Heterotopic Ossification in Complex Orthopaedic Combat Wounds

Davis, Thomas A.; O'Brien, Frederick P.; Anam, Khairul; Grijalva, Steven; Potter, Benjamin K.; Elster, Eric A.
June 2011
Journal of Bone & Joint Surgery, American Volume;6/15/2011, Vol. 93-A Issue 12, p1122
Academic Journal
Background: Heterotopic ossification frequently develops following high-energy blast injuries sustained in modern warfare. We hypothesized that differences in the population of progenitor cells present in a wound would correlate with the subsequent formation of heterotopic ossification. Methods: We obtained muscle biopsy specimens from military service members who had sustained high-energy wartime injuries and from patients undergoing harvest of a hamstring tendon autograft. Plastic-adherent cells were isolated in single-cell suspension and plated to assess the prevalence of colony-forming cells. Phenotypic characteristics were assessed with use of flow cytometry. Individual colony-forming units were counted after an incubation period of seven to ten days, and replicate cultures were incubated in lineage-specific induction media. Immunohistochemical staining was then performed to determine the percentage of colonies that had differentiated along an osteogenic lineage. Quantitative real-time reverse-transcription polymerase chain reaction was used to identify changes in osteogenic gene expression. Results: Injured patients had significantly higher numbers of muscle-derived connective-tissue progenitor cells per gram of tissue (p < 0.0001; 95% confidence interval [CI], 129,930 to 253,333), and those who developed heterotopic ossification had higher numbers of assayable osteogenic colonies (p <0.016; 95% Cl, 12,249 to 106,065). In the injured group, quantitative real-time reverse-transcription polymerase chain reaction performed on the in vitro expanded progeny of connective-tissue progenitors demonstrated upregulation of COL1OA1, COL4A3, COMP, FGFR2, FLT1, IGF2, ITGAM, MMP9, PHEX, SCARB1, SOX9, and VEGFA in the patients with heterotopic ossification as compared with those without heterotopic ossification. Conclusions: Our study suggests that the number of connective-tissue progenitor cells is increased in traumatized tissue. Furthermore, wounds in which heterotopic ossification eventually forms have a higher percentage of connective-tissue progenitor cells committed to osteogenic differentiation than do wounds in which heterotopic ossification does hot form. The early identification of heterotopic ossification-precursor cells and target genes in severe wounds not only may be an effective prognostic tool with which to assess whether heterotopic ossification will develop in a wound, but may also guide the future development of individualized prophylactic measures.


Related Articles

  • Early Characterization of Blast-related Heterotopic Ossification in a Rat Model. Qureshi, Ammar; Crump, Erica; Pavey, Gabriel; Hope, Donald; Forsberg, Jonathan; Davis, Thomas // Clinical Orthopaedics & Related Research;Sep2015, Vol. 473 Issue 9, p2831 

    Background: Heterotopic ossification (HO) affects the majority of combat-related lower extremity wounds involving severe fracture and amputation. Defining the timing of early osteogenic-related genes may help identify candidate prophylactic agents and guide the timing of prophylactic therapy...

  • Research centre seeks to combat blast effects. HARRIS, STEPHEN // Engineer (00137758);12/12/2011, Vol. 296 Issue 7830, p6 

    The article presents information on the study titled "Centre for Blast Injury Studies," launched at Imperial College London, to produce improved body protection and vehicle design for soldiers in Afghanistan. The study is aimed at studying and reducing the effects of injuries caused by...

  • Factors influencing injury severity score regarding Thai military personnel injured in mass casualty incident April 10, 2010: lessons learned from armed conflict casualties: a retrospective study.  // BMC Emergency Medicine;2012, Vol. 12 Issue 1, p1 

    The article focuses on factors influencing injury severity score (ISS) regarding Thai military personnel injured in mass casualty incident April 10, 2010. Study uses descriptive statistics and multiple logistic regressions to display characteristics of the injuries, relationship between...

  • A Retroperitoneal Neuroendocrine Tumor in Ectopic Pancreatic Tissue. Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem // Endoscopic Ultrasound;Aug2013, Vol. 2 Issue 3, p168 

    The article presents a case study of a 72-year-old man presented with aching epigastric and right hypochondrial pain radiating to the back. Topics include diagnosis of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue, use of ultrasound imaging...

  • Trends in traumatic limb amputation in Allied Forces in Iraq and Afghanistan. Wallace, Duncan // Journal of Military & Veterans' Health;Apr2012, Vol. 20 Issue 2, p31 

    Background: Limb amputation has been a common injury occurring in the conflicts in Iraq and Afghanistan. Compared to other injuries, less attention has been given to this serious, disabling wound. Purpose: The article describes the Allied military experience of traumatic limb amputation in Iraq...

  • Mathematical models of blast-induced TBI: current status, challenges, and prospects. Gupta, Raj K.; Przekwas, Andrzej // Frontiers in Neurology;May2013, Vol. 4, p1 

    Blast-induced traumatic brain injury (TBI) has become a signature wound of recent military activities and is the leading cause of death and long-term disability among U.S. soldiers. The current limited understanding of brain injury mechanisms impedes the development of protection, diagnostic,...

  • Use of tourniquets in combat and civilian trauma situations. Niven, Martin; Castle, Nick // Emergency Nurse;Jun2010, Vol. 18 Issue 3, p32 

    The tourniquet as a method of catastrophic haemorrhage control on the battlefield has been in and out of favour over the centuries. However, the recent increase in incidence of blast injuries, in Afghanistan for example, has led to its recent reintroduction in the UK military as a potential...

  • Blast-induced neurotrauma models and their requirements. Cernak, Ibolja; Risling, MÃ¥rten // Frontiers in Neurology;Jul2014, Vol. 5, p1 

    The article looks at research studies concerning neurotrauma caused by blast-exposure. Topics discussed include reasons behind the contradictory results produced by some of the studies concerning blast-induced neurotrauma (BINT), criteria that should be used in choosing the model for traumatic...

  • Preventing Heterotopic Ossification in Combat Casualties-Which Models Are Best Suited for Clinical Use? Alfieri, Keith; Potter, Benjamin; Davis, Thomas; Wagner, Matthew; Elster, Eric; Forsberg, Jonathan // Clinical Orthopaedics & Related Research;Sep2015, Vol. 473 Issue 9, p2807 

    Background: To prevent symptomatic heterotopic ossification (HO) and guide primary prophylaxis in patients with combat wounds, physicians require risk stratification methods that can be used early in the postinjury period. There are no validated models to help guide clinicians in the treatment...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics