[show abstract][hide abstract] ABSTRACT: Osteoporosis is a significant public health concern, particularly for postmenopausal women. Current treatment options may not be appropriate for all women. Selective estrogen-receptor modulators (SERMs) are a class of molecules with tissue-selective activity. Bazedoxifene is currently in clinical development for the prevention and treatment of postmenopausal osteoporosis. In a 2-year, phase III, osteoporosis prevention study (N = 1583), bazedoxifene 10, 20, and 40 mg was shown to preserve bone mineral density and decrease biochemical markers of bone turnover compared with placebo in postmenopausal women at risk for osteoporosis. In a pivotal 3-year, phase III, osteoporosis treatment study (N = 7492), bazedoxifene 20 and 40 mg significantly reduced the incidence of new vertebral fractures compared with placebo (p < 0.05 for both) in postmenopausal women with osteoporosis. In a post hoc subgroup analysis of women at higher risk for fracture (n = 1772), bazedoxifene 20 mg significantly reduced the risk of nonvertebral fractures versus placebo (p = 0.02) and raloxifene 60 mg (p = 0.05). Bazedoxifene 20 mg has demonstrated sustained efficacy in reducing the risk of vertebral fractures over 5 and 7 years. Overall, bazedoxifene was generally safe and well tolerated, with favorable endometrial and breast safety profiles. As with other SERMs, the rate of deep vein thrombosis was higher in the bazedoxifene groups compared with placebo at 3 and 5 years. Considering its demonstrated efficacy and safety, bazedoxifene may be an appropriate osteoporosis therapy for women who cannot take or are unwilling to take bisphosphonates because of safety or tolerability issues. Bazedoxifene may also be appropriate for younger women at increased fracture risk who are concerned about the effects of long-term bisphosphonate therapy. This article reviews the results of key clinical trials of bazedoxifene for the prevention and treatment of postmenopausal osteoporosis and describes its role in clinical practice.
Therapeutic advances in musculoskeletal disease 02/2012; 4(1):21-34.
[show abstract][hide abstract] ABSTRACT: Several selective estrogen receptor modulators are in clinical development for postmenopausal osteoporosis. Bazedoxifene has shown significant reductions in vertebral and non-vertebral (in higher-risk women) fracture risk, with no evidence of breast or endometrial stimulation. Lasofoxifene has demonstrated significant reductions in vertebral and non-vertebral fracture risk, but has been associated with endometrial/uterine effects. Both selective estrogen receptor modulators were generally safe and well tolerated but have been associated with some "class effects" (e.g., hot flushes, venous thromboembolic events). A tissue selective estrogen complex partnering bazedoxifene with conjugated estrogens is under clinical investigation for the treatment of menopausal symptoms and osteoporosis prevention. Future directions in selective estrogen receptor modulator research include ospemifene and RAD 1901.
[show abstract][hide abstract] 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 (-0.65%, 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.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2011; 26(3):519-29. · 6.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis.
Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination.
Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups.
Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis.
Trial registration number: NCT00205777; Trial registration date: September 16, 2005.
[show abstract][hide abstract] ABSTRACT: Postmenopausal osteoporosis is an increasing worldwide health concern affecting an estimated 200 million individuals. Despite a wide range of available treatment options, many patients are not being treated or discontinue therapy. The ongoing need for new osteoporosis therapies has led to the development of new selective estrogen receptor modulators (SERMs) with an ideal tissue selectivity profile and beneficial effects on bone without undesirable effects on the endometrium and breast. Bazedoxifene acetate, a novel SERM in clinical development for the prevention and treatment of postmenopausal osteoporosis, resembles this ideal profile more closely than other currently available SERMs. Results from large prospective phase III trials showed that it increases bone mineral density, reduces bone turnover rate and decreases the risk for new vertebral fractures. Moreover, based on a post hoc analysis of a subgroup of women with a higher risk for fracture, bazedoxifene was demonstrated to significantly reduce the incidence of nonvertebral fractures compared with both raloxifene hydrochloride and placebo. Furthermore, it was reported to be well tolerated, with a favorable safety profile and no evidence of endometrial or breast tissue stimulation. Bazedoxifene represents an important new treatment option for women at risk for osteoporosis and fracture.
[show abstract][hide abstract] ABSTRACT: In this 3-yr, randomized, double-blind, placebo- and active-controlled study, healthy postmenopausal women with osteoporosis (55-85 yr of age) were treated with bazedoxifene 20 or 40 mg/d, raloxifene 60 mg/d, or placebo. The primary endpoint was incidence of new vertebral fractures after 36 mo; secondary endpoints included nonvertebral fractures, BMD, and bone turnover markers. Among 6847 subjects in the intent-to-treat population, the incidence of new vertebral fractures was significantly lower (p < 0.05) with bazedoxifene 20 mg (2.3%), bazedoxifene 40 mg (2.5%), and raloxifene 60 mg (2.3%) compared with placebo (4.1%), with relative risk reductions of 42%, 37%, and 42%, respectively. The treatment effect was similar among subjects with or without prevalent vertebral fracture (p = 0.89 for treatment by baseline fracture status interaction). The incidence of nonvertebral fractures with bazedoxifene or raloxifene was not significantly different from placebo. In a posthoc analysis of a subgroup of women at higher fracture risk (femoral neck T-score <or= -3.0 and/or >or=1 moderate or severe vertebral fracture or multiple mild vertebral fractures; n = 1772), bazedoxifene 20 mg showed a 50% and 44% reduction in nonvertebral fracture risk relative to placebo (p = 0.02) and raloxifene 60 mg (p = 0.05), respectively. Bazedoxifene significantly improved BMD and reduced bone marker levels (p < 0.001 versus placebo). The incidence of vasodilatation, leg cramps, and venous thromboembolic events was higher with bazedoxifene and raloxifene compared with placebo. In conclusion, bazedoxifene significantly reduced the risk of new vertebral fracture in postmenopausal women with osteoporosis and decreased the risk of nonvertebral fracture in subjects at higher fracture risk.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2008; 23(12):1923-34. · 6.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Osteoporosis is an increasingly common health concern in postmenopausal women. In a 2-yr phase III study, bazedoxifene prevented bone loss, reduced bone turnover, and was well tolerated in early postmenopausal women with normal or low BMD.
Bazedoxifene is a novel selective estrogen receptor modulator that has increased BMD and bone strength in experimental models, without stimulating breast or uterus. This 24-mo, randomized, double-blind study assessed the efficacy and safety of three doses of bazedoxifene compared with placebo and raloxifene in the prevention of postmenopausal osteoporosis.
Healthy postmenopausal women with a BMD T-score at the lumbar spine or femoral neck between -1.0 and -2.5 or clinical risk factors for osteoporosis were randomly assigned to one of five groups: bazedoxifene 10, 20, or 40 mg/d, placebo, or raloxifene 60 mg/d. All women received elemental calcium. Efficacy outcomes included changes from baseline through 24 mo in BMD of the lumbar spine, hip, femoral neck, and femoral trochanter and biomarkers of bone metabolism.
The intent-to-treat population included 1434 women (mean age, 58 yr; mean time from last menstrual period, 11 yr). All doses of bazedoxifene and raloxifene prevented bone loss, whereas in the placebo group, there was significant loss of BMD at all skeletal sites. Mean differences in percent change in lumbar spine BMD from baseline to 24 mo relative to placebo were 1.08 +/- 0.28%, 1.41 +/- 0.28%, 1.49 +/- 0.28%, and 1.49 +/- 0.28% for 10, 20, and 40 mg bazedoxifene and 60 mg raloxifene, respectively (p < 0.001 for all comparisons). Comparable BMD responses were observed at other body sites. Significant and comparable decreases in serum osteocalcin and C-telopeptide levels from baseline and relative to placebo with active treatment were observed as early as 3 mo and were sustained through study conclusion (p < 0.001). Overall incidences of adverse events, serious adverse events, and discontinuations caused by adverse events were similar between groups. The most common adverse events included headache, infection, arthralgia, pain, hot flush, and back pain.
Treatment with bazedoxifene prevented bone loss and reduced bone turnover equally as well as raloxifene and was generally well tolerated in postmenopausal women with normal/low BMD.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2008; 23(4):525-35. · 6.04 Impact Factor