High-dose methotrexate causes short-term suppression of growth in rabbits

Bone growth in rabbits was measured using roentgen stereophotogrammetric analysis (RSA), a method for accurate measurement of the distance between metallic markers inserted into long bones. Injections of methotrexate (Mtx) were given to five rabbits and tibial growth was measured daily for 5 days. Im injections of Mtx 100 mg/kg body weight, followed by folinic acid "rescue" 48 h later, had no influence on growth. Intraperitoneal injection of Mtx 1000 mg/kg body weight resulted in a clear reduction in daily growth during the study period. The rabbits were given folinic acid "rescue" 24, 36 and 48 h after Mtx injection and showed no symptoms or signs of Mtx toxicity. Serum levels of Mtx, 3 days after the high-dose injection, declined successively but were still measurable after 72 h. Using RSA, the short-term influence of cytostatic drugs can be evaluated in an experimental setting. The effect of Mtx on growth in rabbits was discernible only at very high doses. Suppression of growth was moderate, appeared soon after injection of Mtx and was of moderate duration.