Romosozumab prevents clinical fracture slightly better than alendronate in women with osteoporosis and previous fracture

Reference

Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 2017;377(15):1417-1422.

Synopsis

Romosozumab is a monoclonal antibody that inhibits sclerostin, a protein involved in bone resorption. This trial identified ambulatory women with osteoporosis and at least one previous fragility fracture in the previous 2 years. All women received 500 mg to 1000 mg calcium and 600 to 800 IU vitamin D during the trial period. The women were randomized to receive romosozumab 210 mg by subcutaneous injection monthly and a weekly placebo, or monthly placebo injection plus alendronate 70 mg weekly. After 1 year, all women were given alendronate 70 mg weekly in open-label fashion. Patients were X-rayed at regular intervals, and the primary outcomes were any new vertebral fractures and any clinical fractures (ie, symptomatic vertebral fracture or any nonvertebral fracture). The latter is the true patient-oriented outcome, as many vertebral fractures are asymptomatic. A total of 4093 women were randomized, and 89% of them completed the 24-month study period. Their mean age was 74 years, one third were Hispanic, and their mean T score at the femoral neck was -2.9. Groups were balanced at baseline, and analysis was by intention to treat. At the end of the study period, there was a lower risk of clinical fracture in the group that initially received romosozumab: 9.7% vs 13.0%; P < .001; NNT = 30 over 2 years to prevent 1 fracture. The risk of nonvertebral fracture was also lower (8.7% vs 10.6%; P = .04; NNT = 53). Although there were no episodes of osteonecrosis there was a higher risk of cardiovascular events in the romosozumab group than in the alendronate group: 16 vs 6 cardiac ischemic events and 16 vs 7 other cardiovascular events (statistical significance not reported).