title: Combinations of radioprotectants spare radiation-induced damage to the physis.
abstract: Radiotherapy used in the treatment of bone and soft tissue sarcomas in pediatric patients often results in undesirable growth plate damage. Radioprotectants may hold promise in the selective protection of growth plate tissue in this setting. In an animal model, the hypothesis tested was that pentoxifylline, selenium, or misoprostol, used in combination with amifostine, would significantly reduce longitudinal growth loss during one radiation dose exposure to a greater extent than the protection provided by only amifostine without increased morbidity or mortality or adverse effects on bone mineral density. Amifostine alone and in combination with each of the other radioprotectants resulted in limb discrepancy reduction to levels significantly less than radiated controls. The tibial length discrepancy in the selenium and amifostine group was 12.1 +/- 0.8%, less than the 15.5 +/- 2.6% tibial length discrepancy in the animals treated with amifostine alone, and less than the mean 18.8% tibial length discrepancy in the radiated limbs without radioprotection. There were no adverse effects on bone density in any group, but the selenium and amifostine group showed some increased mortality. Combinations of amifostine with these radioprotectants show efficacy in growth plate radioprotection and therefore warrant additional study in a clinically relevant fractionated model.
authors.affiliation: Department of Orthopedic Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA. damront@upstate.edu
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Damron
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Spadaro
authors.forename: Jason A
authors.initials: JA
authors.lastname: Horton
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Margulies
authors.forename: Judith A
authors.initials: JA
authors.lastname: Strauss
authors.forename: Cornelia E
authors.initials: CE
authors.lastname: Farnum
mesh_terms: D004999:Amifostine / Q000008:administration & dosage; D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000528:radiation effects; D001846:Bone Development / Q000187:drug effects; D004359:Drug Therapy, Combination; D005269:Femur / Q000528:radiation effects; D006132:Growth Plate / Q000528:radiation effects*; D007870:Leg Length Inequality / Q000209:etiology / Q000517:prevention & control; D008297:Male; D016595:Misoprostol / Q000008:administration & dosage; D010431:Pentoxifylline / Q000008:administration & dosage; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000008:administration & dosage; D013977:Tibia / Q000528:radiation effects
chemical_list: D011837:Radiation-Protective Agents; D016595:Misoprostol; D012643:Selenium; D004999:Amifostine; D010431:Pentoxifylline