8 Phosphate Disorders

Suggested citation: The Endocrine Society. Endocrine Facts and Figures: Bone and Mineral. First Edition. 2015.

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Adults consume approximately 1.5 g of phosphorous per day, and ingestion and excretion of phosphate is tightly regulated because of its structural role in bone and its central role in functions such as the formation of phospholipids and the generation of adenosine triphosphate.134

Hypophosphatasia is a rare inherited disorder that disrupts the development of bones and teeth due to mutations in the tissue non-specific ALPL gene, which is responsible for the production of alkaline phosphatase.135 The disease can affect babies in utero as well as infants, children, and adults.136 Hypophosphatasia has been reported to be especially prevalent in inbred Mennonite families from Manitoba, Canada. About four in 100 individuals are carriers, and one in 2,500 newborn children manifests a severe case of the disease. In addition, the incidence of the severe forms in Toronto, Canada was estimated to be 1 in 100,000 live births.137,138 The first enzyme-replacement therapy139 for patients with hypophosphatasia, Strensiq (asfotase alfa), is currently pending approval consideration by the FDA.

Hypophosphatemia is an uncommon disorder that can result from changes in renal phosphate handling, often as a result of excess fibroblast growth factor 23 (FGF23).140 Osteocytes in bone produce FGF23; in addition to lowering serum 1,25-dihydroxyvitamin D levels, excess FGF23 causes hypophosphatemic osteomalacia. Secondary hyperparathyroidism may result from chronic phosphate supplementation over many years. In contrast, FGF23 deficiency leads to elevated serum 1,25-dihydroxyvitamin D levels and familial hyperphosphatemic tumoral calcinosis.140-142

Researchers have associated excess phosphorus intake with the disruptions of mineral metabolism, vascular calcification, impaired kidney function, and bone loss.143 In addition, it has been suggested that excess extracellular phosphate may be involved in the secretion and actions of FGF23 and PTH. As a result, elevated dietary phosphorus may contribute to renal failure, cardiovascular disease, osteoporosis, and hypocalcaemia.144,145

Little to no information is available regarding the epidemiology of phosphate disorders in the US.

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