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

Authors

Alexis Donneys, Noah S. Nelson, Erin E. Page, Sagar S. Deshpande, Peter A. Felice, Catherine N. Tchanque-Fossuo, Joshua P. Spiegel and Steven R. Buchman

Abstract

Background: Radiotherapy 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 non-unions. 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 35Gy dose prior to surgery. The deferoxamine group received local injections postoperatively. A 40-day healing period was allowed prior to histology. ANOVA (p<0.05) was used for group comparisons.

Results: Radiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to non-radiated fractures (p=0.001). With the addition of deferoxamine, these differences were not appreciated. Further, a 42% increase in bony unions was observed after deferoxamine therapy.

Conclusions: Targeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after radiotherapy

Link To Article

http://dx.doi.org/10.1002/hed.23744