Myeloma is associated with bone disease caused by increased activity of bone-destroying cells (osteoclasts) and reduced numbers of bone-forming cells (osteoblasts). Our group discovered that myeloma cells produce DKK1, a protein that prevents formation of osteoblasts. Our preliminary animal-model study demonstrated that inhibiting DKK1 activity with neutralizing antibodies prevents bone disease and tumor growth. We will expand this study by testing DKK1 antibodies that can also be used in human. We will also determine whether treatments combining DKK1 antibodies with other drugs currently used to treat myeloma will produce a better response that the individual drugs alone.