The discovery of fibroblast growth factor-23 (FGF23), a phosphatonin and member of FGF19 subfamily of FGFs produced by osteocytes and osteoblasts, has led to newer insights into our understanding of phosphate homeostasis [1], [2]. FGF23 was discovered in the year 2000 as the cause for autosomal dominant hypophosphatemic rickets (ADHR), and subsequently several other hypophosphatemic disorders were found to feature elevated circulating FGF23 levels. These include the X-linked hypophosphatemia (XLH, the most common hereditary cause of hypophosphatemic rickets), autosomal recessive hypophosphatemic rickets (ARHR), tumor induced osteomalacia (TIO), fibrous dysplasia/Mc-Cune Albright syndrome (FD/MAS), neurofibromatosis (NF) and epidermal nevus/linear nevus sebaceous syndrome. FGF23 binds and activates FGF receptor 1 (FGFR1) in presence of transmembrane coreceptor protein Klotho and causes renal phosphate wasting and hypophosphatemia by downregulating the expression of sodium-phosphate cotransporters (NaPi2a and NaPi2c) in the brush border of proximal renal tubules. Furthermore, FGF23 reduces 1,25-dihydroxyvitamin D levels by downregulating the expression of 1-α hydroxylase that mediates conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D and by upregulating the expression of 24-hydroxylase, the enzyme responsible for catabolism of 1,25-dihydroxyvitamin D [2].

Hypophosphatemic rickets and osteomalacia resulting from FGF23 excess manifest as bony pains, rachitic deformities, growth retardation, pathological fractures and proximal muscle weakness. Additionally, certain features that are more peculiar to XLH include dental abscess, enthesopathy, osteoarthritis and spinal stenosis. These manifestations impair physical function and affect quality of life of the affected individuals *[3], [4], [5]. The conventional treatment of FGF23-mediated hypophosphatemia targets the consequences of elevated FGF23 and not the elevated FGF23 itself and is associated with long-term complications such as nephrocalcinosis and secondary/tertiary hyperparathyroidism [6]. Burosumab, a fully human anti-FGF23 monoclonal antibody has been shown to improve clinical outcomes and is recently approved for treatment of XLH and TIO in both pediatric and adult population. In this review, we discuss the current evidence and the future prospects for this newer agent in the treatment of hypophosphatemic disorders.