Dysregulation of bone remodeling by imatinib mesylate

Kate Vandyke, Stephen Fitter, Andrea L. Dewar, Timothy P. Hughes, A. C W Zannettino

Research output: Contribution to journalReview article

94 Citations (Scopus)

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.

LanguageEnglish
Pages766-774
Number of pages9
JournalBlood
Volume115
Issue number4
DOIs
Publication statusPublished - 28 Jan 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Vandyke, Kate ; Fitter, Stephen ; Dewar, Andrea L. ; Hughes, Timothy P. ; Zannettino, A. C W. / Dysregulation of bone remodeling by imatinib mesylate. In: Blood. 2010 ; Vol. 115, No. 4. pp. 766-774.
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Dysregulation of bone remodeling by imatinib mesylate. / Vandyke, Kate; Fitter, Stephen; Dewar, Andrea L.; Hughes, Timothy P.; Zannettino, A. C W.

In: Blood, Vol. 115, No. 4, 28.01.2010, p. 766-774.

Research output: Contribution to journalReview article

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