Determining Which Combinatorial Combat-Relevant Factors Contribute to Heterotopic Ossification Formation in an Ovine Model

Richard T. Epperson*, Brad M. Isaacson, David L. Rothberg, Raymond E. Olsen, Brooke Kawaguchi, Ryan M. Rasmussen, Mary Dickerson, Paul F. Pasquina, John Shero, Dustin L. Williams

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Traumatic heterotopic ossification (HO) is frequently observed in Service Members following combat-related trauma. Estimates suggest that ~65% of wounded warriors who suffer limb loss or major extremity trauma will experience some type of HO formation. The development of HO delays rehabilitation and can prevent the use of a prosthetic. To date there are limited data to suggest a standard mechanism for preventing HO. This may be due to inadequate animal models not producing a similar bone structure as human HO. We recently showed that traumatic HO growth is possible in an ovine model. Within that study, we demonstrated that 65% of sheep developed a human-relevant hybrid traumatic HO bone structure after being exposed to a combination of seven combat-relevant factors. Although HO formed, we did not determine which traumatic factor contributed most. Therefore, in this study, we performed individual and various combinations of surgical/traumatic factors to determine their individual contribution to HO growth. Outcomes showed that the presence of mature biofilm stimulated a large region of bone growth, while bone trauma resulted in a localized bone response as indicated by jagged bone at the linea aspera. However, it was not until the combinatory factors were included that an HO structure similar to that of humans formed more readily in 60% of the sheep. In conclusion, data suggested that traumatic HO growth can develop following various traumatic factors, but a combination of known instigators yields higher frequency size and consistency of ectopic bone.

Original languageEnglish
Article number350
Issue number4
StatePublished - Apr 2024
Externally publishedYes


  • backscatter electron imaging
  • ectopic bone
  • heterotopic ossification
  • large animal model
  • trauma
  • undecalcified histology


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