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

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.

Trial registration: NCT00088010.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Resorption
  • Breast Neoplasms / prevention & control*
  • Diphosphonates / therapeutic use
  • Female
  • Fractures, Bone / prevention & control*
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal / prevention & control
  • Piperidines / therapeutic use*
  • Placebos
  • Postmenopause
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Thiophenes / therapeutic use*


  • Diphosphonates
  • Piperidines
  • Placebos
  • Selective Estrogen Receptor Modulators
  • Thiophenes
  • LY 353381

Associated data