Bazedoxifene In Postmenopausal Women Research Articles

Efficacy and safety of conjugated estrogen with bazedoxifene in postmenopausal women

Efficacy and safety of conjugated estrogen with bazedoxifene in postmenopausal women

Efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: A systematic review and meta-analysis.

Introduction:Bazedoxifene may be promising to treat osteoporosis of postmenopausal women. We conducted a systematic review and meta-analysis to explore the efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis.Methods:PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of bazedoxifene on osteoporosis of postmenopausal women were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were vertebral fracture and spine BMD at 3 and 7 years.Results:Four RCTs are included in the meta-analysis. Overall, compared with placebo intervention in postmenopausal women with osteoporosis, bazedoxifene intervention can significantly reduce the risk of vertebral fracture [risk risks (RRs) = 0.69; 95% confidence interval (95% CI) = 0.52–0.93; P = .01], and increase spine BMD at 3 years (Std. mean difference = 1.71; 95% CI = 1.55–1.87; P < .005) and 7 years (Std. mean difference = 8.31; 95% CI = 8.07–8.55; P < .005). Bazedoxifene intervention results in no increase in adverse events (RR = 1.00; 95% CI = 0.99–1.00; P = .34), serious adverse events (RR = 1.04; 95% CI = 0.97–1.12; P = .31), myocardial infarction (RR = 0.88; 95% CI = 0.51–1.52; P = .64), stroke (RR = 0.97; 95% CI = 0.64–1.46; P = .87), venous thromboembolic event (RR = 1.56; 95% CI = 0.92–2.64; P = .10), and breast carcinoma (RR = 1.03; 95% CI = 0.59–1.79; P = .92).Conclusions:Compared with placebo intervention for the osteoporosis of postmenopausal women, bazedoxifene intervention is found to significantly reduce the incidence of vertebral fracture and increase spine BMD at 3 and 7 years, and results in no increase in adverse events, serious adverse events, myocardial infarction, stroke, venous thromboembolic event, and breast carcinoma.

Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast.

Traditional menopausal hormone therapy containing estrogens/progestin has been associated with an increased risk of breast cancer, and estrogen exposure is known to promote growth and proliferation of a majority of breast cancers. Therefore, it is important for clinicians to consider the breast safety profile of any hormone-based therapy used in postmenopausal women. This review provides an overview of the breast safety and tolerability profiles of currently marketed selective estrogen receptor modulators, antiestrogens, and the first tissue selective estrogen complex combining conjugated estrogens with the selective estrogen receptor modulator bazedoxifene in postmenopausal women. Selective estrogen receptor modulators and antiestrogens act as estrogen receptor antagonists in the breast. Tamoxifen, toremifene, and the selective estrogen receptor degrader fulvestrant are used to treat breast cancer, and tamoxifen and raloxifene protect against breast cancer in high-risk women. Postmenopausal women using selective estrogen receptor modulators for prevention or treatment of osteoporosis (raloxifene, bazedoxifene) can be reassured that these hormonal treatments do not adversely affect their risk of breast cancer and may, in the case of raloxifene, even be protective. There are limited data on breast cancer in women who use ospemifene for dyspareunia. Conjugated estrogens/bazedoxifene use for up to two years did not increase mammographic breast density or breast pain/tenderness, and there was no evidence of an increased risk of breast cancer, suggesting that conjugated estrogens/bazedoxifene has an improved breast safety profile compared with traditional menopausal hormone therapies. Future research will continue to focus on development of selective estrogen receptor modulators and selective estrogen receptor modulator combinations capable of achieving the ideal balance of estrogen receptor agonist and antagonist effects.

A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: effects on bone density and fracture.

In a 3-year randomized, double-blind, osteoporosis treatment study (N = 7,492), bazedoxifene 20 mg and bazedoxifene 40 mg significantly (P < 0.05) reduced the risk of new vertebral fractures by 42% and 37%, respectively, compared with placebo in postmenopausal women with osteoporosis. This study evaluated the long-term (7-y) efficacy and safety of bazedoxifene in generally healthy postmenopausal women with osteoporosis. This was a second 2-year extension of the 3-year multicenter outpatient core study. During extension I (years 4-5), women receiving bazedoxifene 40 mg transitioned to bazedoxifene 20 mg. In extension II (years 6-7; N = 1,530), all bazedoxifene-treated women continued bazedoxifene 20 mg. Main outcome measures included year 7 endpoints: incidences of new vertebral and nonvertebral fractures, bone mineral density changes, and safety assessments. At 7 years, the cumulative incidences of new vertebral fractures were significantly lower in the bazedoxifene (6.4%) and bazedoxifene 20 mg (7.6%) groups than in the placebo group (9.9%); the relative risk reductions were 36.5% and 30.4%, respectively (both P < 0.001). Bazedoxifene had no effect on the overall incidence of nonvertebral fractures (bazedoxifene, 11.2%; bazedoxifene 20 mg, 12.0%; placebo, 10.8%). The mean changes from baseline in lumbar spine bone mineral density were 2.95%, 2.73%, and 2.19%, respectively. Seven-year decreases in total hip bone mineral density were significantly smaller in the bazedoxifene (-1.15%) and bazedoxifene 20 mg (-1.19%) groups than in the placebo group (-2.53%; P ≤ 0.002). Bazedoxifene showed a favorable safety/tolerability profile across 7 years, with similar adverse events, serious adverse events, and study discontinuations in all groups. Efficacy and safety of bazedoxifene are sustained across 7 years in postmenopausal women with osteoporosis.

The efficacy and safety of bazedoxifene in postmenopausal women by baseline kidney function status

Introduction Two global, double-blind, placebo- and active-controlled, phase-3 studies (2-year prevention (n = 1583) and 3-year treatment (n = 7492)) have shown that bazedoxifene (BZA) is safe and effective for prevention and treatment of postmenopausal osteoporosis.Objective To evaluate the efficacy/safety of BZA according to baseline kidney function.Methods Data for the BZA 20- and 40-mg and placebo groups from both studies were integrated for assessment of bone turnover markers (BTMs), bone mineral density (BMD), and fracture incidence (treatment study only). Safety was assessed using integrated data for the BZA, placebo, and raloxifene 60-mg groups from both studies. Baseline glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease Study equation; among subjects with baseline GFR, renal function categories were defined by GFR (ml/min per 1.73 m2): normal (GFR ≥ 90; n = 1982), mild impairment (60 ≤ GFR < 90; n = 6032), or moderate/severe impairment (GFR < 60; n = 723).Results Demographics were similar across treatment groups and within GFR subgroups. Across GFR subgroups, BZA 20 and 40 mg reduced BTM levels and improved lumbar spine and total hip BMD versus placebo. At month 24, there were significant treatment-by-GFR (p = 0.003) and treatment-by-serum creatinine (p = 0.034) interactions for the increase in lumbar spine BMD versus placebo. Fracture incidence was lower with BZA than placebo across all GFR categories, with no treatment-by-GFR interaction. There were no significant differences among treatment groups in incidences of overall, serious, or renal-related adverse events across GFR subgroups.Conclusions Mild to moderate kidney impairment did not affect the efficacy and safety of BZA in postmenopausal women.

Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial

Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years. We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis. In the core study, healthy postmenopausal women with osteoporosis (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. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere. A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium. Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years.

Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: Results of A 5-year, randomized, placebo-controlled phase 3 trial

Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: Results of A 5-year, randomized, placebo-controlled phase 3 trial

Safety and Tolerability of Bazedoxifene in Postmenopausal Women With Osteoporosis: Results of a 5-year, Randomized, Placebo-controlled Phase 3 Trial

Summary Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years.