Context. Vitamin D insufficiency and osteoporosis are common and often co-exist in postmenopausal women.

Objective. To test whether the presence of vitamin D insufficiency at the initiation of raloxifene therapy affected the subsequent response of bone mineral density (BMD).

Design, Setting and Participants. We studied 7522 postmenopausal participants of the Multiple Outcomes of Raloxifene Evaluation (MORE), a placebo controlled trial of the effects of raloxifene on BMD and fracture.

Intervention. Upon enrollment, all participants began daily supplements of 500 mg of calcium and 400-600 IU of cholecalciferol; a month later women were randomly assigned to placebo or raloxifene.

Main Outcome Measure. Serum levels of vitamin D (25OHD) were measured at enrollment, randomization and 6 months later. We categorized participants' vitamin D status (Deficient, Insufficient or Sufficient) based on their randomization 25OHD level. We estimated the effects of treatment on BMD within these subgroups using linear regression models.

Results. At enrollment, 3.2% of participants were vitamin D deficient and 51.8% insufficient; after 7 months of cholecalciferol supplementation, 0.2% of all participants remained D deficient and 23.6% insufficient. The effects of raloxifene on hip and spine BMD did not vary by vitamin D status at randomization (P = 0.08 and P = 0.7, respectively).

Conclusion. We conclude that vitamin D status at initiation of raloxifene therapy does not affect the subsequent BMD response when co-administered with cholecalciferol and calcium. After seven months of cholecalciferol therapy, very few women continued to have 25OHD levels in the deficient range; however, 25OHD levels remained suboptimal in nearly a quarter of the cohort. Further research is needed to determine whether these observations can be generalized to other anti-resorptive agents.