Bone mineral aposition rates in juvenile mice exposed to long-term imatinib

Background: Imatinib (IMA) is highly effective in the therapy of chronic myeloid leukemia (CML) by inhibiting the constitutively active tyrosine kinase (TK) domain of the BCR-ABL fusion gene via competition for the ATP binding. However, IMA exhibits off-target effects and also binds to TKs like c-Kit, PDGF-R and c-FMS. As these TKs are ative in osteoblasts and osteoclasts, IMA impairs bone remodelling by inhibiting the development and functional activity of osteoclasts and by promoting the osteoblasts differentiation while inhibiting their proliferation. As a net result the balance between bone resorption and bo…