Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk

ObjectiveWe evaluated efficacy of romosozumab in women from FRAME who had no prior fracture but met other criteria for very high fracture risk (VHFR).MethodsIn FRAME, postmenopausal women received romosozumab or placebo for 12 months (Year 1) followed by denosumab for 12 months (Year 2). In this post hoc analysis, we applied the following criteria from the American Association of Clinical Endocrinology (AACE) to define VHFR: lumbar spine or total hip T-score <–3.0 and/or FRAX probability of major osteoporotic fracture >30% or hip fracture >4.5% to women with no fracture history at baseline (no fracture-VHFR [NF-VHFR]). Incidence of new vertebral, clinical, and nonvertebral fracture and mean bone mineral density (BMD) percentage change from baseline were assessed at Years 1 and 2.ResultsOf 7180 women in FRAME, 2825 were included in the NF-VHFR subgroup analysis. At Year 1, romosozumab vs placebo reduced the incidence of new vertebral fracture (relative risk reduction [RRR]: 76%), clinical fracture (RRR: 60%), and nonvertebral fracture (RRR: 54%) (all P<0.05). This fracture reduction was maintained through Year 2 in women receiving the romosozumab-to-denosumab sequence vs placebo-to-denosumab sequence for new vertebral, clinical, and nonvertebral fractures (RRR: 77%, 54%, and 46%, respectively; all P<0.05). Mean BMD changes in both treatment groups were similar to those in the overall FRAME population at Years 1 and 2.ConclusionRomosozumab significantly reduced vertebral, clinical, and nonvertebral fracture risk and increased BMD more than placebo in women at very high fracture risk.