Heterotopic Ossification Following Combat-Related Trauma

Potter, Benjamin K.; Forsberg, Jonathan A.; Davis, Thomas A.; Evans, Korboi N.; Hawksworth, Jason; Tadaki, Douglas K.; Brown, Trevor S.; Crane, Nicole J.; Burns, Travis C.; O'Brien, Frederick P; Elster, Eric A.

doi:10.2106/jbjs.j.00776

Cited by 140 publications

(111 citation statements)

References 88 publications

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“…These include pain, loss of joint mobility, skin ulceration, overlying skin graft failure, muscle and neurovascular entrapment, and prosthetic limb fitting difficulties [9]. Clinically, HO first presents with pain and swelling in the affected limb [10].…”

Section: Clinical Problemsmentioning

confidence: 99%

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

et al. 2015

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Section: Clinical Problemsmentioning

confidence: 99%

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

et al. 2015

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“…Surgical excision is the only definitive management option and treatment of symptomatic HO if physical therapy and prosthesis alteration fail to provide adequate relief [31]. Other prophylaxis strategies include treatment with nonsteroidal antiinflammatory drugs or external-beam radiotherapy, but these options are more confined in the civilian setting and are generally contraindicated in the setting of combat and blast-induced trauma given nonsteroidal anti-inflammatory drugs may delay fracture healing and cause unacceptably high rates of bleeding complications while radiotherapy must be administered within 48 hours of injury (difficult if not impossible in the combat setting) and is known to cause wound-and implantrelated complications [11,22,23].…”

Section: Introductionmentioning

confidence: 99%

Early Characterization of Blast-related Heterotopic Ossification in a Rat Model

Qureshi

Crump

Pavey

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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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 after blast and other combat-related extremity injuries. Questions/purposes Using a recently developed animal model of combat-related HO, we sought to determine (1) the timing of early chondrogenesis, cartilage formation, and radiographic ectopic bone development; and (2) the early cartilage and bone-related gene and protein patterns in traumatized soft tissue. Methods We used an established rat HO model consisting of blast exposure, controlled femur fracture, crush injury, and transfemoral amputation through the zone of injury. Postoperatively, rats were euthanized on Days 3 to 28. We assessed evidence of early ectopic bone formation by micro-CT and histology and performed proteomic and gene expression analysis. Results All rats showed radiographic evidence of HO within 28 days. Key chondrogenic (collagen type I alpha 1 [COL1a1], p = 0.016) and osteogenic-related genes (RuntThis work was supported by CDMRP (W81XWH-14-2-0010; PI-JAF) and BUMED (602115HP.3720.001.A1014; PI-JAF). Some of the authors are employees of the US 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 defined a US Government work as a work prepared by a military service member or employees of the US Government as part of that person's official duties. The opinions or assertions contained in this paper are the private views of the authors and are not to be construed as reflecting the views, policy or positions of the Department of the Navy, Department of Defense nor the US Government. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research 1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. This work performed at the Naval Medical Research Center, Silver Spring, MD, USA. Conclusions We found that genes that regulate early chondrogenic and osteogenic signaling and bone development (COL1a1, RUNX-2, OCN, PHEX, and POU5F1) are induced early during the tissue reparative/healing phase in a rat model simulating a combat-related extremity injury. Clinical Relevance The ability to correlate molecular events with histologic and morphologic changes will assist re...

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“…Combat injuries tend to result in a higher Injury Severity Score and also higher likelihood of HO development 12, 13. The formation of HO is reported in more than 63% of blast‐injury patients requiring amputation 14, 15, 16, 17. HO occurring as a result of high‐energy blast injury is most commonly reported in men between 20 and 40 years of age 18…”

Section: Trauma Statesmentioning

confidence: 99%

“…They are used to elucidate several aspects of HO formation, including severity at specific locations, mechanism of injury, and timing of HO formation after injury and have been of great importance to furthering HO research efforts (see Table 1, 11, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36). Outside of specific models aimed directly at studying war‐time injuries, such as the Walter‐Reed polytrauma and amputation models, few animal models focus directly on the contribution of blunt‐force trauma to the formation of HO 14, 15, 17, 18, 27. Although small animal models cannot directly mimic the formation of clinically relevant HO, each type of animal study provides the opportunity to better understand the pathophysiology and pathogenesis under unique circumstances.…”

Section: Understanding the Ho Environmentmentioning

confidence: 99%

“…However, in trauma patients, the use of prevention strategies is challenging as practicality, safety, and efficacy of systemic NSAID therapy or RT is debatable and contingent upon several factors, including severity of trauma and ectopic bone formation potential 18, 38, 39, 40. Additionally, patients with polytrauma derived HO often present with concomitant injuries that may be adversely affected by the systemic NSAID or RT 12, 14, 17. NSAID delivery following acute trauma can complicate bleeding, exacerbate gastritis, and potentially impede fracture healing 41, 42.…”

Section: Prevention and Treatmentmentioning

confidence: 99%

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