Title: 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension

Bone, G.H., MD, et al.


What You Need to Know:

According to results of a study extension of the FREEDOM trial, long-term treatment with denosumab is not only safe but is also associated with lower rates of adverse events, decreased fracture incidence, and increased bone mineral density (BMD) compared to the original study.

Trial Design:

  • FREEDOM trial: phase 3 study assessed safety and efficacy of denosumab compared to placebo over 3 years
  • Open-label extension: 7-year extension of FREEDOM trial to evaluate long-term safety of denosumab
  • 4550 eligible patients enrolled in study extension and received denosumab “Crossover group”: patients received placebo during the FREEDOM trial then denosumab during the extension study
  • “Long-term group”: patients received denosumab during the FREEDOM trial and the extension study
  • Primary outcome: safety monitoring (included assessments of adverse events, changes in laboratory findings, and frequency of denosumab antibody formation)
  • Secondary outcomes: vertebral, hip, and non-vertebral fractures; analysis of BMD at lumbar spine, total hip, femoral neck, and one-third radius

Key Outcomes:

  • 2626 patients completed the extension study (1283 crossover patients, 1343 long-term patients)
  • Over 10 years, yearly exposure-adjusted participant incidence of adverse events for patients receiving denosumab was reduced (165.3 to 95.9 per 100 participant-years)
  • Rates of serious adverse events remained stable during study (11.5 to 14.4 per 100 participant-years)
  • 1 case of atypical femoral fracture occurred in each group
  • 7 cases of osteonecrosis of the jaw occurred in the long-term group, 6 cases occurred in the crossover group
  • Annual incidence of new vertebral fractures and non-vertebral fractures was low and found to be similar in occurrence to FREEDOM study (0.90-1.86% and 0.84-2.55%, respectively)
  • Long-term group: BMD increased by 21.7% at the lumbar spine, 9.2% at total hip, 9.0% at femoral neck, and 2.7% at the one-third radius from FREEDOM baseline
  • Crossover group: BMD increased by 16.5% at the lumbar spine, 7.4% at total hip, 7.1% at femoral neck, and 2.3% at the one-third radius from FREEDOM baseline