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Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial
OBJECTIVES: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to bone fragility. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. Aim of this study was a 48-week, open-label, pilot study of the safety and eff...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Society of Musculoskeletal and Neuronal Interactions
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089451/ https://www.ncbi.nlm.nih.gov/pubmed/26944820 |
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author | Hoyer-Kuhn, H. Franklin, J. Allo, G. Kron, M. Netzer, C. Eysel, P. Hero, B. Schoenau, E. Semler, O. |
author_facet | Hoyer-Kuhn, H. Franklin, J. Allo, G. Kron, M. Netzer, C. Eysel, P. Hero, B. Schoenau, E. Semler, O. |
author_sort | Hoyer-Kuhn, H. |
collection | PubMed |
description | OBJECTIVES: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to bone fragility. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. Aim of this study was a 48-week, open-label, pilot study of the safety and efficacy of denosumab in 10 children with OI. METHODS: Ten patients (age range: 5.0-11.0 years; at least two years of prior bisphosphonate treatment) with genetically confirmed OI were studied. Denosumab was administered subcutaneously every 12 weeks with 1 mg/kg body weight. Primary endpoint was change of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 48 weeks. Safety was assessed by bone metabolism markers and adverse event reporting. RESULTS: Mean relative change of lumbar aBMD was +19 % (95%-CI: 7-31%). Lumbar spine aBMD Z-Scores increased from -2.23±2.03 (mean±SD) to -1.27±2.37 (p=0.0006). Mobility did not change (GMFM-88 +2.72±4.62% (p=0.16); one-minute walking test +11.00±15.82 m (p=0.15). No severe side effects occurred. CONCLUSIONS: On average, there was a significant increase in lumbar spine aBMD percent change after 48 weeks of denosumab. There was no change in mobility parameters and no serious adverse events. Further trials are necessary to assess long-term side effects and efficacy. |
format | Online Article Text |
id | pubmed-5089451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | International Society of Musculoskeletal and Neuronal Interactions |
record_format | MEDLINE/PubMed |
spelling | pubmed-50894512016-11-21 Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial Hoyer-Kuhn, H. Franklin, J. Allo, G. Kron, M. Netzer, C. Eysel, P. Hero, B. Schoenau, E. Semler, O. J Musculoskelet Neuronal Interact Original Article OBJECTIVES: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to bone fragility. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. Aim of this study was a 48-week, open-label, pilot study of the safety and efficacy of denosumab in 10 children with OI. METHODS: Ten patients (age range: 5.0-11.0 years; at least two years of prior bisphosphonate treatment) with genetically confirmed OI were studied. Denosumab was administered subcutaneously every 12 weeks with 1 mg/kg body weight. Primary endpoint was change of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 48 weeks. Safety was assessed by bone metabolism markers and adverse event reporting. RESULTS: Mean relative change of lumbar aBMD was +19 % (95%-CI: 7-31%). Lumbar spine aBMD Z-Scores increased from -2.23±2.03 (mean±SD) to -1.27±2.37 (p=0.0006). Mobility did not change (GMFM-88 +2.72±4.62% (p=0.16); one-minute walking test +11.00±15.82 m (p=0.15). No severe side effects occurred. CONCLUSIONS: On average, there was a significant increase in lumbar spine aBMD percent change after 48 weeks of denosumab. There was no change in mobility parameters and no serious adverse events. Further trials are necessary to assess long-term side effects and efficacy. International Society of Musculoskeletal and Neuronal Interactions 2016-03 /pmc/articles/PMC5089451/ /pubmed/26944820 Text en Copyright: © Journal of Musculoskeletal and Neuronal Interactions http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Hoyer-Kuhn, H. Franklin, J. Allo, G. Kron, M. Netzer, C. Eysel, P. Hero, B. Schoenau, E. Semler, O. Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial |
title | Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial |
title_full | Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial |
title_fullStr | Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial |
title_full_unstemmed | Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial |
title_short | Safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial |
title_sort | safety and efficacy of denosumab in children with osteogenesis imperfecta - a first prospective trial |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089451/ https://www.ncbi.nlm.nih.gov/pubmed/26944820 |
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