US Department of Defense
BLAST INJURY RESEARCH
COORDINATING OFFICE
Advancing Blast Injury Research to Protect and Heal Those Who Serve
Heterotopic ossification (HO), bone development where it should not occur, is a common complication after musculoskeletal blast trauma, occurring in approximately 65 percent of Service members in OIF/OEF with a combat-related extremity injury (Forsberg et al., 2009). Wound healing and rehabilitation are negatively affected by HO and prevention and treatment strategies are currently insufficient. To understand better the molecular and cellular events leading to HO, which can inform prevention and treatment options, a group of researchers from the Walter Reed National Military Medical Center, the Uniformed Services University of Health Sciences, the University of Maryland Medical Center, and the Medical University of South Carolina sought to compare the HO response in rat tissue with that in human muscle tissue from Service members who experienced blast trauma (de Vasconcellos et al., 2019).
The researchers used a rat model in which HO naturally develops after hind limb amputation directly caused by blast overpressure. This model differs from other HO animal models in which amputation is surgically administered or HO is chemically induced. Seven days after injury, muscle tissue was collected from the animals’ injured and uninjured limbs. Muscle tissue was also obtained from extremity wounds of Service members injured in a blast event within two weeks of injury. X-ray imaging was performed with both rats and humans 42 days after injury to visualize HO.
To compare the post-trauma response in muscle tissue from rats with that from humans after experiencing blast injury to an extremity, the researchers monitored a set of genes and proteins known to be involved in early bone formation, inflammation, and fibrosis. Both injured rat and human muscle tissue had significantly greater expression of the genes and higher levels of the proteins the researchers assessed than uninjured control samples 7–10 days after injury. Microscopic observation of tissue structure in injured muscle samples from rats and humans revealed similar patterns of fibrosis. These results demonstrate consistency between the rat model and human tissue in the timing of early events contributing to fibrosis and bone development after blast trauma. X-ray imaging 42 days after injury confirmed the occurrence of HO in both injured rats and humans (Figure 1).
This study shows similarities between injured rat and human tissue in the presentation and timing of molecular events and structural characteristics that lead to HO. These similarities suggest that this rat model of traumatic hind limb amputation can illuminate the fundamentals of HO after blast trauma in humans, ultimately facilitating testing of prevention and treatment strategies.
de Vasconcellos, J.F., Zicari, S., Fernicola, S.D., Griffin, D.W., Ji, Y., Shin, E.H., ... Nesti, L.J. (2019). In vivo model of human post-traumatic heterotopic ossification demonstrates early fibroproliferative signature. Journal of Translational Medicine, 17(1), 248.
Forsberg, J.A., Pepek, J.M., Wagner, S., Wilson, K., Flint, J., Andersen, R.C., ... Elster, E.A. (2009). Heterotopic ossification in high-energy wartime extremity injuries: Prevalence and risk factors. Journal of Bone and Joint Surgery, 91(5), 1084-1091.
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