Marked osteoblastopenia and reduced bone formation in a model of multiple myeloma bone disease in severe combined immunodeficiency mice

We report on an in vivo model of human myeloma producing bone disease in ir radiated severe combined immunodeficiency disease mice using the human myel oma cell line JJN-3 and its subline JJN-3 T1. The cell lines are not Epstei n-Barr virus transformed and produce large amounts of hepatocyte growth fac tor (HGF). Mice had radiological signs of osteolysis and mild hypercalcemia . Xenografted cells were predominantly found in bone marrow and brown adipo se tissue, but also in meninges and liver. Take was documented by histopath ological examination, immunophenotyping of cultured bone marrow, and radiog raphy. HGF was detected in serum and bone marrow plasma. Disease generally occurred within 45 days of intravenous inoculation and was signaled by para paresis or signs of intracranial neoplasia. More than 90% of the mice had t ake of xenografts. The subline JJN-3 T1 gave more reproducible bone marrow take than the native cell line. Bone histomorphometric examination revealed a 99% reduction in osteoblast counts and a 33% reduction in osteoclast cou nts in areas of tumor growth. Bone formation rates were reduced by 53%. The results suggest that osteoblastopenia and reduced bone formation is of imp ortance for the occurrence of osteolytic lesions in this model.