The effect of favipiravir on fracture healing

Abstract

The aim of this study was to evaluate the effects of favipiravir on fracture healing. Forty-eight female rats which had a femur fracture with intramedullary Kirschner wire fixation performed were divided into 6 groups; 2 control groups (C1, C2) and 4 experimental groups (F1, F2, F3, F4). The control groups (C1, C2) received physiological saline by oral gavage for 14 days. Two of the experimental groups (F1, F2) received favipiravir by oral gavage for 5 days, whereas the other groups (F3, F4) received it for 14 days. C1, F1 and F3 groups were sacrificed and evaluated on the 14th day, and C2, F2 and F4 groups were sacrificed and evaluated on the 28th day. The fracture sites were assessed for healing radiologically using the Lane and Sandhu scoring system, and assessed histologically using the Huo et al. scoring system. There was no difference between the groups regarding radiological and histological evaluations made on the 14th day (P > .05, P=.216, respectively). On the 28th day, the radiological scores were found to be significantly higher in the control group when compared to the experimental groups (P < .05). Histologically, the control group demonstrated better fracture healing than the groups that had favipiravir administered (P < .001). This study has shown that favipiravir can have negative effects on fracture healing both radiologically and histologically.

Figure 1.

Schematic flowchart of the experiment. Sacr., sacrifice.

Figure 2.

Radiological images of groups C1 (A), C2 (B), F1 (C), F2 (D), F3 (E), and F4 (F), respectively.

Figure 3.

Histological images of fracture healing. A-F: (A) Equal mixture of cartilage and immature bone in fracture area of group C1, H&E × 40×, (B) predominantly fibrous tissue with a small amount of cartilage in fracture area of group F1, H&E × 200×, (C) fibrous tissue in fracture area of group F3, H&E × 20×, (D) predominantly immature bone with a small amount of cartilage in fracture area of group C2, H&E x 100×, (E) predominantly cartilage with a small amount of fibrous tissue in fracture area of group F2, H&E × 40×, (F) fibrous tissue in fracture area of group F4, H&E × 100×. H&E, hematoxylin and eosin.