| [ Summary ] |
Multiple myeloma develops and expands almost exclusively in the bone marrow, and generates devastating bone destruction. Myeloma cells produce a variety of cytokines to stimulate bone resorption by enhancing osteoclast formation and suppress bone formation by inhibiting osteoblast differentiation, leading to bone destruction with a rapid loss of bone. In these lesions, osteoclasts and bone marrow stromal cells or immature osteoblasts create a microenvironment suitable for myeloma cell growth and survival, thereby forming a vicious cycle between bone destruction and myeloma expansion. The potent anti-resorptive agents, zoledronic acid and an anti-RANKL antibody, are currently used to prevent the progression of bone disease. The clinical application of bone anabolic agents, including an anti-DKK-1 antibody and an activin A inhibitor, is envisioned. |