Romosozumab Helps Fracture Prevention in Women with Osteoporosis
Kenneth Saag and colleagues investigated romosozumab, a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption, for fracture prevention in women with osteoporosis.
They enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) for 12 months, followed by open-label alendronate in both groups.
The cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture at the time of the primary analysis were the primary end points. The incidences of nonvertebral and hip fracture at the time of the primary analysis were secondary end points.
Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated.
• Over 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group.
• Clinical fractures occurred in 9.7% of patients in the romosozumab-to-alendronate group compared with 13.0% of patients in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab.
• The risk of nonvertebral fractures and the risk of hip fracture was lower by 19% and by 38%, respectively, in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group.
• Overall adverse events and serious adverse events were balanced between the groups.
• During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate.
• During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw and atypical femoral fracture were observed.
The authors concluded that romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone in postmenopausal women with osteoporosis who were at high risk for fracture.