title: Amifostine Treatment Mitigates the Damaging Effects of Radiation on Distraction Osteogenesis in the Murine Mandible.
abstract: According to the American Society of Clinical Oncology, in 2012, more than 53,000 new cases of head and neck cancers (HNCs) were reported in the United States alone and nearly 12,000 deaths occurred relating to HNC. Although radiotherapy (XRT) has increased survival, the adverse effects can be unrelenting and their management is rarely remedial. Current treatment dictates surgical mandibular reconstruction using free tissue transfer. These complex operations entail extended hospitalizations and attendant complications often lead to delays in initiation of adjuvant therapy, jeopardizing prognosis as well as quality of life. The creation of new bone by distraction osteogenesis (DO) generates a replacement of deficient tissue from local substrate and could have immense potential therapeutic ramifications. Radiotherapy drastically impairs bone healing, precluding its use as a reconstructive method for HNC. We posit that the deleterious effects of XRT on bone formation could be pharmacologically mitigated. To test this hypothesis, we used a rodent model of DO and treated with amifostine, a radioprotectant, to assuage the XRT-induced injury on new bone formation. Amifostine had a profound salutary effect on bone regeneration, allowing the successful implementation of DO as a reconstructive technique. The optimization of bone regeneration in the irradiated mandible has immense potential for translation from the bench to the bedside, providing improved therapeutic options for patients subjected to XRT.
authors.affiliation: From the *Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI; and †Department of Surgery, Plastic Surgery Section, Baylor College of Medicine, Houston, TX.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Monson
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Farberg
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008334:Mandible / Q000187:drug effects* / Q000528:radiation effects / Q000601:surgery; D019857:Osteogenesis, Distraction; D011832:Radiation Injuries / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011878:Radiotherapy / Q000009:adverse effects*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine