Neurological heterotopic ossification (NHO) occurs in approximately 10% of traumatic brain injury (TBI) patients and is characterised by the formation of bone in soft tissue. NHO typically forms in injured muscle and around joints, causing pain, nerve entrapment, soft tissue catabolism, and joint deformation. There are no predictive markers for NHO, therefor NHO can only be identified after the lesion has mineralised. The lack of biomarkers is in large part due to the challenges involved in studying this condition in humans, however, animal models allow for the control of these confounds.
Here we aimed to develop a rat model of TBI-induced NHO that mirrors the injury mechanics and post-injury sequelae of NHO observed in humansand to identify blood-based protein markers that predict the development of NHO.
Eight-week old male rats were given a moderate-severe TBI, a femoral fracture and a muscle crush injury (n=12). Blood was collected at 2, 7-, 21- and 42 days post-injury and analysed using reverse phase protein microarray (RPPM). Rats were euthanised at 6-weeks post-injury and the formation of NHO was assessed via micro computed tomography.
Six of 12 rats had formed NHO at 6 weeks post-injury. The formation of ectopic bone was associated with elevated plasma levels of osteocalcin, a widely used marker of bone formation. Further, rats that developed NHO had significantly reduced plasma levels of interleukin-6 (IL-6) at all measured time-points. These preliminary findings suggest that plasma levels of IL-6 may serve as a predictive biomarker of the formation of NHO. Studies are underway to determine the cellular populations present in NHO lesions via histology.