Role of Sildenafil in Acceleration of Delayed Union Fracture Healing on Sprague-Dawley Rats Model

Abstract

Introduction: Delayed union with its subsequent morbidity remains a major problem in fracture healing. Angiogenesis plays an important role in fracture healing. Sildenafil has been shown to be a potent stimulator of angiogenesis through upregulation of pro-angiogenic factors known as vascular endothelial growth factor (VEGF). This study evaluated the role of sildenafil in accelerating the healing process in delayed union model. Methods: This was an experimental study in delayed union femoral fracture model in male Sprague Dawley rats evaluated by histomorphometry and immunohistochemistry. Twenty four rats were randomized into four groups; control (group 1), administration of sildenafil 3.5 mg/kgbw (group 2), sildenafil 5 mg/kgbw (group 3), and sildenafil 7.5 mg/kgbw (group 4). The parameters evaluated were total area of callus, osseous, cartilage, fibrous tissue, and VEGF expression. The evaluation was carried out at week-2 and -4 after intervention. Results: On week-2 evaluation, ANOVA test showed a significant difference in the total callus area with the p-value of 0.004. ANOVA test also found significant difference among groups in the osseous, cartilage, and fibrous tissue area with p-value of 0.001, 0.015 and 0.005 respectively. On week-4, ANOVA test found no significant difference among all groups in the total callus area with p-value of 0.192. However, in ANOVA test, we found significant difference between groups in the osseous and fibrous tissue area with p-value of 0.015 and 0.001 respectively. Conclusion: Sildenafil is proven to accelerate fracture healing of delayed union and to increase VEGF expression.