Guideline Update: Romosozumab in Osteoporosis

The Endocrine Society has updated treatment guidelines for the treatment of osteoporosis in postmenopausal women to include or alter treatments with romosozumab, selective estrogen receptor modulators, menopausal hormone therapy and tibolone, calcitonin, and calcium and vitamin D.

The update was published in February in The Journal of Clinical Endocrinology & Metabolism. It was issued, in part, due to the recent approval of romosozumab, a monoclonal antibody targeting sclerostin. The treatment was approved by the U.S. Food and Drug Administration, the European Medicines Agency, and Health Canada.

The guideline recommends the use of romosozumab for up to one year for the reduction of vertebral, hip, and nonvertebral fractures in postmenopausal women with severe osteoporosis at very high risk of fracture (defined as T-score less than −2.5 and a prior fracture) or a history of multiple vertebral fractures. The recommended dosage of romosozumab is 210 mg monthly by subcutaneous injection for 12 months.

In postmenopausal women with osteoporosis who have completed a course of romosozumab, treatment with antiresorptive osteoporosis therapies is recommended to maintain bone mineral density gains and reduce fracture risk. The treatment is not recommended for women at high risk of cardiovascular disease and stroke, which includes those with prior myocardial infarction or stroke.

The recommendations are based on a review of data from two large phase three trials that assessed the efficiency of romosozumab in vertebral and nonvertebral fracture risk reduction in post-menopausal women. The FRAME trial showed no imbalances in major adverse cardiovascular events (MACE) or in cardiovascular serious adverse events with romosozumab. However, the ARCH study showed more MACE in the first year with romosozumab, and patients taking romosozumab had a 31 percent higher risk of MACE compared with those taking alendronate.

“The romosozumab label has a boxed warning, recommending careful consideration by the treating clinician as to cardiovascular risk profile in the individual woman who might receive this agent, since clinical trial data from an active comparator study show an imbalance in serious cardiovascular adverse events between romosozumab and alendronate,” the authors wrote.

Other updates for this high risk group includes:

• Selective estrogen receptor modulators raloxifene or bazedoxifene are recommended to reduce the risk of vertebral fractures in patients who are (1) at low risk of deep vein thrombosis (2) women in which bisphosphonates or denosumab are not appropriate (3) women a high risk of breast cancer. 

• Menopausal hormone therapy, using estrogen-only therapy in women with hysterectomy, to prevent all types of fractures for (1) women under 60 years of age or less than 10 years past menopause (2) at low risk of deep vein thrombosis (3) women in whom bisphosphonates or denosumab are not appropriate (4) women vasomotor symptoms (5) women with climacteric symptoms (6) and, in women without contraindications, prior myocardial infarction or stroke, or breast cancer.

• The nasal spray calcitonin is recommended for women who cannot tolerate raloxifene, bisphosphonates, estrogen, denosumab, tibolone, abaloparatide, or teriparatide.

• Calcium and vitamin D are recommended as add-on therapy for postmenopausal women with low bone mineral density and at high risk of fractures with osteoporosis.

• Postmenopausal women with a low bone mineral density who are at high risk of fractures should undergo monitoring for bone mineral density by dual-energy X-ray absorptiometry at the spine and hip every 1 to 3 years to assess treatment response.

REFERENCE

Dolores Shoback, Clifford J Rosen, Dennis M Black, et al. “Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update.” The Journal of Clinical Endocrinology & Metabolism. February 18, 2020. https://doi.org/10.1210/clinem/dgaa048