title: Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women.
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.
authors.affiliation: San Francisco Coordinating Center, California Pacific Medical Center Research Institute and the University of California, San Francisco, CA 94107, USA. scummings@sfcc-cpmc.net
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Michael
authors.initials: M
authors.lastname: McClung
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.forename: David
authors.initials: D
authors.lastname: Cox
authors.forename: Bruce
authors.initials: B
authors.lastname: Mitlak
authors.forename: John
authors.initials: J
authors.lastname: Stock
authors.forename: Messan
authors.initials: M
authors.lastname: Amewou-Atisso
authors.forename: Trevor
authors.initials: T
authors.lastname: Powles
authors.forename: Paul
authors.initials: P
authors.lastname: Miller
authors.forename: José
authors.initials: J
authors.lastname: Zanchetta
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000517:prevention & control*; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control; D010880:Piperidines / Q000627:therapeutic use*; D010919:Placebos; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D004164:Diphosphonates; D010880:Piperidines; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; C115121:LY 353381