Effects of different vardenafil doses on bone healing in a rat fracture model

Jt Dis Relat Surg. 2021;32(2):313-322. doi: 10.52312/jdrs.2021.72. Epub 2021 Jun 11.


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.

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone Density / drug effects
  • Bony Callus / diagnostic imaging
  • Bony Callus / drug effects
  • Bony Callus / pathology
  • Disease Models, Animal
  • Femoral Fractures / diagnostic imaging
  • Femoral Fractures / drug therapy*
  • Femoral Fractures / pathology
  • Femur / diagnostic imaging
  • Femur / pathology
  • Fracture Healing / drug effects*
  • Male
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphodiesterase 5 Inhibitors / administration & dosage*
  • Rats
  • Transforming Growth Factor beta3 / metabolism
  • Vardenafil Dihydrochloride / administration & dosage*
  • X-Ray Microtomography


  • NF-kappa B
  • Phosphodiesterase 5 Inhibitors
  • Tgfb3 protein, rat
  • Transforming Growth Factor beta3
  • Vardenafil Dihydrochloride
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat