The evolution of selective estrogen receptor modulators in osteoporosis therapy

Department of Endocrinology, Reproductive Medicine, and Osteoporosis, Philipps-University of Marburg , Marburg , Germany.
Climacteric (Impact Factor: 2.26). 08/2012; 15(6). DOI: 10.3109/13697137.2012.688079
Source: PubMed


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.


Available from: Peyman Hadji, Feb 18, 2014
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    • "However, diphosphonate demonstrates mutiple adverse effects, such as mandible osteonecrosis, which is a major concern in clinical settings [13-15]. Selective estrogen receptor modulators (SERMs), which have evolved through multiple generations for the prevention and/or treatment of postmenopausal osteoporosis, have been associated with increased venous thromboembolic events and hot flushes[16]. Finding a safe and effective drug for the treatment of PMO is clinically important and has become an important area of research. "
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