IntroductionTransforming growth factor-beta 1(TGF-β1) is a regulatory protein, involved in bone fracture healing. Circulating TGF-β1 levels have been reported to be a predictor of delayed bone healing and non-union, suggesting active relationship between tissue and circulating TGF-β1 in fracture healing. The purpose of this study was to analyse TGF-β1 local and serum concentrations in fracture healing to further contribute to the understanding of molecular regulation of fracture healing.Patients and methodsSerum samples of 113 patients with long bone fractures were collected over a period of 6 months following a standardised time schedule. TGF-β1 serum concentrations were measured using ELISA. Patients were assigned to 2 groups: Group 1 contained 103 patients with physiological healing. Group 2 contained 10 patients with impaired healing. Patients in both groups were matched. One patient of the group 2 had to be excluded because of missing match partner. In addition, fracture haematoma from 11 patients of group 1 was obtained to analyse local TGF-β1 concentrations. 33 volunteers donated serum which served as control.ResultsTGF-β1 serum concentrations increased during the early healing period and were significantly higher in patients with physiological healing compared to controls (P = 0.04). Thereafter, it decreased continuously between weeks 2 and 8 and fell again after week 8. TGF-β1 serum concentrations in patients with physiological healing were significantly higher at week 24 compared to controls (P = 0.05). In non-unions, serum concentrations differed significantly from those of controls at week 6 (P = 0.01). No significant difference in between patients with physiological and impaired fracture healing was observed. Fracture haematoma contained significantly higher TGF-β1 concentrations than peripheral serum of the patients (P = 0.017).ConclusionElevated levels of TGF-β1 in haematoma and in serum after bone fracture especially during the entire healing process indicate its importance for fracture healing.

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Purpose The aim of this study was to analyse the management of displaced paediatric supracondylar humerus fractures at our Level I Trauma Centre and to determine clinical and radiographic long-term results following operative treatment. Methods Clinical and radiological results of 78 paediatric patients (29 female, 49 male; mean age 5.1 years) with supracondylar humerus fractures, treated from 1992 to 2004, were evaluated. Gartland's classification yielded 32 type II, 44 type III and further two flexion injuries. In all patients the follow-up period exceeded 12 months. Assessment after an average of 8.1 years (1.1-19.5) included neurovascular examination, Flynn's criteria (elbow function and carrying angle), pain, complications (infections, growth disturbances or iatrogenic nerve injuries) and measurement of the humeroulnar angle. Results According to Flynn's criteria 73 patients (93.5 %) had a satisfactory outcome, while five (6.4 %) were graded as unsatisfactory (two due to cubitus varus and three because of limited elbow motion). The visual analogue scale (VAS) score averaged 0 (range 0-1) and the mean carrying angle measured 8.4°(−8 to 20°), compared to 10.8°on the contralateral side (2-20°). Injury-related complications yielded absent pulses in four (5.1 %), five (6.4 %) primary median, two (2.6 %) primary radial and one (1.3 %) primary ulnar nerve injury. Treatment-related complications included a secondary displacement and one iatrogenic radial nerve palsy. Based on primary nerve lesion as a dependent variable, statistical analysis showed that age had a significant influence revealing that older paediatric patients had a significantly higher risk (p0 0.02). Functional outcome as a dependent variable revealed an indirect proportion to the clinical carrying angle, achieving statistical significance (p<0.01). Conclusions Crossed pinning in paediatric supracondylar humerus fractures is an effective method. Evaluation of the outcome in our study group demonstrated good results with the treatment approach described.

Purpose Circulating TGF-β1 levels were found to be a predictor of delayed bone healing and non-union. We therefore aimed to investigate some factors that can influence the expression of TGF-β1. The correlation between the expression of TGF-β1 and the different socio-demographic parameters was analysed. Methods Fifty-one patients with long bone fractures were included in the study and divided into different groups according to their age, gender, cigarette smoking status, diabetes mellitus and regular alcohol intake. TGF-β1 levels were analysed in patient's serum and different groups were retrospectively compared. Results Significantly lower TFG-β1 serum concentrations were observed in non-smokers compared to smokers at week 8 after surgery. Significantly higher concentrations were found in male patients compared to females at week 24. Younger patients had significantly higher concentrations at week 24 after surgery compared to older patients. Concentrations were significantly higher in patients without diabetes compared to those with diabetes at six weeks after surgery. Patients with chronic alcohol abuse had significantly higher concentrations compared to those patients without chronic alcohol abuse. Conclusion TGF-β1 serum concentrations vary depending upon smoking status, age, gender, diabetes mellitus and chronic alcohol abuse at different times and therefore do not seem to be a reliable predictive marker as a single-pointin-time measurement for fracture healing.

Human fracture healing is a complex interaction of several cytokines that regulate osteoblast and osteoclast activity. By monitoring OPG (osteoprotegerin) and sRANKL we aimed to possibly predict normal or impaired fracture healing. In 64 patients with a fracture of a long bone serum level of sRANKL and OPG were evaluated with respect to bony union (n ¼ 57) or pseudarthrosis (n ¼ 7). Measurements were carried out at admission and at 1, 2, 4, 6, 8, 12, 24, and 48 weeks after the injury. Patients' serum levels were compared to 33 healthy controls. Fracture hematoma contained significantly higher sRANKL and OPG concentrations compared to patients serum (p ¼ 0.005, p ¼ 0.028). OPG level in fracture hematoma was higher compared to the unions serum level (p ¼ 0.028). sRANKL was decreased in unions during the observation period. In non-unions sRANKL and OPG levels showed a variable course, with no statistical significance. This is the first study to document the course of OPG and sRANKL in normal and delayed human fracture healing emphasizing its local and systemic involvement. We provide evidence of strongly enhanced OPG levels in patients with a long bone fracture compared to healthy controls. Further, levels of free sRANKL were decreased during regular fracture repair.