Naslov
Lasofoxifene in postmenopausal women with osteoporosis

Autori
Cummings, Steven R. ; Ensrud, Kristine ; Delmas, Pierre D. ; LaCroix, Andrea Z. ; Vukičević, Slobodan ; Reid, David M. ; Goldstein, Steven ; Sriram, Usha ; Lee, Andy ; Thompson, John ; Armstrong, Roisin A. ; Thompson, David D. ; Powles, Trevor ; Zanchetta, Jose ; Kendler, David ; Neven, Patrick ; Eastell, Richard ; PEARL Study Investigators

Izvornik
The New England journal of medicine (0028-4793) 362 (2010), 8; 686-696

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
lasofoxifene; osteoporosis; postmenopause; clinical trial; fracture; breast cancer; cardiovascular diseases

Sažetak
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.) 2010 Massachusetts Medical Society

Izvorni jezik
Engleski

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