Lasofoxifene in postmenopausal women with osteoporosis.
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.)
Cummings
Steven R
SR
San Francisco Coordinating Center, California Pacific Medical Center Research Institute, and University of California, San Francisco, San Francisco, USA. scummings@sfcc-cpmc.net
Ensrud
Kristine
K
Delmas
Pierre D
PD
LaCroix
Andrea Z
AZ
Vukicevic
Slobodan
S
Reid
David M
DM
Goldstein
Steven
S
Sriram
Usha
U
Lee
Andy
A
Thompson
John
J
Armstrong
Roisin A
RA
Thompson
David D
DD
Powles
Trevor
T
Zanchetta
Jose
J
Kendler
David
D
Neven
Patrick
P
Eastell
Richard
R
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
D050071:Bone Density Conservation Agents; D011759:Pyrrolidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene