Bone Abstracts

Objective: Hypophosphataemic rickets (HPR) is associated with high concentrations of fibroblast growth factor 23 (FGF23). Chronically elevated FGF23 may impact on cardiac function and the skeleton. There is little evidence on how FGF23 changes with time in HPR or how it is affected by treatment. The aim of this study was to evaluate changes in FGF23 concentrations over time in patients with HPR.

Methods: Retrospective data was collected from our Metabolic Bone Database. FGF23 was measured at diagnosis when possible (n=3) and thereafter at every clinic visit whilst on treatment. Ten patients aged 0–13 years were included. Patients were classified as mild or severe phenotype based on clinical features.

Results: Mean age at diagnosis was 5.5 years (female (6): male (4)). Renal function was normal in all patients. Mean alfacalcidol dose was 32.3 ng/kg per day and mean phosphate dose 30 mg/kg per day. 43 measurements of FGF23 were recorded. Mean FGF23 at diagnosis was 115 RU/ml (S.E.M.±7.69). Mean concentration on treatment was 240.3 RU/ml (±23.0). The severe forms (n=5) of HPR had a mean FGF23 of 221.3 (±23.8), alfacalcidol dose of 35.7 ng/kg per day (S.E.M.±1.4) and phosphate dose of 33.9 mg/kg per day (S.E.M.±3.7), with mean serum phosphate of 0.82 mmol/l (S.E.M.±0.04) (ref range 1.13–2.20). Those with the milder form (n=5) of HPR had a mean FGF23 of 242.3 (±37.8), alfacalcidol dose of 33.1 ng/kg per day (±1.4) and phosphate dose of 22.9 mg/kg per day (±2.0), with mean serum phosphate of 0.90 (±0.03). Mean pre-treatment phosphate concentration was 0.74 mmol/l (n=2). Although phosphate dose was significantly higher in the severe group (P=0.01), FGF23 concentrations were not significantly different between these two groups (P=0.67). There was no correlation between FGF23 and PTH concentration, dose of alfacalcidol or dose of phosphate.

Conclusion: HPR was associated with an increase in FGF23 after commencing treatment. No significant difference in FGF23 concentrations was noted between patients with mild and severe phenotype. Factors contributing to higher FGF23 post treatment remain unclear. Klotho, a membrane protein that affects FGF23 signalling, is being analysed in these patients. Novel strategies to optimize FGF23 concentrations while on conventional treatment are required in patients with HPR.

Disclosure: The authors declared no competing interests.