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

Abstract

Background: To establish the effect of chemotherapeutics on the growing skeleton, male Wistar rats were studied. Design: Between the ages of 4 and 13 weeks the rats were given i.v. doxorubicin 15 mg/m2 body surface area (BSA), methotrexate 60 mg/m2 BSA or cisplatin 7.5 mg/m2 BSA. For each group of drug-treated rats there was a diet-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. Body weight and tibial length were measured weekly. Kidney and liver weight were 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 differ 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 growth. The decrease in growth might be a direct effect of doxorubicin and methotrexate on the tibial growth plate and metaphysis, but may be more pronounced due to the malnutrition.