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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 903097, 8 pages
http://dx.doi.org/10.1155/2011/903097
Review Article

Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

1Sansom Institute for Health Research, and School of Pharmacy and Medical Sciences, University of South Australia, City East Campus, GPO Box 2471, Adelaide, SA 5001, Australia
2Discipline of Paediatrics, University of Adelaide, Adelaide, SA 5005, Australia
3Discipline of Physiology, University of Adelaide, Adelaide, SA 5005, Australia

Received 10 September 2010; Accepted 21 January 2011

Academic Editor: Andrea Vecchione

Copyright © 2011 Chiaming Fan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX), the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.