Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice

J Musculoskelet Neuronal Interact. 2017 Jun 1;17(2):78-85.

Abstract

Patients with traumatic brain injury (TBI) and long-bone fractures can show increased callus formation. This effect has already been reproduced in wild-type (wt) mice. However, the mechanisms remain poorly understood. Leptin is significantly increased following TBI, while its role in bone healing remains unclear. The aim of this study was to evaluate fracture healing in leptin-deficient ob/ob mice and to measure any possible impact of TBI on callus formation. 138 female, 12 weeks old, ob/ob mice were divided into four groups: Control, fracture, TBI and combined trauma. Osteotomies were stabilized with an external fixator; TBI was induced with Controlled Cortical Impact Injury. Callus bridging was weekly evaluated with in vivo micro-CT. Biomechanical testing was performed ex vivo. Micro-CT showed high non-union rates after three and four weeks in the fracture and combined trauma group. No differences were observed in callus volume, density and biomechanical properties at any time point. This study shows that bony bridging is impaired in the present leptin-deficient trauma model. Furthermore, the phenomenon of increased callus formation after TBI could not be reproduced in ob/ob mice, as in wt mice. Our findings suggest that the increased callus formation after TBI may be dependent on leptin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bony Callus / metabolism
  • Brain Injuries, Traumatic / metabolism*
  • Female
  • Femoral Fractures / metabolism
  • Femoral Fractures / pathology
  • Fracture Healing / physiology*
  • Leptin / deficiency*
  • Mice
  • Mice, Obese
  • Random Allocation

Substances

  • Leptin