Purpose
Radiation is known to diminish osteocyte count and function leading to bone weakening. A treatment strategy to mitigate these consequences could have immense therapeutic ramifications. We have previously demonstrated significantly diminished osteocyte count and mineralization capacity in a rat model of fracture healing after radiotherapy. We hypothesize that amifostine (AMF) will preserve osteocyte number and function in this model.
Materials and Methods
Thirty-six rats were divided into three groups: fracture, radiated fracture, and radiated fracture with AMF. Radiated groups underwent human equivalent radiotherapy to the mandible prior to fixator placement and mandibular osteotomy. The AMF group received a subcutaneous injection prior to each dose of radiotherapy. After 40 days, 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 (p<0.05).
Results
Radiated fractures demonstrated significantly diminished Oc, increased EL and diminished capacity to produce new osteoid at the fracture site as measured with OV/TV when compared to non-radiated fractures. In mandibles treated with amifostine, these metrics were not statistically different than control, indicating a preservation of osteocyte number and function.
Conclusions
Our results support the hypothesis that amifostine preserves osteocyte number and function, thereby preventing the pernicious effects of radiotherapy on the cellular environment of fracture healing. Based on these findings, we encourage future investigation of this promising therapy for use in the prevention of pathologic fractures and osteoradionecrosis.
