Mineralization defects and paradoxical mineralizing enthesopathies are hallmarks of X-linked Hypophosphatemia (XLH), a rare skeletal disease caused by inactivating mutations in the PHEX gene (Phosphate-regulating endopeptidase homolog, X-linked). The current medical treatment, which consist in oral phosphorus supplementation and active vitamin D analogues, aimed at counteracting consequences of FGF23 excess and is commonly prescribed from early childhood to the end of growth. Despite childhood treatment of the disease, cartilaginous tissue complications in adults become a dominant feature in the clinical evolution of XLH. Here, we monitored the development of these osteoarticular lesions, characterizing the formation of enthesopathies, calcifications and osteoarthritis through a 12-months (M) Micro-CT longitudinal follow up in the Hyp mouse, a murine model of XLH. These lesions were already present at 3 months and significantly increased from 3 to 12 months, highlighting the relevance of this murine model for pre-clinical studies. We then studied the impact of current treatment on the development of these osteoarticular lesions. Hyp mice were treated with oral phosphorus supplementation and calcitriol injections. The treatment followed two different outlines: i) from 3 weeks to 3 months to analyze the treatment effects during growth and ii) from 2 months to 3 months to analyze the treatment effects on adult lesion development. We showed that the current treatment given since the early stage improved osteoarticular lesions, bone mineralization and micro architecture, and fusion of the growth plate. Future studies should compare the effect of the new therapy based on anti-FGF23 antibody.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology