Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension

Arch Osteoporos. 2019 Jun 5;14(1):59. doi: 10.1007/s11657-019-0608-z.


Romosozumab, which binds sclerostin, rebuilds the skeletal foundation before transitioning to antiresorptive treatment. This subgroup analysis of an international, randomized, double-blind study in postmenopausal women with osteoporosis showed efficacy and safety outcomes for romosozumab followed by denosumab in Japanese women were generally consistent with those for the overall population.

Purpose: In the international, randomized, double-blind, phase 3 FRActure study, in postmenopausal woMen with ostEoporosis (FRAME; NCT01575834), romosozumab followed by denosumab significantly improved bone mineral density (BMD) and reduced fracture risk. This report evaluates Japanese women in FRAME.

Methods: Postmenopausal women with osteoporosis (T-score - 3.5 to - 2.5 at total hip or femoral neck) received romosozumab 210 mg or placebo subcutaneously monthly for 12 months, then each group received denosumab 60 mg subcutaneously every 6 months for 24 months. The key endpoint for Japanese women was BMD change. Other endpoints included new vertebral, clinical, and nonvertebral fracture; the subgroup analysis did not have adequate power to demonstrate statistically significant reductions.

Results: Of 7180 enrolled subjects, 492 (6.9%) were Japanese (247 romosozumab, 245 placebo). BMD increases from baseline were greater (P < 0.001) for romosozumab-to-denosumab than placebo-to-denosumab at the lumbar spine (36 months, 12.7%), total hip (4.2%), and femoral neck (4.1%). Fracture risk was lower through 36 months for romosozumab-to-denosumab vs placebo-to-denosumab for new vertebral (1.7% vs 4.5%; relative risk reduction (RRR) 63%, P = 0.070), clinical (3.2% vs 7.3%; RRR 53%, P = 0.072), nonvertebral (2.8% vs 6.1%; RRR 50%, P = 0.12), and all other fracture types evaluated. Rates of adverse events and positively adjudicated serious cardiovascular events were generally balanced between groups.

Conclusions: Efficacy and safety for romosozumab-to-denosumab were similar between Japanese women and the overall population. The sequence of romosozumab to rebuild the skeletal foundation before transitioning to antiresorptive treatment with denosumab is a promising regimen for Japanese postmenopausal women with osteoporosis at high risk of fracture.

Keywords: Bone mineral density; Denosumab; Fracture; Japanese; Romosozumab.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / administration & dosage*
  • Denosumab / administration & dosage*
  • Double-Blind Method
  • Female
  • Femur Neck
  • Fractures, Bone / epidemiology
  • Fractures, Bone / prevention & control
  • Humans
  • Japan / epidemiology
  • Lumbar Vertebrae
  • Middle Aged
  • Osteoporosis
  • Osteoporosis, Postmenopausal / drug therapy*
  • Risk
  • Risk Reduction Behavior


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

Associated data