Is estrogen therapy effective for treating osteopenia?

From the Guidelines

Estrogen therapy is not recommended as a first-line treatment for osteopenia in postmenopausal women due to its associated risks and the availability of alternative treatments with more favorable risk-benefit profiles. According to the American College of Physicians guideline update from 2017 1, estrogen therapy is not recommended for the treatment of osteoporosis in women due to its potential harms, including an increased risk of blood clots, stroke, and breast cancer.

Instead, the guideline recommends offering pharmacologic treatment with bisphosphonates, such as alendronate, risedronate, or zoledronic acid, to reduce the risk of hip and vertebral fractures in women with known osteoporosis 1. Denosumab is also a recommended option for reducing the risk of vertebral fractures.

For women with osteopenia who are at high risk for fracture, the decision to treat should be based on a discussion of patient preferences, fracture risk profile, and the benefits, harms, and costs of medications 1. Alternative treatments, such as bisphosphonates, RANK ligand inhibitors, or selective estrogen receptor modulators, may be more appropriate for some women, especially those with contraindications to estrogen therapy or who are many years past menopause.

Key points to consider when evaluating treatment options for osteopenia include:

• The patient's fracture risk profile
• The benefits and harms of each treatment option
• The patient's preferences and values
• The cost of treatment
• The potential for alternative treatments to reduce fracture risk.

In terms of specific treatment options, the following are recommended:

• Bisphosphonates, such as alendronate, risedronate, or zoledronic acid, for reducing the risk of hip and vertebral fractures
• Denosumab for reducing the risk of vertebral fractures
• Alternative treatments, such as RANK ligand inhibitors or selective estrogen receptor modulators, for women with contraindications to estrogen therapy or who are many years past menopause.

Overall, the goal of treatment for osteopenia is to reduce the risk of fractures and improve bone health, while also minimizing the risks and harms associated with treatment. By considering the patient's individual needs and preferences, and by selecting the most appropriate treatment option, clinicians can help women with osteopenia achieve optimal bone health and reduce their risk of fractures.

From the FDA Drug Label

When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should be considered only for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate.

Estrogen therapy, specifically estradiol, may be considered for the prevention of osteoporosis in postmenopausal women at significant risk. However, the label does not explicitly address the treatment of osteopenia.

• The effectiveness of estrogen therapy for treating osteopenia is not directly stated in the label.
• The label mentions prevention of osteoporosis, but not treatment of osteopenia. 2

From the Research

Estrogen Therapy for Osteopenia

• Estrogen therapy is not commonly recommended as a first-line treatment for osteopenia, as the efficacy in patients in the osteopenic range is less well established 3.
• However, hormone replacement therapy (HRT) may be considered in younger women with osteopenia, although it is not the primary treatment option 3.
• The majority of osteoporotic fractures occur in individuals with bone mineral density (BMD) t-scores in the osteopenic range, but widespread use of anti-osteoporotic medication in this group is not advisable based on t-score alone 3.
• Antiresorptive treatments, such as bisphosphonates, are generally the treatments of choice for osteopenia, especially in older women 3, 4, 5.

Alternative Treatment Options

• Bisphosphonates have been shown to be effective in reducing fracture risk in patients with osteopenia, particularly in older women 4, 5.
• Other treatment options, such as selective estrogen receptor modulators (SERMs) and denosumab, may also be considered for patients with osteopenia 3, 6.
• Anabolic agents, such as teriparatide and romosozumab, may be considered for patients at very high risk of fracture or with previous vertebral fractures 6.

Considerations for Treatment

• The decision to treat osteopenia should be based on a comprehensive assessment of fracture risk, including BMD, age, fracture history, and other risk factors 3, 5.
• Cost-effectiveness and patient motivation should also be considered when deciding on treatment options 5.
• Lifestyle modifications, such as weight-bearing exercise, smoking cessation, and calcium and vitamin D supplementation, should be recommended for all patients with osteopenia 6.