Aurélia Bertholet-Thomas1, Debora Claramunt-Taberner1, Ségolène Gaillard2, Georges Deschênes3, Elisabeth Sornay-Rendu4, Pawel Szulc4, Martine Cohen-Solal5, Solenne Pelletier6, Marie-Christine Carlier7, Pierre Cochat1,8, Justine Bacchetta9,10,11. 1. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, 59 boulevard Pinel, 69677, Bron Cedex, France. 2. INSERM CIC 1407, CNRS UMR 5558 and Service de Pharmacotoxicologie Clinique, Hospices Civils de Lyon, Bron, France. 3. Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France. 4. INSERM, UMR 1033, Faculté de Médecine Lyon Est, Université Claude Bernard Lyon1, Lyon, France. 5. Service de Rhumatologie, Hôpital Lariboisière, Paris, France. 6. Service de Néphrologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France. 7. Département de Biologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France. 8. Université de Lyon, Lyon, France. 9. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, 59 boulevard Pinel, 69677, Bron Cedex, France. justine.bacchetta@chu-lyon.fr. 10. INSERM, UMR 1033, Faculté de Médecine Lyon Est, Université Claude Bernard Lyon1, Lyon, France. justine.bacchetta@chu-lyon.fr. 11. Université de Lyon, Lyon, France. justine.bacchetta@chu-lyon.fr.
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.
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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