Gender-dependent reductions in vertebrae length, bone mineral density and content by doxorubicin are not reduced by dexrazoxane in young rats: effect on growth plate and intervertebral discs.
Doxorubicin (DOX) is widely used in anti-cancer cocktails. Dexrazoxane (DXR) is a cardioprotectant approved for use with DOX. The effect of DOX, with or without DXR, on bone in children is not well understood. The aim of this study was to examine the effect of DOX on vertebrae and femur length and bone density acquisition in young rats, as well as to test the hypothesis that young females are more susceptible to DOX-induced tissue damage than young males. The results of this study suggest that a single injection of DOX in young female and not male rats is associated with low bone turnover resulting in vertebrae and femur bone growth deficits. DOX selectively decreased BMD and BMC accrual in the lumbar vertebrae that was not prevented by DXR. DOX-treated rats also exhibited growth plate and intervertebral disc defects. This information will be useful in the design of interventions to promote bone growth or retard bone loss during DOX treatment.
Mwale
F
F
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Quebec, Canada H3T 1E2. fmwale@ldi.jgh.mcgill.ca
Antoniou
J
J
Héon
S
S
Servant
N
N
Wang
C
C
Kirby
G M
GM
Demers
C N
CN
Chalifour
L E
LE
D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003720:Densitometry; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006132:Growth Plate / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011929:Razoxane / Q000494:pharmacology*; D012727:Sex Characteristics; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D011929:Razoxane; D004317:Doxorubicin