[Bone metastases: pathogenesis and treatment with diphosphonates]

Tumor-induced osteolysis is essentially mediated by the osteoclasts whose number and activity appear to be stimulated under the influence of tumor secretory products. In cases of hypercalcemia, there is also a variable inhibition of the bone formation rate leading to a characteristic "uncoupling" in bone turnover. An analog of parathyroid hormone--"parathyroid hormone-related protein (PTHrP)"--plays an essential role in the pathogenesis of neoplastic hypercalcemia. PTHrP concentrations are not regulated by calcium levels which is in marked contrast for PTH. We have also shown that osteoblasts could be essential target cells in the process of tumor-induced osteolysis leading to an increase in osteoclast function and number. From a therapeutic point of view, we have contributed to the optimalization of the therapeutic schemes for tumor-induced hypercalcemia and tumor-induced osteolysis for which the dose of 90 mg of pamidronate appears to be optimal.