Recent advances in pediatric metabolic bone disease: the consequences of altered phosphate homeostasis in renal insufficiency and hypophosphatemic vitamin D-resistant rickets
Abstract
Over the past decade our understanding of the pathogenesis of altered mineral homeostasis in chronic renal failure (CRF) and X-linked hypophosphatemic vitamin D-resistant rickets (XLH) has increased, and has provided a rational approach for the use of the 1 alpha-hydroxylated analogues of vitamin D in their therapy. Recent evidence suggests that intracellular phosphate (Pi) retention in CRF plays a major role in decreasing serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, which are responsible for the progressive rise in serum parathyroid hormone (PTH) concentrations through the direct action of 1,25(OH)2D on the parathyroid gland. 1,25(OH)2D levels affect the number of intracellular 1,25(OH)2D receptors, preproPTH mRNA levels and the set point for calcium suppression of PTH release. Further in experimental CRF, the maintenance of normal 1,25(OH)2D levels prevents parathyroid gland hyperplasia. These studies indicate that depressed renal 1 alpha-hydroxylase activity due to Pi retention is a major factor in directly increasing PTH secretion, which in turn contributes significantly to the severity of renal osteodystrophy. Thus the aim of therapy in early CRF should be to maintain normal levels of 1,25(OH)2D which can be achieved by either dietary Pi restriction and oral Pi binders or by administering small doses of 1 alpha-hydroxylated metabolites. The long term consequences of these two different therapeutic regimens still need to be assessed. In XLH, evidence is rapidly…
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