Miller Paul D, Chines Arkadi A, Christiansen Claus, Hoeck Hans C, Kendler David L, Lewiecki E Michael, Woodson Grattan, Levine Amy B, Constantine Ginger, Delmas Pierre D
Colorado Center for Bone Research, Lakewood, Colorado 80227, USA.
J Bone Miner Res. 2008 Apr;23(4):525-35. doi: 10.1359/jbmr.071206.
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.
骨质疏松症在绝经后女性中是一个日益常见的健康问题。在一项为期2年的III期研究中，巴多昔芬可预防骨质流失，降低骨转换，并且在骨密度正常或较低的绝经早期女性中耐受性良好。
巴多昔芬是一种新型选择性雌激素受体调节剂，在实验模型中可增加骨密度和骨强度，且不会刺激乳腺或子宫。这项为期24个月的随机双盲研究评估了三种剂量的巴多昔芬与安慰剂和雷洛昔芬相比在预防绝经后骨质疏松症方面的疗效和安全性。
腰椎或股骨颈骨密度T值在-1.0至-2.5之间或有骨质疏松临床风险因素的健康绝经后女性被随机分配到五组之一：巴多昔芬10、20或40mg/天，安慰剂，或雷洛昔芬60mg/天。所有女性均补充元素钙。疗效指标包括从基线到24个月时腰椎、髋部、股骨颈和股骨转子的骨密度变化以及骨代谢生物标志物。
意向性治疗人群包括1434名女性（平均年龄58岁；距末次月经平均时间11年）。所有剂量的巴多昔芬和雷洛昔芬均可预防骨质流失，而安慰剂组所有骨骼部位的骨密度均有显著下降。相对于安慰剂，从基线到24个月时腰椎骨密度百分比变化的平均差异，10mg、20mg和40mg巴多昔芬组以及60mg雷洛昔芬组分别为1.08±0.28%、1.41±0.28%、1.49±0.28%和1.49±0.28%（所有比较p<0.001）。在其他身体部位也观察到了类似的骨密度反应。早在3个月时就观察到活性治疗组血清骨钙素和C-末端肽水平相对于基线和安慰剂有显著且类似的下降，并持续到研究结束（p<0.001）。各组之间不良事件、严重不良事件以及由不良事件导致的停药的总体发生率相似。最常见的不良事件包括头痛、感染、关节痛、疼痛、潮热和背痛。
巴多昔芬治疗在预防骨质流失和降低骨转换方面与雷洛昔芬效果相当，并且在骨密度正常/较低的绝经后女性中总体耐受性良好。
