Introduction. Despite the increasing numbers of ankle replacements that are being performed there are still limited studies on the survival of ankle replacements and comparisons between different implants. The primary aim of this study is to link NJR data with NHS digital data to determine the true failure rates of ankle replacements. Secondary outcomes include analysis risk factors for failure, patient demographics and outcomes of individual prosthesis. Methods. A data linkage study combined National Joint Registry Data and NHS Digital data. The primary outcome of failure is defined as the removal or exchange of any components of the implanted device inserted during ankle replacement surgery. Life tables and Kaplan Meier survival charts demonstrated survivorship. Cox proportional hazards regression models with the Breslow method used for ties were fitted to compare failure rates. Results. 5,562 primary ankle replacement were recorded on the NJR. The 1-year survivorship was 98.8% (95% CI 98.4%–99.0%), 5-year survival in 2725 patients was 90.2% (95% CI 89.2%–91.1%), and 10-year survival in 199 patients was 86.2% (95% CI 84.6%–87.6%). When using a Cox regression model for all implants with over 100 implantations using the Infinity as the reference, only the Star (Hazard ratio 1.60 95% CI 0.87–2.96) and Inbone (HR 0.38 95% CI 0.05–2.84) did not produce significantly worse survivorship. Conclusion. Ankle replacements have increased in numbers over the past decade, and the currently used implants have lower failure rates than older prosthesis. It is expected that in the future the outcomes of ankle replacements will continue to improve

Purpose: To perform a genome scan for suitable UK multiplex families and identify new genetic loci for AIS. Method: DNA samples from 208 subjects (134 affected, 17 reduced penetrance members and 79 normal) from 25 multi-generation British families with confirmed diagnosis of AIS were selected from our AIS family database, and genotyped for 410 polymorphic markers from the entire genome, spaced at 10 cM intervals. Genotypic data were exported into Cyrillic to construct the most likely inherited haplotypes for each chromosome and in each family. Two–point LOD scores were calculated using MLINK initially for the entire genotypic data, and again for the affected meioses only, followed by GENEHUNTER for multipoint linkage analysis for each family. Results: Overall, 170,560 genotypes were obtained and analysed. DNA samples from 250 subjects from the 25 families are currently available for further genotyping and saturation mapping. Preliminary inspection of inherited haplotypes indicates that a number of these families may be segregating with several new AIS loci with LOD scores ranging from 1.0 – 3.6 for various DNA markers on 15 different chromosomes (1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 16, 17, 20, 21), and absence of linkage to the X chromosome. Linkage evaluation and comprehensive saturation mapping of the 2 loci with the highest LOD scores were conducted and these regions were successfully refined. Candidate genes are currently being screened. Conclusion: Preliminary evidence already indicates genetic heterogeneity of AIS. Candidate genes from the two highest LOD score loci are at present being screened

Introduction: Adolescent idiopathic scoliosis (IS) is the most common spine deformity arising during childhood, but the aetiology of IS remains unknown. A large proportion (75%) of structural scoliosis is clinically classified as idiopathic. Idiopathic scoliosis often appears in several members of the same family, this strongly suggesting a genetic transmission. Clinical studies indicate that approximately 1:4 of the total scoliosis cases and 1:3 of idiopathic scoliosis cases are familial. Also studies on twins showing that concordance of monozygotic twins is greater than that of dizygotic twins suggest a genetic basis for the idiopathic scoliosis. A series of candidate genes, including FBN1, COL1A1, COL1A2, COL2A1 and elastin genes, have already been examined by linkage studies, with negative results, and, at present, the particular mode of inheritance of the idiopathic scoliosis still remains unclear. There are conflicting data in the existing literature. Some reports show that the disorder has many of the characteristics of a complex trait, indicating the presence of a multifactorial inheritance pattern, while other studies indicate a major autosomal dominant gene effect. Even more, not all the linkage studies, which demonstrate that the inheritance pattern of idiopathic scoliosis is based on a major autosomal dominant gene effect, did identify a unique locus responsible for idiopathic scoliosis. A linkage with idiopathic scoliosis has been found at locus 17p11 in a three generation Italian family and at locus 19p13.3 in a Chinese family. Therefore, it is possible that idiopathic scoliosis is caused by alterations in different genes. Study Design: This study aimed at investigating the loci responsible for susceptibility to idiopathic scoliosis in all the population and not only in single families. For this reason, we chose to perform an association study on parent-offspring trios. A genetic study and statistical linkage analysis of a population of 81 trios, each consisting of a daughter/son affected by idiopathic scoliosis (IS) and both parents. Objectives: The objective of this study was to assess a linkage disequilibrium between the matrilin-1 (MATN1) gene and the idiopathic scoliosis (IS). Summary of Background Data: In a previous study (Giampietro et al., 1999), a number of genes, associated with spine musculoskeletal deformity phenotypes in mouse and in synteny between mouse and man, were identified as candidate genes for IS. Among these genes, MATN1, which carries a polymorphic micro-satellite marker within its sequence, was selected for a linkage analysis. MATN1 is localised at 1p35 and is mainly expressed in cartilage. Methods: In all trios components, the region of MATN1 gene containing the microsatellite marker was amplified by a polymerase chain reaction. The amplicons were analysed by a DNA sequencer-genotyper. The statistical analysis was performed using the extended transmission/disequilibrium test. Results: Three microsatellite polymorphisms, respectively consisting of 103 bp, 101 bp and 99 bp, were identified. ETDT evidenced a significant preferential transmission for the 103 bp allele (2 = 5.058, df=1, P=0.024). Main Conclusions: The results suggest that the familial idiopathic scoliosis is linked to the MATN1 gene

Purpose: Ligaments and osseous constraints are the only static stabilizers in a healthy elbow. Following arthroplasty, the use of semi-constrained, or linked, implants provides a potential third static stabilizer. However, this constraint may increase loading on the prosthesis, and hence accelerate polyethylene wear. The presence of competent collateral ligaments and the radial head would be expected to improve elbow stability and decrease loading on the ulnohumeral articulation. This in vitro study determined the effects of the collateral ligaments, radial head, and implant linkage on kinematics and wear-inducing loads in total elbow arthroplasty. Method: Eight cadaveric upper extremities (age 73.5yrs; 5 male), were tested using an elbow motion simulator. Humeral, ulnar, and radial components of an elbow arthroplasty were positioned using a computer-assisted technique. Varus-valgus and internal-external bending loads were measured during flexion using an instrumented humeral component. A tracking receiver attached to the ulna recorded its position during active and passive flexion in the vertical orientation, and passive flexion in the varus and valgus orientations. Kinematics and loading were measured with and without implant linkage, with an intact, resected and replaced radial head, and before and after sectioning of the collateral ligaments. Results: There were no differences in the bending loads with the arm in the vertical orientation regardless of the status of the ligaments, radial head or implant linkage (p> 0.2). Radial head excision produced an increase in valgus angulation of the ulna (6.7±6.4°) but did not influence bending loads in the vertical orientation (p< 0.05). Loading was lowest with the unlinked implant, and with ligaments and radial head intact, with the arm in the valgus (1065±466Nmm) (p< 0.01) and varus (1333±698Nmm) (p< 0.05) orientations. Conclusion: Our results show that the radial head is an important valgus stabilizer for the prosthesis employed in this investigation. Linkage of the articulation increases implant loading during passive flexion with the arm in the varus and valgus orientations, which may increase implant wear. This suggests that, when using prostheses of this design, linkage of the articulation may be unnecessary if adequate bone stock and ligaments are available, whilst preserving or repairing the collateral ligaments and preserving or replacing the radial head

Introduction: Adolescent idiopathic scoliosis (AIS) is described as a sex-influenced autosomal dominantly inherited disorder with females more often affected than males, and operative ratio of 7F:1M (Child et al. 1999). Two AIS loci have been reported on chromosome 17p11 (Salehi et al. 2002) and chromosome 19p13.3 (Chan et al. 2002) in the Italian and Chinese populations, respectively. Three other susceptibility AIS loci on chromosome 6q, distal 10q and 18q (Wise et al. 2000), and more recently primary candidate regions on chromosomes 6, 9, 16, and 17 (Miller et al, 2005) have also been reported. Purpose: o perform a genome scan for suitable UK multiplex families and identify new genetic loci for AIS. Method: NA samples from 208 subjects (134 affected, 17 reduced penetrance members and 79 normal) from 25 multi-generation British families with confirmed diagnosis of AIS were selected from our AIS family database, and genotyped for 410 polymorphic markers from the entire genome, spaced at 10 cM intervals. Genotypic data were exported into Cyrillic to construct the most likely inherited haplotypes for each chromosome and in each family. Two–point LOD scores were calculated using MLINK initially for the entire genotypic data, and again for the affected meioses only, followed by GENEHUNTER for multipoint linkage analysis for each family. Results: Overall, 170 560 genotypes were obtained and analysed. DNA samples from 250 subjects from the 25 families are currently available for further genotyping and saturation mapping. Our AIS families show absence of linkage to the X chromosome as well as previously reported AIS loci, except for chromosome 9q and 17q as reported by Miller et al. (2005). Preliminary inspection of inherited haplotypes indicates that a number of these families may be segregating with several new AIS loci with LOD scores ranging from 1.0 – 3.63 for various DNA markers on 15 different chromosomes. Linkage evaluation and comprehensive saturation mapping of the two loci with the highest LOD scores of 3.63 and 4.08 for chromosomes 9q and 17q respectively were conducted and these regions were successfully refined. Candidate genes are currently being screened. Conclusion: Preliminary evidence already indicates genetic heterogeneity of AIS. Candidate genes from the highest LOD score regions are at present being screened

Introduction: AIS is described as a sex-influenced auto-somal dominantly inherited disorder with females more often affected than males (operative ratio 7F:1M) 1. Two AIS loci have been reported on chromosomes 17p112 and 19p13.33 in the Italian and Chinese populations, respectively. Other susceptibility AIS loci on chromosomes 6p, distal 10q and 18p4, and more recently to chromosomes 6, 9, 16, and 175, and 19p136 have also been reported, in the American population. Purpose: To perform a genome scan for suitable UK multi-generation families and identify new genetic loci for AIS. Method: DNA samples from 208 subjects (116 affected members) from 25 British families with confirmed diagnosis of AIS were selected from our family database, and genotyped for 410 polymorphic markers from the entire genome, spaced at ~10 cM intervals. Using Cyrillic, most likely inherited haplotypes were constructed for each chromosome and family. Statistical analyses were calculated using MLINK and GENEHUNTER, initially for the entire genotypic data, and again for affected meioses only. Results: 170,560 genotypes were obtained and analysed. Our AIS families show no linkage to the X chromosome. Preliminary inspection of inherited haplotypes indicates a number of families may be segregating with several new AIS loci with LOD scores from 1.0–3.64 for markers on 15 different chromosomes. Linkage analysis and saturation mapping of the 2 highest LOD score regions on chromosomes 9q34 and 17q25 were conducted. These regions were successfully refined and candidate genes are being screened. Conclusion: Preliminary evidence already indicates genetic heterogeneity of AIS. Candidate genes from the two highest LOD score loci are at present being screened

Background: About 60% of all cancer patients survive at least 5 years, and therefore have a risk to develop long-term effects after cancer treatment. Most research, the later years, on long-term effects after cancer treatment, has focused on cardiovascular side effects and side effects in the pelvic region. On the other hand, hardly any focus has been on possible side effects on the musclo-skeletal system, though there are multiple reasons that surviving cancer patients may develop such problems. Aim: To determine whether cancer patients have an increased risk for receiving a total hip replacement compared to the population of Norway. Analyses are based on a linkage between The Cancer Register of Norway and The Norwegian Arthroplasty Register. Materials and Methods: By linking these two registers we have connected all cancer diagnosis, all total hip arthroplasties and information about time of death for each patient. Data refers to 741,901 patients, divided into three groups; 652,197 patients with at least one cancer diagnose but none hip arthroplasties. 72,469 patients with at least one hip arthroplasty but no cancer diagnose. The last group of 17,235 patients have at least one cancer diagnose and at least one hip arthroplasty. From the last group 8,629 patients received a cancer diagnoses first and a total hip arthroplasty second. Statistical methods in this study were the Kaplan-Meier method, Cox regression and Standardized Incidence Ratio (SIR). Results: Cancer patients had a slight increased risk to receive a total hip arthroplasty compared to the Norwegian population (SIR=1.13 (95% CI, 1.10–1.15)). For cancer located proximal to the pelvic area there were no significant increase in risk for hip arthroplasty, except for breast cancer (SIR=1.12 (95% CI 1.07–1.17)). Cancer located to the pelvic area (SIR=1.18 (95% CI 1.14–1.22)), lymphoma (SIR=1.29 (95% CI 1.14–1.45)) and leukaemia (SIR=1.16 (95% CI 1.17–1.31)) had an increased risk for receiving a total hip arthroplasty. Conclusion: We found a small increase in risk for receiving total hip arthroplasty after cancer diagnose. Treatment type may affect these results. Radiation dose to the pelvic area may affect the bone structure and increase the need of arthroplasty. Future studies on effect of radiation doses and risk of receiving hip arthroplasty are planed

Cite this article: Bone Joint Res 2023;12(4):256–258.

Aims. Despite the increasing numbers of ankle arthroplasties, there are limited studies on their survival and comparisons between different implants. The primary aim of this study was to determine the failure rates of primary ankle arthroplasties commonly used in the UK. Methods. A data linkage study combined National Joint Registry (NJR) data and NHS Digital data. The primary outcome of failure was defined as the removal or exchange of any components of the implanted device. Life tables and Kaplan-Meier survival charts were used to illustrate survivorship. Cox proportional hazards regression models were fitted to compare failure rates between 1 April 2010 and 31 December 2018. Results. Overall, 5,562 primary ankle arthroplasties were recorded in the NJR. Linked data show a one-year survivorship of 98.8% (95% confidence interval (CI) 98.4% to 99.0%), five-year survival in 2,725 patients of 90.2% (95% CI 89.2% to 91.1%), and ten-year survival in 199 patients of 86.2% (95% CI 84.6% to 87.6%). The five-year survival for fixed-bearing implants was 94.3% (95% CI 91.3% to 96.3%) compared to 89.4% (95% CI 88.3% to 90.4%) for mobile-bearing implants. A Cox regression model for all implants with over 100 implantations using the implant with the best survivorship (Infinity) as the reference, only the STAR (hazard ratio (HR) 1.60 (95% CI 0.87 to 2.96)) and INBONE (HR 0.38 (95% CI 0.05 to 2.84)) did not demonstrate worse survival at three and five years. Conclusion. Ankle arthroplasties in the UK have a five-year survival rate of 90.2%, which is lower than recorded on the NJR, because we have shown that approximately one-third of ankle arthroplasty failures are not reported to the NJR. There are statistically significant differences in survival between different implants. Fixed-bearing implants appear to demonstrate higher survivorship than mobile-bearing implants. Cite this article: Bone Joint J 2023;105-B(3):301–306

Aims. The National Joint Registry for England, Wales and Northern Ireland (NJR) has extended its scope to report on hospital, surgeon and implant performance. Data linkage of the NJR to the London Implant Retrieval Centre (LIRC) has previously evaluated data quality for hip primary procedures, but did not assess revision records. . Methods. We analysed metal-on-metal hip revision procedures performed between 2003 and 2013. A total of 69 929 revision procedures from the NJR and 929 revised pairs of components from the LIRC were included. Results. We were able to link 716 (77.1%) revision procedures on the NJR to the LIRC. This meant that 213 (22.9%) revision procedures at the LIRC could not be identified on the NJR. We found that 349 (37.6%) explants at the LIRC completed the full linkage process to both NJR primary and revision databases. Data completion was excellent (> 99.9%) for revision procedures reported to the NJR. Discussion. This study has shown that only approximately one third of retrieved components at the LIRC, contributed to survival curves on the NJR. We recommend prospective registry-retrieval linkage as a tool to feedback missing and erroneous data to the NJR and improve data quality. Take home message: Prospective Registry – retrieval linkage is a simple tool to evaluate and improve data quality on the NJR. Cite this article: Bone Joint J 2016;98-B:33–9

Aims. The aim of this study was to estimate the 90-day periprosthetic joint infection (PJI) rates following total knee arthroplasty (TKA) and total hip arthroplasty (THA) for osteoarthritis (OA). Methods. This was a data linkage study using the New South Wales (NSW) Admitted Patient Data Collection (APDC) and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), which collect data from all public and private hospitals in NSW, Australia. Patients who underwent a TKA or THA for OA between 1 January 2002 and 31 December 2017 were included. The main outcome measures were 90-day incidence rates of hospital readmission for: revision arthroplasty for PJI as recorded in the AOANJRR; conservative definition of PJI, defined by T84.5, the PJI diagnosis code in the APDC; and extended definition of PJI, defined by the presence of either T84.5, or combinations of diagnosis and procedure code groups derived from recursive binary partitioning in the APDC. Results. The mean 90-day revision rate for infection was 0.1% (0.1% to 0.2%) for TKA and 0.3% (0.1% to 0.5%) for THA. The mean 90-day PJI rates defined by T84.5 were 1.3% (1.1% to 1.7%) for TKA and 1.1% (0.8% to 1.3%) for THA. The mean 90-day PJI rates using the extended definition were 1.9% (1.5% to 2.2%) and 1.5% (1.3% to 1.7%) following TKA and THA, respectively. Conclusion. When reporting the revision arthroplasty for infection, the AOANJRR substantially underestimates the rate of PJI at 90 days. Using combinations of infection codes and PJI-related surgical procedure codes in linked hospital administrative databases could be an alternative way to monitor PJI rates. Cite this article: Bone Joint J 2022;104-B(9):1060–1066

Aims. The aim of this study was to capture 12-month outcomes from a representative multicentre cohort of patients undergoing total ankle arthroplasty (TAA), describe the pattern of patient-reported outcome measures (PROMs) at 12 months, and identify predictors of these outcome measures. Methods. Patients listed for a primary TAA at 19 NHS hospitals between February 2016 and October 2017 were eligible. PROMs data were collected preoperatively and at six and 12 months including: Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ (foot and ankle)) and the EuroQol five-dimension five-level questionnaire (EQ-5D-5L). Radiological pre- and postoperative data included Kellgren-Lawrence score and implant position measurement. This was supplemented by data from the National Joint Registry through record linkage to determine: American Society of Anesthesiologists (ASA) grade at index procedure; indication for surgery, index ankle previous fracture; tibial hind foot alignment; additional surgery at the time of TAA; and implant type. Multivariate regression models assessed outcomes, and the relationship between MOXFQ and EQ-5D-5L outcomes, with patient characteristics. Results. Data from 238 patients were analyzed. There were significant improvements in MOXFQ and EQ-5D-5L among people who underwent TAA at six- and 12-month assessments compared with preoperative scores (p < 0.001). Most improvement occurred between preoperative and six months, with little further improvement at 12 months. A greater improvement in MOXFQ outcome postoperatively was associated with older age and more advanced radiological signs of ankle osteoarthritis at baseline. Conclusion. TAA significantly benefits patients with end-stage ankle disease. The lack of substantial further overall change between six and 12 months suggests that capturing PROMs at six months is sufficient to assess the success of the procedure. Older patients and those with advanced radiological disease had the greater gains. These outcome predictors can be used to counsel younger patients and those with earlier ankle disease on the expectations of TAA. Cite this article: Bone Joint J 2023;105-B(8):895–904

Aims. The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial. Methods. Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale, and quality of life (QoL) assessed with the EuroQol five-dimension questionnaire for younger patients (EQ-5D-Y) will be collected. Each patient will be randomly allocated (1:1, stratified using a minimization algorithm by centre and initial elbow dislocation status (i.e. dislocated or not-dislocated at presentation to the emergency department)) to either a regimen of the operative fixation or non-surgical treatment. Outcomes. At six weeks, and three, six, and 12 months, data on function, pain, sports/music participation, QoL, immobilization, and analgesia will be collected. These will also be repeated annually until the child reaches the age of 16 years. Four weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the PROMIS upper limb score at 12 months post-randomization. All data will be obtained through electronic questionnaires completed by the participants and/or parents/guardians. The NHS number of participants will be stored to enable future data linkage to sources of routinely collected data (i.e. Hospital Episode Statistics). Cite this article: Bone Jt Open 2024;5(1):69–77

Aims. The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Methods. Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls. Results. We found that seven kinds of plasma proteins had genetic correlations with RA, such as Soluble Receptor for Advanced Glycation End Products (sRAGE) (correlation coefficient = 0.2582, p = 0.049), vesicle transport protein USE1 (correlation coefficient = 0.1337, p = 0.018), and spermatogenesis-associated protein 20 (correlation coefficient = 0.3706, p = 0.018). There was a significant causal relationship between sRAGE and RA. By comparing the genes encoding seven plasma proteins, we found that only USE1 was a DEG associated with RA. Conclusion. Our study identified a set of candidate plasma proteins that showed signals correlated with RA. Since the results of this study need further experimental verification, they should be interpreted with caution. However, we hope that this paper will provide new insights for the discovery of pathogenic genes and RA pathogenesis in the future. Cite this article: Bone Joint Res 2022;11(2):134–142

Aims. When a total ankle arthroplasty (TAA) fails, it can be converted to a fusion or a revision arthroplasty. Despite the increasing numbers of TAAs being undertaken, there is little information in the literature about the management of patients undergoing fusion following a failed TAA. The primary aim of this study was to analyze the survival of fusions following a failed TAA using a large dataset from the National Joint Registry (NJR). Methods. A data linkage study combined NJR and NHS Digital data. Failure of a TAA was defined as a fusion, revision to a further TAA, or amputation. Life tables and Kaplan-Meier graphs were used to record survival. Cox proportional hazards regression models were fitted to compare the rates of failure. Results. A total of 131 patients underwent fusion as a salvage procedure following TAA. Their mean age was 65.7 years (SD 10.6) and 73 (55.7%) were male. The mean follow-up was 47.5 months (SD 27.2). The mean time between TAA and fusion was 5.3 years (SD 2.7). Overall, 32 (24.4%) underwent reoperations other than revision and 29 (22.1%) failed. Of these 24 (18.3%) underwent revision of the fusion and five (3.8%) had a below-knee amputation. No patients underwent conversion to a further TAA. Failure usually occurred in the first three postoperative years with one-year survival of fusion being 96.0% (95% confidence interval (CI) 90.7 to 98.3) and three-year survival in 69 patients being 77.5% (95% CI 68.3 to 84.4). Conclusion. Salvage fusion after a failed TAA shows moderate rates of failure and reoperations. Nearly 25% of patients required revision within three years. This study is an extension of studies using the same methodology reporting the failure rates and risk factors for failure, which have recently been published, and also one reporting the outcome of revision TAA for a failed primary TAA, using the same methodology, which will shortly be published. Cite this article: Bone Joint J 2023;105-B(10):1094–1098

Aims. The aim of this study was to review the provision of total elbow arthroplasties (TEAs) in England, including the incidence, the characteristics of the patients and the service providers, the types of implant, and the outcomes. Methods. We analyzed the primary TEAs recorded in the National Joint Registry (NJR) between April 2012 and December 2022, with mortality data from the Civil Registration of Deaths dataset. Linkage with Hospital Episode Statistics-Admitted Patient Care (HES-APC) data provided further information not collected by the NJR. The incidences were calculated using estimations of the populations from the Office for National Statistics. The annual number of TEAs performed by surgeons and hospitals was analyzed on a national and regional basis. Results. A total of 3,891 primary TEAs were included. The annual incidence of TEA was between 0.72 and 0.82 per 100,000 persons before 2020 and declined to 0.4 due to a decrease in elective TEAs during the COVID-19 pandemic, with a slight recovery in 2022. Older patients, those of white ethnicity and females, were more likely to undergo TEA. Those who underwent elective TEA had a median wait of between 89 (IQR 41 to 221) and 122 days (IQR 74 to 189) in the years before 2021, and this increased to 183 days (IQR 66 to 350) in 2021. The number of TEAs performed by surgeons per annum remained unchanged, with a median of two (IQR 1 to 3). The median annual number of TEAs per region was three to six times higher than the median annual case load of the highest volume hospital in a region. Patients in the lowest socioeconomic group had a higher rate of serious adverse events and mortality (11%) when undergoing TEA for acute trauma. Conclusion. In England, TEA is more common in older age groups, those of white ethnicity, and females. The COVID-19 pandemic affected the incidence of elective TEA and waiting times, and the provision of TEA has not yet recovered. The Getting it Right First Time recommendation of centralizing services to one centre per region could result in up to a six-fold increase in the number of TEAs being performed in some centres. Cite this article: Bone Joint J 2024;106-B(11):1312–1320

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22

Several synthetic polymers have been widely investigated for their use in bone tissue engineering applications, but the ideal material is yet to be engineered. Triazine-trione (TATO) based materials and their derivatives are novel in the field of biomedical engineering but have started to draw interest. Different designs of the TATO monomers and introduction of different chemical linkages and end-groups widens the scope of the materials due to a range of mechanical properties. The aim of our work is to investigate novel TATO based materials, with or without hydroxyapatite filler, for their potential in bone tissue engineering constructs. Initially the biocompatibility of the materials was tested, indirectly and directly, according to ISO standards. Following this the osteoconductive properties were investigated with primary osteoblasts and an osteoblastic cell line. Bone marrow derived mesenchymal stem cells were used to evaluate the osteogenic differentiation and consequently the materials potential in bone tissue engineering applications

Device-associated bacterial infections are a major and costly clinical challenge. This project aimed to develop a smart new biomaterial for implants that helps to protect against infection and inflammation, promote bone growth, and is biodegradable. Gallium (Ga) doped strontium-phosphate was coated on pure Magnesium (Mg) through a chemical conversion process. Mg was distributed in a graduated manner throughout the strontium-phosphate coating GaSrPO4, with a compact structure and a Ga-rich surface. We tested this sample for its biocompatibility, effects on bone remodeling and antibacterial activities including Staphylococcus aureus, S. epidermidis and E. coli - key strains causing infection and early failure of the surgical implantations in orthopaedics and trauma. Ga was distributed in a gradient way throughout the entire strontium-phosphate coating with a compact structure and a gallium-rich surface. The GaSrPO4 coating protected the underlying Mg from substantial degradation in minimal essential media at physiological conditions over 9 days. The liberated Ga ions from the coatings upon Mg specimens inhibited the growth of bacterial tested. The Ga dopants showed minimal interferences with the SrPO4 based coating, which boosted osteoblasts and undermined osteoclasts in in vitro co-cultures model. The results evidenced this new material may be further translated to preclinical trial in large animal model and towards clinical trial. Acknowledgements: Authors are grateful to the financial support from the Australian Research Council through the Linkage Scheme (ARC LP150100343). The authors acknowledge the facilities, and the scientific and technical assistance of the RMIT University and John Curtin School of Medical Research, Australian National University

Aims. The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). Methods. This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. Results. There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. Conclusion. The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies. Cite this article: Bone Joint J 2024;106-B(1):77–85