Chemotherapy affects the pattern of failure after shear loading of the proximal tibial growth plate.
BACKGROUND
Tibial bones are shorter and less resistant to shear forces after treatment with doxorubicin, methotrexate, or cisplatin. We investigated the pattern of failure after shear loading of the proximal tibial growth plate in rats treated with these chemotherapeutic agents.


METHODS
Male Wistar rats from the age of 4 weeks were given doxorubicin intravenously at 15 mg/m2 body surface area (BSA), methotrexate 60 mg/m2 BSA, or cisplatin 7.5 mg/m2 BSA. There was one nontreated control group fed ad libitum an d a diet control group for each drug-treated group. At the age of 13 weeks the tibial bones were dissected. The proximal growth plate was shear loaded to failure in the posteroanterior direction. The pattern of failure through the growth plate was examined.


RESULTS
In rats fed ad libitum the failure pattern ran mainly through the transitional zone between proliferating and hypertrophic chondrocytes, but the pattern of failure showed considerable variability. The pattern in rats treated with methotrexate or cisplatin and that in their diet controls were comparable. In rats treated with doxorubicin the fracture ran mainly through the trabecular zone.


CONCLUSIONS
Doxorubicin affects the pattern of failure after shear loading of the proximal tibial growth plate, but methotrexate and cisplatin do not. Special attention should be paid to epiphyseal injuries in children treated with doxorubicin.
van Leeuwen
B L
BL
Department of Surgical Oncology, Groningen University Hospital, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Hartel
R
R
Jansen
H W B
HW
Verkerke
G J
GJ
Veth
R P H
RP
Kamps
W A
WA
Hoekstra
H J
HJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D006132:Growth Plate / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects*
D000970:Antineoplastic Agents; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate