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The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

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 fu...

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Autores principales: Vincze, Jon, Skinner, Brian W., Tucker, Katherine A., Conaway, Kory A., Lowery, Jonathan W., Hum, Julia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232744/
https://www.ncbi.nlm.nih.gov/pubmed/34203792
http://dx.doi.org/10.3390/life11060563
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author Vincze, Jon
Skinner, Brian W.
Tucker, Katherine A.
Conaway, Kory A.
Lowery, Jonathan W.
Hum, Julia M.
author_facet Vincze, Jon
Skinner, Brian W.
Tucker, Katherine A.
Conaway, Kory A.
Lowery, Jonathan W.
Hum, Julia M.
author_sort Vincze, Jon
collection PubMed
description 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 phosphate, 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 patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH 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 (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.
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spelling pubmed-82327442021-06-26 The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology Vincze, Jon Skinner, Brian W. Tucker, Katherine A. Conaway, Kory A. Lowery, Jonathan W. Hum, Julia M. Life (Basel) Review 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 phosphate, 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 patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH 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 (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. MDPI 2021-06-15 /pmc/articles/PMC8232744/ /pubmed/34203792 http://dx.doi.org/10.3390/life11060563 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Vincze, Jon
Skinner, Brian W.
Tucker, Katherine A.
Conaway, Kory A.
Lowery, Jonathan W.
Hum, Julia M.
The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
title The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
title_full The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
title_fullStr The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
title_full_unstemmed The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
title_short The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
title_sort metabolic bone disease x-linked hypophosphatemia: case presentation, pathophysiology and pharmacology
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232744/
https://www.ncbi.nlm.nih.gov/pubmed/34203792
http://dx.doi.org/10.3390/life11060563
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