The Journal of Bone and Joint Surgery (American). 2009;91:1084-1091.
doi:10.2106/JBJS.H.00792
© 2009 The Journal of Bone and Joint Surgery, Inc.
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Heterotopic Ossification in High-Energy Wartime Extremity Injuries: Prevalence and Risk Factors

Jonathan Agner Forsberg, MD1, Joseph M. Pepek, MD2, Scott Wagner, BS2, Kevin Wilson, BS2, James Flint, MD1, Romney C. Andersen, MD1, Doug Tadaki, PhD2, Frederick A. Gage, BS2, Alexander Stojadinovic, MD2 and Eric A. Elster, MD2

1 Integrated Department of Orthopaedics and Rehabilitation, National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889. E-mail address for J.A. Forsberg: jaforsberg{at}mac.com
2 Regenerative Medicine Department, Combat Casualty Care, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910

Investigation performed at National Naval Medical Center, Bethesda, Maryland

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants of less than $10,000 from the U.S. Navy Bureau of Medicine Advanced Development Program. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy of the Department of the Navy, the Department of Defense, or the United States Government. One or more of the authors are military service members or employees of the United States government. This work was prepared as part of their official duties. Title 17 U.S.C. 105 provides that "Copyright protection under this title is not available for any work of the United States Government." Title 17 U.S.C. 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. government as part of that person's official duties.


Background: Heterotopic ossification in the extremities remains a common complication in the setting of high-energy wartime trauma, particularly in blast-injured amputees and in those in whom the definitive amputation was performed within the zone of injury. The purposes of this cohort study were to report the experience of one major military medical center with high-energy wartime extremity wounds, to define the prevalence of heterotopic ossification in these patients, and to explore the relationship between heterotopic ossification and other potential independent predictors.

Methods: We retrospectively reviewed the records and radiographs of all combat-wounded patients admitted to this institution between March 1, 2003, and December 31, 2006. Patients with a minimum of two months of radiographic follow-up who underwent at least one orthopaedic procedure on an extremity constituted our study group; those who underwent at least one orthopaedic procedure but had not had heterotopic ossification develop constituted the control group. Variables recorded for each study subject included age and sex, location and mechanism of injury, method(s) of fracture fixation, number of débridement procedures, duration of negative pressure therapy, location of heterotopic ossification, presence and severity of traumatic brain injury, and Injury Severity Scores.

Results: During the study period, 1213 war-wounded patients were admitted. Of those patients, 243 (157 in the heterotopic ossification group and eighty-six controls) met the inclusion criteria. The observed rate of heterotopic ossification was 64.6%. A significant relationship was detected between heterotopic ossification and the presence (p = 0.006) and severity (p = 0.003) of a traumatic brain injury. Risk factors for the development of heterotopic ossification were found to be an age of less than thirty years (p = 0.007, odds ratio = 3.0), an amputation (p = 0.048, odds ratio = 2.9), multiple extremity injuries (p = 0.002, odds ratio = 3.9), and an Injury Severity Score of ≥16 (p = 0.02, odds ratio = 2.2).

Conclusions: The prevalence of heterotopic ossification in war-wounded patients is higher than that in civilian trauma. Although trends associated with local wound conditions were identified, the risk factors for the development of heterotopic ossification found in this study suggest that systemic causes predominate.

Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.


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