Even after fracture, fewer than 25% of patients receive pharmacologic treatment for osteoporosis. After the discovery that sclerostin deficiency causes rare genetic conditions that are characterized by high bone mass and resistance to fracture, sclerostin has become a therapeutic target for the treatment of this disease. This study assessed the effect of romosozumab, a monoclonal antibody that binds and inhibits sclerostin with the dual effect of increasing bone formation and decreasing bone resorption.

Subjects were ambulatory, postmenopausal women, 55 to 90 years of age, with T scores at the total hip or femoral neck of-2.5 to-3.5. All patients received daily calcium at 500 to 1000 mg and daily vitamin D₃ or D₂ at 600 to 800 IU. The participants were then randomly assigned to receive subcutaneous injections of 210 mg of romosozumab or placebo once per month for 12 months. The subjects then received open label denosumab, 60 mg milligrams, every six months for an additional 12 months. The primary endpoints were new vertebral fracture at 12 months and 24 months.

Of the patients who undenwent randomization, 6006 completed the 24 month study. At 12 months, the romosozumab group had a risk of new vertebral fracture that was 73% lower than that of the placebo group (P<0.0001). The treatment group also had a 36% lower risk of clinical fractures at 12 months, as compared w ith placebo (P＝0.008). At 24 months, the cumulative incidence of new vertebrsl fracture was lowef in the group that had originally received romosozumab, as compared to those who had originally received placebo (P<0.001)．

This study of women with postmenopausal osteoporosis found that treatment with romosozumab, a sclerosin inhibitor, resulted in a significantly lower risk of vertebral fracture and clinical fracture st 12 months.