Lasofoxifene: Evidence of its therapeutic value in osteoporosis

Abstract

Introduction: Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. It is a common disorder in elderly subjects and represents a major public health problem, affecting up to 40% postmenopausal women and 15% of men. Among the several therapeutical interventions, hormone replacement therapy (HRT) was traditionally seen as the gold standard for preventing osteoporotic fractures in postmenopausal women, as well as for the management of menopausal symptoms. However HRT, especially if administered long-term, may lead to an increased risk of breast and, when unopposed by progestins, endometrial cancers. Alternative therapies include bisphosphonates and raloxifene, a selective estrogen receptor modulator (SERM). While the former have been associated with suboptimal adherence, the latter was considerably less potent than estrogen and its effect in the prevention of nonvertebral fractures remain uncertain.

Aims: The purpose of this article is to review the clinical trials of lasofoxifene, a new SERM for the treatment of postmenopausal osteoporosis. The medical literature was reviewed for appropriate articles containing the terms "lasofoxifene" and SERMs".

Evidence review: There are three (phase II or phase III) clinical trials that clearly demonstrate efficacy and safety of this new SERM in the suppression of bone loss and the prevention of vertebral and nonvertebral fractures. Moreover, lasofoxifene treatment also reduced breast cancer risk and the occurrence of vaginal atrophy.

Place in therapy: With its increased potency and efficacy on the prevention of nonvertebral fractures lasofoxifene may be an alternative and cost-effective therapy for osteoporosis in postmenopausal women.

Keywords: SERM; fracture; lasofoxifene; osteoporosis; treatment.

Figure 1

Effects of lasofoxifene on lumbar BMD (% change at two years) (A) in a phase II comparison to raloxifene or placebo and (B) in phase III OPAL studies. Abbreviations: BMD, bone mineral density; LAS, lasofoxifene; RAL, raloxifene; PB, placebo.

Figure 2

Reduction in the risk (HR) for new/worsening radiographic vertebral fractures after three years of lasofoxifene (0.25 and 0.50 mg/day) treatment compared with placebo: the PEARL study. Abbreviations: CI, confidence interval; HR, hazard ratio; PB, placebo.

Figure 3

Reduction in the risk (HR) for nonvertebral fractures after three years of lasofoxifene (0.25 and 0.50 mg/day) treatment, compared with placebo: the PEARL study. Abbreviations: CI, confidence interval; HR, hazard ratio; LAS, lasofoxifine; PB, placebo.

Figure 4

Effects of lasofoxifene treatment (0.25 and 0.50 mg) on breast cancer risk reduction at three and five years: the PEARL study. Abbreviations: CI, confidence interval; HR, hazard ratio; PB, placebo.