When to consider transitioning from Denosumab (Prolia) to another osteoporosis treatment?

When to Consider Transitioning from Denosumab

Bisphosphonate treatment (e.g., zoledronate) should be initiated if denosumab is discontinued for more than 6 months to suppress rebound osteolysis and prevent multiple vertebral fractures. 1

Key Considerations for Transitioning from Denosumab

Risk of Rebound Effect After Discontinuation

Denosumab discontinuation presents significant risks that must be managed appropriately:

• Unlike bisphosphonates, denosumab does not incorporate into bone matrix, making its effects rapidly reversible after discontinuation 2
• Discontinuation leads to:
  • Rapid decrease in bone mineral density (BMD)
  • Steep increase in bone turnover markers
  • Increased risk of multiple vertebral fractures due to rebound bone resorption 2

Timing of Transition Assessment

• A re-evaluation should be performed after 5 years of denosumab treatment 2
• For patients continuing denosumab beyond 5 years, consider:
  • Ongoing fracture risk assessment
  • Monitoring for rare complications like osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF) 3, 4

Transition Algorithm Based on Fracture Risk

High Fracture Risk Patients

If the patient remains at high fracture risk after 5 years of denosumab:

1. Option A: Continue denosumab for up to 10 years 2
2. Option B: Switch to an alternative antiresorptive therapy (preferably bisphosphonate) 3

Low Fracture Risk Patients

If the patient is at low fracture risk after 5 years of denosumab:

1. Consider discontinuation of denosumab
2. Critical step: Initiate bisphosphonate therapy (e.g., zoledronate) to prevent rebound bone turnover 1, 2
3. Monitor BMD and bone turnover markers closely during transition

Specific Transition Protocols

Transitioning to Bisphosphonates

• Zoledronic acid (IV) is often preferred due to its potency and long duration of action
• Oral bisphosphonates (alendronate, risedronate) may also be used but have less evidence for post-denosumab transition 5
• Timing: Initiate bisphosphonate within 6 months of the last denosumab dose 1

Special Patient Populations

Cancer Patients

• For patients with bone metastases on denosumab:
  • Discontinuation is generally not recommended except for those with oligometastatic bone disease in remission 1
  • Denosumab should be administered every 4 weeks; extending intervals beyond this frequency is not recommended 1

Glucocorticoid-Induced Osteoporosis

• For patients who have had a fracture after 18 months of oral bisphosphonate treatment or significant BMD decline:
  • Consider switching to denosumab or teriparatide rather than continuing oral bisphosphonate 1
• When discontinuing glucocorticoids in patients on denosumab:
  • If fracture risk remains high, continue osteoporosis treatment 1
  • If fracture risk is low, discontinue denosumab but transition to bisphosphonate therapy 1

Monitoring During Transition

• BMD measurement within 6-12 months after transition
• Bone turnover markers to assess effectiveness of the transition therapy
• Clinical assessment for new vertebral fractures, especially during the first 24 months after denosumab discontinuation 2

Common Pitfalls to Avoid

1. Never discontinue denosumab without planning follow-up therapy - this can lead to rapid bone loss and multiple vertebral fractures 3, 2
2. Don't delay bisphosphonate initiation - treatment should begin within 6 months of the last denosumab dose 1
3. Avoid assuming bisphosphonates will completely prevent rebound - while they help mitigate the effect, the optimal regimen is still being determined 2
4. Don't overlook calcium and vitamin D supplementation - maintain adequate intake throughout the transition period 1

By following these guidelines, clinicians can safely transition patients from denosumab to alternative therapies while minimizing the risk of rebound-associated fractures.