FGF23 is an important hormonal regulator of
phosphate homeostasis. Together with its co-receptor Klotho, it modulates
phosphate reabsorption and both 1α-hydroxylation and 24-hydroxylation in the renal proximal tubules. The most common FGF23-mediated
hypophosphatemia is
X-linked hypophosphatemia (XLH), caused by mutations in the PHEX gene. FGF23-mediated forms of
hypophosphatemia are characterized by
phosphaturia and low or low-normal
calcitriol concentrations, and unlike nutritional
rickets, these cannot be cured with nutritional
vitamin D supplementation. Autosomal dominant and autosomal recessive forms of FGF23-mediated
hypophosphatemias show a similar pathophysiology, despite a variety of different underlying genetic causes. An excess of FGF23 activity has also been associated with a number of other conditions causing
hypophosphatemia, including
tumor-induced osteomalacia, fibrous dysplasia of the bone, and cutaneous skeletal
hypophosphatemia syndrome. Historically
phosphate supplementation and
therapy using analogs of highly active
vitamin D (eg,
calcitriol,
alfacalcidol,
paricalcitol,
eldecalcitol) have been used to manage conditions involving
hypophosphatemia; however, recently a
neutralizing antibody for FGF23 (
burosumab) has emerged as a promising treatment agent for FGF23-mediated disorders. This review discusses the progression of clinical trials for
burosumab for the treatment of XLH and its recent availability for clinical use.
Burosumab may have potential for treating other conditions associated with FGF23 overactivity, but these are not yet supported by trial data. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and
Mineral Research.