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Bone & Joint Research
Vol. 5, Issue 6 | Pages 263 - 268
1 Jun 2016
Yan J MacDonald A Baisi L Evaniew N Bhandari M Ghert M

Objectives. Despite the fact that research fraud and misconduct are under scrutiny in the field of orthopaedic research, little systematic work has been done to uncover and characterise the underlying reasons for academic retractions in this field. The purpose of this study was to determine the rate of retractions and identify the reasons for retracted publications in the orthopaedic literature. Methods. Two reviewers independently searched MEDLINE, EMBASE, and the Cochrane Library (1995 to current) using MeSH keyword headings and the ‘retracted’ filter. We also searched an independent website that reports and archives retracted scientific publications (. www.retractionwatch.com. ). Two reviewers independently extracted data including reason for retraction, study type, journal impact factor, and country of origin. Results. One hundred and ten retracted studies were included for data extraction. The retracted studies were published in journals with impact factors ranging from 0.000 (discontinued journals) to 13.262. In the 20-year search window, only 25 papers were retracted in the first ten years, with the remaining 85 papers retracted in the most recent decade. The most common reasons for retraction were fraudulent data (29), plagiarism (25) and duplicate publication (20). Retracted articles have been cited up to 165 times (median 6; interquartile range 2 to 19). Conclusion. The rate of retractions in the orthopaedic literature is increasing, with the majority of retractions attributed to academic misconduct and fraud. Orthopaedic retractions originate from numerous journals and countries, indicating that misconduct issues are widespread. The results of this study highlight the need to address academic integrity when training the next generation of orthopaedic investigators. Cite this article: J. Yan, A. MacDonald, L-P. Baisi, N. Evaniew, M. Bhandari, M. Ghert. Retractions in orthopaedic research: A systematic review. Bone Joint Res 2016;5:263–268. DOI: 10.1302/2046-3758.56.BJR-2016-0047


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 52 - 52
2 Jan 2024
den Borre I
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Geometric deep learning is a relatively new field that combines the principles of deep learning with techniques from geometry and topology to analyze data with complex structures, such as graphs and manifolds. In orthopedic research, geometric deep learning has been applied to a variety of tasks, including the analysis of imaging data to detect and classify abnormalities, the prediction of patient outcomes following surgical interventions, and the identification of risk factors for degenerative joint disease. This review aims to summarize the current state of the field and highlight the key findings and applications of geometric deep learning in orthopedic research. The review also discusses the potential benefits and limitations of these approaches and identifies areas for future research. Overall, the use of geometric deep learning in orthopedic research has the potential to greatly advance our understanding of the musculoskeletal system and improve patient care


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 48 - 48
2 Jan 2024
Emmanuel A
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Non-linear methods in statistical shape analysis have become increasingly important in orthopedic research as they allow for more accurate and robust analysis of complex shape data such as articulated joints, bony defects and cartilage loss. These methods involve the use of non-linear transformations to describe shapes, rather than the traditional linear approaches, and have been shown to improve the precision and sensitivity of shape analysis in a variety of applications. In orthopedic research, non-linear methods have been used to study a range of topics, including the analysis of bone shape and structure in relation to osteoarthritis, the assessment of joint deformities and their impact on joint function, and the prediction of patient outcomes following surgical interventions. Overall, the use of non-linear methods in statistical shape analysis has the potential to advance our understanding of the relationship between shape and function in the musculoskeletal system and improve the diagnosis and treatment of orthopedic conditions


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_9 | Pages 45 - 45
1 May 2017
Nikolaou V Chytas D Malahias M Babis G
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Background. The economic crisis has significantly altered the quality of life in Greece. The obvious negative impact on the offered social and health services has been adequately analysed. We aimed to determine whether the economic crisis has influenced the quantity and quality of Orthopaedic research in Greece, as mirrored from the papers presented at the annual meetings of Hellenic Association of Orthopaedic Surgery between the years 2008–2014. Methods. The abstracts of the papers (oral and posters) presented in these meetings have been examined. Details regarding the department of origin were registered. We determined the level of evidence (according to the AAOS classification system), found the amount of papers that were published in PubMed journal and noted if a department of another country participated. Results. Through the years 2008–2014 the papers concerning clinical and basic orthopaedic research that were presented were 146, 207, 304, 331, 318, 234 and 191 respectively. The percentage of those that were level 1 studies was approximately 2%, 3%, 2%, 3%, 2%, 4% and 4% respectively. The percentage of level 2 studies was 2%, 1%, 2%, 3%, 1%, 3% and 0%. Level 3 studies were the 10%, 9%, 7%, 7%, 7%, 9% and 6%. The percentage of level 4 studies was 75%, 74%, 60%, 59%, 61%, 65% and 64%. Level 5 studies were the 10%, 17%, 31%, 27%, 28%, 19% and 26%. Each year, the papers that were published in PubMed were 7%, 21%, 13%, 7%, 6%, 6% and 9%. A department of another country participated in 18%, 17%, 18%, 16%, 16%, 21% and 13% of the total of papers. Conclusion. As the economic crisis deepens, the quantity of the presented papers has been reduced. More importantly, the percentage of level 1 and 2 studies has been remained steadily low. Also, we could remark a reduction on the published studies in PubMed journals. These results raise concerns about the potential impact of the crisis in the future. Level of Evidence. IV


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 1 - 1
1 Mar 2012
Winet H
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Scientific truth is an oxymoron. The goal of modern science is an understanding of the natural world. Truth is the goal of empiricism. In orthopaedic research conflict develops between these goals because empiricists seek to discover ways to improve musculoskeletal health and scientists seek to understand how the musculoskeletal system functions. When resources are limited, a hard choice must be made concerning which path to pursue. The conflict actually has a long history in Western culture that can be traced to differences between Greek and Roman approaches to discovering truths about the natural world. For ancient Greeks, no truth was complete unless a cause-and-effect connection could be established following analysis of observations. For Romans, truths were empirical. They were solutions to solved problems; an aqueduct that did not leak or a healed fracture. Empirical approaches to problems have been a characteristic of Homo sapiens since the Stone Age. They defined the original methodology of medicine and so established it as a “truth” profession. The Romans added engineering to the list of truth professions, although they did not classify it as a profession. Engineering and medicine functioned as truth professions until the 20th century. Science was much slower to mature. The term “scientist” was not coined until 1834. It was not established as a distinct profession until it was freed from scholasticism by the natural philosopher, Francis Bacon, who introduced inductive logic, and Galileo Galilei in the 17th century. They and Isaac Newton launched the Enlightenment which stimulated scientific research for over a century. By the mid-19. th. century, progress in science was sufficient to convince many scientists that they were members of a truth profession that would eventually be able to explain all life functions in terms of physics and chemistry. This reductionist view prevailed until 1927, when it was shown to be invalid by Werner Heisenberg. As a consequence of his ‘Principle of Uncertainty’, science is no longer a “truth” profession. Instead, scientific analysis has become a statistical methodology devoid of final proofs. In place of proofs, the scientist must formulate falsifiable hypotheses that are the reverse of those being proposed. In this approach, developed mainly by Karl Popper, observations are analyzed statistically and if they significantly disagree with the falsifiable hypothesis it may be said to have been disproven and one can say that the data support the proposed hypothesis. Members of truth professions began to perform experiments and employ science as an approach to truth in the 20th century thereby developing an “empirical science”. Since these investigators are constrained by their profession to favor truths, they tend to minimize the Greek and maximize the Roman components of their research. The result has been a dichotomy in science between those whose research success is measured by its contribution to “cures” and those whose research success is measured by its contribution to understanding. In orthopaedics, the dichotomy separates analytical scientists from engineers and physicians. In addition, caught in between are the bioengineers. There is a need for better communication between all


The Bone & Joint Journal
Vol. 96-B, Issue 12 | Pages 1578 - 1585
1 Dec 2014
Rankin KS Sprowson AP McNamara I Akiyama T Buchbinder R Costa ML Rasmussen S Nathan SS Kumta S Rangan A

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.

Cite this article: Bone Joint J 2014; 96-B:1578–85.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 215 - 215
1 Jul 2014
Christou C Rawlinson J Mitchell G Oliver R Walsh W
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Summary

Timing for the application and use of fentanyl patches for pre-emptive analgesia and sedation is crucial to obtain good clinical outcomes. Placement and timing is important to maximise clinical effect and apparent levels of analgesia.

Introduction

The use of sheep as preclinical models for the investigation of orthopaedic conditions is gaining momentum, the control of their pain is a significant ethical issue. The daily need for injecting non-steroidal anti-inflammatory drugs (NSAIDs) and/or the shorter acting opioids increases the demand for handling post-operatively which can increase animal distress and risk of human injury. NSAIDs can have a negative effect on bone healing, complicating results. Opioid analgesics have no impact on bone healing. Fentanyl patches have become another option for use in pain management. Pre-emptive analgesia helps reduce the demand on post-operative analgesic use. Fentanyl has the added benefit of producing mild sedation. This study evaluated the pharmacokinetics of fentanyl patches in sheep in an effort to maximise pre and post-surgical analgesia.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 53 - 53
1 Mar 2021
Carbone V Baretta A Lucano E Palazzin A Bisotti M Bursi R Emili L
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For decades, universities and research centers have been applying modeling and simulation (M&S) to problems involving health and medicine, coining the expression in silico clinical trials. However, its use is still limited to a restricted pool of specialists.

It is here proposed an easy-to-use cloud-based platform that aims to create a collaborative marketplace for M&S in orthopedics, where developers and model creators are able to capitalize on their work while protecting their intellectual property (IP), and researcher, surgeons and medical device companies can use M&S to accelerate time and to reduce costs of their research and development (R&D) processes.

Digital libraries on InSilicoTrials.com are built on collaborations among first-rate research center, model developers, software, and cloud providers (partners). Their access is provided to life science and healthcare companies, clinical centers, and research institutes (users), offering them with several solutions for the different steps of the orthopedics and medical devices R&D process. The platform is built using the Microsoft Azure cloud services, conforming to global standards of security and privacy for healthcare, ensuring that clinical data is properly managed, protected, and kept private. The environment protects the IP of partners against the downloading, copying, and changing of their M&S solutions; while providing a safe environment for users to seamlessly upload their own data, set up and run simulations, analyze results, and produce reports in conformity with regulatory requirements.

The proposed platform allows exploitation of M&S through a Software-as-a-Service delivery model. The pay-per-use pricing: 1. provide partners with a strong incentive to commercialize their high-quality M&S solutions; 2. enable users with limited budget, such as small companies, research centers and hospitals, to use advanced M&S solutions. Pricing of the M&S tools is based on specific aspects, such as particular features and computational power required, in agreement with the developing partner, and is distinct for different types of customers (i.e., academia or industry).

The first medical devices application hosted on InSilicoTrials.com is NuMRis (Numerical Magnetic Resonance Implant Safety), implemented in collaboration with the U.S. F.D.A. Center for Devices and Radiological Health, and ANSYS, Inc. The automatic tool allows the investigation of radiofrequency (RF)-induced heating of passive medical implants, such as orthopedic devices (e.g., rods and screws), pain management devices (e.g., leads), and cardiovascular devices (e.g., stents), following the ASTM F2182-19e2 Standard Test Method. NuMRis promotes the broader adoption of digital evidence in preclinical trials for RF safety analysis, supporting the device submission process and pre-market regulatory evaluation.

InSilicoTrials.com aims at defining a new collaborative framework in healthcare, engaging research centers to safely commercialize their IP, i.e., model templates, simulation tools and virtual patients, by helping clinicians and healthcare companies to significantly expedite the pre-clinical and clinical development phases, and to move across the regulatory approval and HTA processes.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 85 - 85
2 Jan 2024
Zwingenberger S
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Spinal diseases such as unstable fractures, infections, primary or secondary tumors or deformities require surgical stabilization with implants. The long-term success of this treatment is only ensured by a solid bony fusion. The size of the bony defect, the often poor bone quality and metabolic diseases increase the risk of non-union and make the case a great burden for the patient and a challenge for the surgeon. The goal of spinal fusion can only be achieved if the implants used offer sufficient mechanical stability and the local biological regeneration potential is large enough to form sufficient bone. The lecture will present challenging clinical cases. In addition, implant materials and new surgical techniques are discussed. Local therapeutic effects are achieved through the release of osteopromotive or anti-resorbtive drugs, growth factors and antibiotics. By influencing biological pathways, basic orthopedic research has strong potential to further positively change future spinal surgery


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 59 - 59
1 Dec 2021
Vemulapalli KV Kumar KHS Khanduja V
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Abstract. Purpose. Clinical registries are an important aspect of orthopaedic research in assessing the outcomes of surgical intervention and track medical devices. This study aimed to explore the research methodology available to account for patients lost to follow-up (LTFU) specifically in studies related to arthroscopic intervention and whether the rates of patient LTFU are within the acceptable margins for survey studies. Methods. A scoping review, where a literature search for studies from nine arthroscopy registries, was performed on EMBASE, MEDLINE, and the annual reports of each registry. Inclusion criteria included studies with information on patient-reported outcome measures and being based on nine national registries identified. Exclusion criteria included review articles, conference abstracts, studies not based on registry data, and studies from regional, claims-based, or multi-centre registries. Studies were then divided into categories based on method of LTFU analysis used. Results. Thirty-six articles were identified for the final analysis. Categories for LTFU analysis included dropout analyses (n=10), referencing validation studies (n=12), contacting non-responders (n=4), and sensitivity analyses (n=1). Referencing validation studies was the most common method (n=12). Majority (n=35) of the studies exceeded the recommended maximum rates for LTFU. Conclusions. Most arthroscopy studies have rates of LTFU higher than traditionally acceptable. Therefore, any conclusions drawn from these research papers may not be sufficiently valid or free from non-response bias


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 112 - 112
1 Apr 2017
Herregodts S De Baets P Victor J Verstraete M
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Background. Biomechanical joint contact pressure distribution measurements have proven to be a very valuable tool in orthopaedic research to investigate the influence of surgical techniques such as total knee arthroplasty (TKA) on the human knee joint. Quantification of the in vitro tibiofemoral and patellofemoral contact pressure distribution before and after the intervention are an important measure to evaluate the impact of the surgery. The K scan pressure sensor from Tekscan (South Boston USA) is a commonly reported device for these in vitro pressure measurements. Despite the large interest in the sensor, the effective measurement accuracy for in vitro biomechanical joint contact measurement still remains a big question and therefore the reliability of these measurements should be questioned. Methods. Reliable contact pressure measurements can only be done if the sensor behaviour is fully understood. Therefore, a tailored multi-axial testing machine has been designed to profoundly investigate and characterise the sensor behaviour. This test setup is unique through its ability to apply a predefined tangential force or sliding velocity to the sensor's interface next to a normal force. Dynamic effects occurring in knee joint motion can thus be simulated while evaluating the effect on the contact pressure measurements. Results. The change in contact friction coefficient by insertion of the sensor in the joint is quantified. Different interface conditions (dry, lubricated with PTFE spray, lubricated with surgical lubricant) have been evaluated to obtain the best sliding conditions and to minimise the undesired sensor accuracy deteriorating effects. Conclusion. An optimal calibration procedure is put forward and side-effects that deteriorate the measurement accuracy are quantified. The provided knowledge facilitates orthopaedic biomechanics researchers to optimally perform joint contact measurements and to estimate the effective measurement accuracy. In addition, the presented rig provides the opportunity to study the inherent knee kinematics and prosthesis shape optimisation through the inherent degrees of freedom in the rig


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 32 - 32
1 Nov 2018
Hoang-Kim A
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We need to shift our focus to integrating sex and gender into research proposals, so we can answer some of the most basic unanswered questions in the field of fracture management. Current evidence in guidelines indicate a near-to-linear increase from the 1990s for inclusion of sex and gender. However, these recommendations remain expressed in absolute terms, with little explanatory power, affecting uptake and implementation in clinical practice. This co-branded session, with members of the Orthopaedic Research Society – International section of fracture repair (ORS-ISFR), will provide participants with guiding principles and tools to assist researchers and grant reviewers understand what it means to include sex and gender in meaningful ways: from formulating research questions, recruitment strategies, to conducting sex-stratified analyses. In this presentation, we will consider diverse approaches, methods and, analyses to elevate sex and gender within trauma. A strong emphasis on the ways and means of including marginalized and vulnerable populations in research will be addressed


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 31 - 31
1 Dec 2020
Shah DS Taylan O Berger P Labey L Vandenneucker H Scheys L
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Orthopaedic training sessions, vital for surgeons to understand post-operative joint function, are primarily based on passive and subjective joint assessment. However, cadaveric knee simulators, commonly used in orthopaedic research,. 1. could potentially benefit surgical training by providing quantitative joint assessment for active functional motions. The integration of cadaveric simulators in orthopaedic training was explored with recipients of the European Knee Society Arthroplasty Travelling Fellowship visiting our institution in 2018 and 2019. The aim of the study was to introduce the fellows to the knee joint simulator to quantify the surgeon-specific impact of total knee arthroplasty (TKA) on the dynamic joint behaviour, thereby identifying potential correlations between surgical competence and post-operative biomechanical parameters. Eight fellows were assigned a fresh-frozen lower limb each to plan and perform posterior-stabilised TKA using MRI-based patient-specific instrumentation. Surgical competence was adjudged using the Objective Structured Assessment of Technical Skills (OSATS) adapted for TKA. 2. All fellows participated in the in vitro specimen testing on a validated knee simulator,. 3. which included motor tasks – passive flexion (0°-120°) and active squatting (35°-100°) – and varus-valgus laxity tests, in both the native and post-operative conditions. Tibiofemoral kinematics were recorded with an optical motion capture system and compared between native and post-operative conditions using a linear mixed model (p<0.05). The Pearson correlation test was used to assess the relationship between the OSATS scores for each surgeon and post-operative joint kinematics of the corresponding specimen (p<0.05). OSATS scores ranged from 79.6% to 100% (mean=93.1, SD=7.7). A negative correlation was observed between surgical competence and change in post-operative tibial kinematics over the entire range of motion during passive flexion – OSATS score vs. change in tibial abduction (r=−0.87; p=0.003), OSATS score vs. change in tibial rotation (r=−0.76; p=0.02). When compared to the native condition, post-operative tibial internal rotation was higher during passive flexion (p<0.05), but lower during squatting (p<0.033). Post-operative joint stiffness was greater in extension than in flexion, without any correlation with surgical competence. Although trained at different institutions, all fellows followed certain standard intraoperative guidelines during TKA, such as achieving neutral tibial abduction and avoiding internal tibial rotation,. 4. albeit at a static knee flexion angle. However, post-operative joint kinematics for dynamic motions revealed a strong correlation with surgical competence, i.e. kinematic variability over the range of passive flexion post-TKA was lower for more skilful surgeons. Moreover, actively loaded motions exhibited stark differences in post-operative kinematics as compared to those observed in passive motions. In vitro testing on the knee simulator also introduced the fellows to new quantitative parameters for post-operative joint assessment. In conclusion, the inclusion of cadaveric simulators replicating functional joint motions could help quantify training paradigms, thereby enhancing traditional orthopaedic training, as was also the unanimous opinion of all participating fellows in their positive feedback


There has been a recent surge in the creation of medical student-led and foundation trainees-led research collaboratives in surgery. These have mainly been in general surgery. The current study therefore explores the value and feasibility of such collaboratives, highlighting the scope for a similar idea in orthopaedics. Research Collaborative organisations were systematically searched and reviewed to check whether medical students or junior doctors prior to speciality training led them. The advertised research projects and subsequent publication productivity for each identified organisation was also evaluated using the information presented on their websites. Two medical student-led research collaborative organisations and 1 medical student and foundation trainees-led research collaborative were identified. All of which are in general surgery and none in trauma and/or orthopaedics surgery. These include STARSurg, EuroSurg and GlobalSurg respectively. A total of 6 research collaborative projects were identified with 3 leading to subsequent publications. This study highlights the value and feasibility of medical students- and foundation trainees-driven high quality surgical research collaborative. It also emphasises the growing contribution of medical students towards research and policymaking in our global health system, an aspect that may be absent or delayed in the field of orthopaedics. We therefore, explore the idea as well as the need to instigate a similar collaboration in the field of trauma and orthopaedic surgery


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 39 - 39
1 Apr 2018
Riegger J Joos H Palm HG Friemert B Reichel H Ignatius A Brenner R
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Cartilage injury is generally associated with cytokine release and accumulation of reactive oxygen species. These mediators trigger pathologic behaviour of the surviving chondrocytes, which respond by excessive expression of catabolic enzymes, such as matrix metalloproteinase 13 (MMP-13), reduced synthesis of type II collagen (COL2A1) and apoptosis. In the long run, these pathologic conditions can cause a posttraumatic osteoarthritis. With the objective to attenuate the progressive degradation of the extracellular matrix and, what is more, promote chondroanabolic processes, a multidirectional treatment of trauma-induced pathogenesis was tested for the first time. Therefore, we evaluated the combinations of one anabolic growth factor (IGF-1, FGF18 or BMP7) with the antioxidant N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma model and compared the findings with the corresponding monotherapy. Human cartilage tissue was obtained with informed consent from donors undergoing knee joint replacement (n=24). Only macroscopically intact tissue was used to prepare explants. Cartilage explants were subjected to a blunt impact (0.59 J) by a drop-tower and treated by IGF-1 [100 ng/mL], FGF18 [200 ng/mL] or BMP7 [100 ng/mL] and/or NAC [2 mM] for 7 days. Following parameters were analysed: cell viability (live/dead staining), gene expression (qRT-PCR) as well as biosynthesis (ELISA) of type II collagen and MMP-13. For statistical analysisKruskal-Wallis or One-way ANOVA was used. All data were collected in the orthopedic research laboratory of the University of Ulm, Germany. Trauma-induced cell death was completely prevented by NAC treatment and FGF18 or BMP7 to a large extent, respectively (p<0.0001). IGF-1 exhibited only poor cell protection. Combination of NAC and FGF18 or BMP7 did not result in enhanced effectiveness; however, IGF-1 significantly reduced NAC-mediated cell protection. While IGF-1 or BMP7 induced collagen type II gene expression (p=0.0069 and p<0.0001, respectively) and its biosynthesis (p<0.0001 and p=0.0131, respectively), NAC or FGF18 caused significant suppression of this matrix component (each p<0.001). Although COL2A1 mRNA was significantly increased by NAC plus IGF-1 (p<0.0001), biosynthesis of collagen type II was generally abolished after multidirectional treatment. Except for IGF-1, all tested therapeutics exhibited chondroprotective qualities, as demonstrated by attenuated MMP-13 expression and breakdown of type II collagen. In combination with IGF-1, NAC-mediated chondroprotection was reduced. Overall, both chondroanabolic and antioxidative therapy had individual advantages. Since adverse interactions were found by simultaneous application of the therapeutics, a sequential approach might improve the efficacy. In support of this strategy current experiments showed that though cell and chondroprotective effects of NAC were maintained after withdrawal of the antioxidant, type II collagen expression recovered by time


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_7 | Pages 7 - 7
1 Apr 2014
Silverwood R Fairhurst P Tsimbouri P Sjostrom T Young P Su B Meek R Dalby M
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Background. Aseptic loosening remains the primary reason for failure of orthopaedic implants. Therefore a prime focus of Orthopaedic research is to improve osteointegration and outcomes of joint replacements. The topography of a material surface has been shown to alter cell adhesion, proliferation and growth. The use of nanotopography to promote cell adhesion and bone formation is hoped to improve osteointegration and outcomes of implants. We have previously shown that 15nm high features are bioactive. The arrangement of nanofeatures has been shown to be of importance and block-copolymer separation allows nanopillars to be anodised into the titania layer, providing a compromise of control of order and height of nanopillars. Osteoblast/osteoclast stem cell co-cultures are believed to give the most accurate representation of the in vivo environment, allowing assessment of bone remodelling related to biomaterials. Aims. To assess the use of nanotopography on titania substrates when cultured in a human bone marrow derived co-culture method. Hypothesis. Under co-culture conditions 15nm high nanopillars on titania substrate will induce significantly increased levels of osteogenic differentiation, producing a method of enhancing secondary implant fixation. Methods/Design. Bone marrow was aspirated from patients undergoing elective arthroplasty. Co-culture of adherent osteoprogenitors and osteoclast progenitors on polished titania and titania patterned with 15nm nanopillars fabricated by the block copolymer technique was performed. Histochemical staining has been performed to identify and quantify osteoclasts and bone nodule formation. Scanning electron microscopy (SEM) has been conducted to morphologically examine the effect on differentiation of untreated and nanopatterned titania substrates on osteoprogenitors and osteoclasts. Real-Time, quantitative reverse-transcription polymerase chain reaction is currently being utilised to quantify expression of osteoblast, osteoclast and inflammatory response related genes. Results. SEM has shown an increase in bone deposition on titania substrates with 15nm nanopillars. The remaining results of this project will be presented with a discussion of their clinical significance


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_13 | Pages 37 - 37
1 Mar 2013
Smith I Milto K Doherty C Amyes S Simpson A Hall A
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Staphylococcus aureus is a highly virulent pathogen and implicated in approximately 50% of cases of septic arthritis. Studies investigating other S. aureus-related infections suggest that alpha-(Hla), beta-(Hlb) and gamma-(Hlg) toxins are key virulence factors, with the ‘pore-forming’ alpha-toxin considered the most potent. Here, we have assessed the influence of alpha-toxin alone on in situ chondrocyte viability. Osteochondral explants were harvested from the metacarpophalangeal joints of 3-year-old cows and cultured in Dulbecco's Modified Eagle's Medium. The flasks were then inoculated with isogenic ‘knockout’ strains of S. aureus: DU5946 (Hla+Hlb-Hlg-: alpha-toxin only strain) or DU1090 (Hla-Hlb+Hlg+: beta- and gamma-toxin only strain). Explants were incubated (37°C) and stained after 18, 24 and 40hrs with chloromethylfluorescein-di-acetate and propidium iodide, labelling living chondrocytes green and dead cells red, respectively. Axial sections were imaged by confocal microscopy and the percentage cell death determined. Alpha-toxin-producing S. aureus caused 24.8+/−3.7% chondrocyte death at 18hrs and 44.6+/−7.2% death at 24hrs. At 40hrs, there was significantly more chondrocyte death (87.4+/−3.6%;p<0.001) compared to the alpha-toxin knockout strain, which was negligible (4.1+/−1.7%; means+/−SEM; N=4 independent experiments). In this in vitro bovine cartilage explant model, whereby the effects of defined toxins were determined in isolation of a complex host immune response, in situ chondrocyte viability was dramatically and exclusively reduced by alpha-toxin. This work forms the basis for developing a rational treatment to reduce the extent of cartilage destruction during an episode of septic arthritis. IDMS was supported by Orthopaedic Research UK and The Royal College of Surgeons of Edinburgh


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_13 | Pages 28 - 28
1 Mar 2013
Smith I Winstanley J Doherty C Amyes S Simpson A Hall A
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We have demonstrated that toxins produced by Staphylococcus aureus, a common infective agent in septic arthritis (SA), cause rapid in situ chondrocyte death. Here, we have compared the sensitivity of chondrocytes within the superficial and deep zones (SZ, DZ) of cartilage to the same toxins. Culture medium containing the toxins produced by S. aureus strain 8325-4, which include alpha-, beta-, and gamma-toxin, was prepared. Cartilage explants free of subchondral bone were taken from the metacarpophalangeal joints of 3-year-old cows, and incubated (37°C) with the toxins. Explants were stained after 6hrs with chloromethylfluorescein-di-acetate and propidium iodide, labelling living chondrocytes green and dead cells red, respectively. Full-thickness coronal sections were imaged by confocal microscopy and the percentage cell death within the SZ (100μm from articular surface) and DZ (100μm from subchondral bone interface) determined. Both zones were incubated with the same toxin culture medium for the same time period. At 0hrs, chondrocytes within all zones were >98% viable. However, after incubation with toxin-containing culture medium for 6hrs, 71.9+/−11.2% of the SZ cells were dead compared to only 47.4+/−6.7% in the DZ (p=0.03;data are means+/−SEM;N=4). These results suggest that SZ chondrocytes are considerably more sensitive to S. aureus toxins than those within deeper zones. As SZ chondrocytes are close to the synovial fluid harbouring bacterial toxins, these data emphasise the need to remove bacteria and their products aggressively as part of the treatment of SA. IDMS was supported by Orthopaedic Research UK and The Royal College of Surgeons of Edinburgh


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_17 | Pages 6 - 6
1 Apr 2013
Landham P Baker H Gilbert S Pollintine P Robson-Brown KK Adams M Dolan P
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Introduction. Senile kyphosis arises from anterior ‘wedge’ deformity of thoracolumbar vertebrae, often in the absence of trauma. It is difficult to reproduce these deformities in cadaveric spines, because a vertebral endplate usually fails first. We hypothesise that endplate fracture concentrates sufficient loading on to the anterior cortex that a wedge deformity develops subsequently under physiological repetitive loading. Methods. Thirty-four cadaveric thoracolumbar “motion segments,” aged 70–97 yrs, were overloaded in combined bending and compression. Physiologically-reasonable cyclic loading was then applied, at progressively higher loads, for up to 2 hrs. Before and after fracture, and again after cyclic loading the distribution of compressive loading on the vertebral body was assessed from recordings of compressive stress along the sagittal mid-plane of the adjacent intervertebral disc. Vertebral deformity was assessed from radiographs at the beginning and end of testing. Results. Initial overload usually fractured a vertebral endplate, at 2.31 kN (STD 0.85). There was minimal anterior wedging, but pressure in the nucleus of the adjacent disc was reduced by 65.2% on average, and relatively elevated in the annulus and neural arch. Subsequent cyclic loading then caused anterior wedge deformity of the vertebral body, with the height of the anterior and posterior cortex decreasing by 34.3% (13.2) and 12.7% (7.5) respectively, and wedge angle increasing from 5.0° (3.76) to 11.4° (3.93) (all p<0.001). Discussion and Conclusion. Our hypothesis is supported: initial minor damage facilitates progressive anterior wedge deformity by transferring compressive loading on to the anterior cortex. Detecting initial endplate damage is important to minimise subsequent vertebral deformity in patients with osteoporosis. No conflicts of interest. Sources of funding: Funding was provided by a Royal College of Surgeons of England Research Fellowship and by the Gloucestershire Arthritis Trust. This work was presented at the British Orthopaedic Research Society Meeting


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 175 - 175
1 Jul 2014
Razmjou H Gunnis G Holtby R
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Summary. Data of 663 patients with three different pathologies were examined. We found that using patients with significant symptoms and functional difficulty in the opposite shoulder will not bias the results of observational studies if outcomes are based on routine disability measures such as ASES or Constant-Murley scores. Introduction. Recently, using patients with bilateral limb problems as independent cases has raised concerns in orthopaedic research due to violating the assumption of independence. If observations are too similar in characteristics, they become highly correlated which leads to lowering the variance and biasing the results. Type of pathology (impingement, cuff tear, osteoarthritis) and aging are expected to affect the incidence of bilateral shoulder complaints and should be considered when examining potential bias in this area. In addition, the impact of dominant side pathology has not been investigated primarily in patients with shoulder problems. The objectives of this study were: 1) to examine the incidence of bilateral shoulder complaints and pathology on the dominant side in patients with impingement syndrome, rotator cuff tear and osteoarthritis of the glenohumeral joint, 2) to explore the role of sex and age in developing bilateral shoulder complaints, and 3) to examine the impact of bilaterality and hand dominance on pre and one year post-operative disability. Patients and Methods. This study involved review of data of patients with a diagnosis of impingement syndrome, rotator cuff tears and osteoarthritis (OA) of the gleno-humeral joint who had undergone surgery and had returned for their one year follow-up. Two outcome measures were used; the American Shoulder & Elbow Surgeons (ASES) and the Constant Murley score (CMS). Results. Data of 663 patients (317 females; 269 impingement syndrome, 290 rotator cuff tear, 104 osteoarthritis) were included in the analysis. There was a difference in the incidence of bilateral symptoms in patients with different pathologies: osteoarthritis 46%, impingement 26%, and rotator cuff tears 23% (p<0.0001). The incidence of dominant side involvement was 70%, 68% and 50% in patients with rotator cuff tear, impingement syndrome and osteoarthritis (p=0.003). Neither bilaterality nor dominant arm pathology had a negative impact on disability (p>0.05). Discussion/Conclusion. Type of pathology and aging affect the incidence of bilateral shoulder symptoms. Rotator cuff related pathologies affect the dominant side more frequently. The most interesting finding of this study was related to lack of influence of bilateral symptoms or dominant side pathology on reported disability in three different pathology groups with different prevalence of disease