Effect of aluminum and parathyroid hormone on osteoblasts and bone mineralization in chronic renal failure.
Bone aluminum, quantitative bone histology, and plasma parathyroid hormone (PTH) were compared in 29 patients undergoing chronic hemodialysis. Histologic techniques included double tetracycline labeling and histochemical identification of osteoclasts and osteoblasts. Bone aluminum was measured chemically by flameless atomic absorption spectrophotometry, and histochemically. When measured chemically, the bone aluminum was 67 +/- 46 (SD) mg/kg dry weight (normal 2.4 +/- 1.2 mg/kg); histochemically, aluminum was present at 2.9 +/- 4.4% of trabecular surface. The biochemical and histochemical results agreed well (r = 0.80, P less than 0.001). No double tetracycline labels were seen at the mineralization front where aluminum was deposited, indicating cessation of mineralization at these sites. The osteoblast surface correlated positively with plasma PTH (r = 0.67, P less than 0.001) and negatively with bone aluminum level (r = -0.42, P less than 0.05). Multiple linear regression showed a correlation of aluminum with osteoblasts additional to that of PTH, consistent with a direct effect of aluminum in depressing osteoblast numbers. Though a relationship between PTH and chemically determined bone aluminum level could not be demonstrated, there was a negative correlation between osteoclast count and aluminum, and the nine patients with severe hyperparathyroid bone disease had lower chemically determined aluminum levels than the other patients. These results suggest that aluminum (a) directly inhibits mineralization, (b) is associated with decreased PTH activity and hence osteoblast numbers, and (c) directly reduces osteoblast numbers. In addition to inducing severe, resistant osteomalacia, aluminum appears to contribute to the mild osteomalacia commonly seen in renal failure, characterized by extensive thin osteoid and low tetracycline and osteoblast surfaces.
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000535:Aluminum / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology; D010012:Osteogenesis; D010281:Parathyroid Hormone / Q000097:blood*; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis
D010281:Parathyroid Hormone; D010758:Phosphorus; D003404:Creatinine; D000535:Aluminum; D000469:Alkaline Phosphatase; D002118:Calcium