Effects of different vardenafil doses on bone healing in a rat fracture model
Tolgahan Atcı1
, Ender Alagöz2, Elif Yaprak Saraç3, Hakan Özbay4, Mustafa Fatih Daşcı5, Abdurrahman Acar6, Derya Karabulut7, Mehmet Akif Güleç2
1Department of Orthopedics and Traumatology, Sorgun State Hospital, Yozgat, Turkey
2Department of Orthopedics and Traumatology, Health Sciences University, Bağcılar Training and Research Hospital, Istanbul, Turkey
3Molecular Biology Genetics and Biotechnology, Istanbul Technical University, Istanbul, Turkey
4Department of Orthopedics and Traumatology, Ağrı State Hospital, Ağrı, Turkey
5Department of Orthopedics and Traumatology, Cihanbeyli State Hospital, Konya, Turkey
6Department of Orthopedics and Traumatology, Şırnak State Hospital, Şırnak, Turkey
7Mechanical Engineering, Istanbul University-Cerrahpaşa Faculty of Engineering, Istanbul, Turkey
Keywords: Bone healing, femur, rat, vardenafil
Abstract
Objectives: We aimed to investigate the radiological, biomechanical, histopathological, histomorphometric, and immunohistochemical effects of different doses of vardenafil on fracture healing.
Materials and methods: Fifty-one rats were divided into three groups. Group V5 was given 5 mg/kg/day of vardenafil; Group V10 was given 10 mg/kg/day of vardenafil; and the control group was given the same volume of saline. Six rats from each group were sacrificed on Day 14 (early period) and the remaining rats were sacrificed on Day 42 (late period). Callus/femoral volume and bone mineral density were measured using micro- computed tomography. Five femurs from each group in the late period were examined by biomechanical tests. In addition to the histopathological and histomorphometric evaluations, immunohistochemical analyses were performed to examine the levels of inducible nitric oxide synthase (iNOS), transforming growth factor-3 (TGF-β3), and nuclear factor kappa B (NF-κB) proteins.
Results: Both doses of vardenafil increased primary bone volume and maximal bone fracture strength in late period, compared to the control group (p<0.05). Histological healing scores of vardenafil groups were significantly higher in early period (p<0.001). While cartilaginous callus/total callus ratio in early period was higher, callus diameter/femoral diameter ratio in late period was lower in vardenafil groups (p<0.01). The NF-κB immunopositivity in V10 group decreased in early period, compared to control group (p<0.001). The TGF-β3 and iNOS immunopositivity increased in both V5 and V10 groups, compared to the control group in early period, but returned to normal in late period.
Conclusion: During the first period of fracture healing process in which vasodilation is mostly required with increasing inflammation, vardenafil has ameliorating effects on the bone union and supports fracture healing.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.