The effects of methotrexate and doxorubicin (Adriamycin) on intact and fractured bone were studied in a rat model. Methotrexate, 0.1 mg/kg i.p., was administered five times a week, or doxorubicin, 1 mg/kg i.v., was given once a week. Animals were killed and evaluated at 4, 8, 12, and 16 weeks after surgical production of a unilateral femoral osteotomy and initiation of the chemotherapeutic program. Both intact and fractured bones were tested to failure in rapid torsion, and the torque, angular deformation, stiffness, and energy were measured. There was a significant alteration in the strength of the healing osteotomies in doxorubicin- and methotrexate-treated animals compared with the control group. The torsional strength of intact bone was not significantly altered by either drug protocol over the period of this observation.
The effects of irradiation on the normal temporal progression of the physical properties of healing fractures were studied in a rat model. Fractures were surgically produced in the femur, stabilized with an intramedullary pin, and irradiated. One group of rats was exposed to 2,500 rads in divided doses over 2 weeks, beginning 3 days after fracture, and compared to a control group with fractures which were not irradiated. Animals were sacrificed at periodic intervals and the bones were tested to failure in torsion. The torque, stiffness, and energy increased and the angle decreased for the nonirradiated specimens in the expected fashion. This progression was deleteriously altered in the irradiated femurs.
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