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Molecular Control of Phosphorus Homeostasis and Precision Treatment of Hypophosphatemic Disorders

  • Thomas J. WeberEmail author
  • L. Darryl Quarles
Molecular Control of Phosphorus Homeostasis (B van der Eerden, Section Editor)
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Part of the following topical collections:
  1. Topical Collection on Molecular Control of Phosphorus Homeostasis

Abstract

Purpose of Review

Serum phosphorus is maintained in a narrow range by balancing dietary phosphate absorption, influx and efflux of phosphorus from bone and intracellular stores, and renal reabsorption of filtered phosphate. Acute hypophosphatemia, typically caused by transient increases in cellular uptake, can lead to severe complications such as cardiopulmonary dysfunction and rhabdomyolysis that can warrant parenteral phosphate repletion. Chronic hypophosphatemia, however, generally represents true phosphate deficiency and may result in long-term metabolic and skeletal complications, particularly in children due to the critical importance of phosphorus to skeletal mineralization and longitudinal growth.

Recent Findings

In addition to the well-characterized roles of vitamin D and parathyroid hormone (PTH), a new bone-kidney axis has been discovered that regulates phosphate homeostasis through the bone-derived hormone fibroblast growth factor 23 (FGF23) and its phosphaturic actions that are mediated by activation of fibroblast growth factor receptors (FGFRs) complexed with α-Klotho in renal tubules. Chronic hypophosphatemia can now be classified as FGF23 dependent or independent.

Summary

In cases of FGF23-dependent hypophosphatemia, traditional non-specific treatments with elemental phosphorus and 1,25(OH)2 vitamin D (calcitriol) can now be replaced with a targeted approach by using an FGF-23 blocking antibody (Burosumab).

Keywords

Hypophosphatemia Rickets Osteomalacia Fibroblast growth factor 23 Parathyroid hormone Vitamin D Mineral metabolism 

Notes

Compliance with Ethical Standards

Conflict of Interest

Thomas J. Weber has received research funding, consultant fees and travel support from Ultragenyx.

L. Darryl Quarles has received research funding from Inozyme.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medicine, Division of Endocrinology, Metabolism and NutritionDuke University Medical CenterDurhamUSA
  2. 2.Department of Medicine, Division of NephrologyUniversity of Tennessee Health Sciences CenterMemphisUSA

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