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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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11031248 | PMC |
http://dx.doi.org/10.1210/clinem/dgad657 | DOI Listing |
Int Immunopharmacol
September 2025
Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:
Background: Bone remodeling constitutes an intricate physiological process essential for maintaining skeletal integrity. Hyperactivation of osteoclastogenesis precipitates excessive resorption of osseous tissue, consequently engendering osteoporotic pathology. The formulation of effective anti-resorptive therapeutic modalities remains a potential strategy in the clinical management of osteoporosis.
View Article and Find Full Text PDFJ Extracell Vesicles
July 2025
Laboratorio de Biología Periodontal, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
Regulatory T cell (Treg)-derived extracellular vesicles (EVs) represent a contact-independent mechanism by which Tregs suppress dysregulated immune responses. These EVs carry diverse immunomodulatory molecules, including CD73, an ectoenzyme that hydrolyses AMP into adenosine. Adenosine subsequently acts as a potent immunosuppressive mediator that inhibits effector CD4⁺ T cell activation and controls pathological inflammation.
View Article and Find Full Text PDFBiochem Biophys Res Commun
June 2025
Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk, 54538, Republic of Korea. Electronic address:
Peroxisomal biogenesis factor 5 (PEX5), a peroxisomal import receptor, is well recognized for its role in protein trafficking and oxidative stress regulation. However, its function in bone metabolism remains unclear. Given the established impact of oxidative stress on osteoclast differentiation, this study explores the previously uncharacterized role of PEX5 in osteoclastogenesis and bone resorption.
View Article and Find Full Text PDFInt J Mol Sci
March 2025
Honam Regional Center, Korea Basic Science Institute (KBSI), Gwangju 61751, Republic of Korea.
Osteoclast differentiation inhibition is a viable treatment strategy for osteoporosis because osteoclasts play a vital role in disease progression. Rhusflavone (Rhus), a biflavonoid, exhibits a sedative-hypnotic effect via the positive allosteric modulation of GABA(A) receptors. Although several biflavonoids possess activities that help prevent bone loss, the potential effects of Rhus on osteoclastogenesis have not been reported yet.
View Article and Find Full Text PDFFront Public Health
April 2025
Department of Spine Osteopathic, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Background: Osteoporosis is a multifactorial disease influenced by genetic, environmental, and metabolic factors. AKT serine/threonine kinase 1 (AKT1), a central regulator of cellular survival and metabolism, has been implicated in bone remodeling, yet its precise role in osteoporosis remains unclear.
Methodology: Gene expression analysis and molecular docking simulations were performed to identify key pathways and interactions involving bisphenol A (BPA) and AKT1.