Abstract
Nephropathic cystinosis is an orphan autosomal recessive lysosomal storage disease characterized by a deficiency of cystinosin, a cystine transporter protein, leading to tissue damage, primarily in the kidney and cornea. With the introduction of cystine-depleting therapy with cysteamine and the possibility to survive to adulthood, new challenges of skeletal complications are a concern, with sparse data available regarding bone development. The aim of the current study was to gain more information on bone density and geometry in these patients. Fifty-one patients (29 males, 22 females) with genetically proven nephropathic cystinosis were clinically evaluated with a medical history, physical examination, grip strength measurements, and biochemical and imaging studies. Bone mineral density, bone geometry, and muscle cross sectional area were measured, and muscle was evaluated. Results were compared with age- and gender-specific reference data. Z-scores for height (mean [M] = -1.75, standard deviation [SD] = 1.43), weight (M = -1.67, SD = 1.29), and BMI (M = -0.98, SD = 1.29) were lower than reference data. Medullary cross-sectional area (CSA) and cortical density z-scores were not compromised (M = 0.12, SD = 1.56 and M = -0.25, SD = 1.63, respectively), but cortical CSA z-scores and Strength-Strain Index (SSI) were reduced (M = -2.16, SD = 1.08, M = -2.07, SD = 1.08). Muscular deficits were reflected by reduced z-scores for muscle CSA (M = -2.43, SD = 1.27) and grip strength (M = -3.01, SD = 1.10), along with jump force (34% lower than reference value). Multiple regression analyses indicated an association of muscle mass with medullary CSA and SSI, but not with cortical CSA. While bone density parameters were normal, bone geometry was altered, resulting in a thinner cortex with possible impact on bone strength. Muscle weakness be partially responsible for altered bone geometry and could provide a potential treatment target.