When to start Prolia (denosumab) after 12 months of Evenity (romosozumab)?

Timing of Prolia After Evenity: Optimal Sequencing for Osteoporosis Treatment

Prolia (denosumab) should be started immediately after completing the 12-month course of Evenity (romosozumab) without any gap in treatment to prevent bone loss and maintain fracture risk reduction.

Rationale for Immediate Transition

Evenity (romosozumab) is a bone-forming agent with a dual mechanism of action that both increases bone formation and decreases bone resorption. However, its benefits are time-limited:

• The FDA label for Evenity indicates that "After EVENITY discontinuation, BMD returns to approximately baseline levels within 12 months in the absence of follow-on antiresorptive therapy" 1
• This rapid bone loss necessitates immediate transition to an antiresorptive agent like Prolia

Evidence Supporting This Approach

The evidence strongly supports immediate transition from Evenity to Prolia:

• In the pivotal clinical trial for Evenity (Study 1), participants who received 12 months of Evenity were immediately transitioned to denosumab for the next 12 months to maintain and enhance BMD gains 1
• This sequential approach (Evenity followed by denosumab) demonstrated significant reduction in vertebral fracture risk (75% relative risk reduction) compared to placebo followed by denosumab 1
• The BMD differences achieved at month 12 between Evenity and placebo were maintained at month 24 when comparing patients who transitioned from Evenity to denosumab versus those who transitioned from placebo to denosumab 1

Administration Protocol

When transitioning from Evenity to Prolia:

1. Complete the full 12-month course of Evenity (210 mg subcutaneously once monthly)
2. Administer the first dose of Prolia (60 mg subcutaneously) immediately after completing the 12-month Evenity treatment
3. Continue Prolia every 6 months as per standard dosing schedule 2

Important Considerations

Monitoring Requirements

• Check calcium levels before initiating Prolia
• Ensure adequate vitamin D supplementation (800 IU daily) and calcium intake (1000-1200 mg daily) 3
• Monitor renal function before each dose of antiresorptive therapy 3

Potential Risks of Delayed Transition

• Rapid bone loss can occur if there is a gap between Evenity and antiresorptive therapy
• Without follow-on therapy, BMD gains achieved with Evenity may return to baseline within 12 months 1
• This could potentially increase fracture risk during the treatment gap

Special Considerations

• For patients with renal impairment (creatinine clearance <60 ml/min), denosumab is preferred over bisphosphonates 2
• Denosumab should be administered every 4 weeks in cancer patients with bone metastases, but the standard 6-month interval is appropriate for osteoporosis treatment 2

Caution

• If denosumab is ever discontinued after this sequence, a bisphosphonate should be used to prevent rebound bone loss 2
• Bisphosphonate treatment (e.g., zoledronic acid) is recommended if denosumab is discontinued for more than 6 months to suppress rebound osteolysis 2

This sequential approach of 12 months of Evenity followed immediately by Prolia represents the optimal strategy to maximize bone mineral density gains and maintain fracture risk reduction in patients with severe osteoporosis.