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Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension.

  • Cummings SR San Francisco Coordinating Center, CPMC Research Institute, San Francisco, CA, USA.
  • Ferrari S Geneva University Hospital, Geneva, Switzerland.
  • Eastell R The University of Sheffield, Sheffield, UK.
  • Gilchrist N The Princess Margaret Hospital, Christchurch, New Zealand.
  • Jensen JB Hvidovre University Hospital, Hvidovre, Denmark.
  • McClung M Oregon Osteoporosis Center, Portland, OR, USA.
  • Roux C Paris Descartes University, Paris, France.
  • Törring O Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
  • Valter I Center for Clinical and Basic Research, Tallinn, Estonia.
  • Wang AT Amgen Inc., Thousand Oaks, CA, USA.
  • Brown JP Laval University and CHU de Québec-Université Laval (CHUL), Quebec City, Canada.
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  • 2017-11-07
Published in:
  • Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 2018
BONE RESORPTION
DENOSUMAB
DISCONTINUATION
MULTIPLE VERTEBRAL FRACTURES
VERTEBRAL FRACTURES
Aged
Aged, 80 and over
Bone Density
Denosumab
Female
Humans
Logistic Models
Middle Aged
Multivariate Analysis
Osteoporosis, Postmenopausal
Spinal Fractures
Withholding Treatment
English Denosumab reduces bone resorption and vertebral and nonvertebral fracture risk. Denosumab discontinuation increases bone turnover markers 3 months after a scheduled dose is omitted, reaching above-baseline levels by 6 months, and decreases bone mineral density (BMD) to baseline levels by 12 months. We analyzed the risk of new or worsening vertebral fractures, especially multiple vertebral fractures, in participants who discontinued denosumab during the FREEDOM study or its Extension. Participants received ≥2 doses of denosumab or placebo Q6M, discontinued treatment, and stayed in the study ≥7 months after the last dose. Of 1001 participants who discontinued denosumab during FREEDOM or Extension, the vertebral fracture rate increased from 1.2 per 100 participant-years during the on-treatment period to 7.1, similar to participants who received and then discontinued placebo (n = 470; 8.5 per 100 participant-years). Among participants with ≥1 off-treatment vertebral fracture, the proportion with multiple (>1) was larger among those who discontinued denosumab (60.7%) than placebo (38.7%; p = 0.049), corresponding to a 3.4% and 2.2% risk of multiple vertebral fractures, respectively. The odds (95% confidence interval) of developing multiple vertebral fractures after stopping denosumab were 3.9 (2.1-7. 2) times higher in those with prior vertebral fractures, sustained before or during treatment, than those without, and 1.6 (1.3-1.9) times higher with each additional year of off-treatment follow-up; among participants with available off-treatment total hip (TH) BMD measurements, the odds were 1.2 (1.1-1.3) times higher per 1% annualized TH BMD loss. The rates (per 100 participant-years) of nonvertebral fractures during the off-treatment period were similar (2.8, denosumab; 3.8, placebo). The vertebral fracture rate increased upon denosumab discontinuation to the level observed in untreated participants. A majority of participants who sustained a vertebral fracture after discontinuing denosumab had multiple vertebral fractures, with greatest risk in participants with a prior vertebral fracture. Therefore, patients who discontinue denosumab should rapidly transition to an alternative antiresorptive treatment. Clinicaltrails.gov: NCT00089791 (FREEDOM) and NCT00523341 (Extension). © 2017 American Society for Bone and Mineral Research.
Language
  • English
Open access status
bronze
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https://folia.unifr.ch/global/documents/109951
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