Naslov
Lasofoxifene in Postmenopausal Women With Osteoporosis

Autori
Cummings, Steven R. ; Ensrud, Kristine ; Delmas, P.D. ; LaCroix, Andrea Z. ; Vukičević, Slobodan ; Reid, David M. ; Goldstein, S. ; Sriram, U. ; Lee, A. ; Thompson, John R. ; Armstrong, Roisin A. ; Thompson, David D. ; Powles, T. ; Zanchetta, J. ; Kendler, D. ; Neven, P. ; Eastell, Richard

Izvornik
Obstetrical & gynecological survey (0029-7828) 65 (2010), 7; 448-448

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, komentar, stručni

Ključne riječi
osteoporosis; lasofoxifene; postmenopause

Sažetak
Previous studies have demonstrated that lasofoxifene, a nonsteroidal selective estrogen-receptor modulator, decreases bone resorption, bone loss, and low-density lipoprotein cholesterol in postmenopausal women. Its effects of the risk of fractures, breast cancer, and cardiovascular disease are unclear. The postmenopausal evaluation and risk-reduction with lasofoxifene trial was an international, randomized, placebo-controlled trial that investigated the effects of lasofoxifene on the risk of fractures, estrogen receptor (ER)-positive breast cancer, and cardiovascular disease in a population of postmenopausal women with osteoporosis. The study subjects were a population of women between the ages of 59 and 80 years who had a bone mineral density T score of -2.5 or less at the femoral neck or spine. Participants were randomized to receive once-daily lasofoxifene at a dose of either 0.25 mg (low-dose, n = 2852) or 0.5 mg (high-dose, n = 2852) or placebo (n = 2852, control group) for 5 years. The trial was conducted at 113 sites in 32 countries. Vertebral and nonvertebral fractures and ER-positive breast cancer were the primary study end points. Major coronary heart disease events and stroke were the secondary endpoints. Compared with placebo, treatment with the high-dose lasofoxifene was associated with a reduction in the risk of vertebral fractures (13.1 cases vs. 22.4 cases per 1000 person-years ; hazard ratio [HR], 0.58 ; 95% confidence interval [CI], 0.47-0.70), nonvertebral fractures (18.7 vs. 24.5 cases per 1000 person-years ; HR, 0.76 ; 95% CI, 0.64-0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 person-years ; HR, 0.19 ; 95% CI, 0.07-0.56), major coronary heart disease events (5.1 vs. 7.5 cases per 1000 person-years ; HR, 0.68 ; 95% CI, 0.50-0.93), and stroke (2.5 vs. 3.9 cases per 1000 person-years ; HR, 0.64 ; 95% CI, 0.41-0.99). At 5 years compared to the placebo group, postmenopausal women receiving low-dose lasofoxifene showed reduced rates of vertebral fractures (16.0 vs. 22.4 per 1000 person-years ; HR, 0.69 ; 95% CI, 0.57-0.83) and stroke (2.4 vs. 3.9 cases per 1000 person-years ; HR, 0.61 ; 95% CI, 0.39-0.96). Both drug doses were associated with increased risk of a venous thromboembolic event: Compared to the placebo which had 1.4 venous thromboembolic events per 1000 person-years, the low-dose group had 3.8 events per 1000 person-years (HR, 2.67 ; 95% CI, 1.55-4.58) and the high-dose group had 2.9 events per 1000 person-years (HR, 2.06 ; 95% CI, 1.17- 3.61). No increased risk of endometrial hyperplasia or endometrial cancer was observed at 5 years with either dose. Deaths per 1000 person-years were 7.0 and 5.7 for low dose and high dose, respectively, compared to 5.1 for the placebo (P = ns for both comparisons). These findings show that treatment of postmenopausal women with osteoporosis using a daily dose of lasofoxifene of 0.5 mg is associated with reduced risks of vertebral and nonvertebral fractures, ER-positive breast cancer, major coronary heart disease, and stroke, and an increased risk of thromboembolic events.

Izvorni jezik
Engleski

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