-1930.