Selective estrogen receptor modulators for prevention and treatment of osteoporosis
- Harold N Rosen, MD
Harold N Rosen, MD
- Assistant Professor in Medicine
- Harvard Medical School
The selective estrogen receptor modulators (SERMs) bind with high affinity to the estrogen receptor and have estrogen agonist and antagonist properties that vary depending upon the individual target organ [1,2]. The factors that determine the variable estrogen receptor agonist and antagonist activity of SERMs are not fully defined but are under active study. (See "Mechanisms of action of selective estrogen receptor modulators and down-regulators".)
Some SERMs, such as raloxifene and bazedoxifene, have estrogen activity in bone and, therefore, prevent bone loss, improve bone mineral density (BMD), and decrease the risk of vertebral fracture. The use of SERMs for the prevention and treatment of osteoporosis will be discussed here. Their role in breast cancer prevention is discussed in detail elsewhere. (See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention" and "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer".)
An overview of the approach to therapy of osteoporosis in postmenopausal women and the prevention of osteoporosis are also reviewed separately. (See "Overview of the management of osteoporosis in postmenopausal women" and "Prevention of osteoporosis".)
CANDIDATES FOR THERAPY
Patients with the highest risk of fracture are the ones most likely to benefit from drug therapy. Fracture risk is determined by a combination of bone mineral density (BMD) and clinical risk factors. Selecting patients at high risk of fracture for osteoporosis therapy is reviewed in detail separately. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Candidates for therapy' and "Prevention of osteoporosis", section on 'Candidates for pharmacologic therapy'.)
CHOICE OF DRUG
For postmenopausal women who are candidates for and desire pharmacologic therapy for prevention of bone loss, bisphosphonates or raloxifene are reasonable options. There are nonskeletal considerations with raloxifene that may play an important role in the selection of postmenopausal women for therapy: a reduction in breast cancer risk, but an increase in thromboembolic events and hot flashes, and no apparent effect on heart disease or the endometrium. Raloxifene inhibits bone resorption and reduces the risk of vertebral fracture, and is our selective estrogen receptor modulator (SERM) of choice because it has eight-year safety and efficacy data and also reduces the risk of breast cancer. Raloxifene is usually chosen for osteoporosis prevention when there is an independent need for breast cancer prophylaxis. (See "Prevention of osteoporosis".)
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- CANDIDATES FOR THERAPY
- CHOICE OF DRUG
- Bone mineral density
- Combination therapy
- Duration of therapy
- Effects in premenopausal women
- Adverse effects
- - General
- - Venous thromboembolism
- - Stroke
- Other effects
- - Coronary heart disease
- - Breast cancer
- - Mortality
- - Cognitive function
- - Genitourinary effects
- BAZEDOXIFENE-CONJUGATED ESTROGEN
- Adverse effects
- SUMMARY AND RECOMMENDATIONS