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Abstract: SA-PO298

Characteristic Alterations of Bone and Mineral Metabolism in Children and Adults with Nephropathic Cystinosis

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Haffner, Dieter, Hannover Medical School, Hannover, Germany
  • Lahring, Johannes, Hannover Medical School, Hannover, Germany
  • Ewert, Annika, Hannover Medical School, Hannover, Germany
  • Köppl, Christian, Clinic Traunstein, Traunstein, Germany
  • Herzig, Nadine, Schoen Clinic Muenchen Harlaching, Munich, Germany
  • Büscher, Anja K., Essen University Medical Centre, Essen, Germany
  • Thumfart, Julia, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Hohenfellner, Katharina, Ro Med Clinics, Rosenheim, Germany
  • Leifheit-Nestler, Maren, Hannover Medical School, Hannover, Germany
Background

The pathophysiology of nephropathic cystinosis (NC) associated bone disease is poorly understood.

Methods

We examined serum/plasma concentrations of 8 bone markers and routine parameters of mineral metabolism in 63 children (mean age 10.8 years) and 40 adults (mean age 28.3 years) with NC by ELISA and autoanalyzer. Data are given as age- and sex-dependent z-scores as a function of estimated glomerular filtration rate (eGFR).

Results

Pediatric and adult NC patients with eGFR > 60 ml/min/1.73 m2 showed reduced z-scores for serum phosphate and calcium, and elevated bone-specific alkaline phosphatase (BAP) despite treatment for Fanconi syndrome. Hypocalcemia was more pronounced in children, whereas BAP z-scores were more elevated in adults (each p<0.001). Intact and total fibroblast growth factor 23 (FGF23) and parathyroid hormone levels were suppressed in NC patients with eGFR > 60 ml/min/1.73 m2 (each p<0.001). FGF23 z-scores progressively increased in parallel with decreasing eGFR, reaching 6 SD in patients with eGFR < 30 ml/min/1.73 m2, while calcitriol levels progressively declined. The Wnt signaling inhibitor sclerostin was increased by 1 SD in pediatric but not in adults NC patients irrespectively of eGFR. The osteoclast marker tartrate-resistant acid phosphatase 5b (TRAP5b) was increased by 1 SD (children) and 2 SD (adults) independent of eGFR despite the absence of hyperparathyroidism in the majority of patients (each p<0.001). Receptor-activator of NF-κB ligand (RANKL), an inhibitor of osteoclast activity, was reduced by SD 1.0 in pediatric but not in adult NC patients. Finally, the RANKL inhibitor osteoprotegerin (OPG) was increased by 2 SD in children with eGFR < 30 ml/min/1.73 m2, whereas adult patients consistently showed reduced OPG z-scores.

Conclusion

Pediatric and adult NC patients show hypophosphatemia, hypocalcemia, hypovitaminosis D, and increased osteoblast activity indicating persisting rickets/osteomalacia despite treatment for Fanconi syndrome. Increased osteoclast activity despite counter regulation via OPG/RANKL and suppressed PTH levels suggests a primary osteoclast defect in NC resulting in increased bone resorption, which is more pronounced in children compared to adult patients.

Funding

  • Commercial Support – Chiesi