Long-term administration of the tyrosine kinase inhibitor bosutinib via micro-osmotic pumps and resulting skeletal side effects in juvenile rats

Background: In Ph+ chronic myeloid leukemia the up-regulated BCR-ABL1 tyrosine kinase (TK) is the major target of TK-inhibitors (TKI) like imatinib and dasatinib. Bosutinib is a third generation dual TKI – developed to overcome resistance to first and second generation TKIs – inhibiting Abl and also Src kinases. However, first and second generation TKIs show off-target effects on bone metabolism. Skeletal side effects of bosutinib have not been yet investigated. Therefore, we examined the influence of a continuous exposure of bosutinib on the growing skeleton in juvenile rodents. Methods: At an age of four weeks…