Efficacy and safety of bazedoxifene for postmenopausal osteoporosis

Abstract

Bazedoxifene, a novel selective estrogen receptor modulator, has been developed to have favorable effects on bone and the lipid profile while minimizing stimulation of uterine or breast tissues. Two large Phase III clinical trials showed that bazedoxifene, as well as raloxifene, increased bone mineral density, decreased levels of bone turnover markers, and significantly reduced the risk of new vertebral fractures in postmenopausal women compared with placebo. Although the incidence of nonvertebral fractures with bazedoxifene or raloxifene did not differ significantly from that with placebo, a post hoc analysis of a subgroup of women at higher fracture risk revealed that bazedoxifene significantly reduced the nonvertebral fracture risk relative to placebo and raloxifene. Bazedoxifene also improved the lipid profile by reducing the serum concentrations of total cholesterol and low-density lipoprotein cholesterol, with an increase in the serum level of high-density lipoprotein cholesterol. The incidences of vasodilatation (hot flushes), leg cramps, and venous thromboembolic events were significantly higher with bazedoxifene and raloxifene compared with placebo. There was no evidence of endometrial and breast stimulation with bazedoxifene. Taking advantage of the favorable effects of bazedoxifene on the breast and endometrium, the pairing of bazedoxifene with conjugated estrogens is under investigation for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis. A Phase III trial showed that combination therapy of bazedoxifene and conjugated estrogens significantly increased bone mineral density and decreased bone turnover markers, with relief of hot flushes and improvement of vaginal atrophy. This article reviews the clinical efficacy and safety of bazedoxifene in the treatment of postmenopausal osteoporosis.

Keywords: endometrium; estrogen receptor; nonvertebral fracture; osteoporosis; selective estrogen receptor modulators.

Figure 1

Chemical structures of 17β-estradiol and selective estrogen receptor modulators.

Figure 2

Effects of bazedoxifene on the lumbar spine and hip BMD. (A) Mean percent changes from baseline in the lumbar spine (L₁–L₄) BMD. (B) Mean percent changes from baseline in the total hip BMD. Notes: ^aP < 0.001 vs placebo at each time point; ^bP < 0.05 vs raloxifene at each time point; ^cP < 0.01 vs raloxifene at each time point. Adapted from Silverman SL, Christiansen C, Genant HK, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: Results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res. 2008;23(12):1923–1934, with permission from the American Society for Bone and Mineral Research. Abbreviation: BMD, bone mineral density.

Figure 3

Effects of bazedoxifene on the incidence of new vertebral and nonvertebral fractures over 3 years in patients with postmenopausal osteoporosis. The numbers above the bars represent the incidence of fracture (%) in each group. Note: ^aP < 0.05 vs placebo. Adapted from Silverman SL, Christiansen C, Genant HK, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: Results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res. 2008;23(12):1923–1934, with permission from the American Society for Bone and Mineral Research. Abbreviations: RRR, relative risk reduction; HR, hazard ratio; CI, confidence interval; ns, not significant.

Figure 4

Incidence of nonvertebral fractures in subjects at a higher risk for fracture. The higher-risk subgroup was defined as a femoral neck T score of ≤ −3.0 and/or ≥1 moderate or severe vertebral fractures or multiple mild vertebral fractures (n = 1772). The numbers above the bars represent the incidence of fracture (%) in each group over 3 years. Notes: ^aRelative to placebo; ^bRelative to raloxifene. Adapted from Silverman SL, Christiansen C, Genant HK, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: Results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res. 2008;23(12):1923–1934, with permission from the American Society for Bone and Mineral Research. Abbreviations: RRR, relative risk reduction; ns, not significant.