Effect of vitamin D on risk of falls and fractures – The contribution of recent mega-trials

Three recently-completed, large clinical trials in the U.S, New Zealand, and Australia, referred to herein as the ‘mega-trials’, were conducted to determine the impact of supplemental vitamin D on a variety of outcomes including falls and fractures. The trials were similar in design and collectively included over 50,000 generally vitamin D replete, older men and women. The mega-trials established that vitamin D supplementation with the equivalent of 2000 to 3300 IU/d of vitamin D₃ had no favorable effect on risk of falls or fractures. This review focuses on specific design elements of the trials and how they likely influenced these trial findings. While these trials were in progress, evidence emerged that circulating 25-hydroxyvitamin D levels have a U-shaped association with risk of falling, raising concern about a potential untoward effect of high dose supplementation. There is compelling evidence that in older, vitamin D- and calcium-insufficient nursing home residents, the combination of vitamin D and calcium in modest replacement doses dramatically reduces the risk of hip and other fractures. Community-dwelling older adults in many populous countries around the globe have widespread vitamin D and calcium insufficiency. It is time to follow the evidence trail and determine the effect of vitamin D and calcium replacement on their risk of falls and fractures.