title: The effect of host tissue irradiation on large-segment allograft incorporation.
abstract: Therapeutic radiation delivered to bone and the adjacent local tissues before allograft limb-salvage surgery has been associated with poor graft incorporation and higher numbers of clinical complications. Our objective was to determine the effect of preoperative radiation therapy on specific histologic, molecular and structural parameters of large-segment, bone allograft incorporation in a canine model. Skeletally mature dogs received a total of 0, 25, or 50 Gy of radiation to the foreleg (radius and ulna) delivered in 2-Gy fractions during a 5-week period before reconstruction of a 3.5-cm defect in the radius. The dogs were sacrificed at postoperative day 150. Nondestructive four-point bending was done on the harvested allograft-host bone immediately after euthanasia and specimens were compared using biomechanical, histomorphometric, immunohistochemical, and in situ reverse transcription polymerase chain reaction techniques. Preoperative irradiation significantly impaired allograft incorporation as determined by radiographic healing scores, histomorphometry, and frequency of nonunions. Biochemical differences included diminished bone morphogenetic protein-2 and bone morphogenetic protein-4 protein levels and messenger ribonucleic acid expression. Vascular endothelial growth factor expression was not altered. These data suggest that bone morphogenetic protein-2 and bone morphogenetic protein-4 signaling at the allograft-host junction is altered after preoperative fractionated radiation and provides a plausible albeit partial mechanistic explanation for radiation-mediated delays in allograft incorporation.
authors.affiliation: Animal Cancer Center, Department of Clinical Sciences, Colorado State University, 300 West Drake Street, Fort Collins, CO 80523, USA. nicole.ehrhart@colostate.edu
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Ehrhart
authors.forename: JoAnn A
authors.initials: JA
authors.lastname: Eurell
authors.forename: Peter D
authors.initials: PD
authors.lastname: Constable
authors.forename: Dana
authors.initials: D
authors.lastname: Gaddy
authors.forename: Richard W
authors.initials: RW
authors.lastname: Nicholas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004285:Dogs; D016348:Osseointegration / Q000502:physiology / Q000528:radiation effects*; D012333:RNA, Messenger / Q000378:metabolism; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D011884:Radius / Q000378:metabolism / Q000528:radiation effects*; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014184:Transplantation, Homologous; D014457:Ulna / Q000378:metabolism / Q000528:radiation effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology / Q000528:radiation effects*
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A