The pathogenesis of renal osteodystrophy: role of vitamin D, aluminium, parathyroid hormone, calcium and phosphorus.

SUMMARY Biochemical data and bone histology from 44 haemodialysis patients was compared using an histologic technique capable of evaluating separately the individual components of osteodystrophy. Hyperparathyroid bone disease was diagnosed by an elevated osteoclast count, and in advanced disease there was also fibrosis and woven bone. Osteomalacia, defined as an impairment in the rate of bone mineralisation, was present in two distinct forms: osteomalacia type I, characterised by wide osteoid seams, and osteomalacia type II, characterised by extensive thin, inactive osteoid. The histologic diagnoses were hyperparathyroid bone disease (15), osteomalacia type I (3), osteomalacia type II (6), hyperparathyroid bone disease and osteomalacia type I (12), hyperparathyroid bone disease and osteomalacia type II (6), normal (2). Aluminium was evident histochemically in 17 biopsies. Vitamin D metabolite levels were low in most patients and did not correlate with any biochemical or histological parameter. Parathyroid hormone levels were highly correlated with histological features of hyperparathyroid bone disease, and also correlated with plasma calcium, suggesting a degree of autonomy of parathyroid hormone secretion. Urea and creatinine were higher in the hyperparathyroid bone disease than the osteomalacia groups suggesting that poor dialysis contributes to the former. Statistical analysis showed that osteomalacia type I was associated with relatively low plasma calcium and phosphorus levels; osteomalacia type II was associated with increased bone aluminium and with the uraemic process itself, as reflected in the plasma creatinine level. This study shows relationships between renal osteodystrophy and plasma calcium and phosphorus levels, but no relationship with vitamin D metabolites. Aluminium appears to impair mineralisation even at relatively low levels of accumulation. However there are other unidentified factors associated with the uraemic process, contributing to all three components of renal osteodystrophy.