Evaluation of the effect of the use of phosphodiesterase inhibitors in mice with experimental ostonecrosis with biphosphonate

Objective: the aim of this study is to investigate the molecular and morphological effects of phosphodiesterase inhibitors sildenafil and rolipram on bone and soft tissue in mice with experimental osteonecrosis with bisphosphonate. Materials and Methods: For the study, 30 adult female mice weighing 30-35 g, 64 weeks old, were provided. Animals were divided into 3 groups as control, zoledronic acid +sildenafil and zoledronic acid + rolipram. After giving experimental zolendronic acid for 8 weeks in all animals, tooth extraction was performed and the drugs specified in the groups were given for 4 weeks. At the end of the three-month experiment period, blood samples were taken from the animals and the maxillary anterior region of the animals was isolated. Biochemical parameters were measured in blood samples; rt-qPCR, histological and immunohistochemical evaluations were performed on maxilla samples. Results: VEGHscore, blood vessel count and osteocytes count were decreased in the control group compared to the other groups. TNFα, IL-1, IL17 and IL-23 decreased significantly in the sildenafil group compared to the other groups. Decreased VEGF and RANK mRNA expressions due to bisphosphonates increased in rolipram and sildenafil groups, whereas TRAP and TNFα were significantly decreased compared to the control group. Conclusion: Study findings show that rolipram and sildenafil improve bisphosphonate-induced worsening values. In future studies, the full elucidation of the mechanism of action of rolipram and sildenafil on bisphosphonate and proving its safety, may be beneficial for use before and after the surgical procedure in bisphosphonate patients. Keywords:Osteonecrosis,Mronj,Sildenafil,Rolipram,Bisphosphonate