Abstract
Purpose
The focus of current management of soft tissue sarcoma on limb preservation often necessitates that patients undergo multimodal treatment, including both surgery and external beam radiotherapy. Pathologic fracture is a serious, late complication of radiotherapy. In patients who have also undergone wide excision of soft tissue sarcoma, nonunion rates of 80–90% persist despite optimal internal fixationMany sequelae of the treatments for soft tissue sarcoma exhibit the potential to perpetuate failure of bony union. Limb salvage surgery is associated with extensive periosteal excision, disruption of vascular supply and eradication of local osteoprogenitor cells. External beam radiotherapy leads to obliterative endarteritis, decreased osteoblast proliferation and reduction in bone matrix production. We hypothesize that the combination of radiotherapy and surgical periosteal stripping leads to greater impairment in the fracture repair process than either intervention alone will produce.
Method
We developed a method for creating a reproducible, low energy, simple femoral fracture in an animal model designed to proceed to nonunion. Female Wistar, retired breeder rats were separated into four treatment groups of 18 animals each: control, radiotherapy, surgery and combination radiotherapy and surgery. Animals were then further randomized to temporal end-points of 21, 28 and 35 days post-fracture. Designated animals first underwent external beam radiotherapy, followed by surgical stripping of the periosteum three weeks later and femoral fracture with fixation after another three weeks. Animals were sacrificed at their randomly assigned end-points.
Results
The fracture device was shown to produce simple, transverse or short oblique femoral fractures using x-rays obtained immediately following fracture, validating the reliability of the model. No significant differences were observed in the force required for fracture between treatment groups. Mineralized callus was observed in control animals and those undergoing periosteal stripping alone, but was absent in all animals receiving radiotherapy. Reactive bone formation was observed in animals undergoing periosteal stripping alone, but was absent when preceded by radiotherapyMicroCT analysis confirmed the results visualized on plain x-ray. No callus formation was observed in animals undergoing radiotherapy and significantly less mineralized callus was produced in animals undergoing periosteal stripping when compared to control. Preliminary studies have shown an absence of cellular activity in animals undergoing radiotherapy, suggesting that fracture in these animals will proceed to nonunion.
Conclusion
Early results suggest that this pre-clinical model of combined radiation and surgical periosteal stripping prior to controlled fracture reliably results in nonunion. We expect to utilize this model to examine interventions designed to improve fracture healing in this difficult clinical situation.
