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Free access | 10.1172/JCI109578

Evidence for Skeletal Resistance to Parathyroid Hormone in Magnesium Deficiency: STUDIES IN ISOLATED PERFUSED BONE

Jeffrey J. Freitag, Kevin J. Martin, Mary B. Conrades, Ezequiel Bellorin-Font, Steven Teitelbaum, Saulo Klahr, and Eduardo Slatopolsky

Renal Division, Department of Internal Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

Renal Division, Department of Pathology, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

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Renal Division, Department of Internal Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

Renal Division, Department of Pathology, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

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Renal Division, Department of Internal Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

Renal Division, Department of Pathology, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

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Renal Division, Department of Internal Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

Renal Division, Department of Pathology, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

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Renal Division, Department of Internal Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

Renal Division, Department of Pathology, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

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Renal Division, Department of Internal Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

Renal Division, Department of Pathology, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

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Renal Division, Department of Internal Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

Renal Division, Department of Pathology, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri 63110

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Published November 1, 1979 - More info

Published in Volume 64, Issue 5 on November 1, 1979
J Clin Invest. 1979;64(5):1238–1244. https://doi.org/10.1172/JCI109578.
© 1979 The American Society for Clinical Investigation
Published November 1, 1979 - Version history
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Abstract

Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83±0.1 mg/100 ml) and experimental dogs (serum Mg 1.34±0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5±3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1±1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8±0.2 to 17.5±0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5±0.1 pmol/min, and increased to only 7.1±0.4 pmol/min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP production by experimental bones was lower than in control bones perfused with 3 ng/ml. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity. These studies demonstrate decreased uptake of iPTH and diminished cAMP production by bone, which indicates skeletal resistance to PTH in chronic Mg deficiency.

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