Effects of favipiravir and hydroxycloroquine on fracture healing in rats

Objective: Fracture healing or non-unıon of the fracture refers to a process in which many factors interact together. There are many treatments, physical and biological therapy methods that affect different stages of this process, as well as many biological, chemical agents that cause the fracture to be non-union or delayed union. In this study, the radiological and histological effects of Favipiravir and Hydroxychloroquine, which are frequently used in our country and around the world in the treatment of Covid-19, on fracture healing or fracture nonunıon in the rat femur fracture were evaluated. Materials and Methods: In this study, 48 Wistar-Albino male rats weighing an average of 300±50 grams at 2.5 months of age; they were divided into 4 groups as control group (group1, n:12), favipiravir group (group2, n:12), hydroxychloroquine group (group3, n:12), and favipiravir+hydroxychloroquine (group4, n:12). All groups were sacrificed on the 15th and 30th days and divided into 8 subgroups consisting of 6 rats, to be evaluated radiologically and histopathologically. Animals were monitored in the cage with controlled temperature (23-25°C) and a 12:12 hour light/dark cycle. The scoring suggested by Lane and Sandhu was used for radiological evaluation, and the scoring recommended by Hue et al. for histopathological evaluation. Results: A statistically significant difference was observed between the Favipiravir, Hydroxychloroquine, Favi+Hydroxy and Control groups 15th day histological scoring averages (p=0.0001). Hydroxychloroquine group; compared to the Favipiravir and Favi+Hydroxy groups, the 15th day histological scoring averages were found to be statistically significantly higher (p=0.001, p=0.0001). In addition, The histological scoring averages of the control group on the 15th day were found to be statistically significantly higher than the Favipiravir and Favi+Hydroxy groups (p=0.043, p=0.023). There is no statistically significant difference between the 15th Day Histological Scoring averages of other groups (p>0.05). There is no statistically significant difference between the 30th Day histological scoring averages of Favipiravir, Hydroxychloroquine, Favi+Hydroxy and Control Groups (p=0.887). No statistically significant difference was observed between the Favipiravir, Hydroxychloroquine, Favi+Hydroxy and Control groups radiological scoring distributions on day 15 (p=0.330). No statistically significant difference was observed between the 30th day radiological scoring distributions of Favipiravir, Hydroxychloroquine, Favi+Hydroxy and Control groups (p=0.618). iv Conclusions: Favipiravir, Hydroxychloroquine and Favipiravir+Hydroxychloroquine treatment did not have radiological and histological negative or positive effects on fracture healing compared to the Control group. KEY WORDS, Fracture healing, Rat, Favipiravir, Hydroxychloroquine, Favipiravir+Hydroxychloroquine