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Prepublished online as a Blood First Edition Paper on November 7, 2002; DOI 10.1182/blood-2002-09-2684. This Article Full Text (PDF) All Versions of this Article: 2002-09-2684v1 101/6/2094    most recent Alert me when this article is cited Alert me if a correction is posted 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 Sezer, O. Articles by Hofbauer, L. C. Search for Related Content PubMed PubMed Citation Articles by Sezer, O. Articles by Hofbauer, L. C. Social Bookmarking                   What's this? Submitted September 9, 2002 Accepted October 29, 2002 RANK ligand and osteoprotegerin in myeloma bone disease Orhan Sezer, Ulrike Heider, Ivana Zavrski, Christian Alexander Kuehne, and Lorenz Christian Hofbauer* Department of Oncology and Hematology, Universitaetsklinikum Charite, Berlin, Germany Department of Trauma Surgery, University of Essen, Essen, Germany Division of Gastroenterology, Endocrinology and Metabolism, Philipps-University, Marburg, Germany * Corresponding author; email: hofbauer{at}post.med.uni-marburg.de. Myeloma bone disease is due to interactions of myeloma cells with the bone marrow microenvironment, and is associated with pathological fractures, neurological symptoms and hypercalcemia. Adjacent to myeloma cells, the formation and activation of osteoclasts is increased which results in enhanced bone resorption. The recent characterization of the essential cytokine of osteoclast cell biology, receptor activator of NF-B ligand (RANKL) and its antagonist osteoprotegerin (OPG), have led to a detailed molecular and cellular understanding of myeloma bone disease. Myeloma cells induce RANKL expression in bone marrow stromal cells, and direct RANKL expression by myeloma cells may contribute to enhanced osteoclastogenesis in the bone microenvironment in myeloma bone disease. Furthermore, myeloma cells inhibit production and induce degradation of OPG. These effects result in an increased RANKL-to-OPG ratio which favours the formation and activation of osteoclasts. Patients with myeloma bone disease have inappropriately low serum and bone marrow levels of OPG. Specific blockade of RANKL prevented the skeletal complications in various animal models of myeloma, and suppressed bone resorption in a preliminary study of patients with myeloma bone disease. 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