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

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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Bibliographic Details
Published in:Life (Basel, Switzerland) Vol. 11; no. 6; p. 563
Main Authors: Vincze, Jon, Skinner, Brian W., Tucker, Katherine A., Conaway, Kory A., Lowery, Jonathan W., Hum, Julia M.
Format: Journal Article
Language:English
Published: Basel MDPI AG 15-06-2021
MDPI
Subjects:
Adults
Arthritis
Biological effects
Biomedical materials
Bone diseases
Bowing
burosumab
Calciferol
Children & youth
Clinical trials
Crysvita
Dietary supplements
Drug dosages
Family medical history
FDA approval
Fibroblast growth factor 23
Fractures
Growth factors
Hearing loss
Homology
Hypophosphatemia
KRN23
Laboratories
metabolic bone disease
Metabolism
Mutation
Osteoarthritis
Pain
Pediatrics
Pharmacology
Phosphate
Phosphates
Review
Rickets
Serum levels
Spinal stenosis
Surgical equipment
Vitamin D
X-linked hypophosphatemia
United States > US
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Summary: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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ISSN:2075-1729
2075-1729
DOI:10.3390/life11060563