Experimental investigation of the effects of systemic tranexamicacid on new bone formation in a model of critical sized calvarialbone defect created in rat

Introduction and Objectives Tranexamic acid is a lysine analogue. It is one of the antifibrinolytic agents used for the prevention of excessive bleeding in major trauma, postpartum bleeding, major surgery, tooth extraction, epistaxis and menstrual bleeding. It is also used in maxillofacial surgery to reduce bleeding from fracture lines and to prevent edema and ecchymosis that may develop due to bleeding. Experimental studies have shown that fibrin increases bone formation. The importance of the presence of hematoma in the healing zone on early bone healing is also known. However, the effect of antifibrinolytic agents on bone healing has been investigated in a limited number of studies. According to the hypothesis of this study, systemic tranexamic acid will reduce peroperative and postoperative hematoma when administered in the preoperative period; when applied in the postoperative period, it will stabilize the fibrin in the hematoma and will allow the hematoma formed before the application of tranexamic acid to remain in the environment for a longer time and accordingly there will be changes in new bone formation. In this study, we aimed to investigate the effects of systemic tranexamic acid use on new bone formation before and after surgery by creating a critical sized calvarial bone defect model in rat. Methods In this study, we used 3/4-month-old Sprague Dawley male rats weighing between 385 - 515 grams and we divided these rats into 5 groups, with 6 rats in each group. We determined the 1st group as the control group; we injected tranexamic acid 10 mg/kg dose to second group just before the operation; 10 mg/kg dose to third group on the 1st postoperative day; 10 mg/kg dose to fourth group on 1st, 2nd, 3rd postoperative days; 20 mg/kg dose to fifth group on 1st, 2nd, 3rd postoperative days via the dorsal tail vein. With the help of a trephine bur (8 mm diameter), which is frequently used in implant surgery in dentistry. We created a circular bone defect with a diameter of 8 mm on both parietal bones, with the sagittal suture in the center, between bregma and lambda sutures in the rat calvaria. We measured the amount of hematoma formed in the surgical area on the 1st and 3rd postoperative days by ultrasonography (USG). We euthanized the animals on the 28th postoperative day. New bone formation in the defects was measured by microtomography. Total volume (TV), bone volume (BV), bone surface (BS), bone volume ratio (BV/TV), bone surface density (BS/TV), specific bone surface (BS/BV), structural model index (SMI) ), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), standard deviation of trabecular thickness (Tb.Th.SD), standard deviation of trabecular separation (Tb.Sp.SD) parameters evaluated and 3D images were obtained. SPSS 22 program was used for statistical analysis of the data. One-way ANOVA and paired t-test were used in the analyses. The effect size of the study groups relative to the control group and each other (according to Cohen's d formula) was obtained with the web-based "effect size calculator". Values <0.3 were considered very low-effective, values ≥0.3 and <0.5 were considered low-effective, values ≥0.5 and <0.8 were considered moderately effective, and values ≥0.8 and <1 were considered highly-effective, values ≥1 were considered enormously effective. Results There was no statistically significant difference between the groups in the evaluated parameters. The effect sizes of the study groups compared to the control group and each other were calculated over the parameters of bone volume, bone surface density and trabeculae number and the effect size of the intervention was found to be very low effective. Discussion In previous experimental studies in which the results of the rat femoral fracture model were evaluated by direct radiography. Different results were obtained from our study in topical and systemic tranexamic acid applications. In our study, measuring the amount of postoperative hematoma with USG, using different doses of tranexamic acid, and evaluating bone formation parameters with microtomography are the features that make the results of our study more reliable. Another reason for the difference in the results obtained with previous studies is that while these studies are working on the femur, which is formed by endochondral ossification and whose healing can be affected by different dynamics because it is located in a mobile extremity. In our study, the calvarium, which is formed by intramembranous ossification and is located in an immobile region, was preferred. The extent to which tranexamic acid affects healing on different bones has not yet been understood and more studies are needed on this subject. Conclusion In our study, it was found that the effect of tranexamic acid on new bone development was not statistically significant in the critical sized calvarial bone defect model in rat. When a literature review was conducted on previous studies in the field of craniofacial surgery, no similar experimental studies could be found on this subject and it has been demonstrated that tranexamic acid, which is frequently used in the clinic for reducing blood loss, has no effect on new bone formation . Keywords: Microtomography in rat, rat calvarium, tranexamic acid