Elevated concentrations of hypoxia-inducible factor-1α in patients with fracture and concomitant traumatic brain injury

Abstract

Background Compelling evidence indicate that traumatic brain injury is highly related to accelerated bone fracture repair, but the underlying mechanism still remains elusive. Fracture repair process relies greatly on the formation of new blood vessels in fracture site, and angiogenic factors have been confirmed to be essential for the initiation and maintenance of the fracture healing. Hypoxia-inducible factor-1α was demonstrated to be a critical regulator of angiogenic–osteogenic coupling during bone development and regeneration. The aim of the present study was to investigate the local and circulating concentrations of hypoxia-inducible factor-1α in patients with long-bone fractures and concomitant traumatic brain injury and to determine the potential role of hypoxia-inducible factor-1α in fracture healing. Methods Twenty-five patients with a long-bone fracture and concomitant traumatic brain injury (FT group) and 33 without a brain injury (Fr group) were enrolled in this study. Healthy subjects donated serum samples as control. Serum samples were collected over a period of six months, following a standardized time schedule. Hypoxia-inducible factor-1α concentrations were measured in fracture haematoma and serum of patients in both groups using enzyme-linked immunosorbent assay. Results Patients in FT group had a short time to union. Serum hypoxia-inducible factor-1α concentrations elevated in the early healing period and reached the maximum level during intramembranous bone formation phase in both groups. Thereafter, it decreased continuously and approached to the minimum levels until the end of the observation period. Serum hypoxia-inducible factor-1α concentrations in both groups were significantly higher compared with controls and hypoxia-inducible factor-1α concentrations in both serum and fracture haematoma were higher in FT group than that in Fr group. Fracture haematoma contained significantly higher hypoxia-inducible factor-1α concentrations compared with hypoxia-inducible factor-1α concentrations in serum. Serum hypoxia-inducible factor-1α concentrations had a positive correlation with hypoxia-inducible factor-1α concentrations in fracture haematoma in patients with fractures. Conclusions These findings suggest the local and systemic involvement of hypoxia-inducible factor-1α in fracture healing and the accelerated fracture repair in patients with traumatic brain injury might be associated with elevated hypoxia-inducible factor-1α concentrations in fracture haematoma and serum.