Effect of telmisartan on healing of femoral shaft fracture in mice

Abstract

Objective To study the effect of telmisartan on healing of femoral shaft fracture in mice. Methods Models of fracture of right femoral shaft were created by femoral osteotomy in 64 mature male BALB/c mice which were randomized into 2 equal groups (n = 32). The experimental group was treated with telmisartan (30 mg/kg in drinking water) while the control group only with normal drinking water. Fracture healing was analyzed after 2, 5 and 10 weeks postoperatively using X-ray, biomechanical testing, and histomorphometry. Immunohistochemistry was applied to compare the expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) in the callus between the 2 groups. Results Radiological analysis at 2 weeks postoperation showed the callus diameter in the telmisartan treated animals (243.7±38.1%) was significantly larger than in the vehicle treated controls (178.2±24.5%) (P 0.05). Histomorphometric analyses revealed a significantly increased amount of bone formation in the experimental group compared with the control group. Biomechanical testing further showed significantly greater peak torque at failure (31.4±5.1%) and significantly higher torsional stiffness (37.7±8.6%) in the telmisartan-treated group than those (16.7±4.2% and 19.5±7.3%, respectively) in the vehicle-treated group after 2 weeks of fracture healing (P > 0.05). There was an increased fraction of PCNA-positive cells (53.8±7.5%) and VEGF-positive cells (39.2±6.8%) in the telmisartan-treated group compared with the vehicle-treated group (36.1±5.4% and 21.3±4.9%, respectively) after 2weeks of fracture healing (P > 0.05). Conclusions Telmisartan can promote healing of femoral shaft fracture, probably by increasing cell proliferation and neovascularization associated with decreased VEGF expression in hypertrophic chondrocytes. Key words: Fracture healing; Biomechanics; Proliferating cell nuclear antigen; Vascular endothelial growth factors