Introduction. In response to the COVID-19 pandemic, there was a rapidly implemented restructuring of UK healthcare services. The The Royal National Orthopaedic Hospital, Stanmore, became a central hub for the provision of trauma services for North Central/East London (NCEL) while providing a musculoskeletal tumour service for the south of England, the Midlands, and Wales and an urgent spinal service for London. This study reviews our paediatric practice over this period in order to share our experience and lessons learned. Our hospital admission pathways are described and the safety of surgical and interventional radiological procedures performed under general anaesthesia (GA) with regards to COVID-19 in a paediatric population are evaluated. Methods. All paediatric patients (≤ 16 years) treated in our institution during the six-week peak period of the pandemic were included. Prospective data for all paediatric trauma and urgent elective admissions and retrospective data for all sarcoma admissions were collected. Telephone interviews were conducted with all patients and families to assess COVID-19 related morbidity at 14 days post-discharge. Results. Overall, 100 children underwent surgery or interventional radiological procedures under GA between 20 March and 8 May 2020. There were 35 trauma cases, 20 urgent elective orthopaedic cases, two spinal emergency cases, 25 admissions for interventional radiology procedures, and 18 tumour cases. 78% of trauma cases were performed within 24 hours of referral. In the 97% who responded at two weeks following discharge, there were no cases of symptomatic COVID-19 in any patient or member of their households. Conclusion. Despite the extensive restructuring of services and the widespread concerns over the surgical and anaesthetic management of paediatric patients during this period, we treated 100 asymptomatic patients across different orthopaedic subspecialties without apparent COVID-19 or unexpected respiratory complications in the early postoperative period. The data provides assurance for health care professionals and families and informs the consenting process. Cite this article: Bone Joint Open 2020;1-6:287–292

Aims. The migration percentage (MP) is one criterion used for surgery in dislocated or displaced hips in children with cerebral palsy (CP). The MP at which a displaced hip can no longer return to normal is unclear. The aim of this paper was to identify the point of no return of the MP through a large population-based study. Methods. All children registered on the Cerebral Palsy Integrated Pathway Scotland surveillance programme undergo regular pelvic radiographs. Any child who had a MP measuring over 35% since the programme’s inception in 2013, in at least one hip and at one timepoint, was identified. The national radiography database was then interrogated to identify all pelvic radiographs for each of these children from birth through to the date of analysis. A minimum of a further two available radiographs following the initial measurement of MP ≥ 35% was required for inclusion. Results. A total of 239 children (346 hips) were identified as suitable for analysis at a mean of 6.5 years (2.0 to 14.8) follow-up. In all, 1,485 radiographs taken both prior to and after a hip had a MP ≥ 35% were examined and the MP measured to identify any progression of displacement. Interrogation of the data identified that hips with a MP up to 46% returned to a MP below 40% without intervention, and all hips with a MP equal to or greater than 46% displaced further and the MP did not return to the normal range. Statistical analysis showed the result to be 98% specific with this degree of certainty that hips reaching a MP ≥ 46% would not spontaneously regress. Conclusion. These findings are clinically relevant in showing that it may be reasonable to continue to monitor hips with a MP not exceeding 46%. This threshold will also guide referral for further management of a displacing hip. Cite this article: Bone Joint J 2021;103-B(2):411–414

Aims. This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. Methods. TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results. Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. Conclusion. The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss. Cite this article: Bone Joint Res 2020;9(11):827–839

Aims. COVID-19 represents one of the greatest global healthcare challenges in a generation. Orthopaedic departments within the UK have shifted care to manage trauma in ways that minimize exposure to COVID-19. As the incidence of COVID-19 decreases, we explore the impact and risk factors of COVID-19 on patient outcomes within our department. Methods. We retrospectively included all patients who underwent a trauma or urgent orthopaedic procedure from 23 March to 23 April 2020. Electronic records were reviewed for COVID-19 swab results and mortality, and patients were screened by telephone a minimum 14 days postoperatively for symptoms of COVID-19. Results. A total of 214 patients had orthopaedic surgical procedures, with 166 included for analysis. Patients undergoing procedures under general or spinal anaesthesia had a higher risk of contracting perioperative COVID-19 compared to regional/local anaesthesia (p = 0.0058 and p = 0.0007, respectively). In all, 15 patients (9%) had a perioperative diagnosis of COVID-19, 14 of whom had fragility fractures; six died within 30 days of their procedure (40%, 30-day mortality). For proximal femoral fractures, our 30-day mortality was 18.2%, compared to 7% in 2019. Conclusion. Based on our findings, patients undergoing procedures under regional or local anaesthesia have minimal risk of developing COVID-19 perioperatively. Those with multiple comorbidities and fragility fractures have a higher morbidity and mortality if they contract COVID-19 perioperatively; therefore, protective care pathways could go some way to mitigate the risk. Our 30-day mortality of proximal femoral fractures was 18.2% during the COVID-19 pandemic in comparison to the annual national average of 6.1% in 2018 and the University Hospital Coventry average of 7% for the same period in 2019, as reported in the National Hip Fracture Database. Patients undergoing procedures under general or spinal anaesthesia at the peak of the pandemic had a higher risk of contracting perioperative COVID-19 compared to regional block or local anaesthesia. We question whether young patients undergoing day-case procedures under regional block or local anaesthesia with minimal comorbidities require fourteen days self-isolation; instead, we advocate that compliance with personal protective equipment, a negative COVID-19 swab three days prior to surgery, and screening questionnaire may be sufficient. Cite this article: Bone Joint Open 2020;1-9:520–529

The COVID-19 virus is a tremendous burden for the Italian health system. The regionally-based Italian National Health System has been reorganized. Hospitals' biggest challenge was to create new intensive care unit (ICU) beds, as the existing system was insufficient to meet new demand, especially in the most affected areas. Our institution in the Milan metropolitan area of Lombardy, the epicentre of the infection, was selected as one of the three regional hub for major trauma, serving a population of more than three million people. The aims were the increase the ICU beds and the rationalization of human and structural resources available for treating COVID-19 patients. In our hub hospital, the reorganization aimed to reduce the risk of infection and to obtained resources, in terms of beds and healthcare personnel to be use in the COVID-19 emergency. Non-urgent outpatient orthopaedic activity and elective surgery was also suspended. A training programme for healthcare personnel started immediately. Orthopaedic and radiological pathways dedicated to COVID-19 patients, or with possible infection, have been established. In our orthopaedic department, we passed from 70 to 26 beds. Our goal is to treat trauma surgery's patient in the “golden 72 hours” in order to reduce the overall hospital length of stay. We applied an objective priority system to manage the flow of surgical procedures in the emergency room based on clinical outcomes and guidelines. Organizing the present to face the emergency is a challenge, but in the global plan of changes in hospital management one must also think about the near future. We reported the Milan metropolitan area orthopaedic surgery management during the COVID-19 pandemic. Our decisions are not based on scientific evidence; therefore, the decision on how reorganize hospitals will likely remain in the hands of individual countries

Aims. Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. Methods. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. Results. The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. Conclusion. The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data. Cite this article:Bone Joint Res. 2020;9(3):108–119

Objectives. Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data. Method. We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. Results. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10. -4. for LS and 2.7 × 10. -2. for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10. -4. for femoral necks and 2.6 × 10. -2. for lumbar spines BMD in meQTLs-based GSEA). Conclusion. Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article: W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572–576

The Ankle Injury Management (AIM) trial was a pragmatic equivalence randomized controlled trial conducted at 24 hospitals in the United Kingdom that recruited 620 patients aged more than 60 years with an unstable ankle fracture. The trial compared the usual care pathway of early management with open reduction and internal fixation with initially attempting non-surgical management using close contact casting (CCC). CCC is a minimally padded cast applied by an orthopaedic surgeon after closed reduction in the operating theatre. The intervention groups had equivalent functional outcomes at six months and longer-term follow-up. However, potential barriers to using CCC as an initial form of treatment for these patients have been identified. In this report, the results of the AIM trial are summarized and the key issues are discussed in order to further the debate about the role of CCC. Evidence from the AIM trial supports surgeons considering conservative management by CCC as a treatment option for these patients. The longer-term follow-up emphasized that patients treated with CCC need careful monitoring in the weeks after its application to monitor maintenance of reduction. Cite this article: Bone Joint J 2019;101-B:1472–1475

This study examined spinal fractures in patients admitted to a Major Trauma Centre via two independent pathways, a major trauma (MT) pathway and a standard unscheduled non-major trauma (NMT) pathway. A total of 134 patients were admitted with a spinal fracture over a period of two years; 50% of patients were MT and the remainder NMT. MT patients were predominantly male, had a mean age of 48.8 years (13 to 95), commonly underwent surgery (62.7%), characteristically had fractures in the cervico-thoracic and thoracic regions and 50% had fractures of more than one vertebrae, which were radiologically unstable in 70%. By contrast, NMT patients showed an equal gender distribution, were older (mean 58.1 years; 12 to 94), required fewer operations (56.7%), characteristically had fractures in the lumbar region and had fewer multiple and unstable fractures. This level of complexity was reflected in the length of stay in hospital; MT patients receiving surgery were in hospital for a mean of three to four days longer than NMT patients. These results show that MT patients differ from their NMT counterparts and have an increasing complexity of spinal injury. Cite this article: Bone Joint J 2015;97-B:235–9

Aims. The risk to patients and healthcare workers of resuming elective orthopaedic surgery following the peak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been difficult to quantify. This has prompted governing bodies to adopt a cautious approach that may be impractical and financially unsustainable. The lack of evidence has made it impossible for surgeons to give patients an informed perspective of the consequences of elective surgery in the presence of SARS-CoV-2. This study aims to determine, for the UK population, the probability of a patient being admitted with an undetected SARS-CoV-2 infection and their resulting risk of death; taking into consideration the current disease prevalence, reverse transcription-polymerase chain reaction (RT-PCR) testing, and preassessment pathway. Methods. The probability of SARS-CoV-2 infection with a false negative test was calculated using a lower-end RT-PCR sensitivity of 71%, specificity of 95%, and the UK disease prevalence of 0.24% reported in May 2020. Subsequently, a case fatality rate of 20.5% was applied as a worst-case scenario. Results. The probability of SARS-CoV-2 infection with a false negative preoperative test was 0.07% (around 1 in 1,400). The risk of a patient with an undetected infection being admitted for surgery and subsequently dying from the coronavirus disease 2019 (COVID-19) is estimated at approximately 1 in 7,000. However, if an estimate of the current global infection fatality rate (1.04%) is applied, the risk of death would be around 1 in 140,000, at most. This calculation does not take into account the risk of nosocomial infection. Conversely, it does not factor in that patients will also be clinically assessed and asked to self-isolate prior to surgery. Conclusion. Our estimation suggests that the risk of patients being inadvertently admitted with an undetected SARS-CoV-2 infection for elective orthopaedic surgery is relatively low. Accordingly, the risk of death following elective orthopaedic surgery is low, even when applying the worst-case fatality rate. Cite this article: Bone Joint J 2020;102-B(9):1256–1260

Aims. The purpose of this study was to assess total knee arthroplasty (TKA) volume and rates of early complications in morbidly obese patients over the last decade, where the introduction of quality models influencing perioperative care pathways occurred. Methods. Patients undergoing TKA between 2011 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patients were stratified by BMI < 40 kg/m. 2. and ≥ 40 kg/m. 2. and evaluated by the number of cases per year. The 30-day rates of any complication, wound complications, readmissions, and reoperation were assessed. Trends in these endpoints over the study period were compared between groups using odds ratios (ORs) and multivariate analyses. Results. In total, 314,695 patients underwent TKA and 46,362 (15%) had BMI ≥ 40 kg/m. 2. The prevalence of morbid obesity among TKA patients did not change greatly, ranging between 14% and 16%. Reoperation rate decreased from 1.16% to 0.96% (odds ratio (OR) 0.81 (95% confidence interval (CI) 0.66 to 0.99)) for patients with BMI < 40 kg/m. 2. , as did rates of readmission (4.46% to 2.87%; OR 0.61 (0.55 to 0.69)). Patients with BMI ≥ 40 kg/m. 2. also had fewer readmissions over the study period (4.87% to 3.34%; OR 0.64 (0.49 to 0.83)); however, the rate of reoperation did not change (1.37% to 1.41%; OR 0.99 (0.62 to 1.56)). Significant improvements were not observed for infective complications over time for either group; patients with BMI ≥ 40 kg/m. 2. had increased risk of both deep infection and wound complications compared to non-morbidly obese patients. Rate of any complication decreased for all patients. Conclusion. The proportion of TKAs in morbidly obese patients has not significantly changed over the past decade. Although readmission rates improved for all patients, reductions in reoperation in non-morbidly obese patients were not experienced by the morbidly obese, resulting in a widening of the complication gap between these cohorts. Care improvements have not lowered the differential risk of infective complications in the morbidly obese. Cite this article: Bone Joint J 2021;103-B(6 Supple A):38–44

Aims. “Get It Right First Time” (GIRFT) and NHS England’s Best Practice Tariff (BPT) have published directives advising that patients over the ages of 65 (GIRFT) and 69 years (BPT) receiving total hip arthroplasty (THA) should receive cemented implants and have brought in financial penalties if this policy is not observed. Despite this, worldwide, uncemented component use has increased, a situation described as a ‘paradox’. GIRFT and BPT do, however, acknowledge more data are required to support this edict with current policies based on the National Joint Registry survivorship and implant costs. Methods. This study compares THA outcomes for over 1,000 uncemented Corail/Pinnacle constructs used in all age groups/patient frailty, under one surgeon, with identical pre- and postoperative pathways over a nine-year period with mean follow-up of five years and two months (range: nine months to nine years and nine months). Implant information, survivorship, and regular postoperative Oxford Hip Scores (OHS) were collected and two comparisons undertaken: a comparison of those aged over 65 years with those 65 and under and a second comparison of those aged 70 years and over with those aged under 70. Results. Overall revision rate was 1.3% (13/1,004). A greater number of revisions were undertaken in those aged over 65 years, but numbers were small and did not reach significance. The majority of revisions were implant-independent. Single component analysis revealed a 99.9% and 99.6% survival for the uncemented cup and femoral component, respectively. Mean patient-reported outcome measures (PROMs) improvement for all ages outperformed the national PROMs and a significantly greater proportion of those aged over 65/69 years reached and maintained a meaningful improvement in their OHS earlier than their younger counterparts (p < 0.05/0.01 respectively). Conclusion. This study confirms that this uncemented THA system can be used safely and effectively in patient groups aged over 65 years and those over 69 years, with low complication and revision rates. Cite this article: Bone Jt Open 2021;2(5):293–300

Objectives. In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases. Cite this article: J. Zhang, X. Hao, M. Yin, T. Xu, F. Guo. Long non-coding RNA in osteogenesis: A new world to be explored. Bone Joint Res 2019;8:73–80. DOI: 10.1302/2046-3758.82.BJR-2018-0074.R1

Aims. Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods. A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results. There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (. sd. ) 11) vs 37° (. sd. 14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion. Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. doi: 10.1302/2046-3758.51.2000593

Objectives. The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods. The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results. In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion. This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients. Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290–303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1

Aims. We assessed the difference in hospital based and early clinical outcomes between the direct anterior approach and the posterior approach in patients who undergo total hip arthroplasty (THA). Patients and Methods. The outcome was assessed in 448 (203 males, 245 females) consecutive patients undergoing unilateral primary THA after the implementation of an ‘Enhanced Recovery’ pathway. In all, 265 patients (mean age: 71 years (49 to 89); 117 males and 148 females) had surgery using the direct anterior approach (DAA) and 183 patients (mean age: 70 years (26 to 100); 86 males and 97 females) using a posterior approach. The groups were compared for age, gender, American Society of Anesthesiologists grade, body mass index, the side of the operation, pre-operative Oxford Hip Score (OHS) and attendance at ‘Joint school’. Mean follow-up was 18.1 months (one to 50). Results. There was no significant difference in mean length of stay (p = 0.07), pain scores on the day of surgery, the first, second and third post-operative days (p = 0.36, 0.23, 0.25 and 0.59, respectively), the day of mobilisation (p = 0.12), the mean OHS at six and 24 months (p = 0.08, and 0.29, respectively), the incidence of infection (p = 1.0), dislocation (p = 1.0), re-operation (p = 0.21) or 28 days’ re-admission (p = 0.06). Significantly more patients in the DAA group achieved a planned discharge target of three days post-operatively (68% vs 56%, p = 0.007). The rate of periprosthetic femoral fractures was significantly higher in the DAA group (p = 0.04). Conclusion. We conclude that there is no difference in clinical outcomes between the DAA and the posterior approach in patients undergoing THA when an ‘Enhanced Recovery’ pathway is used. However, a significantly higher rate of periprosthetic femoral fractures remains a concern with the DAA, even in experienced hands. Take home message: Our results show that the DAA for THA is not superior to posterior approach when ‘Enhanced Recovery’ pathway is used. Cite this article: Bone Joint J 2016;98-B:754–60

Aims. The purpose of this study was to compare the prevalence of hip displacement and dislocation in a total population of children with cerebral palsy (CP) in Scotland before and after the initiation of a hip surveillance programme. Patients. A total of 2,155 children with CP are registered in the Cerebral Palsy Integrated Pathway Scotland (CPIPS) surveillance programme, which began in 2013. Physical examination and hip radiological data are collected according to nationally agreed protocols. Methods. Age, Gross Motor Function Classification System (GMFCS) level, subtype of CP, migration percentage (MP), and details of hip surgery were analyzed for all children aged between two and 16 years taken from a time of census in March 2019 and compared to the same data from the initial registration of children in the CPIPS. Displacement of the hip was defined as a MP of between 40% and 99%, and dislocation as a MP of 100%. Results. A total of 1,646 children were available for analysis at the time of the census and 1,171 at their first registration in CPIPS. The distribution of age, sex, and GMFCS levels were similar in the two groups. The prevalence of displacement and dislocation of the hip before surveillance began were 10% (117/1,171) and 2.5% (29/1,171) respectively, and at the time of the census were 4.5% (74/1,646) and 1.3% (21/1,646), respectively. Dislocation was only seen in GMFCS levels IV and V and displacement seen in 90.5% (67/74) of these levels and 9.5% (7/74) in levels I to III. In total, 138 children had undergone hip surgery during the study period. The hip redisplaced after the initial surgery in 15 children; seven of these had undergone a second procedure and at the time of the census the hips in all seven had a MP < 40. Conclusion. Hip surveillance appears to be effective and has reduced the prevalence of hip displacement by over half and dislocation almost by half in these children. Cite this article: Bone Joint J 2020;102-B(3):383–387

Aims. The aim of the Scaphoid Magnetic Resonance Imaging in Trauma (SMaRT) trial was to evaluate the clinical and cost implications of using immediate MRI in the acute management of patients with a suspected fracture of the scaphoid with negative radiographs. Patients and Methods. Patients who presented to the emergency department (ED) with a suspected fracture of the scaphoid and negative radiographs were randomized to a control group, who did not undergo further imaging in the ED, or an intervention group, who had an MRI of the wrist as an additional test during the initial ED attendance. Most participants were male (52% control, 61% intervention), with a mean age of 36.2 years (18 to 73) in the control group and 38.2 years (20 to 71) in the intervention group. The primary outcome was total cost impact at three months post-recruitment. Secondary outcomes included total costs at six months, the assessment of clinical findings, diagnostic accuracy, and the participants’ self-reported level of satisfaction. Differences in cost were estimated using generalized linear models with gamma errors. Results. The mean cost up to three months post-recruitment per participant was £542.40 (. sd. £855.20, n = 65) for the control group and £368.40 (. sd. £338.60, n = 67) for the intervention group, leading to an estimated cost difference of £174 (95% confidence interval (CI) -£30 to £378; p = 0.094). The cost difference per participant increased to £266 (95% CI £3.30 to £528; p = 0.047) at six months. Overall, 6.2% of participants (4/65, control group) and 10.4% of participants (7/67, intervention group) had sustained a fracture of the scaphoid (p = 0.37). In addition, 7.7% of participants (5/65, control group) and 22.4% of participants (15/67, intervention group) had other fractures diagnosed (p = 0.019). The use of MRI was associated with higher diagnostic accuracy both in the diagnosis of a fracture of the scaphoid (100.0% vs 93.8%) and of any other fracture (98.5% vs 84.6%). Conclusion. The use of immediate MRI in the management of participants with a suspected fracture of the scaphoid and negative radiographs led to cost savings while improving the pathway’s diagnostic accuracy and patient satisfaction. Cite this article: Bone Joint J 2019;101-B:984–994

Objectives. Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. Methods. We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. Results. Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. Conclusion. These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts. Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601–608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2