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Bone Abstracts (2013) 2 P33 | DOI: 10.1530/boneabs.2.P33

1Hôpital de Lons Le Saunier, Saunier, France; 2INSERM and Paris 11 University, le Kremlin Bicetre, Kremlin, France; 3CHU de Reims, Reims, France; 4CHU de Nantes, Nantes, France; 5Hôpital Robert Debré, Paris, France; 6Paris-Descartes University, Paris, France; 7Hôpital Necker, Paris, France.

Mutations in PHEX and specific missense mutations of FGF23 result in elevated circulating FGF23 and hypophosphatemic rickets, respectively X-linked hypophosphatemic rickets (XLHR) and autosomal dominant HR (ADHR). FGF23, secreted by osteoblasts and osteocytes, regulates phosphate handling and vitamin D metabolism through its action on kidney. Extra renal effects of FGF23, including bone, have been very recently suspected mainly from overexpression or underexpression of FGF23 in mouse models. PHEX is expressed by osteoblasts, osteocytes and odontoblasts; its precise function in controlling circulating FGF23 level is still unclear.

Aim: Examine the role of PHEX on bone and mineral metabolism by comparing the phenotype of patients with elevated FGF23 levels due to PHEX or FGF23 mutations.

Patients: Six patients with FGF23 mutations and ADHR (four children and two untreated adults); 23 patients with PHEX mutations and XLHR (18 children and 5 untreated adults); XLHR patients were matched to ADHR patients for age at start of treatment.

Results: Children with ADHR were diagnosed earlier (1.5±0.0 years) than children with XLHR (2.3±0.2 years, P=0.03), with similar leg bowing (intercondylar distance 7.9±2.3 and 5.0±0 .7, respectively). At diagnosis, they presented with bone demineralization and fractures in one patient, whereas none of the 18 XLHR patients had fractures nor bone demineralization. ADHR children had significantly higher alkaline phosphatases than XLHR children (649±103 and 2037±439, P=0.01, respectively). Phosphate, PTH and calciuria were similar in both groups. Follow-up revealed that, in opposition to XLHR, phosphate supplements and vitamin D analogs easily restored serum phosphate levels in ADHR. Final height of untreated ADHR adults appears higher than that of untreated XLHR.

Conclusion: Despite the limited number of patients, we pinpointed differences in the phenotypes of ADHR and XLHR. This suggests that the phenotype associated with PHEX deficiency does not uniquely result from FGF23 excess, yet advocates a direct role of PHEX on bone mineralization and growth.

Volume 2

6th International Conference on Children's Bone Health

Rotterdam, The Netherlands
22 Jun 2013 - 25 Jun 2013


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