Histopathologic and histomorphometic evaluation of prophylactic effect of pentoxifyllin on a rat model of biphosphonate related osteonecrosis of the jaw

The aim of this experimental study is to investigate the prophylactic effect of Pentoxifylline (PEN) on bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our study, 34 female Sprague-Dawley rats were randomly divided into five groups. Groups 1 (Control) and 2 (SF/PEN) were injected intraperitoneally (IP) with sterile saline solution (SF) for 8 weeks; Groups 3 (ZA/SF), 4 (ZA/PEN) and 5 (ZA/PEN/PEN) were received IP zoledronic acid (ZA) (Zolenat® 4mg/5 ml, Mustafa Nevzat, Türkiye) at a dose of 0.1 mg/kg, 3 times a week for 8 weeks. In the eighth week, rats in group 5 (ZA/PEN/PEN) were received IP 50 mg/kg PEN (Trentillin® 100 mg/5 ml IV, Santa Farma, İstanbul, Türkiye) everyday. The left second molar teeth were extracted and the animals were allowed to recover for 8 weeks before being sacrificed. After tooth extraction, groups 1 (Control) and 3 (ZA/SF) were injected IP SF everyday for 3 weeks; groups 2 (SF/PEN), 4 (ZA/PEN) and 5 (ZA/PEN/PEN) were received 50 mg/kg IP PEN everyday for 3 weeks. At the end of this 16-week period, all rats were sacrificed. The specimens were histopathologically evaluated according to their inflammation, vascularization, bleeding and regeneration degrees. This parameters are valued as none (0), mild (1), moderate (2) and severe (3). The total bone volume and bone percentage were histomorphometrically evaluated. At the beginning of the experiment, weights of the rats were recorded and there were a statistically significant difference between the groups (p=0,043). Within the 16-week process, weights of the rats recorded and rats have continued to gain weight. At the end of the experiment, there was no statistically significant difference between the groups (p>0,05). Between control group and group SF/PEN, there were no statistically significant difference for inflammation (p=0,127), vascularization (p=1), bleeding (p=1) and regeneration (p=1). Between control group and group ZA/SF (Osteonecrosis Group), there were statistically significant difference for inflammation (p=0,013), vascularization (p=0,022), bleeding (p=0,025) and regeneration (p=0,008). Comparison between group ZA/SF and treatment groups has showed: between control group and group ZA/PEN, there were no statistically significant difference for inflammation (p=0,536) vascularization (p=0,642), bleeding (p=0,765) and regeneration (p=0,127). Between group ZA/SF and group ZA/PEN/PEN, there were statistically significant difference for inflammation (p=0,017), vascularization (p=0,04), bleeding (p=0,044) and regeneration (p=0,04). Evaluation of histomorphometrical results have revealed that comparison of the total bone volume has showed statistically significant difference between control group and group SF/PEN (p=0,009); ZA/PEN (p=0,01) and ZA/PEN/PEN (p=0,002). Between control group and group ZA/SF, there was no statistically significant difference for total bone volume (p=0,999). Comparison of the bone percentage in the extraction sockets has showed no statistically significant difference between control group and group SF/PEN (p=0,935); ZA/PEN (0,108) and ZA/PEN/PEN (p=0,530). Between control group and group ZA/SF, control group has showed a statistically significant difference for bone percentage in the extraction sockets (p<0,001). Comparison between group ZA/SF and treatment groups has showed no statistically significant difference with group ZA/PEN (p=0,69); but statistically significant difference with group ZA/PEN/PEN (p=0,008). In this experimental model for BRONJ, it might be concluded that although PEN which was given right after tooth extraction improves new bone formation and in this way it positively affects bone healing, it is not therapeutic. However, PEN that was given before tooth extraction is both prophylactic and therapeutic. In conclusion, PEN might affect healing in a positive way via optimizing inflammatory response.