title: Methotrexate toxicity in growing long bones of young rats: a model for studying cancer chemotherapy-induced bone growth defects in children.
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.
authors.affiliation: Sansom Institute for Health Research, and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors.forename: Chiaming
authors.initials: C
authors.lastname: Fan
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Georgiou
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: King
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001846:Bone Development / Q000187:drug effects*; D001847:Bone Diseases / Q000139:chemically induced*; D002648:Child; D004195:Disease Models, Animal; D006801:Humans; D008727:Methotrexate / Q000633:toxicity*; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D008727:Methotrexate