Effect of methotrexate on distraction osteogenesis

To assess the potential of using distraction osteogenesis to reconstruct bone deficient limbs after limb salvage for musculoskeletal sarcomas, the authors examined the effect of methotrexate on distraction osteogenesis in a rabbit tibial lengthening model. Eighteen rabbits underwent tibial corticotomy and application of a ring external fixator. Rabbits were assigned randomly to one of two groups in which either methotrexate (n = 12) or placebo (n = 6) was administered during a 21-day distraction period. Serum methotrexate levels and complete blood cell counts were monitored during distraction, and radiographs of the tibia were obtained weekly. Half of the animals from each group were sacrificed at the end of distraction, and the remaining animals were sacrificed after 6 weeks of neutral fixation when bone normally bridges the gap. Using methotrexate at serum concentrations similar to those used clinically for the treatment of human osteosarcomas, the authors were unable to show significant radiographic, histologic, or chemical differences in the effect of this antineoplastic drug on distraction osteogenesis in the rabbit model.