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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2106-2111. Prepublished online as a Blood First Edition Paper on October 26, 2006; DOI 10.1182/blood-2006-09-047712. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-047712v1 109/5/2106    most recent 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 Yaccoby, S. Articles by Shaughnessy, J. D. Search for Related Content PubMed PubMed Citation Articles by Yaccoby, S. Articles by Shaughnessy, J. D., Jr Related Collections Neoplasia Immunotherapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo Shmuel Yaccoby1, Wen Ling1, Fenghuang Zhan1, Ronald Walker1, Bart Barlogie1, and John D. Shaughnessy, Jr1 1 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock Dickkopf-1 (DKK1), a soluble inhibitor of Wnt signaling secreted by multiple myeloma (MM) cells contributes to osteolytic bone disease by inhibiting the differentiation of osteoblasts. In this study, we tested the effect of anti-DKK1 therapy on bone metabolism and tumor growth in a SCID-rab system. SCID-rab mice were engrafted with primary MM cells expressing varying levels of DKK1 from 11 patients and treated with control and DKK1-neutralizing antibodies for 4 to 6 weeks. Whereas bone mineral density (BMD) of the implanted myelomatous bone in control mice was reduced during the experimental period, the BMD in mice treated with anti-DKK1 increased from pretreatment levels (P < .001). Histologic examination revealed that myelomatous bones of anti-DKK1–treated mice had increased numbers of osteocalcin-expressing osteoblasts and reduced number of multinucleated TRAP-expressing osteoclasts. The bone anabolic effect of anti-DKK1 was associated with reduced MM burden (P < .04). Anti-DKK1 also significantly increased BMD of the implanted bone and murine femur in nonmyelomatous SCID-rab mice, suggesting that DKK1 is physiologically an important regulator of bone remodeling in adults. We conclude that DKK1 is a key player in MM bone disease and that blocking DKK1 activity in myelomatous bones reduces osteolytic bone resorption, increases bone formation, and helps control MM growth. 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