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AMIFOSTINE OFFERS PROTECTION OF OSTEOCYTE VIABILITY DURING FRACTURE HEALING AFTER RADIOTHERAPY
Presenter: Joshua P Spiegel, Student
Co-Authors: Donneys A; Sarhaddi D; Tchanque-Fossuo CN; Ahsan S; Deshpande SS; Buchman SR
University of Michigan

Purpose: Pathologic fractures and osteoradionecrosis are known morbidities imparted by the ravaging effects of radiotherapy on normal bone. A treatment strategy to mitigate these adverse consequences would have immense therapeutic ramifications. Radiation is known to diminish osteocyte count and function leading to bone weakening over time. We have previously demonstrated diminished osteocyte count and mineralization capacity in a murine model of fracture healing after radiotherapy. We posit that Amifostine will preserve osteocyte number and function in this pathologic model.

Methods: 36 Sprague Dawley rats were divided into three groups: fracture (Fx), radiated fracture (XFx), and radiated fracture with Amifostine (XFxAMF). Radiated groups underwent human equivalent radiotherapy to the mandible 2 weeks prior to fixator placement and mandibular osteotomy. The XFxAMF group received a subcutaneous injection prior to each dose of radiotherapy. After a 40 day healing period, mandibles were harvested for histologic processing. Quantification of osteocyte count (Oc), empty lacunae (EL) and osteoid ratio (OV/TV) was performed and the results were compared using ANOVA with p<0.05 considered statistically significant.

Results: Quantifiable beneficial outcomes were observed for metrics of osteocyte number (Oc, EL) and function (OV/TV). As expected, radiated fractures demonstrated significantly diminished Oc, increased EL and diminished capacity to produce new osteoid at the fracture site (OV/TV) when compared to non-radiated fractures (p=0.001). These metrics were restored to normal levels with the addition of AMF therapy indicating a preservation of osteocyte number and function despite exposure to radiotherapy.

Conclusion: Our results support the hypothesis that Amifostine preserves osteocyte number and function, thereby reversing the pernicious effects of radiotherapy on fracture healing. Based on these findings, we encourage future translational investigation of this promising therapy for potential use in the prevention of pathologic fractures and osteoradionecrosis.


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