Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women - Three-year data from 2double-blind, randomized, placebo-controlled trials

Background: In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive t issues. The studies reported herein evaluated the long-term (3-year) effect s of raloxifene treatment on bone mineral density (BMD), serum lipid levels , and drug tolerability in healthy postmenopausal women. Methods: A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assi gned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo dai ly; all groups received 400 to 600 mg of elemental calcium. Assessments inc luded measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels. Results: Lumbar spine BMD changed from baseline to 36 months as follows: pl acebo (mean percentage change +/- SE), -1.32%+/-0.22%; raloxifene, 30 mg, 0 .71% + 0.23%; raloxifene, 60 mg, 1.28% +/- 0.23%; and raloxifene, 150 mg, 1 .20%+/-0.24%. Comparable BMD changes were observed in the hip and total bod y. Biochemical markers of bone turnover were suppressed by raloxifene to no rmal premenopausal ranges through 3 years. Serum low-density lipoprotein ch olesterol was reduced 7% to 12% below baseline through 3 years. Study withd rawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of the rapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the place bo group); hot flashes were typically reported as mild and were not associa ted with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo). Conclusions: Raloxifene preserves BMD at important skeletal sites, lowers s erum low-density lipoprotein cholesterol levels, and has a tolerability pro file comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women.