The effect of Adriamycin and methotrexate on the repair of segmental cortical autografts in dogs.

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Abstract
An investigation was undertaken to determine whether Adriamycin (doxorubicin) or methotrexate affects the repair of segmental cortical autografts. Mongrel male dogs (32) were used to compare untreated, Adriamycin-treated and methotrexate-treated series of animals. Each dog had a sham-operated left limb. Chemotherapy was initiated 14 days after transplantation. Adriamycin was given at 1 of 3 selected doses (30, 40, or 50 mg/m2 of skin) once every 3 wk. Methotrexate was given at a dose of 20 mg/m2 of skin twice a week. The grafts were analyzed qualitatively by interval roentgenograms. Six months postoperatively, repair processes in the 3 groups were compared quantitatively for biological repair and physical strength using torsional stress-testing, tetracycline labeling and microradiography. Suppression of new-bone formation within and about cortical segmental autografts was shown when animals were treated with Adriamycin or methotrexate. Concomitant mechanical weakening due to increased internal porosity was blocked by Adriamycin but not by methotrexate. Thus, segmental grafts in Adriamycin-treated individuals may be stronger than in those who are treated without chemotherapy (i.e., the incidence of fatigue failure may be decreased). Inhibition of new-bone formation may prolong the interval required for osseous graft-host union, and there may be a greater incidence of graft-host non-union.

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