Effect of single chemotherapeutic agents on the growing skeleton of the rat.
BACKGROUND
To establish the effect of chemotherapeutics on the growing skeleton, male Wistar rats were studied.


METHODS
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.
van Leeuwen
B L
BL
Department of Surgical Oncology, Groningen University Hospital, The Netherlands.
Kamps
W A
WA
Hartel
R M
RM
Veth
R P
RP
Sluiter
W J
WJ
Hoekstra
H J
HJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000254:growth & development; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects / Q000254:growth & development
D000970:Antineoplastic Agents; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate