Hypocalcaemia and Bone Disease in Renal Failure

Abstract

Various aspects of calcium and bone metabolism were studied in 50 cases of chronic renal failure. It was found that elevation of plasma alkaline phosphatase was generally associated with reduced metacarpal cortical thickness and in a small number of biopsies reflected the osteomalacic rather than the resorptive component of renal bone disease. Patients with an elevated plasma alkaline phosphatase tended to have a lower plasma calcium, lower plasma bicarbonate and lower radiocalcium absorption than patients with a normal alkaline phosphatase. Hypocalcaemia was frequently associated with, and attributed by the authors to reduced tubular reabsorption of calcium, which in turn appeared to be related to the degree of metabolic acidosis. The authors conclude that metabolic acidosis predisposes to hypocalcaemia and, therefore, to renal osteomalacia.

Effect of Correction of Metabolic Acidosis on Bone Mineralisation Rates in Patients with Renal Osteomalacia

“…It has previously been shown that metabolic acidosis reduces the intestinal absorption of calcium [4,9,11], and also that it produces an increased urine calcium [18] by reducing tubular calcium reabsorption [8,19]. The results reported in this paper agree entirely with these earlier findings but extend the known effects of acidosis to include an action on bone turnover.…”

“…The relation between calcium uptake by the vesicles and pH is strikingly similar to the variation of alkaline phosphatase activity with pH, and the matrix vesicles contain this enzyme in large quantities [26]. Moreover, alkaline phosphatase is a function of the forming, but not resorbing bone surfaces [9], Holdsworth [27] and Russell el al. [28] have made the interesting suggestion that calcium ATPase in the intestine may be an alkaline phosphatase, and if this is the case at other sites of calcium transport then it would provide a simple explanation for the inhibitory affects of acidosis that we have observed.…”

“…1). We have previously noted that vitamin D causes an increase in the tubular reabsorption of calcium [7,9], and acidosis evidently has the opposite effect. As far as its action on bone is concerned, vitamin D certainly promotes resorption [21][22][23] and may directly promote minerali sation as well.…”

“…incongruous that the isotopic bone mineralisation rate values are generally elevated, sometimes markedly so [9,14]. This apparent inconsistency may be explained in the terms of Frost [29], who pointed out that though in osteo malacia there is a delay in the mineralisation of individual bone forming sites, the total number of these is frequently so great that the overall rate of formation may be raised.…”

“…However, these doses often seem larger than might be expected for the amount of renal function that is present, suggesting that other factors are operating. In previous publications, we have emphasised the possibility that metabolic acidosis might be one such factor [2,[7][8][9] for there is no doubt that it can fundamentally influence calcium metabolism and has been shown to cause both a decreased absorption from the intestine [9][10][11] and a reduced tubular reabsorption in the kidney [8,9,11]. This being the case, it seemed possible that acid-base status might affect the skeleton in an analogous way.…”