3.3 - Osteolytic tumor-induced bone disease

Abstract

Osteolytic tumor-induced bone disease is a condition in which tumors of various origins induce bone destruction, which can lead to fractures, pain, and hypercalcemia. The tumors leading to bone disease destroy bone either through local invasion or at a distance by secreting bone-resorbing products—mostly PTH-related protein—into the bloodstream. Local skeletal erosion is seen mostly in metastases of the breast and lung cancer and in hematological malignancies, especially multiple myeloma. The apparently preferential growth of certain tumors within the bone microenvironment may be explained by the so-called seed and soil concept. Localized bone resorption can lead to pathological fractures and pain, which are the most common features of tumor-induced bone disease. Another consequence is hypercalcemia, and cancer is the most common cause of this disturbance in hospitalized patients. The mechanisms inducing hypercalcemia are complex; the increase in blood calcium is not due to bone lysis alone. The clinical manifestations are those of tumor osteolysis, namely pain and fractures, and of hypercalcemia and its multiple metabolic consequences. Symptoms of hypercalcemia appear mainly in the nervous, gastrointestinal, cardiovascular, and renal systems. In some cases, the hypercalcemia can be life-threatening, and must be dealt with immediately. The main biochemical investigations useful in osteolytic bone disease are, besides the tumor markers, serum calcium and urinary excretion of calcium. Initially, treatment of tumor-induced hypercalcemia included besides excision of the primary tumor, chemotherapy, hormonal therapy, or radiotherapy, and plicamycin (mythramycin), an inhibitor of RNA synthesis.