Vincze, J.; Skinner, B.W.; Tucker, K.A.; Conaway, K.A.; Lowery, J.W.; Hum, J.M. The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology. Life2021, 11, 563.
Vincze, J.; Skinner, B.W.; Tucker, K.A.; Conaway, K.A.; Lowery, J.W.; Hum, J.M. The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology. Life 2021, 11, 563.
Vincze, J.; Skinner, B.W.; Tucker, K.A.; Conaway, K.A.; Lowery, J.W.; Hum, J.M. The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology. Life2021, 11, 563.
Vincze, J.; Skinner, B.W.; Tucker, K.A.; Conaway, K.A.; Lowery, J.W.; Hum, J.M. The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology. Life 2021, 11, 563.
Abstract
The authors present a stereotypical case presentation of x-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact Fibroblast Growth Factor 23 (FGF23) which lead to i) low serum phosphate levels, ii) increased fractional excretion of phosphorus, and iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in XLH patients is due to chronic hypophosphatemia. Additionally, XLH patients experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration’s (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.
Keywords
metabolic bone disease; burosumab; KRN23; x-linked hypophosphatemia; crysvita; xlh
Subject
Medicine and Pharmacology, Pathology and Pathobiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
