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Abstract and Introduction
Abstract
Objective. 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.
Methods. 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.
Results. 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.
Conclusions. Efficacy and safety of bazedoxifene are sustained across 7 years in postmenopausal women with osteoporosis.
Introduction
Osteoporosis disproportionately affects postmenopausal women, in whom declining estrogen production accelerates bone loss. Osteoporosis-related fractures cause increased morbidity and mortality, and impose a heavy economic burden. Currently available therapies for prevention or treatment of postmenopausal osteoporosis include bisphosphonates, hormone therapy, parathyroid hormone, denosumab, strontium ranelate (outside the United States), and selective estrogen receptor modulators (SERMs). Each is associated with unique benefits and risks. As such, not all currently available therapies are appropriate for long-term use. For example, bisphosphonates are associated with atypical, low-impact subtrochanteric stress fractures, the risk of which increases with duration of therapy. Thus, there is a continued need for therapies that are effective in preventing bone loss and in reducing fracture risk and have a favorable long-term safety/tolerability profile.
Bazedoxifene (BZA) is a novel SERM that is available in the European Union, Japan, and Korea for treatment of osteoporosis in postmenopausal women at increased risk for fracture. In a 2-year phase 3 osteoporosis prevention study (N = 1,583), daily oral doses of BZA 10, 20, and 40 mg effectively prevented bone loss in at-risk postmenopausal women. All doses were associated with a favorable safety/tolerability profile and had no adverse effects on the reproductive system. In a 3-year multicenter, randomized, double-blind, placebo (PBO)— and active-controlled phase 3 osteoporosis treatment study (N = 7,492) that was the core study (years 1-3) for the 7-year analyses reported here, BZA 20 mg (BZA20) and BZA 40 mg (BZA40) significantly (P < 0.05) reduced the risk of new vertebral fractures by 42% and 37%, respectively, compared with PBO in postmenopausal women with osteoporosis. There was no overall treatment effect on nonvertebral fractures; however, in a post hoc analysis of women at higher risk for fracture (n = 1,772), BZA20 significantly (P ≤ 0.05) reduced the risk of nonvertebral fractures compared with PBO and raloxifene 60 mg (RLX60). A 2-year extension of the core study (extension I) demonstrated that the efficacy of BZA was sustained through 5 years of treatment. BZA did not stimulate the endometrium or breast and was generally safe and well tolerated for 5 years.
A second 2-year extension (extension II, years 6-7) has been completed. The objective of this report is to describe the efficacy and safety of BZA compared with PBO across 7 years of therapy.
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