A MURINE MODEL OF HUMAN MYELOMA BONE-DISEASE

Myeloma causes a devastating and unique form of osteolytic bone diseas e, Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast act ivity have not been defined, An animal model of human myeloma bone dis ease would help in clarification of these mechanisms, Multiple myeloma occurs spontaneously in aging C57 BL/KaLwRij mice and has all of the features of the disease in humans, including the characteristic bone l esions, The disease can be induced in normal C57 BL/KaLwRij mice by in oculation of fresh marrow-derived cells from mice with myeloma, but th is model is difficult to study because of variability in the number of myeloma cells in marrow-derived preparations, To develop a better ani mal model of human myeloma bone disease, we have established and subcl oned a cell line from this murine myeloma and found that it causes ost eolytic bone lesions in mice characteristic of human myeloma bone dise ase, The cell line produces interleukin-6, but grows independent of ex ogenous interleukin-6, Mice inoculated intravenously with the cultured cells predictably develop an identical disease to the mice injected i ntravenously with fresh bone-marrow-derived myeloma cells, including m onoclonal gammopathy and radiologic bone lesions, We found that some o f the mice became hypercalcemic, and the bone lesions are characterize d by increased osteoclast activity, We found identical results when we inoculated Nu/Bg/XID mice with cultured murine myeloma cells, Because eve can inoculate mice with precise numbers of cells and predict accu rately when the mice will develop bone lesions, become hypercalcemic, and die, this should be a convenient model for determining the mechani sms by which the myeloma cells cause osteoclast activation in this mod el of human myeloma bone disease. (C) 1997 by Elsevier Science Inc.