Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment
Bone impairment appears to be a novel complication of nephropathic cystinosis despite cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study was to evaluate bone status among patients included in the French Crystobs study.
In addition to clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local reference cohorts.
At a median age of 22.5 (10.2–34.6) years, 10 patients with nephropathic cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations, and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HR-pQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520–1100) versus 1225 (480–1680) μm; p < 0.05) and total volumetric bone mineral density (290 (233–360) versus 323 (232–406) mg/cm3; p < 0.05) were observed in cystinotic patients in comparison to controls at the tibia. There were no differences for trabecular parameters. Similar results were observed at the radius.
In this pilot study, bone impairment (rather cortical than trabecular) is a significant clinical problem in nephropathic cystinosis; 70% of patients displayed significant bone symptoms, during teenage or young adulthood. This new complication should be known by physicians because of its potential dramatic impact on quality of life.
KeywordsBone Nephropathic cystinosis HR-pQCT Cysteamine
The authors would like to acknowledge Dr. Cécile Acquaviva-Bourdain (Département de Biologie, Hospices Civils de Lyon, France) for biochemical measurements and Mrs. Eurielle Bodenan (clinical research associate, CIC1407, Bron, France) for her help in data collection. They also would like to thank the patients and their families for being involved in clinical studies aiming at improving outcomes in nephropathic cystinosis.
The study was sponsored by Raptor/Horizon Pharmaceuticals.
Compliance with ethical standards
The study was approved by the local institutional review board (Comité de Protection des Personnes Lyon Sud Est II, initial approval of the Crystobs study 9/8/2010, approval of the 5th amendment 9/7/2016). Written informed consent was obtained from all patients (and parents in case of pediatric patients).
Conflict of interest
JB has received a travel grant from Raptor Pharmaceuticals and an educational research grant for this clinical study.
PC is a medical expert for Raptor Pharmaceuticals and co-investigator for the RP 103-3, 103-4, and 103-7 studies.
ABT is a medical expert for Raptor Pharmaceuticals and co-investigator for the RP 103-3, 103-4, and 103-7 studies.
MCS received travel grants from Amgen.
- 7.Besouw MTP, Schneider J, Janssen MC, Greco M, Emma F, Cornelissen EA, Desmet K, Skovby F, Nobili F, Lilien MR, De Paepe A, Malfait F, Symoens S, van den Heuvel LP, Levtchenko EN (2013) Copper deficiency in patients with cystinosis with cysteamine toxicity. J Pediatr 163(3):754–760CrossRefPubMedGoogle Scholar
- 10.Claramunt-Taberner D, Flammier S, Gaillard S, Cochat P, Peyruchaud O, Machuca-Gayet I, Bacchetta J (2018) Bone disease in nephropathic cystinosis is related to cystinosin-induced osteoclastic dysfunction. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfx362
- 21.Emma F, Nesterova G, Langman C, Labbé A, Cherqui S, Goodyer P, Janssen MC, Greco M, Topaloglu R, Elenberg E, Dohil R, Trauner D, Antignac C, Cochat P, Kaskel F, Servais A, Wühl E, Niaudet P, Van’t Hoff W, Gahl W, Levtchenko E (2014) Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant 29(Suppl 4):iv87–iv94CrossRefPubMedPubMedCentralGoogle Scholar