Background: It is clinically observed that patients suffering from traumatic brain injury (TBI) can show increased callus formation in long-bone fractures. The underlying mechanisms of this phenomenon, however, are poorly understood. In a first experimental study we could reproduce this effect in wild-type mice. Leptin acts as a regulator of bone growth in the central nervous system. The aim of the present study was to assess fracture healing in leptin-deficient mice and to measure the impact of an additional TBI.
Method: 138 female 12 weeks old B6.V-Lep-ob/JRj mice (Janvier Labs, Saint Berthevin, France) (body weight 50,67 g±3,04 g) were divided into 4 groups: Control (n=28), fracture (n=37), TBI (n=35), combined trauma (TBI + fracture) (n=38). Fractures were stabilised using an external fixator (RISystem, Davos, Switzerland) at the left femur, the osteotomy gap was sawed at 0.7 mm. The TBI was induced at the left cortex with a controlled cortical impact injury (CCI). Postoperative in-vivo micro-computed tomography scans (callus volume, callus density) were performed weekly. Using frontal and sagittal reconstructions, the bridging of the osteotomy gap was also evaluated with a scoring system. After 3 and 4 weeks the animals were sacrificed and biomechanical testing (max. torque, max. stiffness) was performed.
Results: Micro-computed tomography showed no significant differences between the fracture and combined trauma group regarding callus volume and callus density. The CT scoring system revealed non-union rates of 93% and 96% at 3 weeks in the fracture and combined trauma group respectively. Also, the biomechanical analysis could not show significant differences in max. torque and max. stiffness between fracture and combined trauma group.
Conclusion: In this study we could show that fracture healing is impaired in leptin-deficient mice. Furthermore, TBI does not have an impact on fracture healing in mice in the absence of leptin. Given that wild-type mice respond to TBI with significantly increased callus formation, leptin seems to play an important role as regulator of the TBI-driven accelerated fracture healing.
Disclosure: The authors declared no competing interests. This study was funded by the German Research Society (DFG, project TS 303/1-1).