Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy

• Published in: Head & neck Vol. 37; no. 9; pp. 1261 - 1267
• Main Authors: Donneys, Alexis, Nelson, Noah S., Page, Erin E., Deshpande, Sagar S., Felice, Peter A., Tchanque-Fossuo, Catherine N., Spiegel, Joshua P., Buchman, Steven R.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2015; Wiley Subscription Services, Inc
• Subjects: Analysis of Variance; angiogenesis; Animals; Biopsy, Needle; Cell Survival; Cells, Cultured; deferoxamine; Deferoxamine - pharmacology; Disease Models, Animal; Dose Fractionation; Fracture Healing - physiology; Fractures, Ununited - prevention & control; Immunohistochemistry; Injections, Intralesional; Male; mandible; Mandible - pathology; Mandible - radiation effects; Mandible - surgery; Mandibular Osteotomy - methods; Neovascularization, Pathologic - prevention & control; nonunion; Osteocytes - drug effects; Osteocytes - radiation effects; Preoperative Care - methods; radiation; Random Allocation; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; mandible; deferoxamine; nonunion; radiation; angiogenesis
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.23744

Background Radiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing. Methods Three groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35‐Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40‐day healing period was allowed before histology. Analysis of variance (ANOVA; p < .05) was used for group comparisons. Results Radiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to nonradiated fractures (p = .001). With the addition of DFO, these differences were not appreciated. Further, a 42% increase in bony unions was observed after DFO therapy. Conclusion Targeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after XRT. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1261–1267, 2015