The traumatic bone: trauma-induced heterotopic ossification

Abstract

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.

Fig 1.

A schematic representation of trauma-induced heterotopic ossification (HO). Multiple forms of trauma, like fractures, burn, spinal cord, and brain injuries and combat injury (left) result in heterotopic ossification. Ensuing the inflammatory phase post-trauma, HO occurs via the same underlying mechanism of endochondral ossification in all these cases.

Fig 2.

A summary of the 2 different forms of heterotopic ossification, trauma-induced and genetic HO. Multiple injury types (trauma) result in local or systemic stimuli that induce HO. The tissues predominantly susceptible to HO development include tendons, ligaments, and skeletal muscle, which is in close association with long bones. Despite the multiple progenitor cells and signaling pathways underlying initiation/development of HO, the ectopic bone is universally ‘endochondral’ in nature. In recent years, several diagnostic and treatment modalities have been developed for the management of HO.