Role of Sildenafil in Acceleration of Delayed Union Fracture Healing on Sprague-Dawley Rats Model
Ahmad Fauzi
Department of Orthopaedic and Traumatology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Achmad Fauzi Kamal *
Department of Orthopaedic and Traumatology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Aryadi Kurniawan
Department of Orthopaedic and Traumatology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Evelina Kodrat
Department of Anatomical Pathology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
*Author to whom correspondence should be addressed.
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.
Keywords: Sildenafil, delayed union, accelerated fracture healing, VEGF