BACKGROUND: Clinical evidence have proved that heterotopic ossification is easily present in bony callus of patients with fracture combined with head injury, and the healing of bone fracture is accelerated obviously. OBJECTIVE: To study the expression and distribution of vascular endothelial growth factor (VEGF) in bony callus among the patients with fracture combined with head injury and simple fracture patients, and to investigate its clinical significance and action mechanism.DESIGN, TIME AND SETTING: Grouping controlled observation was performed in the Xijing Hospital, the Fourth Military Medical University of Chinese PLA between February 2006 and July 2007.PARTICIPANTS: The patients comprised two groups those who had fracture combined with head injury and those who had simple fracture. Each group had 50 patients. The fracture combined head injury group included 41 males and 9 females, aged 19-55 years; simple fracture group included 36 males and 14 females, aged 17-52 years. METHODS: The bony callus specimens were harvested at 7-10, 11-15, 16-20, 21-27 and 28-35 days post-injury. The content of VEGF in bony callus was measured at different phase by using immunohistochemistry methods, and the speed of fracture healing was also observed.MAIN OUTCOME MEASURES: ①X-ray results; ②immunohistochemical image analysis. RESULTS: In different phase of bone healing, the VEGF of the two groups were homogenous, the early expression of VEGF in osteoprogenitor cell, osteoblast and cartilage cell in the fracture combined with head injury group was significantly higher than those in simple fracture group. The osteoprogenitor cell proliferated, and the differentiations of osteoblast and cartilage cell were enhanced obviously. The VEGF level reached the peak at 7-10 days, and kept at the high level for 30 days and then gradually decreased. The peak of VEGF level in simple fracture group came at 11-15 days, kept in the high level for 20 days and then gradually decreased. The peak value in simple fracture group was significantly lower than the fracture combined with head injury group. There was statistical significance in the expression of VEGF between two groups by the paired t-test (P < 0.05). A large mount of osteotylus could be detected at 4 weeks after injury by X-ray in patients with fracture combined, with head injury, but at 7-9 weeks in patients of those who had simple fracture.CONCLUSION: The expression of VEGF in the bony callus in the group of fracture combined with head injury is significantly greater than that in simple fracture patients, and the expression lasts for a longer time. The proliferation and differentiation of osteogenitor call, osteoblast and cartilage cell are also significantly faster in the group of fracture combined with head injury, which might be one of the bone healing mechanisms.