DENOSUMAB IN BONE-RELATED DISORDERS: CURRENT CLINICAL APPLICATIONS AND SAFETY CONSIDERATIONS — A NARRATIVE REVIEW

Weronika Smutkiewicz; Weronika Teterycz; Wiktoria  Goździejewska; Łukasz  Jaworek; Gabriela  Zimka; Krystian  Bjorgen; Lilianna  Jasińska; Magdalena  Roman; Martyna  Lipiarz; Michał Niespodziewański

doi:10.31435/ijitss.2(50).2026.5696

Authors

Weronika Smutkiewicz Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0007-4965-1903
Weronika Teterycz Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0000-7486-458X
Wiktoria Goździejewska Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0007-5302-1883
Łukasz Jaworek Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0007-8117-5644
Gabriela Zimka Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0005-3954-7307
Krystian Bjorgen Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0008-0225-7439
Lilianna Jasińska University of Warmia and Mazury in Olsztyn, Olsztyn, Poland https://orcid.org/0009-0006-0819-8922
Magdalena Roman Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0004-1261-180X
Martyna Lipiarz Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0001-3124-9250
Michał Niespodziewański Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland https://orcid.org/0009-0009-0937-1549

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5696

Keywords:

Denosumab, RANKL, Osteoporosis, Bone Metastases, Multiple Myeloma, Giant Cell Tumor of Bone, Skeletal-Related Events, Rebound Phenomenon

Abstract

Denosumab is a fully human monoclonal antibody directed against the receptor activator of nuclear factor kappa-B ligand (RANKL), a central mediator of osteoclast differentiation, activation, and survival. Denosumab, acting by interfering with the RANKL pathway, provides powerful anti-resorptive activity and serves as an effective treatment modality for numerous conditions associated with bones. This narrative review summarizes the current evidence regarding the mechanism of action, pharmacokinetic and pharmacodynamic properties, clinical applications, and safety profile of denosumab.

Denosumab has demonstrated substantial efficacy in osteoporosis, with significant increases in bone mineral density and reductions in vertebral, non-vertebral, and hip fracture risk. In oncology, it is widely used for the prevention of skeletal-related events in patients with bone metastases and multiple myeloma. It has also emerged as an effective targeted therapy in giant cell tumor of bone.

Despite its broad clinical utility, denosumab therapy is associated with important safety considerations. These include hypocalcemia, osteonecrosis of the jaw, atypical femoral fractures, and the rebound phenomenon following treatment discontinuation. Rebound phenomenon is characterized by rapid bone turnover and increased risk of multiple vertebral fractures. These challenges highlight the importance of careful patient selection, monitoring, and long-term treatment planning.

Denosumab represents a cornerstone therapy in the management of bone-related disorders due to its targeted mechanism and robust clinical efficacy. However, its reversible pharmacological profile necessitates individualized therapeutic strategies to optimize outcomes and minimize long-term risks.

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