Romosozumab treatment for 12 months, followed by treatment with alendronate for 12 months, was shown to reduce the risk of fracture in postmenopausal women with osteoporosis, as compared with treatment with alendronate alone.

Deborah L. Ungerleider, M.D.

March 27, 2020– Postmenopausal women with osteoporosis had a 48% lower risk of vertebral fracture after treatment with romosozumab followed by alendronate compared with those who were treated with alendronate alone.

Kenneth G. Saag, MD, with the Division of Clinical Immunology and Rheumatology, University of Alabama, and colleagues, reported their findings in the October 12, 2017, issue of the New England Journal of Medicine.

Postmenopausal women with osteoporosis who have had a past fracture have been shown to have an increased risk of vertebral fractures. In past studies, alendronate, which is an antiresorptive agent used as a first-line therapy for osteoporosis, has been shown to reduce fractures by up to 50%.

Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increasing bone formation and decreasing bone resorption. Past studies have shown that 12 months of treatment with romosozumab had preventive effects on fracture occurrence; this study builds on those findings by comparing romosozumab to the established drug, alendronate and evaluated the efficacy of romosozumab in a higher-risk population.

This was a phase 3 randomized trial, during which women received either monthly romosozumab subcutaneously or weekly alendronate orally for 12 months. Following that, all patients received oral alendronate for the next 12 months.

This multicenter double-blind study demonstrated that treatment with romosozumab plus alendronate resulted in a 48% lower risk of new vertebral fractures compared with treatment with alendronate alone (6.2% vs 11.9%, risk ratio, 0.52; 95% CI, 0.40-0.66, P < .001). Additional findings in the study included a 27% lower risk of clinical fracture (hazard ratio [HR], 0.73; 95% CI, 0.61-0.88; P < .001) and a 19% lower risk of nonvertebral fracture than with alendronate alone (HR, 0.81; 95% CI, 0.66-0.99; P = .04).

Adverse events that occurred most commonly were injection site reactions (4.4% in the patients receiving romosozumab and 2.8% in those receiving alendronate alone). Serious cardiovascular events (cardiac ischemic events and cerebrovascular events) occurred in 2.5% of the romoosozumab group compared with 1.9% in the alendronate group.

Dr Saag and his colleagues concluded that “…rapid gains in bone mineral density from bone-forming therapy with romosozumab were associated with a lower risk of fracture than with alendronate within 1 year and over the course of romosozumab followed by alendronate. Hip fractures were less frequent with romosozumab followed by alendronate than with alendronate alone, suggesting an important benefit and challenging the common treatment practice of first-line use of alendronate in women who have had a previous fracture.” 

This study was supported by Amgen, Astellas Pharma, and UCB Pharma.

New England Journal of Medicine. Published October 12, 2017