San Francisco Coordinating Center, California Pacific Medical Center Research Institute and the University of California, San Francisco, CA 94107, USA.
J Bone Miner Res. 2011 Feb;26(2):397-404. doi: 10.1002/jbmr.191. Epub 2010 Jul 23.
Arzoxifene is a selective estrogen receptor modulator (SERM) that has been shown to be more potent in preclinical testing than currently available agents. Its effects on clinical outcomes are not known. In a randomized, blinded trial, women aged 60 to 85 years with osteoporosis, defined as a femoral neck or lumbar spine bone mineral density T-score of -2.5 or less or a vertebral fracture, and women with low bone mass, defined as a bone density T-score of -1.0 or less and above -2.5, were assigned to arzoxifene 20 mg or placebo daily. The primary endpoints were new vertebral fracture in those with osteoporosis and invasive breast cancer in the overall population. After 3 years, the cumulative incidence of vertebral fractures in patients with osteoporosis was 2.3% lower in the arzoxifene group than in the placebo group, a 41% relative risk reduction [95% confidence interval (CI) 0.45-0.77, p < .001]. In the overall population, the cumulative incidence of invasive breast cancer over 4 years was reduced by 1.3%, with a 56% relative reduction in risk (hazard ratio = 0.44, 95% CI 0.26-0.76, p < .001); there was no significant decrease in nonvertebral fracture risk. Arzoxifene increased the cumulative incidence of venous thromboembolic events by 0.7%, with a 2.3-fold relative increase (95% CI 1.5-3.7). Like other SERMs, arzoxifene decreased vertebral fractures and invasive breast cancer while the risk of venous thromboembolic events increased.
阿佐昔芬是一种选择性雌激素受体调节剂（SERM），在临床前试验中显示其效力强于目前可用的药物。其对临床结局的影响尚不清楚。在一项随机、双盲试验中，年龄在 60 至 85 岁之间的患有骨质疏松症（定义为股骨颈或腰椎骨密度 T 评分小于等于-2.5 或有椎体骨折）和低骨量（定义为骨密度 T 评分小于-1.0 但大于-2.5）的女性被分配接受阿佐昔芬 20 毫克或安慰剂每日治疗。主要终点是骨质疏松症患者的新发椎体骨折和总体人群的浸润性乳腺癌。3 年后，骨质疏松症患者的椎体骨折累积发生率在阿佐昔芬组比安慰剂组低 2.3%，相对风险降低 41%[95%置信区间（CI）0.45-0.77，p <.001]。在总体人群中，4 年内浸润性乳腺癌的累积发生率降低了 1.3%，风险降低了 56%（风险比=0.44，95%CI 0.26-0.76，p <.001）；非椎体骨折风险无显著降低。阿佐昔芬使静脉血栓栓塞事件的累积发生率增加了 0.7%，相对增加了 2.3 倍（95%CI 1.5-3.7）。与其他 SERM 一样，阿佐昔芬降低了椎体骨折和浸润性乳腺癌的风险，同时增加了静脉血栓栓塞事件的风险。
