Heterotopic Ossification in High-Energy Wartime Extremity Injuries: Prevalence and Risk Factors

Abstract

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.

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

“…The minimum time for radiographic followup was selected based on previous studies from this and other surgical patient populations showing that HO is reliably evident radiographically within 2 months of the inciting event [4,16,34,35,39]. A two-author blinded independent review of radiographs was performed to determine the presence of ectopic bone with complete agreement between reviewers.…”

“…Studies suggest the rate of ectopic bone formation in combat-related injuries is substantially higher than prior estimates reported in civilian trauma populations [16,39]. Despite several studies investigating systemic factors and the in vitro measurement of osteoblastic activity of cells from heterotopic bone [2,27,45], the biological mechanisms responsible for HO as a result of traumatic injury have not been defined.…”

“…Soft tissue injury in the setting of a hyperinflammatory response has been shown to contribute substantially to ectopic skeletogenesis [16,25,32]. Specifically, the expression of BMP-2 and related osteoinductive morphogens by tissue macrophages and other inflammatory mediators is highly Expression values represented as fold change in wounds in which heterotopic ossification (HO) developed compared with control expression values of wounds in which HO did not develop at initial and final surgical débridements.…”

“…Heterotopic ossification has proven to be a common and problematic complication of modern wartime extremity injuries, and it causes patient morbidity and loss of function [16,39]. Studies suggest the rate of ectopic bone formation in combat-related injuries is substantially higher than prior estimates reported in civilian trauma populations [16,39].…”

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…The development of acquired HO is predominantly associated with severe trauma, particularly to muscle or neuronal tissues, such as traumatic brain injury, spinal cord injury, joint arthroplasty, severe burns or combat blast wounds and amputations [4,5]. In fact, of the 80% of war victims who suffer major extremity trauma during combat injury, approximately 64% of these patients go on to develop some degree of HO [6,7]. Aside from physical trauma, HO is also associated with the hereditary condition fibrodysplasia ossificans progressiva (FOP).…”