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Traumatic brain injury (TBI) combined with fractures of long bones or large joints is often associated with enhanced osteogenesis (early fracture healing accompanied by hypertrophic callus formation and/or heterotopic ossifications). Humoral factors that cause enhanced osteogenesis in patients with TBI are not yet identified. The aim of this study was to reveal if post-traumatic change(s) of hormone levels in patients with TBI and bone fractures could be associated with the phenomenon of enhanced osteogenesis. The blood values of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), parathyroid hormone (PTH) and prolactin (PRL) were studied weekly over a period of three months after injury in patients with bone fractures only, those with TBI only or combined bone fractures and TBI (patients exerting enhanced osteogenesis). Stress-hormones, ACTH and cortisol, or the hormones related to the bone growth (GH and PTH) did not show any particular post-traumatic changes in the blood of patients with combined injury that could be associated with the enhanced osteogenesis. On the other hand, patients with combined bone fractures and TBI accompanied by enhanced osteogenesis had significantly elevated PRL levels in blood during the 5th week of the post-traumatic period. Thus, the maximal PRL values were measured at the time when in this group of patients fractures were in consolidation and hypertrophic callus or heterotopic ossifications were developing (as verified by x-ray imaging). Hence, PRL does not only influence physiology of the bone metabolism but also seems to be one of the humoral factors involved in the phenomenon of enhanced osteogenesis in patients with TBI.

This research has revealed the role of lipid peroxidation, as well as its product 4-hydroxynonenal in the process of stimulating osteogenesis assisted by using bioactive glass.

Patients suffering from severe head injury and fractures of long bones or large joints often show enhanced osteogenesis, with hypertrophic callus formation and/or heterotopic ossifications. The advantage of this phenomenon is early consolidation of the fractures. An extreme disadvantage is extensive periarticular calcification, resulting in complete ankylosis of the affected joint. In spite of numerous efforts aimed at clarifying the way in which severe head injury can influence osteogenesis at a distant site, this phenomenon is still not understood. The process, once started, seems irreversible, but if diagnosed in time, could be prevented with non-steroid anti-inflammatory drugs that inhibit development of heterotopic ossifications. The major prerequisite for testing this possibility is to define parameters of an early diagnosis of enhanced osteogenesis. Thus, the aim of this study was to test whether serum values of some parameters related to bone regeneration could allow an early prediction of enhanced ossification following bone fracture in patients with severe head injury. Samples of sera were obtained from three groups of injured patients: fractures of long bones or large joints only (n = 6), severe head injury only (n = 8), severe head injury and fractures of long bones and large joints (n = 7) and from a group of apparently healthy volunteers (n = 10). The values for alkaline phosphatase (ALP), the bone isoenzyme, and the carboxy terminal propeptide of type I procollagen (PICP) were significantly higher (5-20 times as high) in patients with severe head injury and bone or joint fractures than in any other group. Significantly increased concentrations of PICP were already found in the 1st week after injury, and those of ALP and of the bone isoenzyme increased during the 2nd week after injury. Results show that these parameters are helpful for an early diagnosis of enhanced osteogenesis and heterotopic ossifications in patients with severe head injury and bone fractures. Further studies are necessary to verify these findings, while analysis of reasons for the specific patterns of dynamic change of these parameters could lead to better understanding of the mechanisms underlying the uncontrolled bone formation.

Oxidized low density lipoproteins (oLDL) are products of systemic oxidative stress initiated by the mechanism of free-radical induced lipid peroxidation. Oxidatively modified epitopes on LDL molecule are immunogenic and antibodies against such epitopes are generated. The aim of our study was to analyse if traumatic injury and consequent oxidative stress are accompanied by the changes of the titer of autoantibodies against oLDL and to see whether differently injured patients can be distinguished by measuring anti-oLDL titer. Sera of twenty four patients divided into thee groups of eight subjects each were investigated by anti-oLDL ELISA immunoassay (eliTec, Vienna): 1) patients with bone fractures, 2) patients with traumatic brain injury (TBI) and 3) patients with combined bone fractures and TBI. The patients were followed during four weeks after injury and the anti-oLDL titers were determined weekly. Control group consisted of 22 healthy persons. The lowest antibody titer was measured in all the groups in the 1st week after injury. While patients with combined injury did not differ from the other two groups, the values determined for patients with TBI were significantly above those of patients with isolated bone fractures. During the four-week convalescence, a gradual and significant increase of the anti-oLDL titer was seen for all the patients, but it was increased above normal values only in the sera of patients with TBI during the third and the fourth week after injury.

Healing of fractures of long bones or large joints is often accelerated in patients with severe traumatic brain injury (TBI). However, in these patients an early fracture healing is accompanied by hypertrophic callus formation or heterotopic ossifications which might even result in an ankylosis of the affected joints. It seems that enhanced osteogenesis in patients suffering from TBI could be caused by some humoral factors, since the sera of these patients strongly promote the growth of osteoblast cells in vitro. However, humoral growth promoting factors which could perhaps induce enhanced osteogenesis are not yet identified. Hence, the aim of this study was to analyse if basic fibroblast growth factor (bFGF) could be related to the phenomenon of enhanced osteogenesis, since bFGF stimulates the growth of osteoblasts in vitro and could be found both in the brain and the bone tissue. For that purpose the values of bFGF immunoreactivity were determined in the sera of patients with TBI and bone fractures (n = 8) as well as in the sera of patients with either TBI alone (n = 10) or bone fractures alone (n = 7), during a period of three months after injury. Quantification of the bFGF immunoreactivity was done using the ELISA based on monoclonal antibodies raised against the recombinant human bFGF. The bFGF immune-reactivity values obtained were also compared with the values determined in the sera of normal, healthy persons (n = 9). In the group of patients with bone fractures alone only a transient increase of bFGF immunoreactivity (threefold above the normal values) was observed in the second week after injury. A similar increase of the values of bFGF immunoreactivity was also determined in the sera of patients with TBI only, but it lasted longer (from the 1st until the 7th to 8th week after injury). In the case of patients with TBI and bone fractures a specific pattern of post-traumatic dynamic change of the values of serum bFGF immunoreactivity was observed. Namely, the increase of bFGF immunoreactivity (up to seven-fold above the normal values) was determined even during the first week after injury. Afterwards, periods of high values of bFGF immunoreactivity observed during the 2nd, 4th and the 7–10th weeks after injury were interrupted by sudden decreases even to the normal values (during the 3rd and the 5–6th week after injury). Thus, post-traumatic increase of the serum bFGF immunoreactivity was induced both by bone fractures and TBI, while the unusual pattern of its changes could be related to the phenomenon of enhanced osteogenesis in the patients with brain injury.