What is the role of low phosphate levels in the etiology of hypophosphatemic rickets?

Updated: May 02, 2018
  • Author: James CM Chan, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Answer

The pathogenesis of hypophosphatemic rickets is clear; phosphate wasting at the proximal tubule level is the basis of the affected individual's inability to establish normal ossification. This phenomenon is secondary to defective regulation of the sodium-phosphate cotransporter in the epithelial cell brush border.

Normal phosphate reabsorption in response to 1 α,25-dihydroxycholecalciferol (calcitriol) provides clear evidence that the sodium-phosphate cotransporter is capable of proper function and is not intrinsically defective. This evidence also bolsters the hypothesis advanced above, which implicates an additional factor in the pathogenesis of the phosphaturia. [18]

Inadequate levels of inorganic phosphate impair the function of mature osteoblasts (ie, bone matrix ossification), because formation of mature bone involves the precipitation of hydroxyapatite [3-Ca3 (PO4)2: Ca(OH)2] crystals. Although treatment with oral phosphate supplements should remedy the defect, all such attempts have failed. This failure could be due to the enhanced mineralization-inhibiting presence of the ASARM peptide secondary to the mutated PHEX gene in bone.

The advantages of improved technology and hindsight now confirm that phosphate supplementation elicits a parathyroid hormone (PTH) response to the fall in serum calcium from the temporary surge in bone mineralization induced by phosphate ingestion. Following this surge is an immediate return to the initial status quo, because PTH depresses phosphate reabsorption at the renal tubule. Data suggest that hyperparathyroidism may be a part of the clinical disorder preceding any therapy.

Although much has been learned about the etiology of hypophosphatemic rickets, a great deal more remains undiscovered.


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