Romosozumab Treatment Lowers the Incidence of New Vertebral Fractures Across All Fracture Severity Grades Among Postmenopausal Women with Osteoporosis

Abstract

Vertebral fractures (VFx) are the most common type of fracture in postmenopausal osteoporosis (PMO). VFx are generally classified using the Genant grading system as mild (grade 1), moderate (grade 2), or severe (grade 3) according to their degree of compression visualized on spinal x-rays. Regardless of their severity, VFx are associated with significant morbidity and carry the highest subsequent fracture rate of any fragility fracture. We assessed the incidence of new VFx by Genant severity grade in the romosozumab (Romo) vs placebo (Pbo) or alendronate (ALN) arms of the FRAME and ARCH studies, respectively.In FRAME, 7,180 women with PMO were randomized 1:1 to receive monthly Romo 210 mg or Pbo for 12 months followed by biannual denosumab (DMAb) 60 mg (Romo→DMAb or Pbo→DMAb) for 12 months. In ARCH, 4,093 women with PMO and ≥ 1 fracture were randomized 1:1 to receive monthly Romo 210 mg or weekly oral ALN 70 mg for 12 months followed by ALN 70 mg (Romo→ALN or ALN→ALN) for ≥ 12 months. Throughout both studies, lateral radiographs of the spine were assessed for the presence and severity (mild, moderate, or severe) of VFx using the Genant grading at baseline and after 12 and 24 months of treatment.The incidence of new VFx was significantly lower among patients who received Romo during the 12-month double-blind treatment phase in both studies. Over 12 months, the incidence of new VFx was 0.5% Romo vs 1.8% Pbo (P<0.001) in FRAME and 3.2% Romo vs 5.0% ALN (P=0.008) in ARCH. Over 24 months, the incidence of new VFx was 0.6% Romo→DMAb vs 2.5% Pbo→DMAb (P<0.001) in FRAME and 4.1% Romo→ALN vs 8.0% ALN→ALN (P<0.001) in ARCH. Fewer new VFx were observed in the Romo arm of both studies across all fracture severity grades. Specifically, in FRAME, the incidence of mild VFx was 0.2% Romo vs 0.4% Pbo over 12 months and 0.2% Romo→DMAb vs 0.6% Pbo→DMAb over 24 months; the incidence of moderate VFx was 0.1% Romo vs 0.9% Pbo over 12 months and 0.2% Romo→DMAb vs 1.4% Pbo→DMAb over 24 months; and the incidence of severe VFx was 0.2% Romo vs 0.5% Pbo over 12 months and 0.2% Romo→DMAb vs 0.6% Pbo→DMAb over 24 months. Similarly, in ARCH, the incidence of mild VFx was 0.5% Romo vs 1.0% ALN over 12 months and 0.4% Romo→ALN vs 1.4% ALN→ALN over 24 months; the incidence of moderate VFx was 1.3% Romo vs 2.1% ALN over 12 months and 1.8% Romo→ALN vs 3.4% ALN→ALN over 24 months; and the incidence of severe VFx was 1.5% Romo vs 1.9% ALN over 12 months and 1.9% Romo→ALN vs 3.3% ALN→ALN over 24 months.In conclusion, Romo administered over 12 months to women with PMO resulted in reductions in VFx across all fracture severity grades compared with Pbo and standard-of-care ALN. The treatment effect of Romo continued after patients transitioned to an antiresorptive agent. These data will help to foster treatment decisions in postmenopausal women at high risk for VFx.