Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial

J Bone Miner Metab. 2021 Mar;39(2):278-288. doi: 10.1007/s00774-020-01147-5. Epub 2020 Oct 15.

Abstract

Introduction: This post-hoc analysis of the FRAME study investigated the long-term efficacy and safety of romosozumab followed by denosumab in postmenopausal Japanese women with osteoporosis at high fracture risk.

Materials and methods: Data from Japanese women with a high fracture risk participating in the international, randomised, double-blind, placebo-controlled, phase 3 FRAME study were analysed. High risk of fracture was defined as ≥ 1 fragility fracture with bone mineral density (BMD) ≤ - 2.5 standard deviations [SD], > 2 prevalent vertebral fractures, prevalent semiquantitative grade 3 vertebral fracture, or lumbar spine BMD < - 3.3 SD. Endpoints included incidence of new vertebral fracture at 12, 24 and 36 months and percentage change from baseline in BMD at the lumbar spine, total hip and femoral neck.

Results: 187 Japanese subjects at high risk of fracture were enrolled in FRAME. Incidence of new vertebral fractures was lower with romosozumab/denosumab vs. placebo/denosumab at 12, 24 and 36 months (relative risk reduction at all timepoints: 84%; p = 0.056). BMD increases at 12, 24 and 36 months were greater in subjects receiving romosozumab/denosumab than placebo/denosumab (lumbar spine: 16.3%, 21.5% and 23.2% vs 0.4%, 8.1% and 10.4%; total hip: 4.9%, 7.9% and 8.9% vs 0.4%, 2.8% and 4.1%; femoral neck: 4.8%, 7.6% and 8.1% vs 0.3%, 3.3% and 3.7%, respectively; all p < 0.001 vs placebo/denosumab). Adverse events were generally balanced between groups.

Conclusion: Romosozumab/denosumab in Japanese subjects at high risk of fracture resulted in significant BMD gains and numerically lower vertebral fracture rate vs. placebo/denosumab at all timepoints measured.

Keywords: Bone mineral density; Denosumab; Fracture risk; Osteoporosis; Romosozumab.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Asian Continental Ancestry Group*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use
  • Denosumab / adverse effects
  • Denosumab / therapeutic use*
  • Double-Blind Method
  • Female
  • Fractures, Bone / epidemiology*
  • Fractures, Bone / physiopathology
  • Humans
  • Incidence
  • Japan / epidemiology
  • Least-Squares Analysis
  • Postmenopause / drug effects
  • Risk
  • Risk Factors

Substances

  • Antibodies, Monoclonal
  • Bone Density Conservation Agents
  • romosozumab
  • Denosumab