The pathogenesis of heterotopic ossification after traumatic brain injury. A review of current literature.

Neurogenic heterotopic ossification (NHO), mostly defined as a benign process of formation of bone outside the skeletal system, after traumatic brain injury (TBI) is a musculoskeletal disorder that causes pain and reduces the range of motion, often leading to marked impairment of quality of life. The pathogenic factors that link the brain and bone and cause the formation of heterotopic bone are largely unknown. This article will try to summarize the current literature on the pathogenesis of NHO and accelerated fracture healing after TBI. The heterotopic formation of bone after TBI seems to be inducted by a complex interplay between local and systemic factors. For all different forms of HO, the same three conditions are required for the formation of ectopic bone : The presence of osteoprogenitor cells, a permissive environment, and a stimulating factor. The osteoprogenitor cells are thought to be of mesenchymal origin, however recent research suggests a possible neural origin. The permissive environment is created mainly by reactions to hypoxia and both local and sensory nerve inflammation. Many possible inducing factors have been described ; the endogenic route is thought to be the most dominant in the stimulation of HO formation after TBI. The pathogenesis of NHO remains largely unknown, recent research, however, has discovered interesting topics for further research and new possible targets in the prevention of NHO.

Traumatic brain injury enhances the formation of heterotopic ossification around the hip: an animal model study.

INTRODUCTION: The incidence of heterotopic ossification (HO) is at its highest when trauma of the hip or pelvis concurs with traumatic brain injury (TBI). The pathogenic mechanisms underlying the neurogenic enhancement of the formation of HO remain, however, poorly understood. Hence, the goal of the present study was to develop a novel small animal model that combines hip and brain trauma that can prove the enhancement of HO around the hip after TBI. MATERIALS AND METHODS: Forty male Wistar rats were divided into four groups, to undergo hip surgery alone (group 1), hip surgery + moderate TBI (group 2), hip surgery + severe TBI (group 3) and only severe TBI (group 4). The femoral canal was reamed up to 2 mm and a muscle lesion was made to simulate hip surgery. An established controlled cortical impact model was used to create a TBI. Twelve weeks after surgery, the hip with the proximal half of the femur and the pelvic bone was removed and subjected to micro-computed tomography (µCT) analysis. A quantitative analysis using a modified Brooker score as well as a quantitative analysis using a bone-to-tissue ratio was used. RESULTS: No HO could be found in all the ten animals that did not undergo hip surgery (group 4). In the animals that did undergo surgery to the hip, no HO was found in only one animal (group 1). All the other animals developed HO. In this study, significantly more HO was found in animals that underwent an additional severe TBI. CONCLUSION: The newly developed rat model, with a combined hip and brain trauma, showed an enhancement of the HO formation around the hip after severe TBI.