Effect of single chemotherapeutic agents on the growing skeleton of the rat

Background: To establish the effect of chemotherapeutics on the growing ske leton, male Wistar rats were studied. Design: Between the ages of 4 and 13 weeks the rats were given i.v. doxorub icin 15 mg/m(2) body surface area (BSA), methotrexate 60 mg/m(2) BSA or cis platin 7.5 mg/m(2) BSA. For each group of drug-treated rats there was a die t-matched control group that was injected with a placebo only. Rats fed ad libitum served as the basic control group for length and weight growth. Bod y weight and tibial length were measured weekly. Kidney and liver weight we re determined at the end of the study. Results: Weight gain and length growth were significantly decreased in the diet controlled groups (P < 0.05). Doxorubicin reduced length growth with 4 .12 mm or 18 % (P < 0.05). Methotrexate reduced length growth with 1.11 mm or 5 % (P < 0.05). Length growth in the cisplatin treated rats did not diff er from the diet controls. Conclusions: Doxorubicin and methotrexate decrease length growth in the rat tibia by, respectively, 18% and 5%. Cisplatin does not affect length growt h. The decrease in growth might be a direct effect of doxorubicin and metho trexate on the tibial growth plate and metaphysis, but may be more pronounc ed due to the malnutrition.