High-dose Vitamin D and Risk of Falls
High-dose Vitamin D and Risk of Falls
Abstract & Commentary
By Rahul Gupta, MD, MPH, FACP, Clinical Assistant Professor, West Virginia School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationship to this field of study.
Synopsis: In community-dwelling women age 70 years and older, annual oral administration of high-dose vitamin D for 3-5 years resulted in a higher, not lower, incidence of falls and fractures.
Source: Sanders KM, et al. Annual high-dose vitamin D and falls and fractures in older women. JAMA 2010;303:1815-1822.
In medicine, it is often that we gain limited knowledge from research in a subset of patients in clinical trials, but often expand the applicability of the knowledge gained to a much wider group of people. Such has been the case with vitamin D. Vitamin D modulates fracture risk in two ways: by decreasing falls and increasing bone density. There has been a growing body of literature to suggest that vitamin D deficiency is widely prevalent and a corrective intervention may provide many benefits including reducing the risk of falls.1 The most recent meta-analyses of double-blind randomized controlled trials concluded that vitamin D reduces the risk of falls by 19%, the risk of hip fracture by 18%, and the risk of any non-vertebral fracture by 20%; however, this benefit was dose-dependent.2,3 So it is understandable that when physicians find a patient deficient in vitamin D, the logical management would be to rapidly correct it. This has resulted in many of us writing prescriptions for high doses of vitamin D. However, most studies demonstrate that fewer fractures are observed in participants whose study treatment consists of 700-800 IU of vitamin D co-administered with calcium.4
In the current study, Sanders et al hypothesized that high-dose cholecalciferol (500,000 IU) given orally once a year to community-dwelling older women would reduce falls and fractures. In case the hypothesis would prove correct, not only would such high doses of vitamin D treatment prevent decreases in 25-hydroxycholecalciferol over winter, but such an intervention would also address the traditional low adherence to daily intake recommendations. Therefore, the authors conducted a double-blind, placebo-controlled trial of 2256 such women, aged 70 years or older whom they randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3-5 years. Results showed that women assigned to the vitamin D group had many more fractures (171 vs 135) and fell much more often (83.4/100 person-years vs 72.7/100 person-years) than the placebo group. Increased falls in the vitamin D group were observed for each classification of falls: falls with fracture, falls without fracture, and falls with soft-tissue injury.
The authors concluded that contrary to their hypothesis, participants receiving annual high-dose oral cholecalciferol experienced 15% more falls and 26% more fractures than the placebo group. They also noted that women not only experienced additional fractures due to more frequent falls, but also experienced more fractures that were not associated with a fall. Falls were exacerbated in the 3-month period immediately following the annual dose and a similar temporal trend was observed for fractures.
Commentary
Some will ask where is the tipping point, since too little vitamin D causes falls and fractures and high doses seem to do the same. Some will wonder about the possible mechanisms behind the new findings. While we may not completely understand the exact mechanism behind the current findings, it is clear that replacement of vitamin D in high doses is counterproductive. However, it is important to note that any vitamin D deficiency or insufficiency must be treated. Although the level of vitamin D needed for optimal function in many tissues is not yet defined, currently 600 IU (15 µg) per day is recommended for adults 70 years or older in the United States and Canada with an upper limit of 2000 IU per day.5 The current study also raises some concern about the common practice of treating vitamin D deficiency with loading doses of vitamin D (typically 50,000 IU twice weekly for 4-8 weeks, then taper). I have done it so many times myself, but did not keep a track of falls and fractures in my patients since this never occurred to me. Therefore, the recommendation may be to continue to look for vitamin D deficiency, but when found, treat with caution. Adding calcium has its benefits too.
References
1. Dobnig H, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 2008;168:1340-1349.
2. Bischoff-Ferrari H, et al. Falls prevention with supplemental and active forms of vitamin D: A meta-analysis of randomised trials. BMJ 2009;339:b3692.
3. Bischoff-Ferrari H. Vitamin D: What is an adequate vitamin D level and how much supplementation is necessary? Best Pract Res Clin Rheumatol 2009;23:789-795.
4. Bischoff-Ferrari H, et al. Fracture prevention with vitamin D supplementation. JAMA 2005;293:2257-2264.
5. Office of Dietary Supplements, National Institutes of Health. Dietary Supplement Fact Sheet: Vitamin D; Health Professional Fact Sheet. Available at: http://dietary-supplements.info.nih.gov/factsheets/vitamind.asp#h2. Accessed June 01, 2010.
In community-dwelling women age 70 years and older, annual oral administration of high-dose vitamin D for 3-5 years resulted in a higher, not lower, incidence of falls and fractures.Subscribe Now for Access
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