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: Steven R Cummings, Kristine Ensrud, Pierre D Delmas, Andrea Z LaCroix, Slobodan Vukicevic, David M Reid, Steven Goldstein, Usha Sriram, Andy Lee, John Thompson, Roisin A Armstrong, David D Thompson, Trevor Powles, Jose Zanchetta, David Kendler, Patrick Neven, Richard Eastell, PEARL Study Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 362 Issue 8 Pg. 686-96 (Feb 25 2010) ISSN: 1533-4406 [Electronic] United States
• PMID: 20181970 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Massachusetts Medical Society

Chemical References

• Bone Density Conservation Agents
• Pyrrolidines
• Receptors, Estrogen
• Selective Estrogen Receptor Modulators
• Tetrahydronaphthalenes
• Lasofoxifene

Topics

• Aged
• Bone Density (drug effects)
• Bone Density Conservation Agents (adverse effects, therapeutic use)
• Breast Neoplasms (epidemiology, prevention & control)
• Coronary Disease (epidemiology, prevention & control)
• Female
• Fractures, Bone (epidemiology, prevention & control)
• Humans
• Middle Aged
• Osteoporosis, Postmenopausal (complications, drug therapy)
• Pyrrolidines (adverse effects, therapeutic use)
• Receptors, Estrogen (analysis)
• Risk
• Selective Estrogen Receptor Modulators (adverse effects, therapeutic use)
• Spinal Fractures (epidemiology, prevention & control)
• Stroke (epidemiology, prevention & control)
• Tetrahydronaphthalenes (adverse effects, therapeutic use)
• Venous Thromboembolism (chemically induced, epidemiology)