Osteoporosis as a chronic disease: an expert narrative review and practical recommendations on long-term management and sequential therapy after denosumab discontinuation.

purposeDenosumab is a human monoclonal antibody that binds receptor activator of nuclear factor-κB ligand, leading to marked and sustained reductions in fracture risk in osteoporosis. Due to its reversible mechanism and lack of skeletal retention, treatment interruption causes rebound bone turnover, accelerated bone mineral density (BMD) loss, and increased vertebral fracture risk. Optimising denosumab therapy therefore requires a long-term management strategy incorporating uninterrupted dosing and planned sequential antiresorptive therapy.

methodsThis expert narrative review summarises evidence on denosumab pharmacology, efficacy, safety, and discontinuation management and provides practical recommendations informed by the published literature and the clinical experience of the author panel. No formal Delphi process, voting procedure, evidence-grading framework, or predefined consensus threshold was used.

resultsMain topics discussed included transition strategies after withdrawal, particularly alendronate (or zoledronic acid), timing of initiation, and biomarker-guided monitoring using serum C-terminal telopeptide (CTX). This paper also addresses management in special populations (chronic kidney disease, glucocorticoid exposure, malignancy, endocrine disorders) and evaluates health-system factors including infusion capacity, adherence, and coordinated primary-specialist care.

conclusionDenosumab should not be discontinued without subsequent potent antiresorptive therapy. Sequential alendronate or zoledronic acid within six to seven months of the final injection, guided by CTX and BMD monitoring, is likely to be the most effective strategy in preventing rebound bone loss. Structured transition pathways are essential for sustained skeletal protection.