Osteoclasts are required for bone tumors to grow and destroy bone

It has been hypothesized that bone resorption during tumor osteolysis is pe rformed by osteoclasts. Data supporting this hypothesis have been provided from analysis of human biopsy specimens obtained from sites of tumor osteol ysis, as well as from experimentation with in vivo animal models. Experimen ts in this report take this concept one step further by testing the hypothe sis that osteoclasts are required for bone tumors to grow and destroy bone. To test this hypothesis, the influence of an osteolytic sarcoma tumor, NCT C clone 2472 (2472), on bone was studied in animals that are osteoclast def icient (microphthalmic, strain B6C3Fe-ala-Mitf(mi)) but whose osteoclast de ficiency can be reversed following bone marrow transplantation. Femora of t hese mice and unaffected wild-type siblings were injected with 10(5) 2472 c ells, and after 14 days the femora were analyzed by radiographic and histom orphometric analysis. Macroscopic tumor, tumor-induced osteolysis, and incr eased osteoclast number were noted in femora of normal mice but not in femo ra of osteoclast-deficient mice (p < 0.001). Bone marrow transplantation co nverted osteoclast-deficient mice to mice with femora that contained osteoc lasts in 4 weeks. Femora of these mice were then injected with 10(5) 2472 t umor cells; after 14 days, in contrast to the findings in the original oste oclast-deficient mice, macroscopic tumor was present, tumor-induced osteoly sis was noted on roentgenograms, and osteoclast number was increased when t umor-bearing limbs were compared with sham-injected limbs (p < 0.001). Thes e data prove the hypothesis that osteoclasts are required for 2472 tumor-in duced osteolysis, and they introduce the exciting possibility that osteocla sts are also required for tumors to grow in bone.