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      Should orthopedic surgeons consider the effects of gabapentin administration on bone healing while treating a long bone fracture: experimental study in a rat model

      research-article
      1 , * , 1 , 2 , 1 , 1 , 3
      SICOT-J
      EDP Sciences
      Gabapentin, Fracture healing, Rat model

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          Abstract

          Objective: The main purpose of the present study was to assess the radiographic, histological, and mechanical effects of gabapentin on fracture healing in a rat model of femur fracture.

          Materials and methods: A standard transverse fracture of the mid-diaphysis was created. A total of 60 female Wistar-Albino rats with the mean age of 13.5 ± 1.2 weeks were used for this experimental trial. The rats were randomized into four groups with 15 animals included in each group. Group A and B were the control groups whereas C and D were the treatment groups. Drugs were delivered by oral gavage twice a day with the daily dosage calculated according to body surface area conversion to the human equivalent dosing regimen of 1200 mg/day. Radiographic, histological, and biomechanical evaluation was performed.

          Results: We could not detect any statistically significant difference between the control and gabapentin treatment groups according to the comparative assessment of radiographic scores on the 15th and 30th days. Although no significant differences were found between the groups on the 15th day, histological scores were better in the control group on the 30th day. According to the results of biomechanical testing, the fractured femurs resected from the control group exhibited significantly more strength on the 30th day.

          Conclusions: According to the data we acquired during the present study, administration of gabapentin negatively affects the fracture healing process especially in the aspects of histological progression as well as the biomechanical strength of the callus in a rat model.

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          Most cited references35

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          The cell and molecular biology of fracture healing.

          Fracture healing is a complex physiologic process that involves the coordinated participation of several cell types. By using a reproducible model of experimental fracture healing in the rat, it is possible to elucidate the integrated cellular responses that signal the pathways and the role of the extracellular matrix components in orchestrating the events of fracture healing. Histologic characterization of fracture healing shows that intramembranous ossification occurs under the periosteum within a few days after an injury. Events of endochondral ossification occur adjacent to the fracture site and span a period of up to 28 days. Remodeling of the woven bone formed by intramembranous and endochondral ossification proceeds for several weeks. Spatial and temporal expression of genes for major collagens (Types I and II), minor fibrillar collagens (Types IV and XI), and several extracellular matrix components (osteocalcin, osteonectin, osteopontin, fibronectin and CD44) are detected by in situ hybridization. Immunohistochemical studies show that expression of proliferating cell nuclear antigen is both time and space dependent and differentially expressed in the callus tissues formed by the intramembranous and endochondral processes. Chondrocytes involved in endochondral ossification undergo apoptosis (programmed cell death), and early events in fracture healing may be initiated by the expression of early response genes such as c-fos. Additional characterization and elucidation of fracture healing will lay the foundation for subsequent studies aimed at identifying mechanisms for enhancing skeletal repair.
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            Current concepts of molecular aspects of bone healing.

            Fracture healing is a complex physiological process. It involves the coordinated participation of haematopoietic and immune cells within the bone marrow in conjunction with vascular and skeletal cell precursors, including mesenchymal stem cells (MSCs) that are recruited from the surrounding tissues and the circulation. Multiple factors regulate this cascade of molecular events by affecting different sites in the osteoblast and chondroblast lineage through various processes such as migration, proliferation, chemotaxis, differentiation, inhibition, and extracellular protein synthesis. An understanding of the fracture healing cellular and molecular pathways is not only critical for the future advancement of fracture treatment, but it may also be informative to our further understanding of the mechanisms of skeletal growth and repair as well as the mechanisms of aging.
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              • Record: found
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              The biology of fracture healing in long bones.

              B McKibbin (1978)
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                Author and article information

                Journal
                SICOT J
                SICOT J
                sicotj
                SICOT-J
                EDP Sciences
                2426-8887
                2016
                01 November 2016
                : 2
                : ( publisher-idID: sicotj/2016/01 )
                : 36
                Affiliations
                [1 ] Faculty of Medicine, Erzincan University Erzincan 24030 Turkey
                [2 ] Faculty of Medicine, Selcuk University Konya 42075 Turkey
                [3 ] Faculty of Medicine, Atatürk University Erzincan 25030 Turkey
                Author notes
                [* ]Corresponding author: hakansofu@ 123456yahoo.com
                Article
                sicotj160072 10.1051/sicotj/2016028
                10.1051/sicotj/2016028
                5088749
                27801642
                f64da042-fdbb-4afa-835f-164b6b12eaf1
                © The Authors, published by EDP Sciences, 2016

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 July 2016
                : 17 September 2016
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 30, Pages: 6
                Categories
                Lower Limb
                Original Article

                gabapentin,fracture healing,rat model
                gabapentin, fracture healing, rat model

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