From the Guidelines
Estrogen therapy is not recommended for the treatment of osteoporosis in women due to its association with serious harms and lack of evidence showing a reduction in fracture risk in postmenopausal women with established osteoporosis. According to the American College of Physicians guideline update 1, moderate-quality evidence showed that menopausal estrogen treatment did not reduce fracture risk in postmenopausal women with established osteoporosis.
Key Points
- Estrogen therapy may decrease fracture risk in postmenopausal women with low bone density, but its effectiveness in women with established osteoporosis is unclear 1.
- The American College of Physicians recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy for the treatment of osteoporosis in women 1.
- Bisphosphonates, such as alendronate, risedronate, and zoledronic acid, are recommended for the treatment of osteoporosis in women to reduce the risk of hip and vertebral fractures 1.
- Calcium and vitamin D supplements may be added to osteoporosis treatment regimens, but their effectiveness in preventing fractures is unclear 1.
Treatment Options
- Bisphosphonates: alendronate, risedronate, zoledronic acid
- Denosumab
- Teriparatide
- Selective estrogen receptor modulators (raloxifene, bazedoxifene)
- Calcium and vitamin D supplements
Important Considerations
- Estrogen therapy is associated with serious harms, such as cardiovascular events and thromboembolic events 1.
- The decision to treat osteopenic women 65 years of age or older who are at high risk for fracture should be based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications 1.
From the Research
Estrogen's Protective Effects on Bones
- Estrogen has been shown to have a positive effect on bone mineral density (BMD) in postmenopausal women, with studies indicating that it can increase BMD in the lumbar spine and total proximal femur 2, 3.
- The use of estrogen therapy has been found to reduce the incidence of osteoporosis-related fractures in postmenopausal women, with low-dose and transdermal estrogen therapy being considered safer than standard-dose oral therapy 3.
- Estrogen's protective effects on bones are thought to be due to its ability to suppress osteoclastogenic cytokine production and induce the apoptotic death of osteoclasts, leading to a decrease in bone resorption 4.
Comparison with Other Treatments
- Estrogen has been compared to other treatments for osteoporosis, such as alendronate, with studies showing that the combination of estrogen and alendronate can produce greater increases in BMD than either treatment alone 2.
- Selective estrogen receptor modulators (SERMs), such as raloxifene, have also been found to have beneficial effects on bone density, although their effects on fracture risk and cardiovascular disease are still being studied 5, 6.
Mechanisms of Estrogen Action
- The mechanisms of estrogen action on bones are complex and involve the regulation of osteoclast survival and apoptosis, with different models proposing different pathways for estrogen-mediated osteoclast apoptosis 4.
- Estrogen's effects on bones are thought to be mediated by its binding to estrogen receptor alpha (ERalpha), which can induce the expression of genes involved in bone metabolism 4.