RESEARCH ARTICLE


Effect of Dexrazoxane and Amifostine on the Vertebral Bone Quality of Doxorubicin Treated Male Rats



F Mwale*, 1, 2, 3, G Marguier1, J.A Ouellet2, 3, A Petit1, L.M Epure1, J Antoniou1, 2, L.E Chalifour4
1 Lady Davis Institute for Medical Research, SMBD - Jewish General Hospital
2 Division of Orthopaedic Surgery, McGill University
3 McGill Spine & Scoliosis Unit, Montreal Children Hospital
4 Division of Experimental Medicine, McGill University, Lady Meredith House, Montréal, Canada


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Creative Commons License
© Mwale et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Division of Orthopaedic Surgery, McGill University, Lady Davis Institute for Medical Research, SMBD - Jewish General Hospital, 3755 Chemin de la Côte Ste Catherine, Montréal, QC H3T 1E2, Canada; E-mail: fmwale@ldi.jgh.mcgill.ca


Abstract

Doxorubicin (DOX) is widely used in combination cocktails for treatment of childhood hematological cancers and solid tumors. A major factor limiting DOX usage is DOX-induced cardiotoxicity. However, it is not known whether protectants like dexrazoxane (DXR) and amifostine (AMF) can prevent DOX-mediated bone damage. The present study investigated whether administration of AMF alone or in combination with DXR would prevent any DOX-mediated bone damage. Male rat pups were treated with DOX, DXR, AMF, and their combinations. On neonate day 38, the bone mineral density (BMD), bone mineral content (BMC) and the micro-architecture of the lumbar vertebrae were analyzed. We have shown that when male rats are treated with DOX, DXR, DOX+DXR, AMF, DOX+AMF or DOX+DXR+AMF, there is a decrease in lumbar vertebral BMD (p<0.05). Furthermore, the relative bone volume (BV/TV) was decreased by DXR, DOX+DXR, and DOX+AMF treatments. Interestingly, DOX+AMF significantly increased BV/TV when compared to DXR treatment (p<0.04). The trabecular number (Tb.N) decreased with DXR and DOX+DXR and increased with DOX+AMF treatments. This information will be useful in designing better cancer combination therapies that do not lead to vertebrae deterioration.