Clinical Question: Can vitamin D, given every four months, prevent fractures in men and women?

Setting: Outpatient (primary care)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: Investigators enrolled 2,686 adults 65 to 85 years of age who were living at home and were not taking vitamin D. Only 649 of the enrollees were women. Allocation to treatment assignment may not have been concealed from the enrolling investigator. The patients took placebo or vitamin D₃ (cholecalciferol) in a dosage of 100,000 IU every four months; a single capsule was sent by mail and patients were asked to take it immediately. The supplementation regimen lasted five years. Supplemental calcium was not given as part of the study nor was its use controlled.

During the study period, approximately 10 percent of the group (15 percent of the women and 8 percent of the men) experienced a fracture. Overall fracture rates were significantly less in the patients receiving vitamin D (8.8 versus 11.1 percent; number needed to treat [NNT] = 44). Men, on average, did not benefit from the supplemental vitamin D, although women did (fracture rate, 12.9 versus 18 percent; NNT = 20). In the relatively small number of women, hip or vertebral fractures were not decreased individually, although the study probably was too small to find a difference, if one exists.

This trial was designed as a pilot study, with the eventual goal of enrolling 20,000 men and women. Unfortunately, because of lack of funding, the larger study will not be completed. No one seems to be interested in this relatively simple, inexpensive treatment. Still, the authors were able to demonstrate a difference with a smaller number of patients, which makes it highly likely that the larger study would have shown similar benefit and possibly decreased the risk of hip fracture.

Bottom Line:In this preliminary study, taking vitamin D once every four months, without additional calcium, led to a decrease in osteoporotic fractures in older adults, primarily women. The large dosage (100,000 IU) works out to be a little more than 800 IU daily. This daily dosage, along with calcium supplementation, has been shown to decrease fractures (Dawson-Hughes B, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337:670–6). A lower dosage (e.g., 400 IU per day) does not work. Unfortunately, this dosage often is used in comparative trials with other drugs. (Level of Evidence: 1c)