Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal japanese women with osteoporosis

Abstract

This randomized, double-blind, placebo-controlled, dose-response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (À0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo ( p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks ( p < .05 for all) and were sustained throughout the study. Total and low-density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo ( p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis. ß

Safety of bazedoxifene in Korean women with post-menopausal osteoporosis: a post-marketing surveillance study (PMSS)

“…In a 2-year, pivotal bazedoxifene Phase III, multicenter, double-blind, randomized, placebo-and raloxifene-controlled clinical study performed in 101 sites in Canada, Europe, and the United States with 1,583 postmenopausal women, there was no difference in the incidences of AE, SAE and withdrawal due to AEs between all groups, although the incidences of hot flushes were higher in the treatment arms [8]. Similar outcomes were observed in a phase Ⅱ trial of 429 postmenopausal Japanese women with osteoporosis, reporting favorable safety and tolerability profile of bazedoxifene [12].…”

Eldecalcitol, in Combination with Bisphosphonate, Is Effective for Treatment of Japanese Osteoporotic Patients

“…The effectiveness of BP on BMD diminishes over long treatment periods (Bone et al 2004). Itabashi et al (2011) recently described that SERM significantly increased BMD for up to 104 weeks after treatment, although increasing ratio plateaued or worsened slightly after a few years of treatment. Thus, the effects on BMD of BP and SERM presumably decreased over time, which may have favored the assessment of the firstly administered ALF.…”

“…Bisphosphonate (BP) and selective estrogen receptor modulator (SERM) are representative anti-resorptive drugs (Miller et al 2008;Itabashi et al 2011) that are frequently combined with vitamin D analogues to treat osteoporotic patients. Combination therapy of oral BP and vitamin D analogues showed additive anti-osteoporotic effects as compared with BP monotherapy in postmenopausal women (Orimo et al 2011;Sakai et al 2015).…”

Conjugated Estrogens and Bazedoxifene

“…2 Bazedoxifene is not approved as a single agent ingredient; however, there are studies supporting its potential use as monotherapy in the prevention and treatment of osteoporosis in postmenopausal women. [3][4][5][6][7][8][9][10][11][12][13][14][15] Raloxifene, another SERM, is approved 1 Clinical effects observed in animal models include prevention of ovariectomy-associated body weight increases, 17 protection against ovariectomyassociated bone loss, [18][19][20] increased bone mineral density, 21,22 and increased bone compressive strength.…”