Calcified Tissue International

, Volume 88, Issue 1, pp 16–22

Imatinib Mesylate Does Not Increase Bone Volume In Vivo

  • Susannah O’Sullivan
  • Dorit Naot
  • Karen E. Callon
  • Maureen Watson
  • Greg D. Gamble
  • Marianne Ladefoged
  • Morten A. Karsdal
  • Peter Browett
  • Jillian Cornish
  • Andrew Grey
Article

DOI: 10.1007/s00223-010-9429-1

Cite this article as:
O’Sullivan, S., Naot, D., Callon, K.E. et al. Calcif Tissue Int (2011) 88: 16. doi:10.1007/s00223-010-9429-1

Abstract

Imatinib mesylate is a tyrosine kinase inhibitor used in the management of disorders in which activation of c-Abl, PDGFR, or c-Kit signaling plays a critical role. In vitro, imatinib stimulates osteoblast differentiation, inhibits osteoblast proliferation and survival, and decreases osteoclast development. Patients treated with imatinib exhibit altered bone and mineral metabolism, with stable or increased bone mass. However, recovery from the underlying disease and/or weight gain might contribute to these effects. We therefore investigated the skeletal effects of imatinib in healthy rats. We evaluated the effects of imatinib on bone volume, markers of bone turnover, and bone histomorphometry in mature female rats treated for 5 weeks with either vehicle, imatinib 40 mg/kg daily, or imatinib 70 mg/kg daily. Compared to vehicle, imatinib reduced trabecular bone volume/tissue volume (mean [SD]: vehicle 26.4% [5.4%], low-dose imatinib 24.8% [4.9%] [P = 0.5], high-dose imatinib 21.1% [5.7%] [P = 0.05]), reduced osteoblast surface (mean [SD]: vehicle 12.8% [5.8%], low-dose 6.8% [1.9%] [P < 0.01], high-dose 7.8 [3.1%] [P < 0.05]), and reduced serum osteocalcin (mean change from baseline [95% CI]: vehicle −8.2 [−26.6 to 10.2] ng/ml, low dose −79.7 [−97.5 to −61.9] ng/ml [P < 0.01 vs. vehicle], high-dose −66.0 [−82.0 to −50.0] ng/ml [P < 0.05 vs. vehicle]). Imatinib did not affect biochemical or histomorphometric indices of bone resorption. These results suggest that, in healthy animals, treatment with imatinib does not increase bone mass and that the improvements in bone density reported in patients receiving imatinib may not be a direct effect of the drug.

Keywords

Imatinib Bone Bone formation Osteoblast Osteoclast 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Susannah O’Sullivan
    • 1
  • Dorit Naot
    • 1
  • Karen E. Callon
    • 1
  • Maureen Watson
    • 1
  • Greg D. Gamble
    • 1
  • Marianne Ladefoged
    • 3
  • Morten A. Karsdal
    • 3
  • Peter Browett
    • 2
  • Jillian Cornish
    • 1
  • Andrew Grey
    • 1
  1. 1.Department of MedicineUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Molecular Medicine and PathologyUniversity of AucklandAucklandNew Zealand
  3. 3.Nordic BioscienceHerlevDenmark

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