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Bone. 2019 Aug 24;129:115048. doi: 10.1016/j.bone.2019.115048. [Epub ahead of print]

Off-label uses of denosumab in metabolic bone diseases.

Author information

1
First Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: spolyzos@auth.gr.
2
Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force General Hospital, Athens, Greece.
3
Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", National and Kapodistrian University of Athens, KAT Hospital, Athens, Greece.
4
Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.

Abstract

Denosumab (Dmab), a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) which substantially suppresses osteoclast activity, has been approved for the treatment of common metabolic bone diseases, including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis, in which the pathway of the RANK/RANKL/osteoprotegerin is dysregulated. However, the imbalance of RANKL/RANK/osteoprotegerin is also implicated in the pathogenesis of several other rare metabolic bone diseases, including Juvenile Paget disease, fibrous dysplasia, Hajdu Cheney syndrome and Langerhans cell histiocytosis, thus rendering Dmab a potential treatment option for these diseases. Dmab has been also administered off-label in selected patients (e.g., with Paget's disease, osteogenesis imperfecta, aneurysmal bone cysts) due to contraindications or unresponsiveness to standard treatment, such as bisphosphonates. Moreover, Dmab was administered to improve hypercalcemia induced by various diseases, including primary hyperparathyroidism, tuberculosis and immobilization. The aim of this review is to summarize existing evidence on off-label uses of Dmab in metabolic bone diseases and provide opinion for or against its use, which should be always considered on an individual basis.

KEYWORDS:

Denosumab; Kidney disease; Off-label; Orphan disease; Osteoprotegerin; Receptor activator of nuclear factor-κB ligand

PMID:
31454537
DOI:
10.1016/j.bone.2019.115048

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