Effects of social stress and fluoxetine treatment on fracture healing in a rat femur fracture model

Abstract

BackgroundMental stress and depressive disorders have negative effect on bone biology and increase fracture risk. Fluoxetine is a widely used selective serotonin reuptake inhibitor in the treatment of these disorders. We aimed to evaluate the effects of social stress and fluoxetine treatment on fracture healing. MethodsThis study was performed with 32 male Sprague–Dawley® rats. Rats were randomly divided into four groups with eight rats in each group. Social stress regimen was performed in groups 3 and 4 for 15 days. Placebo for groups 1 and 3 and fluoxetine for groups 2 and 4 was administrated. Rat femur open (osteotomy) fracture model was performed. Placebo and fluoxetine were continued to be given to the same groups for four weeks until sacrification of animals. Sacrificed right femurs of subjects were evaluated histologically and radiologically. The obtained data were statistically analyzed using the SPSS 23 (Statistical Package for the Social Sciences) program. ResultsFracture healing score that evaluates the fracture healing quantitatively based on histological scale and bone mineral density of group 3 were significantly lower than other groups, and there was no significant difference between other groups. Inflammation score of group 2 was significantly lower than group 3. Group 1 had higher new callus formation/original cortex volume than group 2 and group 3. In immunohistochemical evaluation, the H-score of BMP-7/osteoblast in group 3 was lower than in group 1. The H-score of CD34 in group 3 was lower than in group 1. DiscussionThe positive and negative effects of fluoxetine, which is used in the treatment of depressive disorders, on wound, tendon, or bone healing have been shown in the literature. In this study, we showed the negative effects of depression on the early stages of fracture healing. Although fluoxetine had no detrimental effect on fracture healing in non-depressive rats, impaired fracture healing was reversed and better radiological and histological findings were obtained in depressive rats treated with fluoxetine. Our findings indicate that fluoxetine, which minimizes the negative effects of social stress on bone healing, can be used safely in the treatment of depressive disorders in patients with fractures.