Repeated mild traumatic brain injury impairs fracture healing in male mice

Abstract

Objectives: The goal of this study was to evaluate the long-term impact of repeated (r) mild traumatic brain injury (mTBI) on the healing of fractures in a mouse model. Ten week-old male mice were subjected to r-mTBI once per day for 4 days followed by closed femoral fracture using a three-point bending technique, 1 week post impact and fracture healing phenotype evaluated at 20 weeks of age. Results: Micro-CT analysis of the fracture callus region at nine weeks post fracture revealed reduced bone volume (30%, p < 0.05) in the r-mTBI fracture group compared to the control-fracture group. The connectivity density of the fracture callus bone was reduced by 40% (p < 0.01) in the r-mTBI fracture group. Finite element analysis of the fracture callus region showed reduced failure load (p = 0.08) in the r-mTBI group compared to control group. There was no residual cartilage in the fracture callus region of either the r-mTBI or control fracture group. The reduced fracture callus bone volume and mechanical strength of fracture callus in r-mTBI mice 9 weeks post fracture are consistent with negative effects of r-mTBI on fracture healing over a long-term resulting in decreased mechanical strength of the fracture callus.