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      The effects of dabigatran etexilate on fracture healing in rats

      Indian Journal of Orthopaedics
      Medknow Publications
      anticoagulant drugs, dabigatran etexilate, fracture healing, thromboembolism, anticoagulant, experimental surgery, thrombolytic agent

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          Abstract

          Background: Deep vein thrombosis leading to pulmonary embolism is one of the major complication after fracture. After a fracture occurs, the coagulation cascade activates thrombin, a protease that finally generates clotting. Dabigatran etexilate reduce clot formation by inhibiting thrombin. Dabigatran etexilate is a widely used drug for thromboprophylaxis. There is no study of the effects of dabigatran etexilate on fracture healing in the literature, so we aimed to evaluate the effects of dabigatran etexilate on fracture healing. Materials and Methods: Thirty-six female Sprague Dawley rats were divided into 6 groups, each consisting of 6 rats. In all rats, right tibias were used for the fracture model. An oral regimen of dabigatran etexilate suspension in 0.5% hydroxyethylcellulose was administered to the rats. Although the first and second groups received 10 mg/kg daily doses, the third and fourth groups received 50 mg/kg daily doses. The fifth and sixth groups were assigned as sham groups and only hydroxyethylcellulose solution was administered. The first, third and fifth groups were sacrificed on 14th days; whereas the second, fourth and sixth groups were sacrificed on 28th days. Results were evaluated radiologically and histologically. Results: Radiologically and histologically no statistically significant differences were observed on the 14th day between the first, third and fifth groups; and on the 28th days between the second, fourth and sixth groups. Conclusion: Radiological and histological evaluations revealed that fracture healing was not affected by dabigatran etexilate. We think that dabigatran etexilate can be used for the prophylaxis of thromboembolism in patients with fractures, but further clinical studies are mandatory.

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          Most cited references25

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          The biology of fracture healing.

          The biology of fracture healing is a complex biological process that follows specific regenerative patterns and involves changes in the expression of several thousand genes. Although there is still much to be learned to fully comprehend the pathways of bone regeneration, the over-all pathways of both the anatomical and biochemical events have been thoroughly investigated. These efforts have provided a general understanding of how fracture healing occurs. Following the initial trauma, bone heals by either direct intramembranous or indirect fracture healing, which consists of both intramembranous and endochondral bone formation. The most common pathway is indirect healing, since direct bone healing requires an anatomical reduction and rigidly stable conditions, commonly only obtained by open reduction and internal fixation. However, when such conditions are achieved, the direct healing cascade allows the bone structure to immediately regenerate anatomical lamellar bone and the Haversian systems without any remodelling steps necessary. In all other non-stable conditions, bone healing follows a specific biological pathway. It involves an acute inflammatory response including the production and release of several important molecules, and the recruitment of mesenchymal stem cells in order to generate a primary cartilaginous callus. This primary callus later undergoes revascularisation and calcification, and is finally remodelled to fully restore a normal bone structure. In this article we summarise the basic biology of fracture healing. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Current approaches to experimental bone grafting.

            A number of osteogenic, osteoinductive, and osteoconductive substances currently are being investigated for use in bone repair. It is conceivable that a selected combination of osteogenic cells, osteoinductive factors, and osteoconductive matrices can be combined and fabricated into an implantable material custom-suited to particular clinical demands. Consequently, it is crucial that potential graft substances be experimentally characterized in terms of their precise contribution to the bone-forming mechanisms. In this article, the authors review current areas of research in the realm of experimental grafting, including the current understanding of materials that manifest osteogenic, osteoinductive, or osteoconductive properties.
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              Dabigatran etexilate: a new oral thrombin inhibitor.

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                Author and article information

                Journal
                26015639
                4443421
                10.4103/0019-5413.156227
                http://creativecommons.org/licenses/by-nc-sa/3.0

                Orthopedics
                anticoagulant drugs,dabigatran etexilate,fracture healing,thromboembolism,anticoagulant,experimental surgery,thrombolytic agent

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