Hypothetical schema for the effects of imatinib on osteoclasts and osteoblasts. The proliferation and survival of osteoclast precursors (pre-OC) and the survival of mature osteoclasts (OC) are driven by M-CSF signaling through the receptor tyrosine kinase c-fms. The inhibition of c-fms signaling by imatinib decreases osteoclast numbers and activity. In addition, inhibition of c-kit may decrease pre-OC numbers and inhibit osteoclast activity. Imatinib also inhibits the proton-generating activity of CAII, preventing the dissolution of mineral from bone and, hence, inhibiting bone resorption. Further, the inhibition of PDGFR signaling on osteoblasts (OB) inhibits the production of osteoclastogenic cytokines, including M-CSF and RANKL. In addition, inhibition of PDGFR by imatinib in pre-osteoblasts (pre-OB) and osteoblasts (OB) inhibits cell proliferation but also relieves the inhibitory effects of PDGF on OB maturation, resulting in decreased cell numbers but increased OB activity. HSC indicates hemopoietic stem cell; and MSC, mesenchymal stem cell.