Laboratory Investigation

Kidney International (1983) 23, 327–335; doi:10.1038/ki.1983.23

Animal model of aluminum-induced osteomalacia: Role of chronic renal failure

John A Robertson1, Arnold J Felsenfeld1, Carl C Haygood1, Paul Wilson1, Cheryl Clarke1 and Francisco Llach1

1Department of Medicine, University of Oklahoma Health Sciences Center and the Veterans Administration Medical Center, Oklahoma City, Oklahoma

Correspondence: Dr A J Felsenfeld, Nephrology Section (111G), Veterans Administration Medical Center, 921 N.E. 13th Street, Oklahoma City, Oklahoma 73104, USA

Received 19 April 1982; Revised 6 July 1982.

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Abstract

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 < 0.02) and the osteoid seam width (P < 0.001) were increased in HDA, CRF, and CRF-HDA rats. Percent resorption and osteoclasts/mm2 were increased in CRF rats (P < 0.02) and decreased in HDA rats (P < 0.05). Compared to N rats, the amino terminal parathyroid hormone was decreased in HDA rats (P < 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.

Un modèle animal d'ostéomalacie induite par l'aluminium: Rôle de l'insuffisance rénale chronique et de l'hormone parathyroïdienne. La toxicité de l'aluminium et un déficit relatif en hormone parathyroïdienne ont tous les deux été impliqués dans le développement de l'ostéomalacie chez les malades en dialyse. Afin d'étudier l'effet d'injections intrapéritonéales (IP) d'aluminium sur l'histologie osseuse et l'hormone parathyroïdienne et de déterminer si l'insuffisance rénale chronique accentue la toxicité de l'aluminium, des rats ont été divisés en cinq groupes: normaux (N); faible dose d'aluminium (LDA), 0,1 mg d'aluminium IP par jour; forte dose d'aluminium (HDA), 1,0 mg d'aluminium IP par jour; insuffisance rénale chronique (CRF); insuffisance rénale chronique plus forte dose d'aluminium (CRF-HDA). A la fin de l'étude il n'y avait pas de différence entre les rats N et LDA. Des différences importantes ont été observées entre les autres groupes. Par rapport aux rats N, le volume ostéoïde relatif (P < 0,02) et l'épaisseur des bordures ostéoïdes (P < 0,001) étaient augmentés chez les rats HDA, CRF, et CRF-HDA. Le pourcentage de résorption et les ostéoclastes/mm2 étaient augmentés chez les rats CRF (P < 0,02) et diminués chez les rats HDA (P < 0,05). Par rapport aux rats N, l'hormone parathyroïdienne aminoterminale était diminuée chez les rats HDA (P < 0,02) malgré l'existence d'une hypocalcémie. Ces données suggèrent que (1) la toxicité aluminique entraîne une ostéomalacie; (2) un déficit relatif en hormone parathyroïdienne peut être un facteur contributif; (3) l'insuffisance rénale chronique augmente la sévérité de l'ostéomalacie induite par l'aluminium; (4) l'insuffisance rénale chronique seule n'entraîne pas d'ostéomalacie.

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