LOCALIZED, TUMOR-ASSOCIATED OSTEOLYSIS INVOLVES THE RECRUITMENT AND ACTIVATION OF OSTEOCLASTS

The cellular and biochemical mechanisms that direct destruction of bon e at the site of tumor osteolysis are unknown. In order to understand this process better, a murine model designed for the study of tumor os teolysis was developed and the influence of osteolytic and nonosteolyt ic tumors on bone was investigated. Tumors developed following femoral intramedullary injection of sarcoma (2472) and melanoma (G3.26) cell lines; however, only tumors from the 2472 cell line caused osteolysis. It was determined that 2472 tumor-induced osteolysis commenced 6 days after the femora had been inoculated with 2472 cells. There were more osteoclasts per millimeter of bone surface in 2472 tumor-bearing limb s (16.7 +/- 5.0) than in sham-injected limbs (3.8 +/- 0.9) (p < 0.015) . In addition, an increase in the osteoclast size (area) was detected in 2472 tumor-bearing limbs: 412 +/- 65 mu m(2) compared with 187 +/- 17 mu m(2) (p < 0.01). In vitro bone resorption experiments indicated that 2472 tumor cells had a limited ability to destroy bone in compari son with macrophages and osteoclasts. Taken in total, these findings d efine a model that is useful for the study of tumor osteolysis, and th e data from analyses of the model demonstrate that the cellular mechan isms responsible for 2472 tumor-induced osteolysis include both an inc rease in the number of osteoclasts and activation of mature osteoclast s.