Effects of ethylenediaminetetraacetate (EDTA) on urinary excretion of hydroxyproline, calcium and phosphorus in the rat

The effects of ethylenediaminetetraacetate (EDTA) were studied in rats. Intravenous infusion of 4.84 mM Na₂EDTA increased the urinary excretion of calcium six-fold, phosphorus three-fold and hydroxyproline 55% in 158 g thyroparathyroidectomized (TPTXed) rats. Calcitonin (25 MRC mU/rat/h) abolished the sodium EDTA-induced increase in hydroxyproline excretion, presumptive evidence that sodium EDTA was acting on bone. To determine whether the changes induced by sodium EDTA are due to lowering of plasma calcium, rats were infused with 4.84 mM ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), a more specific calcium chelator. EGTA increased the urinary excretion of calcium and phosphorus (P<0.001) but not hydroxyproline in thyroparathyroidectomized rats. Furthermore, when TPTXed rats were infused with calcium EDTA (4.84 mM Ca₂EDTA) in order that ionic calcium concentration would not be altered, hydroxyproline excretion was again markedly increased but phosphorus excretion was decreased by 26%. Since the displacement of the sodium ions in Na₂EDTA by calcium in vivo is instantaneous, and since calcium EDTA itself induces collagenolysis, the increase in urinary hydroxyproline excretion due to sodium EDTA cannot be attributed solely to lowering of plasma calcium. From these data two conclusions are drawn. First, sodium EDTA enhances bone breakdown independently of its effect on parathyroid hormone secretion. Second, since bone plays a major role in the maintenance of plasma calcium, interpretation of results should be made with caution in those investigations in which EDTA is used to study calcium homeostasis.