Animal model of aluminum-induced osteomalacia: role of chronic renal failure.

Both aluminum toxicity and a relative deficiency of parathyroid hormone have been implicated in the development of osteomalacia in dialysis patients. To study the effect of intraperitoneal (IP) aluminum injections on bone histology and parathyroid hormone and to determine if chronic renal failure accentuates aluminum toxicity, rats were divided into five groups: normals (N); low dose aluminum (LDA), 0.1 mg IP aluminum daily; high dose aluminum (HDA), 1.0 mg IP aluminum daily; chronic renal failure (CRF); and chronic renal failure plus high dose aluminum (CRF-HDA). At the conclusion of the study, there were no differences between N and LDA rats. Between the other groups, marked differences were observed. Compared to N rats, the relative osteoid volume (P less than 0.02) and the osteoid seam width (P less than 0.001) were increased in HDA, CRF, and CRF-HDA rats. Percent resorption and osteoclasts/mm2 were increased in CRF rats (P less than 0.02) and decreased in HDA rats (P less than 0.05). Compared to N rats, the amino terminal parathyroid hormone was decreased in HDA rats (P less than 0.02) despite the presence of hypocalcemia. These data suggest that (1) aluminum toxicity produces osteomalacia; (2) a relative parathyroid hormone deficiency may be a contributory factor; (3) chronic renal failure increases the severity of aluminum-induced osteomalacia; and (4) chronic renal failure alone does not result in osteomalacia.