Effects of glucocorticoids on osteoclast-activating factor

Glucocorticoids lower the serum calcium in patients with hypercalcemia due to myeloma and related lymphoproliferative disorders. OAF is a potent bone-resorbing lymphokine which is probably responsible for the bone lesions and hypercalcemia which occur in patients with these hematological neoplasms. In this study, we have examined the effects of cortisol on the production of OAF and its biological activity in order to clarify the mechanism of action of glucocorticoids in lowering the serum calcium in these disorders. The effects of OAF-containing media on bone resorption were inhibited by cortisol at concentrations from 10^-5M to 10^-9M. In contrast, OAF production was not inhibited by cortisol at concentrations less than 10^-5M. These data support the hypothesis that glucocorticoids inhibit the effects of OAF in vivo primarily by a direct effect on bone resorption.