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. 1984 Jan;73(1):171–181. doi: 10.1172/JCI111188

Short-term aluminum administration in the rat. Effects on bone formation and relationship to renal osteomalacia.

W G Goodman, J Gilligan, R Horst
PMCID: PMC424990  PMID: 6690476

Abstract

Aluminum may be pathogenic in the osteomalacia observed in some patients receiving hemodialysis. To study the early effects of Al on bone growth, bone formation, mineralization, and resorption were measured during short-term Al exposure in the tibial cortex of pair-fed control (C, n = 10), aluminum-treated (AL, n = 9), subtotally nephrectomized control (NX-C, n = 7), and subtotally nephrectomized aluminum-treated (NX-AL, n = 8) rats using double tetracycline labeling of bone. Animals received 2 mg/d of elemental Al intraperitoneally for 5 d/wk over 4 wk. Total bone and matrix (osteoid) formation, periosteal bone and matrix formation, and periosteal bone and matrix apposition fell by 20% in AL from C, P less than 0.05 for all values, and by 40% in NX-AL from NX-C, P less than 0.01 for all values. Moreover, each measurement was significantly less in NX-AL than in AL, P less than 0.05 for all values. Osteoid width did not increase following aluminum administration in either AL or NX-AL. Resorption surface increased from control values in both AL and NX-AL; also, resorptive activity at the endosteum was greater in NX-AL than in NX-C, P less than 0.05. Thus, aluminum impairs new bone and matrix formation but does not cause classic osteomalacia in the cortical bone of rats whether renal function is normal or reduced. These findings may represent either a different response to aluminum administration in cortical bone as contrasted to trabecular bone or an early phase in the development of osteomalacia. Aluminum may increase bone resorption and contribute to osteopenia in clinical states associated with aluminum accumulation in bone.

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Selected References

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  1. Alfrey A. C., Hegg A., Craswell P. Metabolism and toxicity of aluminum in renal failure. Am J Clin Nutr. 1980 Jul;33(7):1509–1516. doi: 10.1093/ajcn/33.7.1509. [DOI] [PubMed] [Google Scholar]
  2. Baylink D., Stauffer M., Wergedal J., Rich C. Formation, mineralization, and resorption of bone in vitamin D-deficient rats. J Clin Invest. 1970 Jun;49(6):1122–1134. doi: 10.1172/JCI106328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boyce B. F., Fell G. S., Elder H. Y., Junor B. J., Elliot H. L., Beastall G., Fogelman I., Boyle I. T. Hypercalcaemic osteomalacia due to aluminium toxicity. Lancet. 1982 Nov 6;2(8306):1009–1013. doi: 10.1016/s0140-6736(82)90049-6. [DOI] [PubMed] [Google Scholar]
  4. Cann C. E., Prussin S. G., Gordan G. S. Aluminum uptake by the parathyroid glands. J Clin Endocrinol Metab. 1979 Oct;49(4):543–545. doi: 10.1210/jcem-49-4-543. [DOI] [PubMed] [Google Scholar]
  5. Chan Y. L., Alfrey A. C., Posen S., Lissner D., Hills E., Dunstan C. R., Evans R. A. Effect of aluminum on normal and uremic rats: tissue distribution, vitamin D metabolites, and quantitative bone histology. Calcif Tissue Int. 1983 May;35(3):344–351. doi: 10.1007/BF02405056. [DOI] [PubMed] [Google Scholar]
  6. Chertow B. S., Baylink D. J., Wergedal J. E., Su M. H., Norman A. W. Decrease in serum immunoreactive parathyroid hormone in rats and in parathyroid hormone secretion in vitro by 1,25-dihydroxycholecalciferol. J Clin Invest. 1975 Sep;56(3):668–678. doi: 10.1172/JCI108137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cournot-Witmer G., Zingraff J., Plachot J. J., Escaig F., Lefèvre R., Boumati P., Bourdeau A., Garabédian M., Galle P., Bourdon R. Aluminum localization in bone from hemodialyzed patients: relationship to matrix mineralization. Kidney Int. 1981 Sep;20(3):375–378. doi: 10.1038/ki.1981.149. [DOI] [PubMed] [Google Scholar]
  8. Drüeke T. Dialysis osteomalacia and aluminum intoxication. Nephron. 1980;26(5):207–210. doi: 10.1159/000181985. [DOI] [PubMed] [Google Scholar]
  9. Ellis H. A., McCarthy J. H., Herrington J. Bone aluminium in haemodialysed patients and in rats injected with aluminium chloride: relationship to impaired bone mineralisation. J Clin Pathol. 1979 Aug;32(8):832–844. doi: 10.1136/jcp.32.8.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FROST H. M. Measurement of human bone formation by means of tetracycline labelling. Can J Biochem Physiol. 1963 Jan;41:31–42. [PubMed] [Google Scholar]
  11. Heinegård D., Tiderström G. Determination of serum creatinine by a direct colorimetric method. Clin Chim Acta. 1973 Feb 12;43(3):305–310. doi: 10.1016/0009-8981(73)90466-x. [DOI] [PubMed] [Google Scholar]
  12. Hodsman A. B., Sherrard D. J., Alfrey A. C., Ott S., Brickman A. S., Miller N. L., Maloney N. A., Coburn J. W. Bone aluminum and histomorphometric features of renal osteodystrophy. J Clin Endocrinol Metab. 1982 Mar;54(3):539–546. doi: 10.1210/jcem-54-3-539. [DOI] [PubMed] [Google Scholar]
  13. Hodsman A. B., Sherrard D. J., Wong E. G., Brickman A. S., Lee D. B., Alfrey A. C., Singer F. R., Norman A. W., Coburn J. W. Vitamin-D-resistant osteomalacia in hemodialysis patients lacking secondary hyperparathyroidism. Ann Intern Med. 1981 May;94(5):629–637. doi: 10.7326/0003-4819-94-5-629. [DOI] [PubMed] [Google Scholar]
  14. Horst R. L., Littledike E. T., Riley J. L., Napoli J. L. Quantitation of vitamin D and its metabolites and their plasma concentrations in five species of animals. Anal Biochem. 1981 Sep 1;116(1):189–203. doi: 10.1016/0003-2697(81)90344-4. [DOI] [PubMed] [Google Scholar]
  15. Jha G. J., Deo M. G., Ramalingaswami V. Bone growth in protein deficiency. A study in rhesus monkeys. Am J Pathol. 1968 Dec;53(6):1111–1123. [PMC free article] [PubMed] [Google Scholar]
  16. Kovalchik M. T., Kaehny W. D., Hegg A. P., Jackson J. T., Alfrey A. C. Aluminum kinetics during hemodialysis. J Lab Clin Med. 1978 Nov;92(5):712–720. [PubMed] [Google Scholar]
  17. Le Roith D., Pimstone B. L. Bone metabolism and composition in the protein-deprived rat. Clin Sci. 1973 Apr;44(4):305–319. doi: 10.1042/cs0440305. [DOI] [PubMed] [Google Scholar]
  18. Lieberherr M., Grosse B., Cournot-Witmer G., Thil C. L., Balsan S. In vitro effects of aluminum on bone phosphatases: a possible interaction with bPTH and vitamin D3 metabolites. Calcif Tissue Int. 1982 May;34(3):280–284. doi: 10.1007/BF02411251. [DOI] [PubMed] [Google Scholar]
  19. Maloney N. A., Ott S. M., Alfrey A. C., Miller N. L., Coburn J. W., Sherrard D. J. Histological quantitation of aluminum in iliac bone from patients with renal failure. J Lab Clin Med. 1982 Feb;99(2):206–216. [PubMed] [Google Scholar]
  20. Morrissey J., Rothstein M., Mayor G., Slatopolsky E. Suppression of parathyroid hormone secretion by aluminum. Kidney Int. 1983 May;23(5):699–704. doi: 10.1038/ki.1983.81. [DOI] [PubMed] [Google Scholar]
  21. Ott S. M., Maloney N. A., Coburn J. W., Alfrey A. C., Sherrard D. J. The prevalence of bone aluminum deposition in renal osteodystrophy and its relation to the response to calcitriol therapy. N Engl J Med. 1982 Sep 16;307(12):709–713. doi: 10.1056/NEJM198209163071202. [DOI] [PubMed] [Google Scholar]
  22. Parfitt A. M. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part I of IV parts: mechanisms of calcium transfer between blood and bone and their cellular basis: morphological and kinetic approaches to bone turnover. Metabolism. 1976 Jul;25(7):809–844. doi: 10.1016/0026-0495(76)90151-7. [DOI] [PubMed] [Google Scholar]
  23. Parkinson I. S., Ward M. K., Feest T. G., Fawcett R. W., Kerr D. N. Fracturing dialysis osteodystrophy and dialysis encephalopathy. An epidemiological survey. Lancet. 1979 Feb 24;1(8113):406–409. doi: 10.1016/s0140-6736(79)90883-3. [DOI] [PubMed] [Google Scholar]
  24. Pierides A. M., Edwards W. G., Jr, Cullum U. X., Jr, McCall J. T., Ellis H. A. Hemodialysis encephalopathy with osteomalacic fractures and muscle weakness. Kidney Int. 1980 Jul;18(1):115–124. doi: 10.1038/ki.1980.117. [DOI] [PubMed] [Google Scholar]
  25. Platts M. M., Goode G. C., Hislop J. S. Composition of the domestic water supply and the incidence of fractures and encephalopathy in patients on home dialysis. Br Med J. 1977 Sep 10;2(6088):657–660. doi: 10.1136/bmj.2.6088.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Riggs B. L., Wahner H. W., Dunn W. L., Mazess R. B., Offord K. P., Melton L. J., 3rd Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981 Feb;67(2):328–335. doi: 10.1172/JCI110039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Robertson J. A., Felsenfeld A. J., Haygood C. C., Wilson P., Clarke C., Llach F. Animal model of aluminum-induced osteomalacia: role of chronic renal failure. Kidney Int. 1983 Feb;23(2):327–335. doi: 10.1038/ki.1983.23. [DOI] [PubMed] [Google Scholar]
  28. Shires R., Avioli L. V., Bergfeld M. A., Fallon M. D., Slatopolsky E., Teitelbaum S. L. Effects of semistarvation on skeletal homeostasis. Endocrinology. 1980 Nov;107(5):1530–1535. doi: 10.1210/endo-107-5-1530. [DOI] [PubMed] [Google Scholar]
  29. Ward M. K., Feest T. G., Ellis H. A., Parkinson I. S., Kerr D. N. Osteomalacic dialysis osteodystrophy: Evidence for a water-borne aetiological agent, probably aluminium. Lancet. 1978 Apr 22;1(8069):841–845. doi: 10.1016/s0140-6736(78)90191-5. [DOI] [PubMed] [Google Scholar]
  30. el-Maraghi N. R., Platt B. S., Stewart R. J. The effect of the interaction of dietary protein and calcium on the growth and maintenance of the bones of young, adult and aged rats. Br J Nutr. 1965;19(4):491–509. doi: 10.1079/bjn19650045. [DOI] [PubMed] [Google Scholar]

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