Background: The role of vitamin D in reducing fractures has been questioned by several recent trials, including a 2007 meta-analysis that found no benefit. However, epidemiologic data support a positive association between 25-hydroxyvitamin D levels and fracture reduction. This disparity might be explained if fracture reduction occurred only at higher levels of vitamin D intake, because previous reviews did not stratify results based on vitamin D dosage. Bischoff-Ferrari and colleagues performed a meta-analysis of oral vitamin D supplementation in preventing nonvertebral and hip fractures in adults older than 65 years.

The Study: The study evaluated 12 double-blind trials, including 42,279 participants with a mean age of 78 years. Only randomized controlled trials with at least one year of follow-up were reviewed. Studies were excluded if they included patients with organ transplantation or stroke, or who were receiving corticosteroid therapy. The primary outcome was the relative risk of a nonvertebral or hip fracture in persons receiving supplemental vitamin D with or without calcium supplementation, compared with those receiving placebo. Studies were screened for result heterogeneity, which could mask notable changes if the results were nonselectively pooled. In these cases, the data were stratified according to vitamin D dosage (less than or equal to 400 IU per day or greater than 400 IU per day) and achieved 25-hydroxyvitamin D level.

Results: No benefit of vitamin D supplementation was found in general, but a dose-response effect occurred when results were stratified by dosage. Patients receiving less than 400 IU per day of vitamin D continued to show no reduction in fractures compared with placebo. However, patients receiving more than 400 IU per day of vitamin D (482 to 770 IU per day) were less likely to have a nonvertebral or hip fracture (relative risk = 0.80 and 0.82, respectively; numbers needed to treat = 93 and 168, respectively). Calcium supplementation in addition to high-dose vitamin D intake was not associated with further decrease in nonvertebral fracture risk.

Conclusion: High-dose supplemental vitamin D (482 to 770 IU per day) can reduce risk of nonvertebral fractures by at least 20 percent, and hip fractures by at least 18 percent. Lower vitamin D intake does not appear to confer any protective benefit.