Quantitation and localisation of aluminum in human cancellous bone in renal osteodystrophy

There is increasing evidence that aluminium toxicity may be responsible for a type of vitamin D-resistant osteomalacia and an unusually severe form of dementia ("dialysis dementia") occurring in some patients with chronic renal failure on regular haemodialysis. High concentrations of Al have been found in blood, bone and brain tissue from these patients. The A1 comes either from the water used during dialysis (added in some public water supplies during purification to precipitate contaminants) or from aluminium salts taken orally to bind phosphates and so restrict their dietary adsorption. Recent X-ray microanalytical studies have demonstrated Al in lysosomes of cerebral cells and at the calcification front in bone of patients dying of dialysis dementia but its concentration at this site in bone has not been measured using this technique. We have examined transiliac bone biopsies from 3 patients with dialysis dementia and 6 non-demented patients on regular haemodialysis, Atomic absorption spectrometry (AAS) reveals high Al content in bone from the 3 demented and 2 of the non-demented patients. All had vitamin D-resistant osteomalacia. Using X-ray microanalysis Al was located in the bone of these five patients only. The Al had a highly focal distribution and was measured at up to 40 times higher concentration than by AAS but only in mineralisation nuclei of the calcification front or less than 2 micrometer into the mineralized bone. The study was done retrospectively on biopsies fixed in 10% buffered formalin, which almost certainly eluted some of the Al. In life, Al levels may have been higher than those we have detected.