Identification of new targets for therapy of osteolytic bone disease in multiple myeloma.

One of the most characteristic features of multiple myeloma is the development of osteolytic bone lesions. Myeloma-associated bone disease is caused by an increase in osteoclastic bone resorption and a decrease in osteoblastic new bone formation. Insight into the molecular mechanisms of osteoclastogenesis has been provided by the detection of receptor activator of NF-kappaB ligand (RANKL), its specific receptor (RANK) and its decoy receptor antagonist osteoprotegerin (OPG). The RANK signaling system is abnormally regulated in multiple myeloma and targeting this system may ameliorate myeloma bone disease. Less is known about the development of osteoblastic dysfunction, and further knowledge about the interaction between myeloma cells and osteoblasts is required. The aim of this review is to focus on the principles of bone biology for a better understanding of the development of myeloma bone disease and to identify possible therapeutic targets.