IINFLUENCE OF THE IMMUNOSUPPRESSANT TACROLIMUS (FK-506) ON THE FLEXURAL STRENGTH OF FEMUR: A STUDY IN RATS

ABSTRACTObjective: To evaluate the resistance to femoral fractures among rats treated with the immunosuppressant tacrolimus FK-506 and compare these to untreated rats and rats treated with placebo. Methods: Ninety male Wistar rats were used. The animals were nine weeks old and weighed between 220 g and 280 g. The immunosuppressive agent tacrolimus was used in this study at a dose of 2 mg/kg/day, administered orally. The suspension was administered using an insulin syringe, and the maintenance therapeutic dose was sufficient to maintain the immunosuppressive activity. The animals were randomly divided into three groups (n = 30): group 1, no substance administered; group 2, administration of the immunosuppressant tacrolimus FK-506; and group 3, administration of the vehicle alone. Treatment with FK-506 was administered for 28 days. Total leukocyte counts and differential counts (lymphocytes, monocytes, eosinophils and neutrophils) were evaluated in order to monitor the immunosuppressive effect. Bone densitometry analysis by means of dual-energy x-ray absorptiometry (DXA) was also performed before and after administration of the drug. To evaluate the resistance to flexion, a support device was developed so that mechanical tests using an EMIC universal testing machine could be carried out. Results: The results from the flexion resistance tests showed statistical differences between groups 1 and 2 (p = 0.001) and between groups 2 and 3 (p = 0.001). No statistical difference was found between groups 1 and 3 (p = 0.995). Conclusions: The femurs of rats treated with the immunosuppressive agent had lower mechanical strength than did those of normal rats and those that received placebo