A Deodati1, D Fintini1, E Levtchenko2, M Rossi3, G Ubertini1, H Segers2, G Battafarano3, M Cappa1, A Del Fattore4. 1. Endocrinology Unit, University Pediatric Clinical Department, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy. 2. Department of Pediatrics, University Hospitals Leuven, 3000, Leuven, Belgium. 3. Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146, Rome, Italy. 4. Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146, Rome, Italy. andrea.delfattore@opbg.net.
Abstract
PURPOSE: Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract the bone loss induced by exacerbated osteoclast activity. Indeed, its binding to RANK-L prevents the interaction RANK-L/receptor RANK that is essential for osteoclastogenesis and bone resorbing activity. Although there are many medications available to treat bone loss diseases, including bisphosphonates, Denosumab is highly effective since it reduces the bone erosion. The use in pediatric patients is safe. However, some concerns are related to the interruption of the treatment. Indeed, in this study, we reported hypercalcemia in two pediatric patients and alterations of circulating osteoclast precursors. METHODS: Peripheral Blood Mononuclear Cells (PBMC) were isolated from two pediatric patients with hypercalcemia after Denosumab interruption and from 10 controls. Cytofluorimetric analysis and in vitro osteoclastogenesis experiments were performed. RESULTS: Increase of CD16-CD14+CD11b+ cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis. CONCLUSION: Our data suggest that precautions must be taken when Denosumab therapy is interrupted and gradual decrease of dose and/or timing of treatment should be performed. To prevent the onset of hypercalcemia that could be in the discontinuation phase, cytofluorimetric analysis of PBMC should be performed to evaluate osteoclast precursors.
PURPOSE: Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract the bone loss induced by exacerbated osteoclast activity. Indeed, its binding to RANK-L prevents the interaction RANK-L/receptor RANK that is essential for osteoclastogenesis and bone resorbing activity. Although there are many medications available to treat bone loss diseases, including bisphosphonates, Denosumab is highly effective since it reduces the bone erosion. The use in pediatric patients is safe. However, some concerns are related to the interruption of the treatment. Indeed, in this study, we reported hypercalcemia in two pediatric patients and alterations of circulating osteoclast precursors. METHODS: Peripheral Blood Mononuclear Cells (PBMC) were isolated from two pediatric patients with hypercalcemia after Denosumab interruption and from 10 controls. Cytofluorimetric analysis and in vitro osteoclastogenesis experiments were performed. RESULTS: Increase of CD16-CD14+CD11b+ cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis. CONCLUSION: Our data suggest that precautions must be taken when Denosumab therapy is interrupted and gradual decrease of dose and/or timing of treatment should be performed. To prevent the onset of hypercalcemia that could be in the discontinuation phase, cytofluorimetric analysis of PBMC should be performed to evaluate osteoclast precursors.
Authors: Paul J Kostenuik; Hung Q Nguyen; James McCabe; Kelly S Warmington; Carol Kurahara; Ning Sun; Ching Chen; Luke Li; Russ C Cattley; Gwyneth Van; Shelia Scully; Robin Elliott; Mario Grisanti; Sean Morony; Hong Lin Tan; Frank Asuncion; Xiaodong Li; Michael S Ominsky; Marina Stolina; Denise Dwyer; William C Dougall; Nessa Hawkins; William J Boyle; William S Simonet; John K Sullivan Journal: J Bone Miner Res Date: 2009-02 Impact factor: 6.741