拉索昔芬治疗绝经后骨质疏松症女性。

Lasofoxifene in postmenopausal women with osteoporosis.

机构信息

San Francisco Coordinating Center, California Pacific Medical Center Research Institute, and University of California, San Francisco, San Francisco, USA.

出版信息

N Engl J Med. 2010 Feb 25;362(8):686-96. doi: 10.1056/NEJMoa0808692.

DOI:10.1056/NEJMoa0808692

PMID:20181970

Abstract

BACKGROUND

The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascular disease are uncertain.

METHODS

In this randomized trial, we assigned 8556 women who were between the ages of 59 and 80 years and had a bone mineral density T score of -2.5 or less at the femoral neck or spine to receive once-daily lasofoxifene (at a dose of either 0.25 mg or 0.5 mg) or placebo for 5 years. Primary end points were vertebral fractures, estrogen receptor (ER)-positive breast cancer, and nonvertebral fractures; secondary end points included major coronary heart disease events and stroke.

RESULTS

Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1000 person-years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 person-years; hazard ratio, 0.19; 95% CI, 0.07 to 0.56), coronary heart disease events (5.1 vs. 7.5 cases per 1000 person-years; hazard ratio, 0.68; 95% CI, 0.50 to 0.93), and stroke (2.5 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.64; 95% CI, 0.41 to 0.99). Lasofoxifene at a dose of 0.25 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (16.0 vs. 22.4 cases per 1000 person-years; hazard ratio, 0.69; 95% CI, 0.57 to 0.83) and stroke (2.4 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.61; 95% CI, 0.39 to 0.96) Both the lower and higher doses, as compared with placebo, were associated with an increase in venous thromboembolic events (3.8 and 2.9 cases vs. 1.4 cases per 1000 person-years; hazard ratios, 2.67 [95% CI, 1.55 to 4.58] and 2.06 [95% CI, 1.17 to 3.60], respectively). Endometrial cancer occurred in three women in the placebo group, two women in the lower-dose lasofoxifene group, and two women in the higher-dose lasofoxifene group. Rates of death per 1000 person-years were 5.1 in the placebo group, 7.0 in the lower-dose lasofoxifene group, and 5.7 in the higher-dose lasofoxifene group.

CONCLUSIONS

In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events. (ClinicalTrials.gov number, NCT00141323.)

摘要

背景

拉索昔芬对骨折、乳腺癌和心血管疾病风险的影响尚不确定。

方法

在这项随机试验中，我们将 8556 名年龄在 59 岁至 80 岁之间且股骨颈或脊柱处的骨密度 T 评分为-2.5 或更低的女性随机分配，每日接受一次拉索昔芬（剂量分别为 0.25 毫克或 0.5 毫克）或安慰剂治疗，为期 5 年。主要终点是椎体骨折、雌激素受体（ER）阳性乳腺癌和非椎体骨折；次要终点包括主要冠心病事件和中风。

结果

与安慰剂相比，每日 0.5 毫克剂量的拉索昔芬可降低椎体骨折风险（每 1000 人年 13.1 例与 22.4 例；风险比，0.58；95%置信区间[CI]，0.47 至 0.70）、非椎体骨折（每 1000 人年 18.7 例与 24.5 例；风险比，0.76；95%CI，0.64 至 0.91）、ER 阳性乳腺癌（每 1000 人年 0.3 例与 1.7 例；风险比，0.19；95%CI，0.07 至 0.56）、冠心病事件（每 1000 人年 5.1 例与 7.5 例；风险比，0.68；95%CI，0.50 至 0.93）和中风（每 1000 人年 2.5 例与 3.9 例；风险比，0.64；95%CI，0.41 至 0.99）。与安慰剂相比，每日 0.25 毫克剂量的拉索昔芬可降低椎体骨折风险（每 1000 人年 16.0 例与 22.4 例；风险比，0.69；95%CI，0.57 至 0.83）和中风风险（每 1000 人年 2.4 例与 3.9 例；风险比，0.61；95%CI，0.39 至 0.96）。与安慰剂相比，低剂量和高剂量组的静脉血栓栓塞事件发生率均有所增加（每 1000 人年分别为 3.8 例和 2.9 例与 1.4 例；风险比分别为 2.67[95%CI，1.55 至 4.58]和 2.06[95%CI，1.17 至 3.60]）。安慰剂组有 3 名女性发生子宫内膜癌，低剂量拉索昔芬组有 2 名女性，高剂量拉索昔芬组有 2 名女性。每 1000 人年的死亡率分别为安慰剂组 5.1 例、低剂量拉索昔芬组 7.0 例和高剂量拉索昔芬组 5.7 例。