Heterotopic ossification and lessons learned from fifteen years at war: A review of therapy, novel research, and future directions for military and civilian orthopaedic trauma

Heterotopic ossification, the formation of bone in soft tissues, is a common complication of the high-energy extremity trauma sustained in modern armed conflict. In the past 15 years, military treatment facilities and aligned laboratories have been in a unique position to study and treat this process due to the high volume of patients with these injuries secondary to blast trauma. The devastating nature of these wounds has limited traditional therapeutic options, necessitating alternative solutions to prophylaxis and initial treatment producing substantial advances in modeling, prophylaxis, detection, and therapy. Specific developments include establishment of an animal model that reproduces the systemic and local tissue injury of blast injuries, the use of molecular assays and predictive modeling in clinical decision making, advances in early detection including Raman spectroscopy, and investigation of prophylactic and therapeutic pharmacotherapy targeting the molecular pathways of aberrant bone formation. In this review article, we will present the literature to date, ongoing studies, and future directions for investigation of heterotopic ossification, with a focus on military-specific research.