Bone Abstracts

The vision of calcium/phosphate metabolism has been completely modified during the last decade with the description of the FGF23/Klotho regulation axis. Renal regulation of phosphate handling in the proximal tubule is a complex and highly-regulated process. At least three transport proteins are responsible for renal phosphate reabsorption: NAPI-IIa (SLC34A1), NAPI-IIc (SLC34A3) and PIT-2 (SLC20A2). These transporters are highly regulated by various cellular mechanisms and factors including acid–base status, electrolyte balance and hormones such as dopamine, glucocorticoids, IGF1, calcitriol, parathyroid hormone, FGF23 and Klotho. Hypophosphatemic rickets are secondary to increased FGF23 levels, due to various mutations directly in the FGF23 gene or in its regulators (PHEX, DMP1, Klotho, …). Mutations in the NAPI-IIc or NAPI-IIb transporters as well as mutations in the sodium-hydrogen exchanger regulatory factor 1 (NHERF1) can induce hypophosphatemia and/or bone demineralization and/or hypercalciuria. The objectives of this talk are therefore: 1/ to detail renal phosphate handling in physiology, 2/ to develop genetic diseases associated with renal phosphate handling such as hypophosphatemic rickets but also genetic nephrolithiasis, and 3/ to discuss their impact on bone status.

Disclosure: Research grants received from Amgen, Sandoz, Crine and Novartis. Consultation fee or speaker for Amgen, Genzyme-Sanofi, Otzuka, Pfizer, Kyowa-Kirin and Alexion. Travel grants receved from Amgen, Genzyme-Sanofi and Alexion.