[Pathophysiological and therapeutic aspects of bone lesions in patients with multiple myelomas]

Multiple myeloma (MM) is an uncontrolled malignant proliferation of plasma cells. Today, it is the best studied form of hemoblastomas, but many pathophysiological and therapeutic aspects of this condition await a deeper insight. The medico-social significance of the disease is emphasized by its continuous growth, variable clinical manifestations, low quality of the patients" life, mean life expectancy of 3-5 years, and numerous complications. One clinical feature of MM is bone lesions that occur in all patients as osteolysis (OL), osteoporosis (OP), hypercalcemia, and combination of these disorders. Progressive degeneration of bone tissue even in patients responding to chemotherapy results in severe pain, pathological fractures, and neurologic problems. Molecular mechanisms of OL and OP in MM have recently attracted much attention. This review summarizes data on the role of cytokines, growth factors, osteopontin, OPG-RANK-RANK system, macrophage inflammatory proteins, and matrix metalloproteinases in MM-related osteodestruction. Iatrogenic origin of bone lesions is considered. Treatment of MM using thalidomide (lenlalidomide), proteasome inhibitors (bortesamide), and biphosphonates (pamidronate, zoledronic acid) is discussed as the most promising therapeutic strategy promoting plasma cell apoptosis, inhibition of bone resorption, stabilization of osteoblast function, and pain alleviation.