[Pathogenesis of bone metastasis and tumor osteopathies]

The development of bone metastases is a selective process in which the hematogenous dissemination of tumor cells into the bone marrow does not play a decisive role. In addition to the peculiarities of blood flow within the marrow sinuses, leading to an accumulation of circulating tumor cells, host organ specific factors (adhesion molecules, chemotactic signals, cytokines and growth factors) are pathogenetically involved. These factors are liberated from the bone matrix by osteoclasts, which are activated by a variety of osteotropic tumor factors. Thereby a tumor osteopathy develops, which by osteolytic bone destruction and tumor-enhanced remodelling may cause bone pain, pathological fractures and hypercalcemia of malignancy. So far only the late stage of macrometastases and the concomitant osteopathy can be diagnosed. Using immunocytological methods, tumor cells can now be detected in bone marrow aspirates during the early subclinical stage of tumor cell shedding. Tumor cell-positive bone marrow aspirates in general mean a worsening of the prognosis and may in breast cancer indicate those patients who are threatened by the development of bone metastases.