What is the recommended protocol when switching from Prolia (denosumab) to Fosamax (alendronate)?

Switching from Prolia (Denosumab) to Fosamax (Alendronate)

Critical Warning: This Switch Requires Immediate Action to Prevent Rebound Fractures

If denosumab must be discontinued, bisphosphonate treatment with alendronate must be initiated within 6 months to suppress rebound osteolysis and prevent potentially catastrophic vertebral fractures. 1, 2 Denosumab has a reversible mechanism of action, and stopping it abruptly causes rapid bone loss and dramatically increased fracture risk. 1

Timing of the Switch

• Start alendronate 70 mg weekly within 6 months of the last denosumab injection to prevent rebound bone loss. 1, 2
• The optimal timing appears to be starting alendronate shortly after the denosumab effect begins to wane (around 6 months after the last dose), though earlier initiation may be considered in very high-risk patients. 3
• Never allow a gap longer than 6 months between the last denosumab dose and first alendronate dose. 1

Pre-Transition Requirements

Before initiating alendronate after denosumab discontinuation:

• Complete a comprehensive dental evaluation and finish any necessary invasive dental procedures before starting alendronate, as the risk of osteonecrosis of the jaw exists with both agents (approximately 1-2% with oral bisphosphonates). 1, 4, 2
• Correct vitamin D deficiency prior to bisphosphonate initiation, as deficiency may attenuate efficacy and increase risk of hypocalcemia. 1, 2
• Check serum calcium levels to ensure normocalcemia before starting alendronate. 1, 4
• Assess renal function: Alendronate is contraindicated in patients with GFR < 35 ml/min/1.73 m². 5, 2 If significant renal impairment exists, continuing denosumab may be preferable as it requires no dose adjustment. 1, 2

Alendronate Dosing Protocol

• Alendronate 70 mg orally once weekly is the standard dose for osteoporosis treatment. 1, 5
• Patients must take alendronate with a full glass of water (6-8 ounces), remain upright for at least 30 minutes, and avoid food/drink during this period to minimize esophageal risk. 2
• Continue supplementation with calcium 1200 mg daily and vitamin D 800-1000 IU daily throughout treatment. 1, 4

Duration of Alendronate After Denosumab

The evidence suggests:

• At least 12 months of alendronate is necessary to maintain BMD gains achieved with denosumab and prevent rebound bone turnover. 3
• Research demonstrates that both 1 and 2 years of alendronate effectively maintain BMD gains after 1 year of denosumab, though a transient decrease in hip BMD occurred between months 6-12 in those stopping alendronate after 1 year. 3
• For patients who received longer durations of denosumab (multiple years), 2 years or more of alendronate may be prudent, though definitive data are lacking. 3
• After completing the initial alendronate course post-denosumab, follow standard bisphosphonate guidelines: reassess fracture risk at 5 years and consider a drug holiday in lower-risk patients. 2

Ongoing Monitoring

• Monitor serum calcium periodically, especially in the first few months after transition. 1, 4
• Perform BMD testing with vertebral fracture assessment every 1-2 years to ensure maintenance of bone density. 4
• Maintain excellent oral hygiene and avoid invasive dental procedures when possible during bisphosphonate therapy. 4
• Reassess fracture risk if new fractures occur or clinical status changes significantly. 2

Why This Switch May Be Necessary

Valid reasons for switching from denosumab to alendronate include:

• Cost considerations: Alendronate costs approximately $78 annually versus $2,292 for denosumab. 1
• Patient preference for oral versus subcutaneous administration. 6
• Concerns about long-term denosumab commitment, as discontinuation without transition therapy is dangerous. 1

Critical Pitfalls to Avoid

• Never discontinue denosumab without a transition plan to bisphosphonates. The rebound effect can cause multiple vertebral fractures within months. 1, 2
• Do not delay alendronate initiation beyond 6 months after the last denosumab dose. 1, 2
• Do not use alendronate in patients with GFR < 35 ml/min—these patients should remain on denosumab. 5, 2
• Do not skip calcium and vitamin D supplementation, as adequate levels are essential for bisphosphonate efficacy and prevention of hypocalcemia. 1, 2
• Do not perform invasive dental work while on alendronate without careful risk-benefit assessment and appropriate precautions. 1, 4, 2

Lifestyle Recommendations to Maintain

• Engage in weight-bearing exercise regularly. 4
• Stop smoking if applicable. 4
• Limit alcohol consumption to two or fewer units daily. 4
• Ensure adequate dietary calcium intake with supplementation as needed. 4