Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries, extensive burns in the civilian setting, and combat-related extremity injuries in the battlefield. Irrespective of the form of trauma, heterotopic bone is typically endochondral in structure and is laid down via a cartilaginous matrix. Once formed, the heterotopic bone typically needs to be excised surgically, which may result in wound healing complications, in addition to a risk of recurrence. Refinements of existing diagnostic modalities, like micro- and nano-CT are being adapted toward early intervention. Trauma-induced HO is a consequence of aberrant wound healing, systemic and local immune system activation, infections, extensive vascularization, and innervation. This intricate molecular crosstalk culminates in activation of stem cells that initiate heterotopic endochondral ossification. Development of animal models recapitulating the unique traumatic injuries has greatly facilitated the mechanistic understanding of trauma-induced HO. These same models also serve as powerful tools to test the efficacy of small molecules which specifically target the molecular pathways underlying ectopic ossification. This review summarizes the recent advances in the molecular understanding, diagnostic and treatment modalities in the field of trauma-induced HO.

Introduction: NSAIDs inhibit osteogenesis and may result in delayed union or nonunion. The purpose of this meta-analysis was to determine whether their use leads to delayed union or nonunion. Methods: We systematically reviewed the literature reporting the effect of NSAIDs on bone healing. We included studies of pediatric and adult patients NSAID exposure and healing bone. The outcomes of interest were delayed union, nonunion, or pseudarthrosis with at least six months of follow-up. A maximum likelihood random-effects model was used to conduct meta-analysis and meta-regression. Results: NSAID exposure increased delayed union or nonunion (odds ratio [OR], 2.07; confidence interval [CI], 1.19 to 3.61). No effect was noted in pediatrics (OR, 0.58; CI, 0.27 to 1.21) or low dose/short duration of exposure (OR, 1.68; CI, 0.63 to 4.46). Conclusion: Analysis of the literature indicates a negative effect of NSAIDs on bone healing. In pediatric patients, NSAIDs did not have a significant effect. The effect may be dose or time dependent because low-dose/short-duration exposure did not affect union rates.