Aims <p>Traumatic brain injuries (TBI) and spinal cord injuries (SCI) are associated with an increased risk to develop heterotopic ossifications (HO). Aim of the study was to analyze biochemical markers and osteogenic differentiation capacity of patients’ plasma during the early posttraumatic period to assess the risk for HO.</p> Methods <p>To evaluate predictive markers of HO in response to TBI/SCI, comparative cytokine array analyses of plasma obtained from patients with TBI/SCI were performed to identify expressed proteins. The expression of 105 proteins in plasma of patients with TBI (<i>n</i> = 9) and SCI (<i>n</i> = 9) was compared to patients with multiple trauma (MT; <i>n</i> = 9) and controls (norm). Additionally, the effect of patients’ plasma on osteogenic differentiation of bone marrow-derived human mesenchymal stem cells (MSC) was tested by in vitro cell assay.</p> Results <p>Cytokine array analyses showed that plasma of TBI-group had a different protein expression profile compared to SCI-, MT- or norm-group. TBI-group exhibited the greatest number of up-regulated proteins and the greatest magnitude of alterations. Conversely, MT-group showed the greatest number of down-regulated proteins. In vitro cell assay showed that MSC exhibited a stronger capacity for osteogenic differentiation after treatment with plasma of TBI-/SCI-group with clinical signs of HO, than TBI-/SCI-group without HO or MT- and norm-group.</p> Conclusion <p>This pilot study demonstrates distinct plasma factors in SCI/TBI patients and suggests a possible correlation between HO development and enhanced in-vitro osteogenesis of MSCs. The applied osteogenic differentiation assay could therefore represent a simple and reproducible tool to predict early stages of HO and to identify patients at risk. However, these findings do not allow causal conclusions, and further studies are required to clarify the underlying mechanisms and the predictive value of the assay.</p> Level of evidence <p>III.</p>