Radiation decreases formation of heterotopic ossification in a clinically relevant animal model
Faculty and Abstracts
Purpose: Heterotopic ossification (HO) is a common debilitating condition affecting majority of burns and major combat injuries in which ectopic bone forms in soft tissues such as muscles and tendons. Current prevention and treatment strategies are limited and often lead to HO reoccurrence. Here, at our institution, we routinely use postoperative radiation to a dose of 7Gy in one fraction to treat patients for hip, elbow, and shoulder HO prophylaxis. Although radiation therapy has been proven to be an effective prophylaxis especially in patients with high risk of HO in several prospective and retrospective studies, the efficacy and mechanism remains unknown. To investigate this unknown efficacy and mechanism of radiation-induced HO suppression, we sought to establish and recapitulate this phenotype in a clinically relevant animal model.
Methodology: We used a well-established HO mouse model that has previously demonstrated HO development following concurrent burn and Achilles tendon tenotomy. Thirty C57BL/6J mice were randomly assigned to control (n=10), post-operative day 1 (POD1) radiation treatment (n=10), and post-operative day 3 (POD3) radiation treatment (n=10). Weekly X-rays at five weeks were used to assess HO volume and progression. After nine weeks, mice were euthanized and range of motion evaluation and microCT analysis of the hind limbs were performed.
Results: The mean heterotopic bone volume in the control group was significantly greater compared to the POD1 radiation treatment and POD3 radiation treatment groups in both weekly Xrays and endpoint 9 week microCT imaging. In our microCT analysis, a reduction of 36.1% and 47.4% of total ectopic bone was found with POD1 radiation treatment and POD3 radiation treatment, respectively (Figure 1). Range of motion analysis demonstrate statistically significant decreased range of motion in the control group vs. POD1 and POD3 radiation treatment groups.
Conclusions: We found a statistically significant reduction in HO formation when radiation was administered on POD1 and POD3. With this model, we will investigate the mechanism of radiation-induced changes in decreasing HO development at the microenviroment level as well as the cellular level. By understanding this efficacy and mechanism, we can thereby determine optimal radiation dose and timing and explore the combination of radiation and drugs to further inhibit HO formation.
