Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma

Multiple myeloma is a B-cell malignancy characterized by the accumulation o f plasma cells in the bone marrow and the development of osteolytic bone di sease. The present study demonstrates that myeloma cells express the critic al osteoclastogenic factor RANKL (the ligand for receptor activator of NF-k appaB). Injection of 5T2MM myeloma cells into C57BL/KaL-wRij mice resulted in the development of bone disease characterized by a significant decrease in cancellous bone volume in the tibial and femoral metaphyses, an increase in osteoclast formation, and radiologic evidence of osteolytic bone lesion s. Dual-energy x-ray absorptiometry demonstrated a decrease in bone mineral density (BMD) at each of these sites. Treatment of mice with established m yeloma with recombinant osteoprotegerin (OPG) protein, the soluble decoy re ceptor for RANKL, prevented the development of lytic bone lesions. OPG trea tment was associated with preservation of cancellous bone volume and Inhibi tion of osteoclast formation. OPG also promoted an increase In femoral, tib ial, and vertebral BMD. These data suggest that the RANKL/RANK/OPG system m ay play a critical role In the development of osteolytic bone disease In mu ltiple myeloma and that targeting this system may have therapeutic potentia l. (C) 2001 by The American Society of Hematology.