Romosozumab shows promise for fracture prevention in women with osteoporosis
medwireNews: Results of the phase III ARCH trial suggest that women with osteoporosis who are treated with romosozumab are less likely to experience fractures, but may have an increased risk for cardiovascular events, compared with those given alendronate.
As reported in The New England Journal of Medicine, the ARCH (Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk) investigators randomly assigned postmenopausal women with osteoporosis and a fragility fracture to receive 1 year of treatment with subcutaneous romosozumab at a dose of 210 mg once monthly, or oral alendronate 70 mg once weekly, followed by open-label alendronate therapy in both groups.
“Romosozumab […] is a new bone-forming monoclonal antibody that binds to and inhibits sclerostin, with a dual effect of increasing bone formation and decreasing bone resorption,” whereas the antiresorptive drug alendronate is a frequent first-line treatment for osteoporosis, explain study lead Kenneth Saag (University of Alabama, Birmingham, USA) and co-authors.
In all, 6.2% of 2046 patients receiving romosozumab and 11.9% of 2047 patients in the alendronate group experienced new vertebral fractures over 2 years of follow-up, giving a significant 48% lower risk for fracture with romosozumab treatment.
Over 2 years, women receiving romosozumab also had a 27% reduced risk for clinical fractures – a composite of nonvertebral and symptomatic vertebral fractures – than those given alendronate, with rates of 9.7% versus 13.0%.
And this reduction in fracture risk with romosozumab versus alendronate was also seen during the first year of follow-up, with romosozumab-treated patients having a 37% reduced risk for new vertebral fractures and a 28% lower risk for clinical fractures at 1 year.
Saag and team observed a “similar overall” incidence of adverse events and serious adverse events among women in the romosozumab and alendronate groups, with rates of 75.7% versus 78.6% and 12.8% versus 13.8%, respectively, at the 1-year follow-up.
However, patients receiving romosozumab were 31% more likely to experience adjudicated serious cardiovascular events than those in the alendronate group. Such events occurred in 2.5% versus 1.9% of participants, with rates of 0.8% versus 0.3% for both cardiac ischemic and cerebrovascular events.
Clifford Rosen, from Tufts University Medical School in Boston, Massachusetts, USA, believes that “the cardiovascular signal for romosozumab is particularly troubling.”
Writing in an accompanying editorial, he notes that the cardiovascular effects of romosozumab are “very consistent with our recent understanding of the skeleton as an endocrine tissue that modulates whole-body homeostasis by secreting peptides such as sclerostin.”
And he concludes that “romosozumab has great potential as a short-term anabolic treatment for osteoporosis.”
“However, until the cardiovascular and endocrine effects of this antibody are clarified, romosozumab will remain more a part of our expectations than our armamentarium.”
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