Skeletal Consequences of Nephropathic Cystinosis

J Bone Miner Res. 2018 Oct;33(10):1870-1880. doi: 10.1002/jbmr.3522. Epub 2018 Jul 20.


Nephropathic cystinosis is a rare lysosomal storage disorder. Patients present in the first year of life with renal Fanconi syndrome that evolves to progressive chronic kidney disease (CKD). Despite the multiple risk factors for bone disease, the frequency and severity of skeletal disorders in nephropathic cystinosis have not been described. We performed systematic bone and mineral evaluations of subjects with cystinosis seen at the NIH (n = 30), including history and physical examination, serum and urine biochemistries, DXA, vertebral fracture assessment, skeletal radiographs, and renal ultrasound. Additionally, histomorphometric analyses are reported on six subjects seen at the UCLA Bone and Mineral Metabolism Clinic. In NIH subjects, mean age was 20 years (range, 5 to 44 years), 60% were CKD stages G1 to G4, and 40% had a renal transplant. Mean bone mineral density (BMD) Z-scores were decreased in the femoral neck, total hip, and 1/3 radius (p < 0.05). Low bone mass at one or more sites was present in 46% of subjects. Twenty-seven percent of subjects reported one or more long bone fractures. Thirty-two percent of subjects had incidental vertebral fractures, which were unrelated to transplant status. Long-bone deformity/bowing was present in 64%; 50% had scoliosis. Diffuse osteosclerosis was present in 21% of evaluated subjects. Risk factors included CKD, phosphate wasting, hypercalciuria, secondary hyperparathyroidism, hypovitaminosis D, male hypogonadism, metabolic acidosis, and glucocorticoid/immunosuppressive therapy. Sixty-one percent of the non-transplanted subjects had ultrasonographic evidence of nephrocalcinosis or nephrolithiasis. Histomorphometric analyses showed impaired mineralization in four of six studied subjects. We conclude that skeletal deformities, decreased bone mass, and vertebral fractures are common and relevant complications of nephropathic cystinosis, even before renal transplantation. Efforts to minimize risk factors for skeletal disease include optimizing mineral metabolism and hormonal status, combined with monitoring for nephrocalcinosis/nephrolithiasis. © 2018 This article is a U.S. Government work and is in the public domain in the USA.


Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Bone Density
  • Bone and Bones / pathology*
  • Calcification, Physiologic
  • Child
  • Child, Preschool
  • Cystinosis / complications*
  • Female
  • Fibroblast Growth Factor-23
  • Fractures, Bone / etiology
  • Humans
  • Kidney / diagnostic imaging
  • Kidney / pathology
  • Kidney Diseases / complications*
  • Male
  • Risk Factors
  • Young Adult