Purpose of review: To describe emerging understanding of fibroblast growth factor 23 (FGF23) - a bone-derived hormone that inhibits phosphate reabsorption and calcitriol production by kidney and participates as the principle phosphaturic factor in a bone-kidney axis coordinating systemic phosphate homeostasis and bone mineralization.
Recent findings: FGF23 (a circulating factor made by osteocytes in bone) inhibits phosphate reabsorption and 1,25(OH)2D production by kidney. Physiologically, FGF23 is a counter-regulatory phosphaturic hormone for vitamin D and coordinates systemic phosphate homeostasis with skeletal mineralization. Pathologically, high circulating FGF23 levels cause hypophosphatemia, decreased 1,25(OH)2D production, elevated parathyroid hormone and rickets/osteomalacia. FGF23 mutations impairing its degradation cause autosomal dominant hypophosphatemic rickets. Respective loss-of-function mutations of osteocyte gene products DMP1 and Phex cause autosomal recessive hypophosphatemic rickets and X-linked hypophosphatemic rickets, initiating increased FGF23 production. Low FGF23 levels lead to hyperphosphatemia, elevated 1,25(OH)2D, and soft-tissue calcifications. FGF23 is markedly increased in chronic renal disease, but its role remains undefined.
Summary: FGF23 discovery has uncovered primary regulatory pathways and new systems biology governing bone mineralization, vitamin D metabolism, parathyroid gland function, and renal phosphate handling. FGF23 assessment will become important in diagnosing hypophosphatemic and hyperphosphatemic disorders, for which pharmacological regulation of FGF23 levels may provide novel treatments.