X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive
musculoskeletal disease that often causes
pain and short stature, as well as decreased physical function, mobility, and quality of life.
Hypophosphatemia in XLH is caused by loss of function mutations in the
phosphate-regulating endopeptidase homolog X-linked (PHEX) gene, resulting in excess levels of the
phosphate-regulating
hormone fibroblast growth factor 23 (FGF23), which leads to renal
phosphate wasting and decreased serum
1,25-dihydroxyvitamin D production. Historically, treatment options were limited to oral
phosphate and active
vitamin D analogues (conventional management) dosed several times daily in an attempt to improve skeletal mineralization by increasing serum
phosphorus. The recent approval of
burosumab, a fully human
monoclonal antibody to FGF23, has provided a new, targeted treatment option for patients with XLH. This review summarizes our current understanding of XLH, the safety and efficacy of conventional management and
burosumab, existing recommendations for managing patients, and unanswered questions in the field.