Blast injuries and heterotopic ossification

Abstract

Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using Raman spectroscopy may become a feasible modality for early detection, and a wound-specific model designed to detect the early gene transcript signatures associated with HO is being tested. Through a combined effort, the goals of early detection, risk stratification, and development of novel systemic and local prophylaxis may soon be attainable.

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

“…This treatment schedule, however, may be feasible; the anatomical location of trauma-induced HO is highly predictable [1,2,17]. Furthermore, the inflammatory processes preceding bone formation may provide a therapeutic window in which we ultimately deliver HO prophylaxes [62].…”

“…Heterotopic ossification (HO) may occur as a consequence of musculoskeletal trauma from blast and high-energy injuries [2,21,40,52], total joint arthroplasty (TJA) [1], traumatic brain injury [17], or spinal cord injury [4,33,55,61]. The incidence rate for HO varies from 15% to 90%, depending on the source of trauma and the grading criteria used [1,7,39,43,51].…”

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…This distinguishes the process of HO from other pathological conditions characterised by the deposition of ectopic mineral within soft tissues, such as progressive osseous heteroplasia (lacks endochondral ossification) and dystrophic calcification (associated with the development of kidney stones and lacking the presence of bone marrow) [2,3]. 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].…”

“…This can cause difficulty with diagnosis as the symptoms overlap with infection and deep vein thrombosis, which are also common diagnoses in these patients. Nerve blocks or ablations, and excisions form the mainstay of surgical treatments [5]. Rest, analgesia, non-steroidal anti-inflammatory drugs (NSAIDs), radiotherapy, bisphosphonates, and physiotherapy are common non-surgical approaches [5].…”

Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification

“…At this point, there can be significant damage to the soft tissues that is not recoverable. Further, one of the only treatments is surgical removal, which is often difficult in that the new bone often is adjacent to, or encompassing peripheral nerves [Nauth et al, 2012] and in many cases the bone immediately grows back [Alfieri et al, 2012]. …”