The effect of chemotherapy on the morphology of the growth plate and metaphysis of the growing skeleton

Abstract

Aim: To establish the effect of three single chemotherapeutic agents on the growing skeleton, male Wistar rats were studied.Methods: From the age of 4 weeks the rats were given iv doxorubicin (DOX) 15mg/m2 body surface area (BSA), methotrexate (MTX) 60mg/m2 BSA or cisplatin (CDDP) 7.5mg/m2 BSA. One non-treated control group was fed ad libitum (ad lib) and for every drug-treated group there was a diet-control group. After dissection at 13 weeks of age, morphology of the proximal tibial growth plate and metaphysis were studied.Results: Compared to the ad lib group, DOX significantly decreased and MTX increased growth plate height (P<0.05). CDDP decreased height of the proliferating layer (P<0.05). Trabecular volume was decreased in the DOX and CDDP treated rats compared to the ad lib group (P=0.054). Compared to the diet control group trabecular bone volume was unaffected in the DOX group and decreased in the MTX and CDDP group (P<0.05).Conclusions: Doxorubicin causes growth plate thinning, methotrexate increases growth plate height and cisplatin does not affect growth plate height. All three chemotherapeutic agents decrease the trabecular volume of the proximal tibial metaphysis. Part of the effect of DOX, MTX and CDDP is related to the treatment induced malnutrition.