Discontinuing Long-Term Denosumab in Treating Fragile Bone: Why, for Whom, and How?

Area of Science:

• Bone Metabolism and Pharmacology
• Osteoporosis Management
• Drug Safety and Efficacy

Background:

• Denosumab (Dmab) is a key osteoporosis treatment.
• Discontinuation is sometimes necessary due to adverse events or risk-benefit profiles.
• Evidence shows significant rebound phenomena post-Dmab withdrawal.

Purpose of the Study:

• To review the mechanistic and clinical evidence for denosumab rebound effects.
• To identify patient populations requiring careful transition planning after Dmab cessation.
• To outline optimal discontinuation and sequential treatment strategies for denosumab therapy.

Main Methods:

• Literature review of mechanistic and clinical studies on denosumab.
• Analysis of patient data regarding rebound phenomena and fracture risk.
• Evaluation of sequential treatment options post-denosumab discontinuation.

Main Results:

• Denosumab withdrawal is associated with rebound effects, including increased vertebral fractures and potential mortality.
• Specific patient groups require tailored transition plans due to Dmab risks.
• Concurrent teriparatide and zoledronate may mitigate rebound risk, pending validation.

Conclusions:

• Understanding denosumab rebound is crucial for safe treatment cessation.
• Personalized strategies are needed for Dmab discontinuation and sequential therapy.
• Further research is required to validate novel approaches for managing denosumab withdrawal.