Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/60802
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Type: Journal article
Title: Dysregulation of bone remodeling by imatinib mesylate
Author: Vandyke, K.
Fitter, S.
Dewar, A.
Hughes, T.
Zannettino, A.
Citation: Blood, 2010; 115(4):766-774
Publisher: Amer Soc Hematology
Issue Date: 2010
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Kate Vandyke, Stephen Fitter, Andrea L. Dewar, Timothy P. Hughes and Andrew C. W. Zannettino
Abstract: Imatinib mesylate is a rationally designed tyrosine kinase inhibitor that has revolutionized the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Although the efficacy and tolerability of imatinib are a vast improvement over conventional chemotherapies, the drug exhibits off-target effects. An unanticipated side effect of imatinib therapy is hypophosphatemia and hypocalcemia, which in part has been attributed to drug-mediated changes to renal and gastrointestinal handling of phosphate and calcium. However, emerging data suggest that imatinib also targets cells of the skeleton, stimulating the retention and sequestration of calcium and phosphate to bone, leading to decreased circulating levels of these minerals. The aim of this review is to highlight our current understanding of the mechanisms surrounding the effects of imatinib on the skeleton. In particular, it examines recent studies suggesting that imatinib has direct effects on bone-resorbing osteoclasts and bone-forming osteoblasts through inhibition of c-fms, c-kit, carbonic anhydrase II, and the platelet-derived growth factor receptor. The potential application of imatinib in the treatment of cancer-induced osteolysis will also be discussed.
Keywords: Osteoclasts; Humans; Osteolysis; Gastrointestinal Stromal Tumors; Piperazines; Pyrimidines; Protein Kinase Inhibitors; Bone Remodeling; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Rights: Copyright © 2010 by American Society of Hematology
RMID: 0020094926
DOI: 10.1182/blood-2009-08-237404
Appears in Collections:Medicine publications

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