Work

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

Year: 2026

Type: article

Abstract: Discontinuation of denosumab (Dmab) may be necessary due to adverse events or an unfavorable long-term risk-benefit profile. However, accumulating evidence demonstrates pronounced rebound phenomena after withdrawal, most notably a marked increase in multiple vertebral fractures, and, in some reports, elevated mortality. This review addresses three key clinical considerations: (1) the mechanistic and clinical evidence for rebound effects and indications for Dmab cessation ("Why?"); (2) patient populations in whom Dmab initiation or continuation may be inappropriate and who therefore require careful transition planning ("For whom?"); and (3) optimal discontinuation and sequential treatment strategies, including scenarios in which continued or lifelong therapy may be advisable ("How?"). Emerging data suggest that concurrent teriparatide and zoledronate may attenuate rebound risk in long-term Dmab users requiring urgent discontinuation, although prospective validation is needed before routine adoption.

Source: Clinical Pharmacology & Therapeutics

DOI: 10.1002/cpt.70323

Authors: Ko‐Hsiu Lu, Renn‐Chia Lin, Ing‐Lin Chang, Shau‐Huai Fu, Meng‐Ying Tsai, Shun‐Fa Yang

Institutions: Chung Shan Medical University Hospital, Chung Shan Medical University, Changhua Christian Hospital, National Taiwan University Hospital

Language: English

Topic: Bone health and osteoporosis research

Subfield: Orthopedics and Sports Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,410