Positive effect of tadalafil, a phosphodiesterase-5 inhibitor, on fracture healing in rat femur
Güray Toğral1, Ş. Murat Arıkan1, Petek Korkusuz2, Ramin Hashemi Hesar2, M. Fatih Ekşioğlu1
1Department of Orthopedics and Traumatology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
2Department of Histology & Embryology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
Keywords: Angiogenesis; fracture; phosphodiesterase-5 inhibitors; sildenafil; tadalafil.
Objectives: This study aims to investigate whether tadalafil accelerates fracture healing with an efficiency equal to that of sildenafil. Materials and methods: Fracture healing was studied using a rat closed femur fracture model. Forty-eight male Wistar albino rats (mean age 13 weeks; range 12 to 14 weeks) were divided into three groups: 16 received sildenafil (5 mg/kg/day per oral), 16 received tadalafil (1 mg/kg/day per oral), and 16 (control group) received saline daily. After two and five weeks, eight rats from each group were euthanized and bone healing was evaluated using radiographic, histologic, and histomorphometric analyses.
Results: At second week, radiologic score of tadalafil group was higher than the sildenafil treated groups and the sildenafil and tadalafil groups both had higher radiographic scores than the control group, all groups had similar scores at fifth week. The sildenafil and tadalafil treated group exhibited smaller callus diameter at the second week comparing to control group but the difference was not statistically significant, while callus diameter was significantly smaller in tadalafil group when compared to the control group in fifth week. Compared with the control group, cartilage percentage of the callus was lower in the sildenafil group at two weeks and lower in both the tadalafil and sildenafil groups at five weeks. There were no differences between the tadalafil and sildenafil groups regarding the radiographic scores, callus size, cartilage and osseous callus percentage, and the qualitative bridging scores at second or fifth week.
Conclusion: This study demonstrated that tadalafil accelerates fracture healing by enhancing osseous tissue formation similar to sildenafil.