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      The effects of cephalexin on fracture healing in a rat femur fracture model

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          Abstract

          Objectives

          The aim of this study was to examine the effects of cephalexin on the fracture union histomorphometrically, radiologically, biomechanically, immunohistochemically, and histopathologically in a rat femur fracture model and to evaluate the effects of the antibiotics to be used in the prophylaxis of fracture infection on the union of the fracture.

          Materials and methods

          A total of 48 male Wistar rats were divided into four groups as two-week control (C2) and cephalexin (CEP2) and four-week control (C4) and cephalexin (CEP4). After establishment of standard fracture model on right femurs, 60 mg/kg/day of cephalexin was applied to CEP2 and CEP4 by oral gavage. Radiological, biomechanical, histopathological, immunohistochemical, and histomorphometric examinations were performed on amputated femurs.

          Results

          Callus volume of CEP4 group significantly increased compared to CEP2 group (p=0.005), while no significant difference was found in the bone mineral density and callus/bone volume among the groups (p>0.05). There was no significant difference in flexural strength between the C4 and CEP4 groups (p=0.093). Histological healing scores increased from Week 2 to Week 4 (p=0.002) and inflammation scores decreased in both control and cephalexin groups (p=0.010 and p=0.008); however, no significant difference was found in healing and inflammation scores (p>0.05). The CD34+ immunoreactivity in the CEP2 group was significantly higher than the C2 group (p=0.029). Collagen type III level was significantly lower in the CEP2 and CEP4 groups compared to the corresponding control groups (p=0.008 and p=0.016, respectively).

          Conclusion

          Cephalexin did not exert any radiological, histopathological, histomorphometric, biomechanical, and immunohistochemical adverse effects on the femoral fracture healing model in rats; however, it showed positive effects on CD34 and Collagen type III levels. Based on these findings, antibiotherapy with cephalexin may be considered as a safe treatment for fracture union.

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          Most cited references40

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          Oral versus Intravenous Antibiotics for Bone and Joint Infection

          The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.
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            Inhibition of fracture healing.

            This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.
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              Effect of various concentrations of antibiotics on osteogenic cell viability and activity.

              Infection is a common complication of open fractures. Systemic antibiotics often cause adverse events before eradication of infected bone occurs. The local delivery of antibiotics and the use of implants that deliver both growth factors and antimicrobials are ways to circumvent systemic toxicity while decreasing infection and to reach extremely high levels required to treat bacterial biofilms. When choosing an antibiotic for a local delivery system, one should consider the effect that the antibiotic has on cell viability and osteogenic activity. To address this concern, osteoblasts were treated with 21 different antibiotics over 8 concentrations from 0 to 5000 µg/ml. Osteoblast deoxyribonucleic acid content and alkaline phosphatase activity (ALP) were measured to determine cell number and osteogenic activity, respectively. Antibiotics that caused the greatest decrement include rifampin, minocycline, doxycycline, nafcillin, penicillin, ciprofloxacin, colistin methanesulfonate, and gentamicin; their cell number and ALP were significantly less than control at drug concentrations ≤ 200 µg/ml. Conversely, amikacin, tobramycin, and vancomycin were the least cytotoxic and did not appreciably affect cell number and ALP until very high concentrations were used. This comprehensive evaluation of numerous antibiotics' effects on osteoblast viability and activity will enable clinicians and researchers to choose the optimal antibiotic for treatment of infection and maintenance of healthy host bone. Copyright © 2011 Orthopaedic Research Society.
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                Author and article information

                Journal
                Jt Dis Relat Surg
                Jt Dis Relat Surg
                Joint Diseases and Related Surgery
                Bayçınar Medical Publishing
                2687-4784
                2687-4792
                August 2023
                26 April 2023
                : 34
                : 2
                : 413-424
                Affiliations
                [1 ] Department of Orthopedics and Traumatology, Health Sciences University, Bağcılar Training and Research Hospital, Istanbul, Türkiye
                [2 ] Department of Orthopedics and Traumatology, Birecik State Hospital, Şanlıurfa, Türkiye
                [3 ] Department of Orthopedics and Traumatology, Istanbul Spine Center & Orthopedics, Group Florence Nightingale Hospitals, Istanbul, Türkiye
                [4 ] Department of Molecular Biology-Genetics and Biotechnology, Istanbul Technical University, Istanbul, Türkiye
                [5 ] Department of Mechanical Engineering, Yıldız Technical University, Istanbul, Türkiye
                Author notes
                Muhammed Uslu, MD. SBÜ Bağcılar Eğitim ve Araştırma Hastanesi Ortopedi ve Travmatoloji Kliniği, 34200 Bağcılar, İstanbul, Türkiye. dr.muhammeduslu@ 123456gmail.com .
                Author information
                http://orcid.org/0000-0002-1810-2713
                http://orcid.org/0000-0002-1568-0112
                http://orcid.org/0000-0003-1385-5721
                http://orcid.org/0000-0002-2443-4802
                http://orcid.org/0000-0001-6691-1235
                http://orcid.org/0000-0002-0399-5467
                http://orcid.org/0000-0001-5029-0825
                http://orcid.org/0000-0001-9796-5033
                Article
                10.52312/jdrs.2023.994
                10367145
                37462646
                9db4636d-d36e-43ea-9683-15c7afe689e7
                Copyright © 2023, Turkish Joint Diseases Foundation

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 20 December 2022
                : 08 March 2023
                Categories
                Original Article

                cephalexin,femur,fracture healing,rat.
                cephalexin, femur, fracture healing, rat.

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