Should a patient continue bisphosphonate until starting Prolia (denosumab)?

Transitioning from Bisphosphonate to Denosumab (Prolia)

When transitioning from a bisphosphonate to denosumab (Prolia), the patient should discontinue the bisphosphonate and start denosumab immediately without a gap in treatment to prevent bone loss and increased fracture risk.

Rationale for Immediate Transition

The pharmacokinetics and mechanism of action of these medications necessitate different approaches to transition:

• Bisphosphonates: Incorporate into bone matrix and continue to suppress bone turnover even after discontinuation 1
• Denosumab: Does not incorporate into bone matrix; its effect is rapidly reversible after discontinuation 1

This fundamental difference creates significant clinical implications when transitioning between these medications.

Risks of Gaps in Treatment

A gap between stopping bisphosphonate and starting denosumab could lead to:

• Rebound bone turnover: Especially if the patient has been on bisphosphonate for a short duration
• Potential bone loss: During the transition period
• Increased fracture risk: Particularly vertebral fractures

Evidence Supporting Immediate Transition

The European Calcified Tissue Society (ECTS) position statement emphasizes that denosumab discontinuation without alternative treatment leads to:

• Rapid decrease in bone mineral density (BMD)
• Steep increase in bone turnover markers
• Potential rebound increase in vertebral fracture risk 2

This suggests that maintaining continuous bone resorption inhibition is critical when transitioning between these agents.

Clinical Approach to Transition

1. Stop bisphosphonate at the scheduled end of treatment cycle
2. Start denosumab immediately (60mg subcutaneously every 6 months)
3. Ensure adequate calcium and vitamin D supplementation throughout the transition and during denosumab therapy 1
4. Monitor serum calcium levels regularly, especially early in denosumab treatment, as hypocalcemia is more frequent and likely to be symptomatic with denosumab than with bisphosphonates 1

Important Considerations

• Superior efficacy: Transitioning to denosumab from oral bisphosphonates leads to greater BMD increases and bone turnover reduction compared to switching to another oral bisphosphonate 3
• Renal function: Denosumab is preferred in patients with renal disease 1
• Long-term planning: Consider that if denosumab is ever discontinued in the future, a bisphosphonate should be administered to prevent the rebound effect 2, 4

Cautions

• Osteonecrosis of jaw risk: Both medications carry this risk, with higher incidence in monthly dosing for metastatic disease than in osteoporosis dosing 1
• Atypical femoral fractures: Long-term use of both medications has been associated with this rare complication 1
• Dental procedures: Schedule any invasive dental procedures before starting denosumab when possible 5

The seamless transition from bisphosphonate to denosumab without a gap ensures continuous protection against bone loss and fracture risk while maximizing the benefits of changing to this more potent bone resorption inhibitor.