Bone-Resorbing Activity in Supernatants from Lymphoid Cell Lines

To study the pathogenesis of osteolytic lesions and hypercalcemia in neoplastic disease, supernatant fluids of cultured lymphoid cell lines were tested for their ability to stimulate bone resorption in vitro. Lines from patients with myeloma, Burkitt's lymphoma, and malignant lymphoma secreted a potent bone-resorbing material. Four lines from normal subjects or patients with other neoplasms did not have this activity. The lymphoid cell-line agent (or agents) could be distinguished from parathyroid hormone, prostaglandin E2 and vitamin-D-like sterols by dose-response curves, Sephadex G-100 chromatography, heat inactivation, dialysis and ultrafiltration, extraction with lipid solvents and immunoassays, but could not be distinguished from the osteoclast-activating factor secreted by human leukocytes. Osteolytic lesions in patients with lymphocytic neoplasms may be due to excessive secretion of stimulators of osteoclast-mediated bone resorption. (N Engl J Med 290:867–871, 1974)