The evolution of selective estrogen receptor modulators in osteoporosis therapy

Abstract

Selective estrogen receptor modulators (SERMs), which exhibit estrogen receptor agonist or antagonist activity based on the target tissue, have evolved through multiple generations for the prevention and/or treatment of postmenopausal osteoporosis. An ideal SERM would protect bone without stimulating the breast or endometrium. Raloxifene, lasofoxifene, and bazedoxifene have demonstrated unique preclinical profiles. Raloxifene, lasofoxifene, and bazedoxifene have shown significant reduction in the risk of vertebral fracture and improvement in bone mineral density versus placebo in postmenopausal women with osteoporosis. Raloxifene has been shown to reduce the risk of non-vertebral fractures in women with severe prevalent fractures at baseline. Lasofoxifene 0.5 mg, but not lasofoxifene 0.25 mg, has shown reduction in the incidence of non-vertebral fractures. Bazedoxifene 20 mg has been associated with a significant reduction in the risk of non-vertebral fracture versus placebo and raloxifene 60 mg in women at higher baseline fracture risk. Neither raloxifene, lasofoxifene, nor bazedoxifene has shown an increase in the incidence of endometrial hyperplasia or carcinoma. All SERMs have been associated with increased venous thromboembolic events and hot flushes. SERMs are effective alternatives for women who cannot tolerate or are unwilling to take bisphosphonates and may be appropriate for women at higher risk of fracture, particularly younger women who expect to remain on therapy for many years and are concerned about the long-term safety of bisphosphonates.

Key words::

• POSTMENOPAUSAL
• OSTEOPOROSIS
• SERMs
• BAZEDOXIFENE
• RALOXIFENE
• LASOFOXIFENE

ACKNOWLEDGEMENTS

Medical writing support for this manuscript was provided by Katie Gersh, PhD, of MedErgy and was funded by Pfizer Inc. The author was not compensated and retained full editorial control over the content of the article.

Conflict of interest Dr Hadji has received unrestricted educational grants, honoraria, and research funding from Amgen, Astra Zeneca, Daichii Sankyo, Eli Lilly, GSK, Pfizer Inc, Novartis, and Roche.

Source of funding Medical writing support for this manuscript was provided by Katie Gersh, PhD, of MedErgy and was funded by Pfizer Inc.