Endocrine Abstracts (2019) 65 S3.3 | DOI: 10.1530/endoabs.65.S3.3

FGF23-related hypophosphatemic diseases: prospect for new treatment

Seiji Fukumoto


Tokushima University, Tokushima, Japan


FGF23 is a phosphotropic hormone produced by bone. FGF23 23 reduces serum phosphate by suppressing proximal tubular phosphate reabsorption and intestinal phosphate absorption. Since the identification of FGF23 in 2000, several hypophosphatemic diseases such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO) have been shown to be caused by excessive actions of FGF23. TIO is a paraneoplastic disease and can be cured by complete removal of responsible tumors. However, it is not always possible to find and remove the responsible tumors. XLH is the most frequent cause of genetic hypophosphatemic rickets. Patients with XLH and inoperable TIO have been treated with neutral phosphate and active vitamin D. However, these medications can cause several adverse events such as secondary hyperparathyroidism and gastrointestinal symptoms. The inhibition of FGF23 activity by anti-FGF23 antibodies improved hypophosphatemia, renal phosphate wasting, growth retardation, rickets and reduced grip power of Hyp mouse, a model of XLH. Based on these preclinical studies, human monoclonal anti-FGF23 antibody, burosumab, has been developed as a new drug for FGF23-related hypophosphatemic diseases. Several clinical trials indicated that burosumab ameliorates biochemical abnormalities, radiographic findings of rickets and growth in child patients with XLH. Burosumab was also shown to improve hypophosphatemia, fracture healing and histological findings of osteomalacia in adult patients with XLH. Phase 3 studies indicated that burosumab is more effective than conventional therapy. From these results, burosumab has been approved for patients with XLH in several countries. The effects of burosumab in patients with TIO are currently investigated in clinical trials. No serious safety problems have been reported for burosumab. However, it is possible that burosumab use will be restricted because of its high cost.

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