VEGF serum concentrations in patients with long bone fractures: A comparison between impaired and normal fracture healing

Abstract

Vascular endothelial growth factor (VEGF) plays an important role in the bone repair process as a potent mediator of angiogenesis and it influences directly osteoblast differentiation. Inhibiting VEGF suppresses angiogenesis and callus mineralization in animals. However, no data exist so far on systemic expression of VEGF with regard to delayed or failed fracture healing in humans. One hundred fourteen patients with long bone fractures were included in the study. Serum samples were collected over a period of 6 months following a standardized time schedule. VEGF serum concentrations were measured. Patients were assigned to one of two groups according to their course of fracture healing. The first group contained 103 patients with physiological fracture healing. Eleven patients with delayed or nonunions formed the second group of the study. In addition, 33 healthy volunteers served as controls. An increase of VEGF serum concentration within the first 2 weeks after fracture in both groups with a following decrease within 6 months after trauma was observed. Serum VEGF concentrations in patients with impaired fracture healing were higher compared to the patients with physiological healing during the entire observation period. However, statistically significant differences were not observed at any time point between both groups. VEGF concentrations in both groups were significantly higher than those in controls. The present results show significantly elevated serum concentrations of VEGF in patients after fracture of long bones especially at the initial healing phase, indicating the importance of VEGF in the process of fracture healing in humans. ß

Is the expression of Transforming Growth Factor-Beta1 after fracture of long bones solely influenced by the healing process?

“…In a recent study our group demonstrated a significant increase in the TGF-β1 concentration in fracture haematoma and in serum of patients with long bone fracture. These results indicated the importance of this cytokine for fracture healing and confirmed other clinical and experimental studies [8][9][10][11][12][13][14][15][16][17]. Circulating TGF-β1 levels were found to be a predictor of delayed bone healing and non-union [11].…”

“…Patients gave informed written consent to be enrolled in the study, and were 18-90 years old. The recruitment parameters, sample collection schedule, matching process, patient demographics and exclusion criteria of this study have been previously published in detail [8][9][10]. In brief, between 2006 and 2008 a consecutive series of 113 patients with meta-/ diaphyseal fractures of long bone (humerus, femur, lower leg and forearm) and surgical treatment were included.…”

“…Evidence exists that the local and systemic concentrations of different osteogenic growth factors are increased during fracture healing [8][9][10][11][12][13][14][15][16][17]. Among these factors TGF-β1 is known to be pivotal for the bone healing.…”

The influence of low molecular weight heparin on the expression of osteogenic growth factors in human fracture healing

“…Therefore, we analysed the expression of important osteogenic growth factors M-CSF, VEGF and TGF-ß1 during the fracture healing process with and without the use of LMWHs to detect a possible impact. Numerous studies have previously shown that the growth factors measured in our study play a cardinal role in the regulation of human fracture healing [4,[24][25][26]. Interestingly, our results could not confirm the results of the experimental studies as we did not observe a significant decrease in the expression of the analysed growth factors due to the use of enoxaparin.…”

“…VEGF is known to be an important factor for angiogenesis and bone formation [22]. Moreover, VEGF is actively involved in the process of fracture healing [23,24]. Oncological studies have shown that LMWHs prolong survival time not only by having antithrombotic properties but also by their antiangiogenic effect [18][19][20].…”