Thomas J Weber1, L Darryl Quarles2. 1. Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, 303 Baker House, DUMC 3470, Duke University Medical Center, Durham, NC 27710. 2. Department of Medicine, Division of Nephrology 956 Court Ave, Suite B266, University of Tennessee Health Sciences Center, Memphis, TN 38163.
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).
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).
Entities:
Keywords:
Hypophosphatemia; fibroblast growth factor 23; mineral metabolism; osteomalacia; parathyroid hormone; rickets; vitamin D
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