The influence of non-osteogenic factors on the expression of M-CSF and VEGF during fracture healing

Introduction: Macrophage colony stimulating factor (M-CSF) as well as vascular endothelial growth factor (VEGF) play an important role in bone homeostasis and in the process of fracture healing. To date, limited data regarding the influence of age, gender, diabetes, smoking, and alcohol consumption on the systemic expression of M-CSF and VEGF after long bone fracture exist.

Methods: From a total of 113 patients with long bone fractures 51 patients met inclusion criteria and were finally enrolled in this study. Patient's serum was collected over a period of 6 months following a standardised time schedule. M-CSF and VEGF serum concentrations were measured. Patient's history with special focus on cigarette smoking, diabetes mellitus, and regular alcohol intake was recorded. All patients were followed up clinically and radiologically for at least 24 weeks after trauma. A total of 22 male and 29 female patients formed the study population.

Results: The present results show significantly elevated mean overall M-CSF serum concentration in women, older patients as well as in non-smoking individuals. The mean overall VEGF serum concentration was significantly higher in women, older patients, and diabetic individuals as well as in non-smokers. Statistically significant differences were not observed at any time point regarding alcohol consumption.

Conclusion: These results suggest that age, gender, diabetes mellitus and cigarette smoking significantly influence the expression of M-CSF and VEGF after fracture of long bones in human. Of note, diabetic patients showed significantly elevated overall VEGF levels when compared to non-diabetic patients. Therefore, further studies with larger patient cohorts are needed to better understand the influence of these endogenous and exogenous factors on the expression of the osteogenic during human fracture healing.