The Endocrine Society has released new guidelines for the pharmacological management of osteoporosis in postmenopausal women. These guidelines aim to decrease ambiguity around who to treat, how to best screen for osteoporosis, and the risks and benefits associated with several management strategies.

In 2017, the American College of Physicians (ACP) published guidelines on the treatment of osteoporosis in men and women. Since then, questions have been raised about certain aspects and recommendations in these guidelines, including a lack of differentiation between duration of use for bisphosphonates vs denosumab, no data on the use of abaloparatide, and recommendations against the use of menopausal hormone therapy, raloxifene, and teriparatide.

After review of clinical evidence from 107 randomized controlled trials, the Endocrine Society’s international guideline writing committee formulated different recommendations for pharmacotherapy in postmenopausal women with primary osteoporosis.

In a second qualitative review, the guideline authors assessed values and preferences relevant to osteoporosis management in women. The Society’s recommendations are summarized below.

Principles of management 

  1. Incident fracture risk in postmenopausal women should be assessed with country-specific assessment tools to guide clinical decision-making.
  2. Patient preferences should be considered when making treatment plans.
  3. Nutritional and lifestyle interventions and fall prevention strategies should be implemented in addition to pharmacotherapy.
  4. There are multiple pharmacologic treatment options with acceptable risk-benefit profiles that can reduce fracture incidence in postmenopausal women.

Who to treat

Postmenopausal women who are at high risk for fracture should be treated with pharmacologic therapies, particularly women who have experienced a recent fracture.

Pharmacologic agent(s)Recommendation(s)
Bisphosphonates• Bisphosphonates are recommended as the initial therapy in postmenopausal women at high risk for fractures.
• Ibandronate is not recommended to reduce risk for nonvertebral or hip fractures.
• After 3 to 5 years of use, fracture risk should be reassessed. Women with a low-to-moderate risk for fracture should be considered for a bisphosphonate drug holiday.
Denosumab• Denosumab is recommended as an alternative initial treatment in postmenopausal women with osteoporosis and high fracture risk. Recommended dosage is 60 mg every 6 months.
• Fracture risk should be reassessed after 5 to 10 years and therapy should be continued in women who remain at high risk.
Teriparatide and abaloparatide• Teriparatide or abaloparatide treatment is recommended for ≤2 years in postmenopausal women with osteoporosis at very high risk for fractures.
• To maintain improvements in bone mineral density (BMD), antiresorptive therapy should be prescribed after completing a course of teriparatide or abaloparatide.
Selective estrogen receptor modulators• Raloxifene or bazedoxifene are recommended to reduce the risk for vertebral fractures in postmenopausal women with osteoporosis and high fracture risk. Treatment should be initiated in women with a low risk for deep vein thrombosis for whom bisphosphonates or denosumab are not appropriate.
• Treatment with raloxifene has an added benefit of reducing incidence of breast cancer, and may be particularly suitable for women at high risk for invasive estrogen receptor-positive breast cancer.
Menopausal hormone therapy• To prevent fractures, menopausal hormone therapy is suggested for patients age <60 years or <10 years past menopause with bothersome vasomotor symptoms who have a low risk for deep vein thrombosis.
• Estrogen-only hormone therapy should be used in women with hysterectomy.
• Patients prescribed menopausal hormone therapy should not have breast cancer or a history or myocardial infarction or stroke.
Calcitonin• Nasal spray calcitonin can be prescribed to women who cannot tolerate raloxifene, bisphosphonates, estrogen, denosumab, tibolone, abaloparatide, or teriparatide.
Calcium and vitamin D• Calcium and vitamin D should be used as adjunct therapies to osteoporosis treatment in postmenopausal women with low BMD and high fracture risk.
• In women unable to tolerate other osteoporosis treatment, daily calcium and vitamin D supplementation is recommended to prevent hip fractures.

Monitoring

To assess response to treatment, dual-energy X-ray absorptiometry at the spine and hip should be performed every 1 to 3 years in postmenopausal women who have low BMD and high fracture risk. Bone turnover markers can also be monitored to identify poor response or nonadherence to treatment. Serum C-terminal crosslinking telopeptide can be used to indicate response to antiresorptive therapy, and procollagen type 1 N-terminal propeptide can be used to monitor response to bone anabolic therapy.

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Considerations for long-term treatment

Drug holidays

There has been substantial research on long-term use of bisphosphonate therapy. Data indicate a residual effect after treatment stops, which supports bisphosphonate holidays. Bisphosphonate drug holidays are defined as temporary discontinuation of bisphosphonate for up to 5 years, but this period can be extended. After initiating a bisphosphonate holiday, fracture risk should be reassessed at 2- to 4-year intervals. Therapy should be reinitiated before the 5-year suggested maximum if there are changes in clinical risk status, such as a significant decline in BMD or an intervening fracture.

For medications other than bisphosphonates, benefits are quickly lost after discontinuation. Ending treatment with denosumab, for example, has been associated with loss of BMD and increased risk for vertebral fractures. As such, these therapies must be continued indefinitely or followed with bisphosphonates or an alternative to retain protective therapeutic benefits.

Atypical femoral fractures

A possible association between stress fractures of the femoral shaft and bisphosphonate therapy has been reported. In addition, atypical femoral fractures have been reported with use of other osteoporosis medications (denosumab, odanacatib, and romosozumab).

Studies evaluating atypical femoral fracture risk from bisphosphonate therapy that used formal radiologic fracture classification, as opposed to ICD codes, showed that incidence is very low. However, these studies still found significant increases in atypical femoral fractures with long-term bisphosphonate use. This risk may be reduced by implementing a bisphosphonate drug holiday in patients at low to moderate risk for fracture.

Osteonecrosis of the jaw

Routine dental care is important for preventing osteonecrosis of the jaw in patients receiving antiresorptive therapy. The estimated absolute risk for osteonecrosis of the jaw J in patients with osteoporosis was reported in 2015 to be between 0.0001% and 0.01%. Currently, major dental associations have different recommendations for bisphosphonate therapy; the American Dental Association does not generally recommend a bisphosphonate holiday for dental procedures, while the American Association of Oral and Maxillofacial Surgeons recommends a 2-month holiday for patients who have been receiving bisphosphonates for >4 years.

General preferences

Women receiving treatment for osteoporosis considered both the convenience of taking the medication and its impact on their daily routine. Efficacy and adverse events seemed to be considered equally. Cost and duration of treatment were found to be less important factors to choosing treatment. “When making decisions regarding who to treat, patient preferences and patient-specific clinical factors should be taken into account,” wrote the guideline authors.

Reference

Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1-28.

This article originally appeared on Endocrinology Advisor