title: Lasofoxifene in postmenopausal women with osteoporosis.
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.)
authors.affiliation: San Francisco Coordinating Center, California Pacific Medical Center Research Institute, and University of California, San Francisco, San Francisco, USA. scummings@sfcc-cpmc.net
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Kristine
authors.initials: K
authors.lastname: Ensrud
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Delmas
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: Slobodan
authors.initials: S
authors.lastname: Vukicevic
authors.forename: David M
authors.initials: DM
authors.lastname: Reid
authors.forename: Steven
authors.initials: S
authors.lastname: Goldstein
authors.forename: Usha
authors.initials: U
authors.lastname: Sriram
authors.forename: Andy
authors.initials: A
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: Thompson
authors.forename: Roisin A
authors.initials: RA
authors.lastname: Armstrong
authors.forename: David D
authors.initials: DD
authors.lastname: Thompson
authors.forename: Trevor
authors.initials: T
authors.lastname: Powles
authors.forename: Jose
authors.initials: J
authors.lastname: Zanchetta
authors.forename: David
authors.initials: D
authors.lastname: Kendler
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D003327:Coronary Disease / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000032:analysis; D012306:Risk; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D016103:Spinal Fractures / Q000453:epidemiology / Q000517:prevention & control*; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D050071:Bone Density Conservation Agents; D011759:Pyrrolidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene