Management of RANKL-mediated Disorders With Denosumab in Children and Adolescents: A Global Expert Guidance Document

J Clin Endocrinol Metab. 2024 Apr 19;109(5):1371-1382. doi: 10.1210/clinem/dgad657.

Abstract

Context: Denosumab is an effective treatment for many receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated disorders but there are potential safety considerations and limited data to guide its use in children and adolescents.

Objective: This document seeks to summarize the evidence and provide expert opinion on safe and appropriate use of denosumab in pediatric RANKL-mediated disorders.

Participants: Ten experts in pediatric bone and mineral medicine from 6 countries with experience in the use of denosumab participated in the creation of this document.

Evidence: Data were sourced from the published literature, primarily consisting of case reports/series and review articles because of the lack of higher level evidence. Expert opinion of the authors was used substantially when no published data were available.

Conclusion: Denosumab is an effective treatment for RANKL-mediated disorders in children and adolescents but is often not curative and, in some cases, is best used in conjunction with surgical or other medical treatments. Careful multidisciplinary planning is required to define the goals of treatment and expert oversight needed to manage the risk of mineral abnormalities. Substantive, collaborative research efforts are needed to determine optimal treatment regimens and minimize risks.

Keywords: aneurysmal bone cyst; bone mineral density; fibrous dysplasia; giant cell tumor; hypocalcemia; rebound hypercalcemia.

MeSH terms

  • Adolescent
  • Bone Density Conservation Agents* / adverse effects
  • Bone Density Conservation Agents* / therapeutic use
  • Bone and Bones
  • Child
  • Denosumab* / adverse effects
  • Denosumab* / therapeutic use
  • Humans
  • Ligands
  • Minerals
  • RANK Ligand

Substances

  • Bone Density Conservation Agents
  • Denosumab
  • Ligands
  • Minerals
  • RANK Ligand