Abstract: SA-PO361

Cystinosis Is Associated with Abnormal Bone Microarchitecture and Sarcopenia in Children and Adults

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Sheldon, Candice, Stanford, Palo Alto, California, United States
  • Grimm, Paul C., Stanford University Medical Center, Stanford, California, United States
  • Whalen, Jessica R, Stanford University, Palo Alto, California, United States
  • Kent, Kyla, Stanford School of Medicine, Palo Alto, California, United States
  • Long, Jin, Stanford University, Palo Alto, California, United States
  • Simas, Maira, Stanford University, Palo Alto, California, United States
  • Leonard, Mary B., Stanford School of Medicine, Palo Alto, California, United States
Background

Cystinosis is associated with multiple risk factors for abnormal bone metabolism, including phosphate wasting, metabolic acidosis, malnutrition, chronic kidney disease, hypothyroidism, myopathy, delayed puberty and male hypogonadism. Prior bone studies are limited to case reports and a case series. Muscle mass has not been quantified.

Methods

Regional and whole body DXA scans were obtained in 37 cystinosis patients, age 6-49 yr. High-resolution quantitative CT (QCT) tibia scans were obtained in cystinosis patients and 61 matched controls. DXA results were converted to sex, race and age-specific Z-scores using robust population-based reference data in children and adults. Linear regression was used to assess group differences in QCT results, adjusted for age, sex and tibia length.

Results

Total Hip (mean ± SD: -0.96 ± 1.22), femoral neck (-1.23 ± 1.14), and 1/3rd radius (-1.02 ± 1.48) bone mineral density (BMD) Z-scores were reduced compared with reference data (all p<0.001) and were comparable in children and adults. Appendicular lean mass Z-scores were reduced in children (-0.93 ± 1.27, p<0.01) and adults (-1.80 ± 1.32, p<0.0001), and were positively associated with DXA BMD Z-scores at all sites (R 0.46-0.50, p<0.01). Median (interquartile range) eGFR was 58 (32-76) ml/min/1.73m2. DXA Z-scores were not associated with eGFR. Tibia diaphysis cortical thickness and BMD (p<0.02), metaphysis trabecular bone volume fraction, thickness and number (p<0.01) and finite element estimates of failure load in the diaphysis and distal tibia (p<0.0001) were lower in cystinosis vs. controls in multivariate analyses. Appendicular mass was highly associated with failure load (p<0.001) independent of age, sex and tibia length. Adjustment for lean mass eliminated group differences in cortical thickness and failure load in the diaphysis (p>0.20) and attenuated differences in failure load in the distal tibia (p=0.06). In contrast, trabecular deficits persisted.

Conclusion

Cystinosis is associated with severe musculoskeletal deficits in children and adults. Bone deficits were correlated with sarcopenia suggesting a role of decreased biomechanical loading. Studies are needed to identify interventions to improve bone strength and muscle mass in cystinosis.

Funding

  • Private Foundation Support