Lasofoxifene in osteoporosis and its place in therapy.

Selective estrogen-receptor modulators (SERMs), which have estrogen-like effects on bone and "antiestrogen effects" on other tissues, have been in development for osteoporosis prevention and treatment in postmenopausal women as a safer alternative to long-term estrogen. We conducted a literature review of the skeletal and extraskeletal effects of lasofoxifene, a new generation SERM approved by the European Commission for osteoporosis treatment. Published data on the effects of lasofoxifene are based on 23 clinical pharmacology studies with over 10,000 participants from 17 phase 2 and 3 randomized controlled trials (RCTs). In RCTs, lasofoxifene decreases bone turnover markers (BTMs), increases bone mineral density (BMD) at the spine and hip, and decreases the incidence of vertebral and nonvertebral nonhip fractures compared with placebo. Compared with raloxifene, lasofoxifene gave greater decreases in BTMs, and greater increases in lumbar spine BMD. Lasofoxifene also decreased the risk of breast cancer, major coronary heart disease events, and stroke, but-similar to raloxifene-there was an increased risk of venous thromboembolism. In one trial, endometrial hypertrophy and uterine polyps were more common with lasofoxifene than with placebo, but endometrial cancer and hyperplasia were not. Lasofoxifene is probably most appropriate for use among women in their early or middle menopausal years (age 55-65) who have, or are at risk of developing, osteoporosis and in particular vertebral fractures. At the time of publication, lasofoxifene is not approved for use by the US Food and Drug Administration, and as such is not used in North America.