Romosozumab prevents new vertebral fractures in postmenopausal women with osteoporosis

Twelve months of treatment with romosozumab produce marked reductions in new vertebral fractures (VFs), especially moderate-to-severe fractures, among postmenopausal women with osteoporosis, according to a study.

“Reductions in the incidence of new VFs were sustained through 24 months of treatment, after transition from romosozumab to denosumab or alendronate at 12 months,” the investigators noted. “Moreover, the effect of romosozumab was independent of baseline VF prevalence or severity.”

The development of a VF is telling of poor bone quality and strength among patients with osteoporosis. While any VF implies elevated risk, the degree of vertebral deformity (ie, the fracture severity grade) also serves as important indicator of further risk, such that the greater the VF severity, the higher the risk and morbidity. [JAMA 2007;298:2761-2767; Bone 2003;33:522-532; Eur J Rheumatol 2017;4:46-56; Osteoporos Int 2003;14:43-55]

“Accordingly, understanding the efficacy of a therapeutic agent across a range of fracture grades is important to tailor individualized treatment,” the investigators said.

In the study, the investigators pooled data from two phase III clinical trials (n=11,273), namely FRAME and ARCH. Patients in FRAME received romosozumab (n=3,589) vs placebo (n=3,591) for 12 months, followed by denosumab through 24 months. Those in ARCH received romosozumab (n=2,046) or alendronate (n=2,047) for 12 months, after which all patients entered an open-label period and received alendronate through 24 months.

At 12 months, the incidence of new moderate or severe VFs was significantly lower among patients treated with romosozumab vs placebo (FRAME: 0.25 percent vs 1.42 percent; p<0.001) or vs alendronate (ARCH: 2.78 percent vs 4.00 percent; p=0.042). Of note, consistent reductions in new moderate or severe VFs were seen with romosozumab regardless of prevalent (FRAME: p=0.18) or severe (ARCH: p=0.52) VFs at baseline. [Bone 2021;doi:10.1016/j.bone.2021.116209]

The protective effect of romosozumab on the incidence of new moderate or severe VFs was sustained through 24 months, after transition from romosozumab to denosumab or alendronate. There were no significant interactions observed between the incidence of new moderate or severe VFs and the presence of prevalent (FRAME; p=0.81) or severe (ARCH; p=0.99) VFs at baseline.

“The data reported here further characterize the previously reported efficacy of romosozumab for the reduction of VF risk, and support that for postmenopausal women at very high fracture risk, romosozumab treatment for 1 year, followed by an antiresorptive agent, provides sustained reductions across VF severity grades, in particular the moderate and severe grades, in patients with and without VFs at baseline,” the investigators said. [N Eng J Med 2016;375:1532-1543; N Eng J Med 2017;377:1417-1427]

“With increasing recommendations for initial treatment with bone-forming agents for postmenopausal women with osteoporosis, these analyses will help to inform treatment decisions for patients at very high risk of VF,” they added.

The study was limited by the failure to incorporate other indicators of high fracture risk, such as recency of VFs. Also, the findings could not be extrapolated beyond patients who receive romosozumab as a first-line treatment, given that only a small percentage of patients had received prior bisphosphonate therapy before enrolling in FRAME or ARCH.