Grant: Operating Grant - PA: Regional Partnership Program - Newfoundland and Labrador

Phosphorus initiates critical steps in the formation of the skeleton and in its subsequent mineralization; without phosphorus, calcium cannot bind, and the skeleton is deformed and weak (rickets or osteomalacia). Recently fibroblast growth factor-23 (FGF23) has been shown to be a key regulator of phosphorus balance in the adult. Osteocytes secrete FGF23 to cause the kidneys to excrete phosphorus. Certain hereditary and acquired conditions are now known to be due to excess or deficiency of FGF23 which causes specific disturbances in serum phosphorus levels, skeletal morphology and strength, and muscle strength and function. Despite the explosion of knowledge pertaining to the role of FGF23 in adult skeletal and mineral metabolism, essentially nothing is known about its role during fetal development. Phosphorus plays essential roles in the formation and mineralization of the fetal skeleton, it is actively pumped across the placenta from the maternal circulation, and it circulates at higher blood levels than in adult. Does FGF23 play a role in regulating these processes? The hypothesis is that FGF23 acts during fetal development to regulate placental phosphorus transport, stimulate renal phosphorus excretion, prevent excessive hyperphosphatemia, and facilitate skeletal mineralization. The clinical relevance is that not only will the normal physiological role of FGF23 in fetal life have been clarified, but the data will inform whether the human conditions of tumor calcinosis and X-linked hypophosphatemic rickets (XLH) alter phosphorus and skeletal metabolism before birth.