Bisphosphonate Therapy Duration After Stopping Prolia (Denosumab)
Bisphosphonate treatment (e.g., zoledronic acid) is recommended if denosumab is discontinued for more than 6 months to suppress rebound osteolysis and prevent vertebral fractures. 1
Understanding Denosumab Discontinuation Risks
- Unlike bisphosphonates, denosumab does not incorporate into bone matrix, and bone turnover is not suppressed after its cessation 1
- After stopping denosumab, there is a steep increase in bone turnover markers and rapid decrease in bone mineral density (BMD) 1
- Clinical case series and re-analyses of osteoporosis trials report multiple vertebral fractures occurring after discontinuation of denosumab, due to rebound increase in bone resorption 1, 2
- This rebound effect appears to be associated with a marked increase in vertebral fracture risk 1
Recommended Management After Stopping Prolia
Timing of Bisphosphonate Initiation
- Bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover after stopping denosumab 1, 2
- Bisphosphonate treatment is specifically recommended if denosumab is discontinued for more than 6 months 1
Duration of Bisphosphonate Therapy
- Currently, the optimal bisphosphonate regimen post-denosumab is not definitively established 1, 2
- Many osteoporosis clinicians use a single 4- or 5-mg treatment of zoledronic acid 1
- Recent evidence suggests that both 1 and 2 years of alendronate effectively maintain BMD gains achieved with 1 year of denosumab and prevent rebound in bone turnover marker levels 3
- In patients who received delayed zoledronate after romosozumab/denosumab therapy, bone turnover markers increased at 12 months post-treatment, suggesting that repeat zoledronate dosing is needed at 1 year to maintain BMD gains 4
Practical Considerations
- A re-evaluation should be performed after 5 years of denosumab treatment to determine ongoing management 2
- For patients at high fracture risk, either continue denosumab therapy for up to 10 years or switch to an alternative treatment 2
- For patients at low fracture risk, discontinuation of denosumab could be considered after 5 years, but bisphosphonate therapy should be implemented 2
- The timing of bisphosphonate administration may affect efficacy - delaying administration of intravenous bisphosphonate when transitioning from short-term denosumab appears to increase the extent to which BMD gains are maintained 4
Important Caveats
- Denosumab should not be stopped without considering alternative treatment to prevent rapid BMD loss and potential rebound in vertebral fracture risk 2
- Patients and clinicians should be aware of the potential risk of multiple vertebral fractures after discontinuation of denosumab 2
- Close monitoring is suggested after denosumab discontinuation due to the possibility of rebound fractures 5
- The optimal choice and duration of antiresorptive therapy after denosumab discontinuation are still being defined through ongoing research 3