Obesity does not affect the healing of femur fractures in mice

• Published in: Injury 2016-07, Vol.47 (7), p.1435-1444
• Main Authors: Histing, T., M.D, Andonyan, A, Klein, M., M.D, Scheuer, C., M.D, Stenger, D., M.D, Holstein, J.H., M.D, Veith, N.T., M.D, Pohlemann, T., M.D, Menger, M.D., M.D
• Format: Article
• Language: English
• Subjects: Animals; Biomechanical Phenomena; Blotting, Western; Bone formation; Bone Morphogenetic Protein 2 - metabolism; Bone Remodeling; Bone remodelling; Bony Callus - pathology; Callus adiposity; Core Binding Factor Alpha 1 Subunit - metabolism; Diet, High-Fat; Disease Models, Animal; Femoral Fractures - pathology; Fracture healing; Fracture Healing - physiology; Fractures, Bone - pathology; Male; Mice; Mice, Inbred C57BL; Obesity; Obesity - pathology; Orthopedics; PPAR gamma - metabolism; X-Ray Microtomography
• ISSN: 0020-1383; 1879-0267
• DOI: 10.1016/j.injury.2016.04.030

Abstract Obesity is reported to be both protective and deleterious to bone. Lipotoxicity and inflammation might be responsible for bone loss through inhibition of osteoblasts and activation of osteoclasts. However, little is known whether obesity affects the process of fracture healing. Therefore, we studied the effect of high fat diet-induced (HFD) obesity on callus formation and bone remodeling in a closed femur fracture model in mice. Thirty-one mice were fed a diet containing 60 kJ% fat (HFD) for a total of 20 weeks before fracture and during the entire postoperative observation period. Control mice (n = 31) received a standard diet containing 10 kJ% fat. Healing was analyzed using micro-CT, biomechanical, histomorphometrical, immunohistochemical, serum and protein biochemical analysis at 2 and 4 weeks after fracture. HFD-fed mice showed a higher body weight and increased serum concentrations of leptin and interleukin-6 compared to controls. Within the callus tissue Western blot analyses revealed a higher expression of transcription factor peroxisome proliferator-activated receptor y (PPARy) and a reduced expression of runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein (BMP)-4. However, obesity did not affect the expression of BMP-2 and did not influence the receptor activator of nuclear factor k B (RANK)/RANK ligand/osteoprotegerin (OPG) pathway during fracture healing. Although the bones of HFD-fed animals showed an increased number of adipocytes within the bone marrow, HFD did not increase callus adiposity. In addition, radiological and histomorphometric analysis could also not detect significant differences in bone formation between HFD-fed animals and controls. Accordingly, HFD did not affect bending stiffness after 2 and 4 weeks of healing. These findings indicate that obesity does not affect femur fracture healing in mice.