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Stopping Denosumab.

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Discontinuing denosumab can cause a rebound effect, leading to multiple vertebral fractures. Prompt bisphosphonate treatment may mitigate this risk, but further studies are needed.

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Area of Science:

  • Bone Metabolism and Osteoporosis Research
  • Pharmacological Interventions in Skeletal Diseases

Background:

  • Denosumab discontinuation is linked to a significant rebound effect, increasing the risk of multiple spontaneous vertebral fractures.
  • This phenomenon highlights the need for careful management strategies upon treatment cessation.

Purpose of the Study:

  • To thoroughly characterize the risk of vertebral fractures following denosumab discontinuation.
  • To identify and evaluate potential solutions for mitigating this rebound effect.

Main Methods:

  • Review of recent case series and existing literature on denosumab discontinuation.
  • Analysis of fracture incidence and timing post-denosumab cessation.

Main Results:

  • Multiple vertebral fractures are common (≥1/100 and <1/10) without potent bisphosphonate cover.
  • Median of 5 vertebral fractures observed 7-20 months post-denosumab in case series.
  • Bisphosphonate use before or after denosumab may reduce fracture risk, though evidence is limited.

Conclusions:

  • Denosumab discontinuation poses a substantial risk of vertebral fractures due to a rebound effect.
  • Prophylactic bisphosphonate therapy is a potential strategy to reduce this risk.
  • Urgent research is required to establish optimal management protocols for denosumab cessation.