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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Croucher, P. I. Articles by Vanderkerken, K. Search for Related Content PubMed PubMed Citation Articles by Croucher, P. I. Articles by Vanderkerken, K. Related Collections Neoplasia Plenary Papers Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2001, Vol. 98, No. 13, pp. 3534-3540 PLENARY PAPER Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma Peter I. Croucher, Claire M. Shipman, Jennifer Lippitt, Mark Perry, Kewal Asosingh, Anja Hijzen, Alex C. Brabbs, Edwin J. R. van Beek, Ingunn Holen, Timothy M. Skerry, Colin R. Dunstan, Graham R. Russell, Ben Van Camp, and Karin Vanderkerken From the Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, United Kingdom; Division of Genomic Medicine, University of Sheffield Medical School, United Kingdom; Department of Medicine, University of Bristol, United Kingdom; Department of Hematology and Immunology, Free University Brussels, Belgium; Department of Biology, University of York, United Kingdom; Department of Academic Radiology, Royal Hallamshire Hospital, Sheffield, United Kingdom; and Department of Pathology, Amgen, Thousand Oaks, CA. Multiple myeloma is a B-cell malignancy characterized by the accumulation of plasma cells in the bone marrow and the development of osteolytic bone disease. The present study demonstrates that myeloma cells express the critical osteoclastogenic factor RANKL (the ligand for receptor activator of NF-B). Injection of 5T2MM myeloma cells into C57BL/KaLwRij 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 lesions. Dual-energy x-ray absorptiometry demonstrated a decrease in bone mineral density (BMD) at each of these sites. Treatment of mice with established myeloma with recombinant osteoprotegerin (OPG) protein, the soluble decoy receptor for RANKL, prevented the development of lytic bone lesions. OPG treatment was associated with preservation of cancellous bone volume and inhibition of osteoclast formation. OPG also promoted an increase in femoral, tibial, and vertebral BMD. These data suggest that the RANKL/RANK/OPG system may play a critical role in the development of osteolytic bone disease in multiple myeloma and that targeting this system may have therapeutic potential. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Immunocytochemistry reveals RANKL expression of myeloma cells Orhan Sezer, Ulrike Heider, Christian Jakob, Ivana Zavrski, Jan Eucker, Kurt Possinger, Christine Sers, Veit Krenn, Nicola Giuliani, Regis Bataille, Cristina Mancini, Mirca Lazzaretti, and Sophie Barille Blood 2002 99: 4646-4647. [Full Text] [PDF] This article has been cited by other articles: J. A. Fowler, G. R. Mundy, S. T. Lwin, C. C. Lynch, and C. M. Edwards A murine model of myeloma that allows genetic manipulation of the host microenvironment Dis. Model. Mech., November 1, 2009; 2(11-12): 604 - 611. [Abstract] [Full Text] [PDF] O. 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