Evidence for the Secretion of an Osteoclast Stimulating Factor in Myeloma

In an effort to describe the mechanism of bone erosion in patients with multiple myeloma, supernatant fluids from the short-term cultures of bone marrow aspirated from seven patients with myeloma were examined. Six contained a factor that stimulated osteoclastic bone resorption (calcium release greater than controls) in organ culture. This factor was biologically and chemically similar to osteoclast-activating factor, a mediator produced by phytohemagglutinin-activated normal peripheral blood leukocytes. Cultures of bone-marrow cells obtained from seven other patients with a variety of hematologic disorders did not produce a stimulator of bone resorption. Morphologic examination of autopsy and biopsy samples of bone from 37 patients with myeloma showed osteoclasts on bone-resorbing surfaces adjacent to areas of heavy myeloma-cell infiltration. It is suggested that osteolytic bone lesions and hypercalcemia in myeloma are due to the secretion of a soluble factor by myeloma cells that in turn stimulates osteoclastic activity in adjacent bone. N Engl J Med 291: 1041–1046, 1974), THE mechanism of bone resorption and hypercalcemia in myeloma is unknown. Bone resorption has been ascribed to a pressure effect of the neoplastic cells themselves,.