Bone histomorphometric and biochemical marker results of a 2-year placebo-controlled trial of raloxifene in postmenopausal women.

Raloxifene is a selective estrogen receptor modulator that has been shown to increase bone density. The purpose of this study was to examine the effects of raloxifene on bone tissue by studying bone biopsy specimens before and after 2 years of raloxifene or placebo therapy. The women in this study were participants of the double-blind, placebo-controlled, multicenter study, the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. Subjects from two U.S. sites and two European sites were included if they consented to a bone biopsy. Iliac crest bone biopsies were performed at baseline and after 2 years. Tetracycline labeling preceded each biopsy. A total of 65 paired biopsy specimens were evaluated with 25, 22, and 18 patients in the placebo, raloxifene HCl (60 mg) and raloxifene HCl (120 mg) treatment groups, respectively. They were analyzed using standard histomorphometry. None of the biopsy specimens showed evidence of toxic effects on bone or bone cells or met criteria for osteomalacia. Biopsy specimens in the placebo and raloxifene groups had the appearance of normal bone, with no evidence of marrow fibrosis or increases in the amount of woven bone or numbers of empty osteocyte lacunae. Compared with the baseline, the bone formation rate (BFR) decreased significantly in both raloxifene groups. The change in BFR in the group treated with 120 mg of raloxifene was -62.3%, which was significantly lower than the change in the placebo group of -21.0% (p = 0.03). No change in resorption parameters could be measured by histomorphometry, but there was a decrease in urinary type I collagen excretion. The results from this study suggest that raloxifene has actions on bone tissue that are similar to those observed with estrogen. The depressive effects on bone remodeling are less marked than the effects seen with alendronate.