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Acta Physiologica 2011; Volume 202, Supplement 685
Scandinavian Physiological Society's Annual Meeting
8/12/2011-8/14/2011
Bergen, Norway
IMATINIB MESYLATE DISTURBS BONE GROWTH AND REMODELLATION IN POSTNATAL RATS
Abstract number: 8.1.60
NURMIO1 M, JOKI1 H, KALLIO1 J, MAATTA1 JA, VAANANEN1 HK, TOPPARI1 J, JAHNUKAINEN1 K, LAITALA-LEINONEN1 T
1Physiology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland Email: [email protected]
Aims:
Imatinib mesylate (STI571, Glivec®, Novartis) is a well-tolerated receptor tyrosine kinase (RTK) inhibitor used to treat chronic myelogenous leukaemia (CML), Philadelphia-positive acute lymphoblastic leukaemia and gastrointestinal stromal tumors (GIST). It has recently become evident that bone forming and bone resorbing cells are affected by imatinib. Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. In the present study we investigated the effects of imatinib in growing bone.
Methods:
Young rats were exposed to imatinib (150mg/kg on postnatal days 57, or 100mg/kg on postnatal days 513), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo.
Results:
Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction and shifted the balance from bone resorption toward bone formation, thereby altering bone modeling. At the distal bone trabeculae, in turn, the balance was turned towards bone resorption leading to a bone loss.
Conclusion:
The present study shows that inhibition of RTK receptors during longitudinal bone growth leads to long-term adverse effects on bone growth and remodeling in rats.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 202, Supplement 685 :8.1.60