FRAME

Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

Cosman F, Crittenden DB, Adachi JD, et al. The New England journal of medicine 2016 · PMID 27641143 · doi:10.1056/nejmoa1607948

Question

Does 12 months of the anti-sclerostin antibody romosozumab reduce fractures in postmenopausal women with osteoporosis?

Design

International multicentre double-blind placebo-controlled RCT, with both arms then switched to denosumab.

Patients

Postmenopausal women with a T-score of -2.5 to -3.5 at the total hip or femoral neck.

Intervention

Romosozumab 210 mg subcutaneously monthly for 12 months, then denosumab

Comparison

Placebo for 12 months, then denosumab

Primary outcome

New vertebral fracture at 12 and 24 months

Key result

Romosozumab significantly reduced new vertebral fractures at 12 months, with the benefit maintained after switching to denosumab; non-vertebral fracture reduction was not significant.

Limitations

Non-vertebral benefit not shown; trial not designed to detect cardiovascular harm, which emerged in the alendronate-controlled ARCH trial.

Impact on practice

Demonstrated the dual-action (anabolic and antiresorptive) mechanism of sclerostin inhibition and the need for follow-on antiresorptive therapy.