Program for Osteoporosis and Bone Health, Division of Endocrinology and Metabolism, Virginia Commonwealth University, 1101 E Marshall Street, 7-015, P.O. Box 980111, Richmond, VA 23298-0111, USA.
Osteoporos Int. 2010 Jul;21(7):1215-26. doi: 10.1007/s00198-009-1060-5. Epub 2009 Oct 2.
In this Phase 2 study of postmenopausal women with low bone, arzoxifene (a selective estrogen receptor modulator (SERM)) significantly reduced bone turnover marker levels and increased bone mineral density (BMD) versus placebo. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene, a SERM in current clinical use. Arzoxifene's safety profile appeared similar to raloxifene.
This 6-month, Phase 2, double-blind, placebo- and raloxifene-controlled study was designed to assess the effects of arzoxifene on bone turnover and overall safety in postmenopausal women with low bone mass.
Postmenopausal women (N = 219; mean age, 59 years) with a T-score between -1 and -2.5 were randomly assigned to daily arzoxifene 5, 10, 20, or 40 mg, raloxifene 60 mg, or placebo. All received daily calcium.
All arzoxifene doses significantly reduced osteocalcin (primary endpoint), type 1 collagen C-telopeptide, bone specific alkaline phosphatase, and procollagen type I amino-terminal propeptide versus placebo, and increased lumbar spine BMD. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene. Arzoxifene decreased cholesterol, low-density lipoprotein cholesterol, and fibrinogen versus placebo. Endometrial thickness change with arzoxifene was not significantly different from placebo or raloxifene; no cases of endometrial hyperplasia or adenocarcinoma were observed. Adverse event reporting with arzoxifene was similar to that with raloxifene, as were hot flush and night sweat reporting.
Arzoxifene suppressed bone turnover and increased BMD. Within the limitations of this study, the endometrial safety profile of arzoxifene appeared similar to that of raloxifene. While no clear dose effect was evident, arzoxifene 20 and 40 mg/day appeared the optimal doses for reducing bone turnover.
本研究旨在评估阿佐昔芬对绝经后低骨量妇女骨转换标志物水平和骨密度的影响及其安全性。
共纳入 219 名绝经后妇女（平均年龄 59 岁），骨密度 T 值在-1 到-2.5 之间，按 1:1:1:1:1:1 比例随机分为阿佐昔芬 5、10、20、40mg 组，雷洛昔芬 60mg 组和安慰剂组，所有患者均接受每日钙剂治疗。
与安慰剂相比，所有剂量的阿佐昔芬均能显著降低骨钙素（主要终点）、I 型胶原 C 端肽、骨碱性磷酸酶、I 型前胶原氨基端前肽，并能增加腰椎骨密度；阿佐昔芬对骨转换和骨密度的影响一般大于雷洛昔芬。与安慰剂相比，阿佐昔芬可降低胆固醇、低密度脂蛋白胆固醇和纤维蛋白原。阿佐昔芬组子宫内膜厚度的变化与安慰剂和雷洛昔芬无显著差异，也未观察到子宫内膜增生或腺癌病例。阿佐昔芬组不良事件的报告与雷洛昔芬相似，且潮红和盗汗的报告也相似。
阿佐昔芬能抑制骨转换并增加骨密度。在本研究的限制范围内，阿佐昔芬的子宫内膜安全性与雷洛昔芬相似。虽然没有明显的剂量效应，但阿佐昔芬 20 和 40mg/天似乎是降低骨转换的最佳剂量。
