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Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

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.

Funding

The study was sponsored by Raptor/Horizon Pharmaceuticals.

Author information

Authors and Affiliations

  1. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, 59 boulevard Pinel, 69677, Bron Cedex, France

    Aurélia Bertholet-Thomas, Debora Claramunt-Taberner, Pierre Cochat & Justine Bacchetta

  2. INSERM CIC 1407, CNRS UMR 5558 and Service de Pharmacotoxicologie Clinique, Hospices Civils de Lyon, Bron, France

    Ségolène Gaillard

  3. Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France

    Georges Deschênes

  4. INSERM, UMR 1033, Faculté de Médecine Lyon Est, Université Claude Bernard Lyon1, Lyon, France

    Elisabeth Sornay-Rendu, Pawel Szulc & Justine Bacchetta

  5. Service de Rhumatologie, Hôpital Lariboisière, Paris, France

    Martine Cohen-Solal

  6. Service de Néphrologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France

    Solenne Pelletier

  7. Département de Biologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France

    Marie-Christine Carlier

  8. Université de Lyon, Lyon, France

    Pierre Cochat & Justine Bacchetta

Authors
  1. Aurélia Bertholet-Thomas
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  2. Debora Claramunt-Taberner
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  3. Ségolène Gaillard
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  4. Georges Deschênes
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  5. Elisabeth Sornay-Rendu
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  6. Pawel Szulc
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  7. Martine Cohen-Solal
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  8. Solenne Pelletier
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  9. Marie-Christine Carlier
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  10. Pierre Cochat
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  11. Justine Bacchetta
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Corresponding author

Correspondence to Justine Bacchetta.

Ethics declarations

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.

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Bertholet-Thomas, A., Claramunt-Taberner, D., Gaillard, S. et al. Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment. Pediatr Nephrol 33, 1165–1172 (2018). https://doi.org/10.1007/s00467-018-3902-x

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  • DOI: https://doi.org/10.1007/s00467-018-3902-x

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