The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase.Aims
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Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq).Aims
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Aims. A core outcome set for adult, open lower limb fracture has been established consisting of ‘Walking, gait and mobility’, ‘Being able to return to life roles’, ‘Pain or discomfort’, and ‘Quality of life’. This study aims to identify which outcome measurement instruments (OMIs) should be recommended to measure each core outcome. Methods. A systematic review and quality assessment were conducted to identify existing instruments with evidence of good measurement properties in the open lower limb fracture population for each core outcome. Additionally, shortlisting criteria were developed to identify suitable instruments not validated in the target population. Candidate instruments were presented, discussed, and voted on at a consensus meeting of key stakeholders. Results. The Wales Lower Limb Trauma Recovery scale was identified, demonstrating validation evidence in the target population. In addition, ten candidate OMIs met the shortlisting criteria. Six patients, eight healthcare professionals, and 11
Aims. Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture. Methods. Candidate outcomes were identified from a previously published systematic review and a secondary thematic analysis of 25 patient interviews exploring the lived experience of recovery from open lower limb fracture. Outcomes were categorized and sequentially refined using healthcare professional and patient structured discussion groups. Consensus methods included a multi-stakeholder two-round online Delphi survey and a consensus meeting attended by a purposive sample of stakeholders, facilitated discussion, and voting using a nominal group technique. Results. Thematic analysis and systematic review identified 121 unique outcomes, reduced to 68 outcomes following structured discussion groups. Outcomes were presented to 136 participants who completed a two-round online Delphi survey. The Delphi survey resulted in 11 outcomes identified as consensus ‘in’ only. All outcomes were discussed at a consensus meeting attended by 15 patients, 14 healthcare professionals, 11
A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing.Aims
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Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood. MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay.Aims
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Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture. A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months.Aims
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In this study, we aimed to explore surgical variations in the Femoral Neck System (FNS) used for stable fixation of Pauwels type III femoral neck fractures. Finite element models were established with surgical variations in the distance between the implant tip and subchondral bone, the gap between the plate and lateral femoral cortex, and inferior implant positioning. The models were subjected to physiological load.Aims
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Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation. The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation.Aims
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The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus. A cohort of ten closed tibial shaft fractures managed with intramedullary nailing underwent ultrasound scanning at two, six, and 12 weeks post-surgery. Ultrasound capture was performed using infrared tracking technology to map each image to a 3D lattice. Using echo intensity, semi-automated mapping was performed to produce an anatomical 3D representation of the fracture site. Two reviewers independently performed 3D reconstructions and kappa coefficient was used to determine agreement. A further validation study was undertaken with ten reviewers to estimate the clinical application of this imaging technique using the intraclass correlation coefficient (ICC).Aims
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Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing. A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.Aims
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To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme.Aims
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A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis.Aims
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CT-based three-column classification (TCC) has been widely used in the treatment of tibial plateau fractures (TPFs). In its updated version (updated three-column concept, uTCC), a fracture morphology-based injury mechanism was proposed for effective treatment guidance. In this study, the injury mechanism of TPFs is further explained, and its inter- and intraobserver reliability is evaluated to perfect the uTCC. The radiological images of 90 consecutive TPF patients were collected. A total of 47 men (52.2%) and 43 women (47.8%) with a mean age of 49.8 years (Objectives
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The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”.Objectives
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The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels. Serum obtained from 51 patients with long bone fractures was collected over 48 weeks. The OPG and serum sRANKL (soluble RANKL) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Smoking habit, diabetes, and alcohol consumption were recorded.Objectives
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The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular. English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers.Objectives
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