Objective: To review the effect of vitamin D on bone density and fractures in postmenopausal women.
Data source: We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data.
Study selection: We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr.
Data extraction: For each trial, three independent reviewers assessed the methodological quality and abstracted data.
Data synthesis: Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 microg yield larger effects than lower doses. Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88), an effect that was similar in trials of standard and hydroxylated vitamin D.
Conclusions: Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures. The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.