Similar to osteoclastogenesis, angiogenesis is enhanced in the bone marrow in myeloma in parallel with tumor progression. Myeloma cells and stromal cells secrete angiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Of note, osteoclasts constitutively secrete a large amount of a proangiogenic factor, osteopontin, which cooperates with VEGF from myeloma cells to enhance angiogenesis and also induce osteoclastogenic activity by vascular endothelial cells. Therefore, a close link between myeloma cells, osteoclasts and vascular endothelial cells can be established in myeloma bone lesions, thereby forming a vicious cycle between bone destruction, angiogenesis and myeloma expansion.