Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Bone Diseases/*etiology ; Cysteamine/*therapeutic use ; Cystinosis/*drug therapy; Amino Acid Transport Systems, Neutral/genetics ; Animals ; Bone Remodeling ; Chronic Kidney Disease-Mineral and Bone Disorder/etiology ; Cystinosis/complications ; Cystinosis/genetics ; Humans ; Mutation
    • Abstract:
      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.
      Competing Interests: A.B.-T. has received speaker fees and travel grants from Chiesi.
    • References:
      J Am Soc Nephrol. 2016 Jun;27(6):1678-88. (PMID: 26449607)
      Cell Mol Life Sci. 2018 Sep;75(18):3411-3422. (PMID: 29549422)
      Nat Med. 2013 Feb;19(2):179-92. (PMID: 23389618)
      J Bone Miner Res. 2018 Oct;33(10):1870-1880. (PMID: 29905968)
      N Engl J Med. 2002 Jul 11;347(2):111-21. (PMID: 12110740)
      Nat Rev Nephrol. 2017 Feb;13(2):115-131. (PMID: 27990015)
      Am J Pathol. 2019 May;189(5):1053-1064. (PMID: 30794806)
      J Transl Med. 2015 May 07;13:143. (PMID: 25947233)
      Cell Cycle. 2013 Sep 1;12(17):2744-52. (PMID: 23966172)
      Kidney Int. 2019 Aug;96(2):275-277. (PMID: 31331465)
      Kidney Int. 2006 Jun;69(11):1945-53. (PMID: 16641930)
      Skeletal Radiol. 2013 Sep 28;:. (PMID: 24077756)
      Nephrol Dial Transplant. 2018 Sep 1;33(9):1525-1532. (PMID: 29365190)
      Curr Opin Organ Transplant. 2013 Oct;18(5):555-62. (PMID: 23995376)
      N Engl J Med. 2014 Apr 3;370(14):1366-7. (PMID: 24693916)
      J Biol Chem. 1985 Apr 25;260(8):4791-8. (PMID: 3921538)
      Int J Mol Sci. 2019 Dec 26;21(1):. (PMID: 31888107)
      Mol Biol Cell. 2014 Feb;25(3):380-96. (PMID: 24284899)
      Nat Rev Nephrol. 2019 Sep;15(9):577-589. (PMID: 31197263)
      Mol Cell Biol. 2002 Nov;22(21):7622-32. (PMID: 12370309)
      J Pediatr. 2017 Apr;183S:S2-S4. (PMID: 28343472)
      J Biol Chem. 2020 May 8;295(19):6629-6640. (PMID: 32165499)
      J Am Soc Nephrol. 2016 Feb;27(2):543-50. (PMID: 26139439)
      Commun Biol. 2018 Apr 5;1:29. (PMID: 30271915)
      N Engl J Med. 2013 Aug 15;369(7):649-58. (PMID: 23944302)
      J Inherit Metab Dis. 2019 Sep;42(5):1019-1029. (PMID: 31177550)
      Pediatr Nephrol. 2018 Jul;33(7):1165-1172. (PMID: 29435659)
      Am J Med Genet A. 2012 Jun;158A(6):1422-6. (PMID: 22528245)
      Nephron. 2019;141(2):133-146. (PMID: 30554218)
      Kidney Int. 2019 Feb;95(2):412-419. (PMID: 30665572)
      Pediatr Nephrol. 2013 Jan;28(1):51-9. (PMID: 22903658)
      Bonekey Rep. 2016 Aug 17;5:828. (PMID: 27579165)
      J Pediatr. 2011 Dec;159(6):1004-11. (PMID: 21784456)
      JIMD Rep. 2014;13:27-31. (PMID: 24097416)
      Nephrol Dial Transplant. 2012 Aug;27(8):3063-71. (PMID: 22851629)
      Biochem Biophys Res Commun. 2019 Aug 13;516(1):202-208. (PMID: 31204051)
      J Pediatr. 2013 Sep;163(3):754-60. (PMID: 23651769)
      Bone. 2018 Jan;106:187-193. (PMID: 29051055)
      Kidney Int. 2003 Jan;63(1):266-75. (PMID: 12472792)
      Kidney Int. 2017 Jul;92(1):26-36. (PMID: 28646995)
      J Inherit Metab Dis. 2016 May;39(3):457-464. (PMID: 26909499)
      Nat Commun. 2018 Jan 11;9(1):161. (PMID: 29323117)
    • Grant Information:
      2018 Cystinosis Research Foundation
    • Contributed Indexing:
      Keywords: Bone; CKD-MBD; Nephropathic cystinosis; Orphan disease; Osteoblast; Osteoclast; Renal osteodystrophy (ROD); mTor signaling
    • Accession Number:
      0 (Amino Acid Transport Systems, Neutral)
      0 (CTNS protein, human)
      5UX2SD1KE2 (Cysteamine)
    • Publication Date:
      Date Created: 20200502 Date Completed: 20210202 Latest Revision: 20210202
    • Publication Date:
      20240829
    • Accession Number:
      PMC7246679
    • Accession Number:
      10.3390/ijms21093109
    • Accession Number:
      32354056