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Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy
Patients with chronic kidney disease (CKD) display significant mineral and bone disorders (CKD-MBD) that induce significant cardiovascular, growth and bone comorbidities. Nephropathic cystinosis is an inherited metabolic disorder caused by the lysosomal accumulation of cystine due to mutations in th...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246679/ https://www.ncbi.nlm.nih.gov/pubmed/32354056 http://dx.doi.org/10.3390/ijms21093109 |
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author | Machuca-Gayet, Irma Quinaux, Thomas Bertholet-Thomas, Aurélia Gaillard, Ségolène Claramunt-Taberner, Débora Acquaviva-Bourdain, Cécile Bacchetta, Justine |
author_facet | Machuca-Gayet, Irma Quinaux, Thomas Bertholet-Thomas, Aurélia Gaillard, Ségolène Claramunt-Taberner, Débora Acquaviva-Bourdain, Cécile Bacchetta, Justine |
author_sort | Machuca-Gayet, Irma |
collection | PubMed |
description | Patients with chronic kidney disease (CKD) display significant mineral and bone disorders (CKD-MBD) that induce significant cardiovascular, growth and bone comorbidities. Nephropathic cystinosis is an inherited metabolic disorder caused by the lysosomal accumulation of cystine due to mutations in the CTNS gene encoding cystinosin, and leads to end-stage renal disease within the second decade. The cornerstone of management relies on cysteamine therapy to decrease lysosomal cystine accumulation in target organs. However, despite cysteamine therapy, patients display severe bone symptoms, and the concept of “cystinosis metabolic bone disease” is currently emerging. Even though its exact pathophysiology remains unclear, at least five distinct but complementary entities can explain bone impairment in addition to CKD-MBD: long-term consequences of renal Fanconi syndrome, malnutrition and copper deficiency, hormonal disturbances, myopathy, and intrinsic/iatrogenic bone defects. Direct effects of both CTNS mutation and cysteamine on osteoblasts and osteoclasts are described. Thus, the main objective of this manuscript is not only to provide a clinical update on bone disease in cystinosis, but also to summarize the current experimental evidence demonstrating a functional impairment of bone cells in this disease and to discuss new working hypotheses that deserve future research in the field. |
format | Online Article Text |
id | pubmed-7246679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72466792020-06-10 Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy Machuca-Gayet, Irma Quinaux, Thomas Bertholet-Thomas, Aurélia Gaillard, Ségolène Claramunt-Taberner, Débora Acquaviva-Bourdain, Cécile Bacchetta, Justine Int J Mol Sci Review Patients with chronic kidney disease (CKD) display significant mineral and bone disorders (CKD-MBD) that induce significant cardiovascular, growth and bone comorbidities. Nephropathic cystinosis is an inherited metabolic disorder caused by the lysosomal accumulation of cystine due to mutations in the CTNS gene encoding cystinosin, and leads to end-stage renal disease within the second decade. The cornerstone of management relies on cysteamine therapy to decrease lysosomal cystine accumulation in target organs. However, despite cysteamine therapy, patients display severe bone symptoms, and the concept of “cystinosis metabolic bone disease” is currently emerging. Even though its exact pathophysiology remains unclear, at least five distinct but complementary entities can explain bone impairment in addition to CKD-MBD: long-term consequences of renal Fanconi syndrome, malnutrition and copper deficiency, hormonal disturbances, myopathy, and intrinsic/iatrogenic bone defects. Direct effects of both CTNS mutation and cysteamine on osteoblasts and osteoclasts are described. Thus, the main objective of this manuscript is not only to provide a clinical update on bone disease in cystinosis, but also to summarize the current experimental evidence demonstrating a functional impairment of bone cells in this disease and to discuss new working hypotheses that deserve future research in the field. MDPI 2020-04-28 /pmc/articles/PMC7246679/ /pubmed/32354056 http://dx.doi.org/10.3390/ijms21093109 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Machuca-Gayet, Irma Quinaux, Thomas Bertholet-Thomas, Aurélia Gaillard, Ségolène Claramunt-Taberner, Débora Acquaviva-Bourdain, Cécile Bacchetta, Justine Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy |
title | Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy |
title_full | Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy |
title_fullStr | Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy |
title_full_unstemmed | Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy |
title_short | Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy |
title_sort | bone disease in nephropathic cystinosis: beyond renal osteodystrophy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246679/ https://www.ncbi.nlm.nih.gov/pubmed/32354056 http://dx.doi.org/10.3390/ijms21093109 |
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