Effects of radiation and surgery on healing of femoral fractures in a rat model

Abstract

Management of soft tissue sarcoma involves multimodality treatment, including surgery and radiotherapy. Pathologic fracture of the femur after such treatment in the thigh is one serious, late complication and nonunion rates of 80-90% are reported. We hypothesize that the combination of radiotherapy and periosteal stripping (during tumor resection) leads to greater impairment of the fracture repair process than either intervention alone. Female Wistar retired breeder rats were randomized into four treatment groups (control, radiotherapy, surgery, and combination of radiotherapy and surgery) and three end-points (21, 28, and 35 days post-fracture). Designated animals first underwent radiotherapy, followed by surgical stripping of the periosteum 3 weeks later and femoral fracture with fixation after another 3 weeks. Animals were sacrificed and fractures examined using microCT and histomorphometry. Simple transverse or short oblique femoral fractures were produced. By 35 days, control animals formed unions, periosteum-stripped animals formed hypertrophic non-unions and irradiated animals formed atrophic non-unions. Histomorphometry revealed an absence of chondroid and osteoid production in animals undergoing radiotherapy. The relative contribution of periosteal stripping to occurrence of non-union was statistically insignificant. Radiation prior to fracture reliably resulted in atrophic non-union in our model. The contribution of periosteal stripping was negligible. ß

Periosteal Mesenchymal Progenitor Dysfunction and Extraskeletally-Derived Fibrosis Contribute to Atrophic Fracture Nonunion

“…A remarkably increased incidence of delayed and nonunion fracture within a prior irradiated bone has been a well‐known clinical observation for many years. Several previous rodent studies reported that radiation before or immediately after fracture causes alterations in the histology and radiology of the reparative processes . However, all those studies used whole‐body radiation, which limited the local radiation dosage that could be applied and was always accompanied by systematic effects, which primarily affect hematopoiesis and had abscopal effects on radiation‐shielded bones .…”

Internal fixation of radiation-induced pathological fractures of the femur has a high rate of failure

“…Since these were all low-energy fractures located within the irradiated surgical field, altered bone biology is likely to be the cause. 14 Cao et al 15 reported that irradiated mouse femora had fewer mesenchymal stem cells, osteoblasts and osteoclasts, blood vessels were destroyed and the number of free radicals increased. The rates of nonunion of radiation-induced fractures stand in stark contrast to typical traumatic fractures of the femur that have a rate of nonunion < 3%.…”

Comparison of the effect on bone healing process of different implants used in minimally invasive plate osteosynthesis: limited contact dynamic compression plate versus locking compression plate

“…The bulb tube parameters were 50–55 kV and 5–10 mAs. The fracture union was defined as the presence of a bridged callus in at least three of four cortices on two radiographic views45.…”

“…As in previous publications, the mineralized tissues were classified as bone or callus depending on its density relative to that of the undisturbed cortical bone45. A callus was defined as bone having a density of 35–70% of the maximum density of the undisturbed cortical bone.…”