X-Linked Hypophosphataemia and Burosumab: A Systemic Disease With a New Treatment

Abstract

X linked hypophosphataemia (XLH) is a systemic, chronic condition that significantly impairs quality of life. In XLH, a phosphate regulating endopeptidase homologue X-linked (PHEX) gene mutation leads to excess fibroblast growth factor 23 (FGF23), causing hypophosphataemia and subsequent rickets, lower limb deformity, pain and other sequelae, however there are likely other non-FGF23 mediated mechanisms contributing to disease. Burosumab is an FGF23 inhibiting monoclonal antibody that has been shown to be significantly more effective in treating X linked hypophosphataemia than previously available treatment ("conventional therapy" with oral phosphate and active vitamin D). Clinical trials and real-world studies have shown that burosumab can improve lower limb deformity, growth, pain, exercise capacity, biochemistry, rickets, and quality of life. However, the full effect of burosumab on the lives of individuals with X linked hypophosphataemia is yet to be determined. How burosumab may impact some of the lesser understood clinical features, including dental abscesses, craniosynostosis, enthesopathy, and osteoarthritis, is unclear. Whether burosumab mitigates the risk of complications associated with conventional therapy (nephrocalcinosis and hyperparathyroidism) has also not been established. There are conflicting recommendations on who should receive burosumab, when they should start it, and for how long they should continue taking it. This review summarises what is known, and more importantly what is unknown, about burosumab use in X linked hypophosphataemia. We highlight important areas for future research to better understand the impact of burosumab in XLH, improve management of XLH, assess cost benefit of, and advocate for fair and equitable access to burosumab.

Keywords: adolescent; endocrinology; hypophosphataemia; orthopaedics; rickets.