Pathogenesis of hypercalcemia in lymphosarcoma cell leukemia. Role of an osteoclast activating factor-like substance and a mechanism of action for glucocorticoid therapy

Gregory R. Mundy, Margaret E. Rick, Robert Turcotte, Mary Ann Kowalski

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67 Scopus citations

Abstract

The pathogenesis of hypercalcemia and mode of action of glucocorticoid therapy was examined in a patient with lymphosarcoma cell leukemia. Circulating neoplastic cells were cultured in vitro and secreted a bone-resorbing factor. The bone-resorbing factor was partially purified with the use of a bioassay for bone resorption, and was found to be chromatographically and pharmacologically similar to osteoclast activating factor (OAF), which is produced by normal mitogen-activated peripheral blood lymphocytes. Other factors which stimulate bone resorption, such as parathyroid hormone, prostaglandins and the vitamin D metabolites, were excluded by criteria which included dose-response curves, radioimmunoassays, extraction in organic solvents and failure of glucocorticoids to inhibit bone-resorbing activity. The patient's hypercalcemia responded rapidly to prednisone therapy. The effects of the bone-resorbing factor secreted by the neoplastic cells on bone cultures to which cortisol was added were examined. Cortisol inhibited bone resorption directly at low doses (10-8 M), which suggests that prednisone may have lowered the serum calcium in this patient by direct inhibition of bone resorption.

Original languageEnglish (US)
Pages (from-to)600-606
Number of pages7
JournalThe American Journal of Medicine
Volume65
Issue number4
DOIs
StatePublished - Oct 1978
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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