{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:06:55Z","timestamp":1780340815708,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005674","name":"Cystinosis Research Foundation","doi-asserted-by":"publisher","award":["2018"],"award-info":[{"award-number":["2018"]}],"id":[{"id":"10.13039\/100005674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u201ccystinosis metabolic bone disease\u201d 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.<\/jats:p>","DOI":"10.3390\/ijms21093109","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T10:30:58Z","timestamp":1588069858000},"page":"3109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy"],"prefix":"10.3390","volume":"21","author":[{"given":"Irma","family":"Machuca-Gayet","sequence":"first","affiliation":[{"name":"Pathophysiology, Diagnosis and Treatment of Bone Diseases, INSERM UMR 1033, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Quinaux","sequence":"additional","affiliation":[{"name":"Pathophysiology, Diagnosis and Treatment of Bone Diseases, INSERM UMR 1033, 69008 Lyon, France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales Rares, Centre de R\u00e9f\u00e9rence des Maladies Rares du Calcium et du Phosphore, H\u00f4pital Femme M\u00e8re Enfant, 69500 Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lia","family":"Bertholet-Thomas","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales Rares, Centre de R\u00e9f\u00e9rence des Maladies Rares du Calcium et du Phosphore, H\u00f4pital Femme M\u00e8re Enfant, 69500 Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-7366","authenticated-orcid":false,"given":"S\u00e9gol\u00e8ne","family":"Gaillard","sequence":"additional","affiliation":[{"name":"INSERM CIC 1407, CNRS UMR 5558 and Service de Pharmacotoxicologie Clinique, Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Claramunt-Taberner","sequence":"additional","affiliation":[{"name":"Pathophysiology, Diagnosis and Treatment of Bone Diseases, INSERM UMR 1033, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Acquaviva-Bourdain","sequence":"additional","affiliation":[{"name":"Service de Biochimie et Biologie Mol\u00e9culaire, Groupement Hospitalier Est, 69500 Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Bacchetta","sequence":"additional","affiliation":[{"name":"Pathophysiology, Diagnosis and Treatment of Bone Diseases, INSERM UMR 1033, 69008 Lyon, France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales Rares, Centre de R\u00e9f\u00e9rence des Maladies Rares du Calcium et du Phosphore, H\u00f4pital Femme M\u00e8re Enfant, 69500 Bron, France"},{"name":"Facult\u00e9 de M\u00e9decine Lyon Est, Universit\u00e9 de Lyon, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1093\/ndt\/gfs299","article-title":"The consequences of chronic kidney disease on bone metabolism and growth in children","volume":"27","author":"Bacchetta","year":"2012","journal-title":"Nephrol. 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