Level 1 (likely reliable) evidence
Vitamin D deficiency is associated with musculoskeletal complications including pain and weakness, osteomalacia, osteoporosis, and secondary hyperparathyroidism. Vitamin D deficiency is especially prevalent in postmenopausal women who are already at an increased risk of osteoporosis and osteoporosis-related fractures (QJM. 2005;98(9):667-676).
Evidence supporting the use of vitamin D supplements for the treatment and prevention of osteoporosis is limited, and recommendations from current guidelines are inconsistent on the use of vitamin D for these purposes (Clinician’s guide to prevention and treatment of osteoporosis, available at http://nof.org/files/nof/public/content/file/950/upload/523.pdf; Ann Intern Med. 2013;158:691-696). Recent data has suggested that vitamin D supplementation may also reduce the risk of falls in patients with low vitamin D levels (Cochrane Database Syst Rev. 2012;:CD007146). This data has led the American Geriatrics Society and British Geriatrics Society to recommend at least 800 units/day of vitamin D supplements to older persons with proven vitamin D deficiency and to consider supplementation for all older adults at increased risk of falls (J Am Geriatr Soc. 2011;59:148-157).
A recent randomized trial compared high-dose vitamin D3, low-dose vitamin D3, and placebo for 1 year in 230 postmenopausal women with vitamin D insufficiency (25-hydroxyvitamin D, 14-27 ng/mL; JAMA Intern Med. 2015;175:1612-1621). The primary outcome was change in calcium absorption, but rate of falls was one of the secondary outcomes investigated. The high-dose regimen included 50,000 units of vitamin D3 twice monthly plus placebo daily, and the low-dose regimen consisted of 800 units of vitamin D3 daily plus placebo twice monthly. The placebo group received placebos both daily and twice monthly to maintain blinding. Participants were also counseled to consume 600 mg to 1,400 mg of calcium daily by diet or supplement, if needed. From days 30 to 365, the mean 25-hydroxyvitamin D level increased to 56 ng/mL with high-dose vitamin D3 and 28 ng/mL with low-dose vitamin D3, compared to 19 ng/mL with placebo (p< 0.001 across groups). The change in total fractional calcium absorption at 1 year was significantly increased in the high-dose vitamin D3 group, compared to the low-dose vitamin D3 and placebo groups (+1% vs. -2% vs. -1.3%, respectively). This difference did not correlate with any clinical outcomes. There were no significant differences in the number of falls or percent of fallers across groups, with 35 falls in 29.7% of women in the high-dose vitamin D3 group, 36 falls in 32.9% of women in the low-dose vitamin D 3 group, and 33 falls in 30.3% of women in the placebo group. There were also no significant differences in other clinical or bone health outcomes, including fracture, Timed Up and Go Test, Five Sit-to-Stand Test, functional status measures, or physical activity.
This study contrasts with 2 previous systematic reviews (Cochrane Database Syst Rev. 2012;:CD007146; JAMA. 2004;291:1999-2006) that found a decrease in the risk of falls with vitamin D supplementation. The discrepancy may be explained in part by the populations studied, with the systematic reviews including older adults in general compared to the specific population of postmenopausal women with vitamin D deficiency included in the JAMA Intern Med trial. Also, the mean age of the patients analyzed in the systematic reviews was approximately 10 years older than the women included in this trial. Finally, although there were no differences seen in bone health or functional status, this trial may have been too short to adequately assess these outcomes.
Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester.
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