Summary
Calcium homeostasis and bone pathology were studied in weanling rats fed a low (70 ppm) magnesium diet for 2–21 days. The rats developed significant, progressive hypercalcemia after 6 days on the diet. The increase in blood calcium was accompanied by progressive hypoactivity of the parathyroid gland (PTG), as determined by histologic and morphometric analyses. Thus hyperactivity of the PTG could not have been responsible for the hypercalcemia observed.
Histologic examination of femora and humeri from magnesium-deficient rats showed progressive subperiosteal hyperplasia, consisting of undifferentiated osteoprogenitor cells and fibrous tissue, after 7 days of deficiency. The presence of unmineralized osteoid tissue in the metaphyses indicated that mineralization was not proceeding normally. The alterations in differentiation of osteoprogenitor cells, together with the failure of mineralization, resulted in significantly lower rates of bone formation (as measured by fluorochrome labeling) in the magnesium-deficient rats. Basophilic cementing lines and inactive osteocytes in the cortices of bones from magnesium-deficient rats indicated that bone resorption was also severely reduced in magnesium deficiency. We postulate that bone magnesium depletion (66% by day 21) has a direct negative effect on osteoblastic and osteocytic activity, and may explain, in part, the decreased responsiveness of bone to parathyroid hormone (PTH) that has been observed in magnesium-deficient animals.
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Shils, M.E.: Magnesium deficiency and calcium and parathyroid gland interrelations. In A.S. Prasad (ed.): Trace Elements in Human Health and Disease, Vol. II, pp. 23–46. Academic Press, New York, 1976
MacManus, J., and Heaton, F.: The effect of magnesium deficiency on calcium homeostasis in the rat, Clin. Sci.36:297–306, 1969
Rayssiguier, Y., and Larvor, P.: Nephrocalcinose et carence en magnesium. Ann. Bio. Anim. Biochim. Biophys.14:145–156, 1974
Gitelman, H., Kukolj, S., Welt, L.: The influence of the parathyroid glands on the hypercalcemia of experimental magnesium depletion in the rat, J. Clin. Invest.47:118–126, 1968
Hahn, T., Chase, L., Alvioli, L.: Effect of magnesium depletion on responsiveness to parathyroid hormone in parathyroidectomized rats, J. Clin. Invest.51:886–891, 1972
Heaton, F.W.: The parathyroid glands and magnesium metabolism in the rat, Clin. Sci.28:543–553, 1965
Walling, M., Favus, M., Kimber, D.: Effects of magnesium deficiency and thyro-parathyroidectomy on calcium active transport by rat duodenum, Proc. Soc. Exp. Biol. Med.148:1038–1043, 1975
Chou, H., Wasserman, R., Schwartz, R.: Effect of magnesium deficiency on intestinal calcium transport in rats, Proc. Soc. Exp. Biol. Med.159:171–175, 1978
Lifschitz, F., Harrison, H.E., Harrison, H.C.: Intestinal transport of calcium and phosphorus in experimental magnesium deficiency, Proc. Soc. Exp. Biol. Med.125:19–25, 1967
Krawitt, E.: Effect of dietary magnesium deficiency on calcium transport by the rat small intestine, Proc. Soc. Exp. Biol. Med.141:569–572, 1972
Alcock, N., MacIntyre, I.: Interrelations of calcium and magnesium absorption, Clin. Sci.22:185–193, 1962
Kessner, D., Epstein, F.: Effect of magnesium deficiency on gastrointestinal transfer of calcium, Proc. Soc. Exp. Biol. Med.122:721–725, 1966
Parker, H.M., Forbes, R.: Influence of dietary calcium, magnesium and phosphorus on cyclic AMP excretion and kidney calcification in the rat, Proc. Soc. Exp. Biol. Med.151:215–220, 1976
George, F., Heaton, F.: Changes in cellular composition during Mg deficiency, Biochem. J.152:609–615, 1975
Lai, C., Singer, L., Armstrong, W.: Bone composition and phosphatase activity in magnesium deficiency in rats, J. Bone Joint Surg.15A:516–522, 1975
Nielsen, S.P.: Effects of magnesium on calcification of young bone in tissue culture, Calcif. Tissue Res.11:78–94, 1973
Clark, T., Belanger, L.F.: The effects of alterations in dietary magnesium on calcium phosphorus and skeletal metabolism, Calcif. Tissue Res.1:204–218, 1967
Rayssiguier, Y., Larvor, P.: Mineral bone composition and some elements of calcium metabolism in magnesium-deficient growing rats, Ann. Biol. Anim. Biochim. Biophys.18:157–166, 1978
Larvor, P., Labat, M.: The influence of magnesium deficiency on calcium metabolism in the rat, Ann. Biol. Anim. Biochim. Biophys.18:149–155, 1978
Bogoroch, R., Belanger, L.F.: Skeletal effects of magnesium deficiency in normal, ovariectomized and estrogen-treated rats, Anat. Rec.183:437–438, 1975
Hunt, B., Belanger, L.: Localized, multiform sub-periosteal hyperplasia and generalized osteomyeosclerosis in magnesium deficient rats, Calcif. Tissue Res.9:17–27, 1972
Neafsey, P.J., Schwartz, R.: Serum alkaline phosphatase levels in fed and fasted magnesium-deficient rats, J. Nutr.107:1061–1067, 1977
Krook, L., Belanger, L., Henrikson, P., Lutwak, L., Sheffy, B.: Bone flow, Rev. Can. Biol.29:157–167, 1970
Levi, J., Massry, S., Coburn, J., Llach, F., Kleeman, C.: Hypocalcemia in magnesium depleted dogs. Evidence for reduced responsiveness to PTH and relative failure of parathyroid gland function, Metabolism23:323–345, 1974
Chase, L., Slatopolsky, E.: Secretion and metabolic efficacy of parathyroid hormone in patients with severe hypomagnesemia, J. Clin. Endocrinol. Metab.38:363–371, 1974
Suh, S., Tashjian, A., Matsuo, N., Parkinson, D., Fraser, D.: Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end organ responsiveness to parathyroid hormone, impaired parathyroid gland function, J. Clin. Invest.52:153–160, 1973
Hamilton, J.W., Spierto, F.W., MacGregor, R.R., Cohn, D.V.: Studies on the biosynthesis in vitro of parathyroid hormone. II. The effect of calcium and magnesium on synthesis of parathyroid hormone isolated from bovine parathyroid tissue and incubation medium, J. Biol. Chem.246:3224–3233, 1971
Larvor, P., Girard, A., Brochart, M., Parodi, A. Sevestre, J.: Etude de la carence experimentale en magnesium chez le veau. 1. Observations cliniques, biochimiques et anatamopathologiques, Ann. Biol. Anim. Biochim. Biophys.4:345–369, 1964
Chou, H., Schwartz, R., Krook, L., Wasserman, R.: Intestinal calcium absorption and bone morphology in magnesium deficient chicks, Cornell Vet.69:88–103, 1979
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Jones, J.E., Schwartz, R. & Krook, L. Calcium homeostasis and bone pathology in magnesium deficient rats. Calcif Tissue Int 31, 231–238 (1980). https://doi.org/10.1007/BF02407186
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DOI: https://doi.org/10.1007/BF02407186