Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women

• DOI: 10.1002/jbmr.191
• Publication Date: 2010-07-23T18:07:58Z
• Authors: Steven R Cummings; Michael McClung; Jean-Yves Reginster; David Cox; Bruce Mitlak; John Stock; Messan Amewou-Atisso; Trevor Powles; Paul Miller; José Zanchetta; Claus Christiansen
• Keywords: Selective Estrogen Receptor Modulators; Breast Neoplasms; Thiophenes; Placebos; Fractures, Bone; 03 medical and health sciences; breast cancer; 0302 clinical medicine; Piperidines; Humans; Bone Resorption; vertebral fracture; Osteoporosis, Postmenopausal; Aged; Aged, 80 and over; Diphosphonates; controlled trial; Middle Aged; osteoporosis; serms; 3. Good health; Postmenopause; fracture; randomized; Female; arzoxifene

Abstract 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. © 2011 American Society for Bone and Mineral Research.