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.