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Tumor Resection and Antibodies to Parathyroid Hormone-Related Protein Cause Similar Changes on Bone Histomorphometry in Hypercalcemia of Cancer^*

Departments of Medicine and Nuclear Medicine, Veterans Administration West Side and University of Illinois Medical Centers (S.C.K., S.A.W., D.H.S., E.I.B.) Chicago, Illinois 60612
Department of Veterinary Pathobiology, Ohio State University (T.J.R.), Columbus, Ohio 43210; and St. Vincent Institute of Medical Research (V.G., T.J.M.) Melbourne 3065, Australia

Address all correspondence and requests for reprints to: Subhash C. Kukreja, M.D., Endocrinology Section and Nuclear Medicine Service, Veterans Administration West Side Medical Center (M.P. 115), 820 South Damen Avenue, Chicago, Illinois 60612.

Abstract

Bone resorption is increased in both humoral hypercalcemia of malignancy (HHM) and primary hyperparathyroidism. On the other hand, bone formation parameters are increased in primary hyperparathyroidism and decreased in HHM. Recently, a PTH-related protein (PTHrP) has been shown to be responsible for the hypercalcemia in the syndrome of HHM. In the present study we evaluated the effects of a neutralizing antiserum to PTHrP on bone histomorphometric parameters in hypercalcemic athymic mice bearing a human squamous cell lung cancer. These effects were compared to those of tumor resection. Similar to the effects of tumor resection, the antiserum to PTHrP resulted in a decrease in serum Ca levels, a decrease in bone resorption, and an increase in bone formation parameters. The studies, therefore, indicate that PTHrP is the major factor responsible for all of the features, including the decreased bone formation seen in HHM. (Endocrinology 127: 305–310,1990)

Footnotes

^* A portion of this work was presented at the National Meeting of the American Federation for Clinical Research, Washington D.C., April 28–May 1,1989. This work was supported by the V.A. Medical Research Service and the National Health and Medical Research Council of Australia.

Received January 11, 1990.

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