Aims. Periprosthetic joint infection (PJI) occurs in approximately 1% to 2% of total knee arthroplasties (TKA) presenting multiple challenges, such as difficulty in diagnosis, technical complexity, and financial costs. Two-stage exchange is the gold standard for treating PJI but emerging evidence suggests 'two-in-one' single-stage revision as an alternative, delivering comparable outcomes, reduced morbidity, and cost-effectiveness. This study investigates five-year results of modified single-stage revision for treatment of PJI following TKA with bone loss. Methods. Patients were identified from prospective data on all TKA patients with PJI following the primary procedure. Inclusion criteria were: revision for PJI with bone loss requiring reconstruction, and a minimum five years’ follow-up. Patients were followed up for recurrent infection and assessment of function. Tools used to assess function were Oxford Knee Score (OKS) and American Knee Society Score (AKSS). Results. A total of 24 patients were included with a mean age of 72.7 years (SD 7.6), mean BMI of 33.3 kg/m. 2. (SD 5.7), and median ASA grade of 2 (interquartile range 2 to 4). Mean time from primary to revision was 3.0 years (10 months to 8.3 years). At revision, six patients had discharging sinus and three patients had negative cultures from tissue samples or aspirates. Two patients developed recurrence of infection: one was treated successfully with antibiotic suppression and one underwent debridement, antibiotics, and implant retention. Mean AKSS scores at two years showed significant improvement from baseline (27.1 (SD 10.2 ) vs 80.3 (SD 14.8); p < 0.001). There was no significant change in mean AKSS scores between two and five years (80.3 (SD 14.8 ) vs 74.1 (SD 19.8); p = 0.109). Five-year OKS scores were not significantly different compared to two-year scores (36.17 (SD 3.7) vs 33.0 (SD 8.5); p = 0.081). Conclusion. ‘Two-in-one’ single-stage revision is effective for treating PJI following TKA with bone loss, providing patients with sustained improvements in outcomes and infection clearance up to five years post-procedure. Cite this article: Bone Jt Open 2022;3(2):107–113

Aims. This study aims to describe a new method that may be used as a supplement to evaluate humeral rotational alignment during intramedullary nail (IMN) insertion using the profile of the perpendicular peak of the greater tuberosity and its relation to the transepicondylar axis. We called this angle the greater tuberosity version angle (GTVA). Methods. This study analyzed 506 cadaveric humeri of adult patients. All humeri were CT scanned using 0.625 × 0.625 × 0.625 mm cubic voxels. The images acquired were used to generate 3D surface models of the humerus. Next, 3D landmarks were automatically calculated on each 3D bone using custom-written C++ software. The anatomical landmarks analyzed were the transepicondylar axis, the humerus anatomical axis, and the peak of the perpendicular axis of the greater tuberosity. Lastly, the angle between the transepicondylar axis and the greater tuberosity axis was calculated and defined as the GTVA. Results. The value of GTVA was 20.9° (SD 4.7°) (95% CI 20.47° to 21.3°). Results of analysis of variance revealed that females had a statistically significant larger angle of 21.95° (SD 4.49°) compared to males, which were found to be 20.49° (SD 4.8°) (p = 0.001). Conclusion. This study identified a consistent relationship between palpable anatomical landmarks, enhancing IMN accuracy by utilizing 3D CT scans and replicating a 20.9° angle from the greater tuberosity to the transepicondylar axis. Using this angle as a secondary reference may help mitigate the complications associated with malrotation of the humerus following IMN. However, future trials are needed for clinical validation. Cite this article: Bone Jt Open 2024;5(10):929–936

Aims. The goal was to evaluate tibiofemoral knee joint kinematics during stair descent, by simulating the full stair descent motion in vitro. The knee joint kinematics were evaluated for two types of knee implants: bi-cruciate retaining and bi-cruciate stabilized. It was hypothesized that the bi-cruciate retaining implant better approximates native kinematics. Methods. The in vitro study included 20 specimens which were tested during a full stair descent with physiological muscle forces in a dynamic knee rig. Laxity envelopes were measured by applying external loading conditions in varus/valgus and internal/external direction. Results. The laxity results show that both implants are capable of mimicking the native internal/external-laxity during the controlled lowering phase. The kinematic results show that the bi-cruciate retaining implant tends to approximate the native condition better compared to bi-cruciate stabilized implant. This is valid for the internal/external rotation and the anteroposterior translation during all phases of the stair descent, and for the compression-distraction of the knee joint during swing and controlled lowering phase. Conclusion. The results show a better approximation of the native kinematics by the bi-cruciate retaining knee implant compared to the bi-cruciate stabilized knee implant for internal/external rotation and anteroposterior translation. Whether this will result in better patient outcomes remains to be investigated. Cite this article: Bone Joint Res 2023;12(4):285–293

Aims. The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model. Methods. In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties. Results. Our results indicated that bone mass was reduced and bone mechanical properties were impaired in DIO mice. Lipidomic sequencing and bioinformatic analysis identified 373 differential lipids, 176 of which were upregulated and 197 downregulated. Functional enrichment analysis revealed a significant downregulation of the pathways: fat digestion and absorption (ko04975) and lipolysis regulation in adipocytes (ko04923) in DIO mice, leading to local fat accumulation. The use of 3D imaging confirmed the increase in fat accumulation within the bone marrow cavity of obese mice. Conclusion. Our study sheds light on the intricate interplay between fat and bone, and provides a non-toxic and non-invasive method for measuring marrow adipose tissue. Cite this article: Bone Joint Res 2023;12(9):580–589

Aims. Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Methods. Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test. Results. A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R. 2. = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI. Conclusion. The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE. Cite this article: Bone Joint Res 2024;13(11):682–693

Aims. Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA. Methods. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy. Cite this article: Bone Joint Res 2022;11(12):862–872

Aims. Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods. pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 10. 9. particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results. Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion. In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676

Aims. Posterior malleolar (PM) fractures are commonly associated with ankle fractures, pilon fractures, and to a lesser extent tibial shaft fractures. The tibialis posterior (TP) tendon entrapment is a rare complication associated with PM fractures. If undiagnosed, TP entrapment is associated with complications, ranging from reduced range of ankle movement to instability and pes planus deformities, which require further surgeries including radical treatments such as arthrodesis. Methods. The inclusion criteria applied in PubMed, Scopus, and Medline database searches were: all adult studies published between 2012 and 2022; and studies written in English. Outcome of TP entrapment in patients with ankle injuries was assessed by two reviewers independently. Results. Four retrospective studies and eight case reports were accepted in this systematic review. Collectively there were 489 Pilon fractures, 77 of which presented with TP entrapment (15.75%). There were 28 trimalleolar fractures, 12 of which presented with TP entrapment (42.86%). All the case report studies reported inability to reduce the fractures at initial presentation. The diagnosis of TP entrapment was made in the early period in two (25%) cases, and delayed diagnosis in six (75%) cases reported. Using modified Clavien-Dindo complication classification, 60 (67%) of the injuries reported grade IIIa complications and 29 (33%) grade IIIb complications. Conclusion. TP tendon was the commonest tendon injury associated with pilon fracture and, to a lesser extent, trimalleolar ankle fracture. Early identification using a clinical suspicion and CT imaging could lead to early management of TP entrapment in these injuries, which could lead to better patient outcomes and reduced morbidity. Cite this article: Bone Jt Open 2024;5(3):252–259

Aims. This study reports the results of 38 total hip arthroplasties (THAs) in 33 patients aged less than 50 years, using the JRI Furlong hydroxyapatite ceramic (HAC)-coated femoral component. Methods. We describe the survival, radiological, and functional outcomes of 33 patients (38 THAs) at a mean follow-up of 27 years (25 to 32) between 1988 and 2018. Results. Of the surviving 30 patients (34 THAs), there were four periprosthetic fractures: one underwent femoral revision after 21 years, two had surgical fixation as the stem was deemed stable, and one was treated nonoperatively due to the patient’s comorbidities. The periprosthetic fracture patients showed radiological evidence of change in bone stock around the femoral stem, which may have contributed to the fractures; this was reflected in change of the canal flare index at the proximal femur. Two patients (two hips) were lost to follow-up. Using aseptic loosening as the endpoint, 16 patients (18 hips; 48%) needed acetabular revision. None of the femoral components were revised for aseptic loosening, demonstrating 100% survival. The estimate of the cumulative proportion surviving for revisions due to any cause was 0.97 (standard error 0.03). Conclusion. In young patients with high demands, the Furlong HAC-coated femoral component gives excellent long-term results. Cite this article: Bone Jt Open 2024;5(4):286–293

Aims. After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Methods. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed. Results. Coexpression of both transgenes (SV40 and hTERT) were observed in the nuclei of transduced chondrocytes. Generated chondrocyte cell lines showed a high proliferation capacity and less than 2% of senescent cells. These cell lines were able to form 3D aggregates analogous to those generated by primary articular chondrocytes, but were unsuccessful in synthesizing cartilage-like tissue when seeded on type I collagen sponges. However, generated chondrocyte cell lines maintained the potential to respond to IL-1β stimulation. Conclusion. Through SV40LT and hTERT transduction, we successfully immortalized chondrocytes. These immortalized chondrocytes were able to overcome senescence in vitro, but were incapable of synthesizing cartilage-like tissue under the experimental conditions. Nonetheless, these chondrocyte cell lines could be advantageous for OA investigation since, similarly to primary articular chondrocytes, they showed capacity to upregulate inflammatory mediators in response to the IL-1β cytokine. Cite this article: Bone Joint Res 2023;12(1):46–57

Aims. Ankle fracture fixation is commonly performed by junior trainees. Simulation training using cadavers may shorten the learning curve and result in a technically superior surgical performance. Methods. We undertook a preliminary, pragmatic, single-blinded, multicentre, randomized controlled trial of cadaveric simulation versus standard training. Primary outcome was fracture reduction on postoperative radiographs. Results. Overall, 139 ankle fractures were fixed by 28 postgraduate year three to five trainee surgeons (mean age 29.4 years; 71% males) during ten months' follow-up. Under the intention-to-treat principle, a technically superior fixation was performed by the cadaveric-trained group compared to the standard-trained group, as measured on the first postoperative radiograph against predefined acceptability thresholds. The cadaveric-trained group used a lower intraoperative dose of radiation than the standard-trained group (mean difference 0.011 Gym. 2. , 95% confidence interval 0.003 to 0.019; p = 0.009). There was no difference in procedure time. Conclusion. Trainees randomized to cadaveric training performed better ankle fracture fixations and irradiated patients less during surgery compared to standard-trained trainees. This effect, which was previously unknown, is likely to be a consequence of the intervention. Further study is required. Cite this article: Bone Jt Open 2023;4(8):594–601

Aims. The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI). Methods. Patients with tSCI requiring surgical spinal decompression presenting to 17 centres in Europe were recruited. Depending on the timing of decompression, patients were divided into early (≤ 12 hours after injury) and late (> 12 hours and < 14 days after injury) groups. The American Spinal Injury Association neurological (ASIA) examination was performed at baseline (after injury but before decompression) and at 12 months. The primary endpoint was the change in Lower Extremity Motor Score (LEMS) from baseline to 12 months. Results. The final analyses comprised 159 patients in the early and 135 in the late group. Patients in the early group had significantly more severe neurological impairment before surgical treatment. For unadjusted complete-case analysis, mean change in LEMS was 15.6 (95% confidence interval (CI) 12.1 to 19.0) in the early and 11.3 (95% CI 8.3 to 14.3) in the late group, with a mean between-group difference of 4.3 (95% CI -0.3 to 8.8). Using multiply imputed data adjusting for baseline LEMS, baseline ASIA Impairment Scale (AIS), and propensity score, the mean between-group difference in the change in LEMS decreased to 2.2 (95% CI -1.5 to 5.9). Conclusion. Compared to late surgical decompression, early surgical decompression following acute tSCI did not result in statistically significant or clinically meaningful neurological improvements 12 months after injury. These results, however, do not impact the well-established need for acute, non-surgical tSCI management. This is the first study to highlight that a combination of baseline imbalances, ceiling effects, and loss to follow-up rates may yield an overestimate of the effect of early surgical decompression in unadjusted analyses, which underpins the importance of adjusted statistical analyses in acute tSCI research. Cite this article: Bone Joint J 2023;105-B(4):400–411

Aims. To investigate the risk factors for unsuccessful radial head reduction (RHR) in children with chronic Monteggia fractures (CMFs) treated surgically. Methods. A total of 209 children (mean age 6.84 years (SD 2.87)), who underwent surgical treatment for CMFs between March 2015 and March 2023 at six institutions, were retrospectively reviewed. Assessed risk factors included age, sex, laterality, dislocation direction and distance, preoperative proximal radial metaphysis width, time from injury to surgery, reduction method, annular ligament reconstruction, radiocapitellar joint fixation, ulnar osteotomy, site of ulnar osteotomy, preoperative and postoperative ulnar angulation, ulnar fixation method, progressive ulnar distraction, and postoperative cast immobilization. Independent-samples t-test, chi-squared test, and logistic regression analysis were used to identify the risk factors associated with unsuccessful RHR. Results. Redislocation occurred during surgery in 48 patients (23%), and during follow-up in 44 (21.1%). The mean follow-up of patients with successful RHR was 13.25 months (6 to 78). According to the univariable analysis, time from injury to surgery (p = 0.002) and preoperative dislocation distance (p = 0.042) were identified as potential risk factors for unsuccessful RHR. However, only time from injury to surgery (p = 0.007) was confirmed as a risk factor by logistic regression analysis. Receiver operating characteristic curve analysis and chi-squared test confirmed that a time from injury to surgery greater than 1.75 months increased the rate of unsuccessful RHR above the cutoff (p = 0.002). Conclusion. Time from injury to surgery is the primary independent risk factor for unsuccessful RHR in surgically treated children with CMFs, particularly in those with a time from injury to surgery of more than 1.75 months. No other factors were found to influence the incidence of unsuccessful RHR. Surgical reduction of paediatric CMFs should be performed within the first two months of injury whenever possible. Cite this article: Bone Jt Open 2024;5(7):581–591

Aims. To assess the cost-effectiveness of a two-layer compression bandage versus a standard wool and crepe bandage following total knee arthroplasty, using patient-level data from the Knee Replacement Bandage Study (KReBS). Methods. A cost-utility analysis was undertaken alongside KReBS, a pragmatic, two-arm, open label, parallel-group, randomized controlled trial, in terms of the cost per quality-adjusted life year (QALY). Overall, 2,330 participants scheduled for total knee arthroplasty (TKA) were randomized to either a two-layer compression bandage or a standard wool and crepe bandage. Costs were estimated over a 12-month period from the UK NHS perspective, and health outcomes were reported as QALYs based on participants’ EuroQol five-dimesion five-level questionnaire responses. Multiple imputation was used to deal with missing data and sensitivity analyses included a complete case analysis and testing of costing assumptions, with a secondary analysis exploring the inclusion of productivity losses. Results. The base case analysis found participants in the compression bandage group accrued marginally fewer QALYs, on average, compared with those in the standard bandage group (reduction of 0.0050 QALYs (95% confidence interval (CI) -0.0051 to -0.0049)), and accumulated additional mean costs (incremental cost of £52.68 per participant (95% CI 50.56 to 54.80)). Findings remained robust to assumptions tested in sensitivity analyses, although considerable uncertainty surrounded the outcome estimates. Conclusion. Use of a two-layer compression bandage is marginally less effective in terms of health-related quality of life, and more expensive when compared with a standard bandage following TKA, so therefore is unlikely to provide a cost-effective option. Cite this article: Bone Jt Open 2024;5(7):550–559

Aims. Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis. Methods. Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology. Results. Berberine inhibited proliferation and adhesion of RA-FLS cells, and significantly reduced the expression of MMP-1, MMP-3, RANKL, and TNF-α. Transcriptional results suggested that berberine intervention mainly regulated forkhead box O (FOXO) signal pathway, prolactin signal pathway, neurotrophic factor signal pathway, and hypoxia-inducible factor 1 (HIF-1) signal pathway. Conclusion. The effect of berberine on RA was related to the regulation of RAS/mitogen-activated protein kinase/FOXO/HIF-1 signal pathway in RA-FLS cells. Cite this article: Bone Joint Res 2023;12(2):91–102

Aims. To report the outcomes of patients with a fracture of the distal tibia who were treated with intramedullary nail versus locking plate in the five years after participating in the Fixation of Distal Tibia fracture (FixDT) trial. Methods. The FixDT trial reported the results for 321 patients randomized to nail or locking plate fixation in the first 12 months after their injury. In this follow-up study, we report the results of 170 of the original participants who agreed to be followed up until five years. Participants reported their Disability Rating Index (DRI) and health-related quality of life (EuroQol five-dimension three-level questionnaire) annually by self-reported questionnaire. Further surgical interventions related to the fracture were also recorded. Results. There was no evidence of a difference in patient-reported disability, health-related quality of life, or the need for further surgery between participants treated with either type of fixation at five years. Considering the combined results for all participants, there was no significant change in DRI scores after the first 12 months of follow-up (difference between 12 and 24 months, 3.3 (95% confidence interval -1.8 to 8.5); p = 0.203), with patients reporting around 20% disability at five years. Conclusion. This study shows that the moderate levels of disability and reduced quality of life reported by participants 12 months after a fracture of the distal tibia persist in the medium term, with little evidence of improvement after the first year. Cite this article: Bone Joint J 2023;105-B(7):795–800

Aims. The purpose of this survey study was to examine the demographic and lifestyle factors of women currently in orthopaedic surgery. Methods. An electronic survey was conducted of practising female orthopaedic surgeons based in the USA through both the Ruth Jackson Society and the online Facebook group “Women of Orthopaedics”. Results. The majority of surveyed female orthopaedic surgeons reported being married (76.4%; 285/373) and having children (67.6%; 252/373). In all, 66.5% (247/373) were collegiate athletes; 82.0% (306/373) reported having no female orthopaedic surgeon mentors in undergraduate and medical school. Their mean height is 65.8 inches and average weight is 147.3 lbs. Conclusion. The majority of female orthopaedic surgeons did not have female mentorship during their training. Additionally, biometrically, their build is similar to that of the average American woman. Cite this article: Bone Jt Open 2024;5(5):419–425

Aims. This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426

Aims. This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment. Methods. A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not. Results. A total of 147 patients were included in the no-mNGS group and 88 in the mNGS group. The mNGS group had a higher detection rate of rare pathogens than the no-mNGS group (21.6% vs 10.2%, p = 0.016). However, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and higher infection control rates compared with the no-mNGS group (p = 0.017, p = 0.003, and p = 0.028, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.957). In culture-negative cases, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and a higher infection control rate than the no-mNGS group (p = 0.036, p = 0.033, p = 0.022, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.748). Conclusion. mNGS improves detection of rare pathogens in BJIs. mNGS testing reduces antibiotic-related complications, shortens hospital stay and antibiotic use duration, and improves treatment success rate, benefits which are particularly evident in culture-negative cases. Cite this article: Bone Joint Res 2024;13(8):401–410

Aims. The aim of this study was to perform a systematic review and bias evaluation of the current literature to create an overview of risk factors for re-revision following revision total knee arthroplasty (rTKA). Methods. A systematic search of MEDLINE and Embase was completed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The studies were required to include a population of index rTKAs. Primary or secondary outcomes had to be re-revision. The association between preoperative factors and the effect on the risk for re-revision was also required to be reported by the studies. Results. The search yielded 4,847 studies, of which 15 were included. A majority of the studies were retrospective cohorts or registry studies. In total, 26 significant risk factors for re-revision were identified. Of these, the following risk factors were consistent across multiple studies: age at the time of index revision, male sex, index revision being partial revision, and index revision due to infection. Modifiable risk factors were opioid use, BMI > 40 kg/m. 2. , and anaemia. History of one-stage revision due to infection was associated with the highest risk of re-revision. Conclusion. Overall, 26 risk factors have been associated with an increased risk of re-revision following rTKA. However, various levels of methodological bias were found in the studies. Future studies should ensure valid comparisons by including patients with identical indications and using clear definitions for accurate assessments. Cite this article: Bone Jt Open 2024;5(8):644–651

Aims. The aim of this study was to identify the optimal lip position for total hip arthroplasties (THAs) using a lipped liner. There is a lack of consensus on the optimal position, with substantial variability in surgeon practice. Methods. A model of a THA was developed using a 20° lipped liner. Kinematic analyses included a physiological range of motion (ROM) analysis and a provocative dislocation manoeuvre analysis. ROM prior to impingement was calculated and, in impingement scenarios, the travel distance prior to dislocation was assessed. The combinations analyzed included nine cup positions (inclination 30-40-50°, anteversion 5-15-25°), three stem positions (anteversion 0-15-30°), and five lip orientations (right hip 7 to 11 o’clock). Results. The position of the lip changes the ROM prior to impingement, with certain combinations leading to impingement within the physiological ROM. Inferior lip positions (7 to 8 o’clock) performed best with cup inclinations of 30° and 40°. Superior lip positions performed best with cup inclination of 50°. When impingement occurs in the plane of the lip, the lip increases the travel distance prior to dislocation. Inferior lip positions led to the largest increase in jump distance in a posterior dislocation provocation manoeuvre. Conclusion. The lip orientation that provides optimal physiological ROM depends on the orientation of the cup and stem. For a THA with stem anteversion 15°, cup inclination 40°, and cup anteversion 15°, the optimal lip position was posterior-inferior (8 o’clock). Maximizing jump distance prior to dislocation while preventing impingement in the opposite direction is possible with appropriate lip positioning. Cite this article: Bone Joint Res 2023;12(9):571–579

Aims. This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Methods. Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes. Results. WGCNA revealed critical gene modules for OB and OP, identifying the Toll-like receptor (TLR) signalling pathway as a common factor. TLR2 was the most significant gene, with a pronounced expression in macrophages. Elevated TLR2 expression correlated with increased adipose accumulation, inflammation, and osteoclast differentiation, linking it to OP development. Conclusion. Our study underscores the pivotal role of TLR2 in connecting OP and OB. It highlights the influence of TLR2 in macrophages, driving both diseases through a pro-inflammatory mechanism. These insights propose TLR2 as a potential dual therapeutic target for treating OP and OB. Cite this article: Bone Joint Res 2024;13(10):573–587

Aims. To systematically review the predominant complication rates and changes to patient-reported outcome measures (PROMs) following osteochondral allograft (OCA) transplantation for shoulder instability. Methods. This systematic review, following PRISMA guidelines and registered in PROSPERO, involved a comprehensive literature search using PubMed, Embase, Web of Science, and Scopus. Key search terms included “allograft”, “shoulder”, “humerus”, and “glenoid”. The review encompassed 37 studies with 456 patients, focusing on primary outcomes like failure rates and secondary outcomes such as PROMs and functional test results. Results. A meta-analysis of primary outcomes across 17 studies revealed a dislocation rate of 5.1% and an increase in reoperation rates from 9.3% to 13.7% post-publication bias adjustment. There was also a noted rise in conversion to total shoulder arthroplasty and incidence of osteoarthritis/osteonecrosis over longer follow-up periods. Patient-reported outcomes and functional tests generally showed improvement, albeit with notable variability across studies. A concerning observation was the consistent presence of allograft resorption, with rates ranging from 33% to 80%. Comparative studies highlighted similar efficacy between distal tibial allografts and Latarjet procedures in most respects, with some differences in specific tests. Conclusion. OCA transplantation presents a promising treatment option for shoulder instability, effectively addressing both glenoid and humeral head defects with favourable patient-reported outcomes. These findings advocate for the inclusion of OCA transplantation in treatment protocols for shoulder instability, while also emphasizing the need for further high-quality, long-term research to better understand the procedure’s efficacy profile. Cite this article: Bone Jt Open 2024;5(7):570–580

Aims. With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting. Methods. MEDLINE, EMBASE via OVID, CINAHL, and EBSCO were searched from inception to January 2022. Any study addressing surgical treatment of primary patellofemoral joint OA using second generation PFA and TKA in patients aged above 18 years with follow-up data of 30 days were included. Studies relating to OA secondary to trauma were excluded. ROB-2 and ROBINS-I bias tools were used. Results. A total of nine studies were included, made up of four randomized controlled trials (domain 1) and five cohort studies (domain 2). PROMs and knee function specific scores developed for reporting TKA were unable to detect any difference between PFA and TKA. There was no significant difference in complications between PFA and TKA. PFAs were found to have a better postoperative range of motion. Conclusion. TKA and PFA are both viable options for patients with primary PFJ OA. Over time, we have seen an emphasis on patient satisfaction and better quality of life. Recommending sacrificing healthy medial and lateral compartments to treat patellofemoral joint arthritis should be given further thought. Cite this article: Bone Jt Open 2023;4(12):948–956

Aims. In the Netherlands, general practitioners (GPs) can request radiographs. After a radiologically diagnosed fracture, patients are immediately referred to the emergency department (ED). Since 2020, the Máxima Medical Centre has implemented a new care pathway for minor trauma patients, referring them immediately to the traumatology outpatient clinic (OC) instead of the ED. We investigated whether this altered care pathway leads to a reduction in healthcare consumption and concomitant costs. Methods. In this retrospective cohort study, patients were included if a radiologist diagnosed a fracture on a radiograph requested by the GP from August to October 2019 (control group) or August to October 2020 (research group), on weekdays between 8.30 am and 4.00 pm. The study compared various outcomes between groups, including the length of the initial hospital visit, frequency of hospital visits and medical procedures, extent of imaging, and healthcare expenses. Results. A total of 634 patients were included. The results show a median reduction of 25 minutes in duration of initial hospital visits, one fewer hospital visit, overall fewer medical procedures, and a decrease in healthcare costs of €303.40 per patient in the research group compared to the control group. No difference was found in the amount of imaging. Conclusion. The implementation of the new care pathway has resulted in a substantial reduction in healthcare use and costs. Moreover, the pathway provides advantages for patients and helps prevent crowding at the ED. Hence, we recommend immediately referring all minor trauma patients to the traumatology OC instead of the ED. Cite this article: Bone Jt Open 2023;4(10):728–734

Aims. To determine whether side-bending films in scoliosis are assessed for adequacy in clinical practice; and to introduce a novel method for doing so. Methods. Six surgeons and eight radiographers were invited to participate in four online surveys. The generic survey comprised erect and left and right bending radiographs of eight individuals with scoliosis, with an average age of 14.6 years. Respondents were asked to indicate whether each bending film was optimal (adequate) or suboptimal. In the first survey, they were also asked if they currently assessed the adequacy of bending films. A similar second survey was sent out two weeks later, using the same eight cases but in a different order. In the third survey, a guide for assessing bending film adequacy was attached along with the radiographs to introduce the novel T1-45B method, in which the upper endplate of T1 must tilt ≥ 45° from baseline for the study to be considered optimal. A fourth and final survey was subsequently conducted for confirmation. Results. Overall, 12 (86%) of 14 respondents did not use any criteria to assess the bending film adequacy; the remaining two each described a different invalidated method. In total, 12 (86%) of the respondents felt T1-45B was easy to learn and apply. There was fair to substantial intra-rater reliability (k = 0.25 to 0.88) which improved to fair to almost perfect (k = 0.38 to 0.88) post-introduction of the guide. Inter-rater reliability varied considerably among the rater groups but similarly increased following introduction of the guide (k. S1. = 0.19 to 0.34, k. S2. = 0.33 to 0.43 vs k. S3. = 0.49 to 0.5, k. S4. = 0.35 to 0.43). Conclusion. Many surgeons and radiographers do not assess spinal bending films for adequacy. We propose that the change in the plane of the upper endplate of T1 on side-bending can be used in this evaluation. In the T1-45B method, a change of ≥ 45° on side bending qualifies as an adequate bend effort. Cite this article: Bone Jt Open 2023;4(9):689–695

Aims. The aim of this study was to compare a bicruciate-retaining (BCR) total knee arthroplasty (TKA) with a posterior cruciate-retaining (CR) TKA design in terms of kinematics, measured using fluoroscopy and stability as micromotion using radiostereometric analysis (RSA). Methods. A total of 40 patients with end-stage osteoarthritis were included in this randomized controlled trial. All patients performed a step-up and lunge task in front of a monoplane fluoroscope one year postoperatively. Femorotibial contact point (CP) locations were determined at every flexion angle and compared between the groups. RSA images were taken at baseline, six weeks, three, six, 12, and 24 months postoperatively. Clinical and functional outcomes were compared postoperatively for two years. Results. The BCR-TKA demonstrated a kinematic pattern comparable to the natural knee’s screw-home mechanism in the step-up task. In the lunge task, the medial CP of the BCR-TKA was more anterior in the early flexion phase, while laterally the CP was more posterior during the entire movement cycle. The BCR-TKA group showed higher tibial migration. No differences were found for the clinical and functional outcomes. Conclusion. The BCR-TKA shows a different kinematic pattern in early flexion/late extension compared to the CR-TKA. The difference between both implants is mostly visible in the flexion phase in which the anterior cruciate ligament is effective; however, both designs fail to fully replicate the motion of a natural knee. The higher migration of the BCR-TKA was concerning and highlights the importance of longer follow-up. Cite this article: Bone Joint J 2023;105-B(1):35–46

Aims. This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm. 3. ). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm. 2. . Conclusion. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):590–597

Aims. Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we sought to determine if a difference in functional outcomes exists between monopolar and bipolar hemiarthroplasty (HA). Methods. This study is a secondary analysis of patients aged 50 years or older with a displaced femoral neck fracture who were enrolled in the HEALTH trial and underwent monopolar and bipolar HA. Scores from the Western Ontario and McMaster University Arthritis Index (WOMAC) and 12-Item Short Form Health Survey (SF-12) Physical Component Summary (PCS) and (MCS) were compared between the two HA groups using a propensity score-weighted analysis. Results. Of 746 HAs performed in the HEALTH trial, 404 were bipolar prostheses and 342 were unipolar. After propensity score weighting, adequate balance between the bipolar and unipolar groups was obtained as shown by standardized mean differences less than 0.1 for each covariable. A total of 24 months after HA, the total WOMAC score and its subcomponents showed no statistically significant difference between the unipolar and bipolar groups. Similarly, no statistically significant difference was found in the PCS and MCS scores of the SF-12 questionnaire. In participants aged 70 years and younger, no difference was found in any of the functional outcomes. Conclusion. From the results of this study, the use of bipolar HA over unipolar design does not provide superior functional outcomes at 24 months postoperatively. The theoretical advantage of reduced acetabular wear with bipolar designs does not appear to influence functional outcomes in the first two years postoperatively. Cite this article: Bone Jt Open 2023;4(5):370–377

Aims. It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs. Methods. The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome. Results. The SF-36 physical component summary mean at baseline was 30.9 (95% CI 29.7 to 32.0). At one month, it was unchanged (30.5; 95% CI 29.5 to 31.5; p = 0.447); it had improved statistically significantly at six months (35.5; 95% CI 34.2 to 36.7; p < 0.001) and at 12 months (37.9; 95% CI 36.4 to 39.3; p < 0.001). The SF-36 mental component summary mean at baseline was 42.5 (95% CI 40.8 to 44.2). At one month, it was unchanged (43.1; 95% CI 41.4 to 44.8; p = 0.458); it had improved statistically significantly at six months (47.1; 95% CI 45.4 to 48.7; p < 0.001) and at 12 months (46.7; 95% CI 45.0 to 48.5; p < 0.001). All mental subscales had improved by the end of the study, but mental health status remained compromised in comparison with the average USA population. Conclusion. BJIs considerably impact HRQoL, particularly mental health. Patients suffering from BJIs reported considerable limitations in their daily and social activities due to psychological problems. Impaired mental health may be explained by the chronic nature of BJIs, and therefore the mental wellbeing of these patients should be monitored closely. Cite this article: Bone Jt Open 2024;5(9):721–728

Aims. The present study seeks to investigate the correlation of pubofemoral distances (PFD) to α angles, and hip displaceability status, defined as femoral head coverage (FHC) or FHC during manual provocation of the newborn hip < 50%. Methods. We retrospectively included all newborns referred for ultrasound screening at our institution based on primary risk factor, clinical, and PFD screening. α angles, PFD, FHC, and FHC at follow-up ultrasound for referred newborns were measured and compared using scatter plots, linear regression, paired t-test, and box-plots. Results. We included 2,735 newborns, of whom 754 received a follow-up hip ultrasound within six weeks of age. After exclusion, 1,500 hips were included for analysis. Sex distribution was 372 male and 380 female, and the mean age at examination was 36.6 days (4 to 87). We found a negative linear correlation of PFD to α angles (p < 0.001), FHC (p < 0.001), and FHC during provocation (p < 0.001) with a 1 mm increase in PFD corresponding to a -2.1° (95% confidence interval (CI) -2.3 to -1.9) change in α angle and a -3.4% (95% CI -3.7 to -3.0) change in FHC and a -6.0% (-6.6 to -5.5) change in FHC during provocation. The PFD was significantly higher with increasing Graf types and in displaceable hips (p < 0.001). Conclusion. PFD is strongly correlated to both α angles and hip displaceability, as measured by FHC and FHC during provocation, in ultrasound of newborn hips. The PFD increases as the hips become more dysplastic and/or displaceable. Cite this article: Bone Jt Open 2023;5(1):3–8

Aims. The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry. Methods. All TEAs recorded in the Dutch national registry between 2014 and 2020 were included. The Kaplan-Meier method was used for survival analysis, and a logistic regression model was used to assess the factors associated with revision. Results. A total of 514 TEAs were included, of which 35 were revised. The five-year implant survival was 91%. Male sex, a higher BMI, and previous surgery to the same elbow showed a statistically significant association with revision (p < 0.036). Of the 35 revised implants, ten (29%) underwent a second revision. Conclusion. This study reports a five-year implant survival of TEA of 91%. Patient factors associated with revision are defined and can be used to optimize informed consent and shared decision-making. There was a high rate of secondary revisions. Cite this article: Bone Jt Open 2023;4(2):110–119

Aims. A substantial fraction of patients undergoing knee arthroplasty (KA) or hip arthroplasty (HA) do not achieve an improvement as high as the minimal clinically important difference (MCID), i.e. do not achieve a meaningful improvement. Using three patient-reported outcome measures (PROMs), our aim was: 1) to assess machine learning (ML), the simple pre-surgery PROM score, and logistic-regression (LR)-derived performance in their prediction of whether patients undergoing HA or KA achieve an improvement as high or higher than a calculated MCID; and 2) to test whether ML is able to outperform LR or pre-surgery PROM scores in predictive performance. Methods. MCIDs were derived using the change difference method in a sample of 1,843 HA and 1,546 KA patients. An artificial neural network, a gradient boosting machine, least absolute shrinkage and selection operator (LASSO) regression, ridge regression, elastic net, random forest, LR, and pre-surgery PROM scores were applied to predict MCID for the following PROMs: EuroQol five-dimension, five-level questionnaire (EQ-5D-5L), EQ visual analogue scale (EQ-VAS), Hip disability and Osteoarthritis Outcome Score-Physical Function Short-form (HOOS-PS), and Knee injury and Osteoarthritis Outcome Score-Physical Function Short-form (KOOS-PS). Results. Predictive performance of the best models per outcome ranged from 0.71 for HOOS-PS to 0.84 for EQ-VAS (HA sample). ML statistically significantly outperformed LR and pre-surgery PROM scores in two out of six cases. Conclusion. MCIDs can be predicted with reasonable performance. ML was able to outperform traditional methods, although only in a minority of cases. Cite this article: Bone Joint Res 2023;12(9):512–521

Aims. The purpose of this study was to assess the reliability and responsiveness to hip surgery of a four-point modified Care and Comfort Hypertonicity Questionnaire (mCCHQ) scoring tool in children with cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels IV and V. Methods. This was a population-based cohort study in children with CP from a national surveillance programme. Reliability was assessed from 20 caregivers who completed the mCCHQ questionnaire on two occasions three weeks apart. Test-retest reliability of the mCCHQ was calculated, and responsiveness before and after surgery for a displaced hip was evaluated in a cohort of children. Results. Test-retest reliability for the overall mCCHQ score was good (intraclass correlation coefficient 0.78), and no dimension demonstrated poor reliability. The surgical intervention cohort comprised ten children who had preoperative and postoperative mCCHQ scores at a minimum of six months postoperatively. The mCCHQ tool demonstrated a significant improvement in overall score from preoperative assessment to six-month postoperative follow-up assessment (p < 0.001). Conclusion. The mCCHQ demonstrated responsiveness to intervention and good test-retest reliability. The mCCHQ is proposed as an outcome tool for use within a national surveillance programme for children with CP. Cite this article: Bone Jt Open 2023;4(8):580–583

Aims. The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG. Methods. A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP). Results. We found that RANKL and RUNX2 gene expression was upregulated more in recurrent than in non-recurrent GCTB tissues, while OPG gene expression was downregulated more in recurrent than in non-recurrent GCTB tissues. Additionally, we proved that changes in DNA methylation contribute to upregulating the expression of RANKL and downregulating the expression of OPG, which are critical for bone homeostasis and GCTB development. Conclusion. Our results suggest that the overexpression of RANKL/RUNX2 and the lower expression of OPG are associated with recurrence in GCTB patients. Cite this article: Bone Joint Res 2024;13(2):84–91

Aims. Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis. Methods. Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression. Results. Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. Conclusion. Taken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA. Cite this article: Bone Joint Res 2023;12(1):33–45

Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion. Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351

Aims. Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters. Methods. We used the PRISMA extension for scoping reviews for this literature search in three databases. After screening, 16 studies were included for the final analysis. Results. The studies assessed different hip conditions like labrum status, the biomechanical effect of the cam, femoral version, acetabular coverage, and the effect of rim trimming. The testing and loading conditions were also quite diverse, and this disparity limits direct comparisons between the different researches. With normal anatomy the mean contact pressures ranged from 1.54 to 4.4 MPa, and the average peak contact pressures ranged from 2 to 9.3 MPa. Labral tear or resection showed an increase in contact pressures that diminished after repair or reconstruction of the labrum. Complete cam resection also decreased the contact pressure, and acetabular rim resection of 6 mm increased the contact pressure at the acetabular base. Conclusion. To date there is no standardized methodology to access hip contact biomechanics in hip arthroscopy, or with the preservation of the periarticular soft-tissues. A tendency towards improved biomechanics (lower contact pressures) was seen with labral repair and reconstruction techniques as well as with cam correction. Cite this article: Bone Joint Res 2023;12(12):712–721

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360

Aims. Repeated lumbar spine surgery has been associated with inferior clinical outcomes. This study aimed to examine and quantify the impact of this association in a national clinical register cohort. Methods. This is a population-based study from the Norwegian Registry for Spine surgery (NORspine). We included 26,723 consecutive cases operated for lumbar spinal stenosis or lumbar disc herniation from January 2007 to December 2018. The primary outcome was the Oswestry Disability Index (ODI), presented as the proportions reaching a patient-acceptable symptom state (PASS; defined as an ODI raw score ≤ 22) and ODI raw and change scores at 12-month follow-up. Secondary outcomes were the Global Perceived Effect scale, the numerical rating scale for pain, the EuroQoL five-dimensions health questionnaire, occurrence of perioperative complications and wound infections, and working capability. Binary logistic regression analysis was conducted to examine how the number of previous operations influenced the odds of not reaching a PASS. Results. The proportion reaching a PASS decreased from 66.0% (95% confidence interval (CI) 65.4 to 66.7) in cases with no previous operation to 22.0% (95% CI 15.2 to 30.3) in cases with four or more previous operations (p < 0.001). The odds of not reaching a PASS were 2.1 (95% CI 1.9 to 2.2) in cases with one previous operation, 2.6 (95% CI 2.3 to 3.0) in cases with two, 4.4 (95% CI 3.4 to 5.5) in cases with three, and 6.9 (95% CI 4.5 to 10.5) in cases with four or more previous operations. The ODI raw and change scores and the secondary outcomes showed similar trends. Conclusion. We found a dose-response relationship between increasing number of previous operations and inferior outcomes among patients operated for degenerative conditions in the lumbar spine. This information should be considered in the shared decision-making process prior to elective spine surgery. Cite this article: Bone Joint J 2023;105-B(4):422–430

Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610

Aims. This study aimed to investigate the optimal sagittal positioning of the uncemented femoral component in total knee arthroplasty to minimize the risk of aseptic loosening and periprosthetic fracture. Methods. Ten different sagittal placements of the femoral component, ranging from -5 mm (causing anterior notch) to +4 mm (causing anterior gap), were analyzed using finite element analysis. Both gait and squat loading conditions were simulated, and Von Mises stress and interface micromotion were evaluated to assess fracture and loosening risk. Results. During gait, varied sagittal positioning did not lead to excessive Von Mises stress or micromotion. However, under squat conditions, posterior positioning (-4 and -5 mm) resulted in stress exceeding 150 MPa at the femoral notch, indicating potential fracture risk. Conversely, +1 mm and 0 mm sagittal positions demonstrated minimal interface micromotion. Conclusion. Slightly anterior sagittal positioning (+1 mm) or neutral positioning (0 mm) effectively reduced stress concentration at the femoral notch and minimized interface micromotion. Thus, these positions are deemed suitable to decrease the risk of aseptic loosening and periprosthetic femoral fracture

Aims. While residual fixed flexion deformity (FFD) in unicompartmental knee arthroplasty (UKA) has been associated with worse functional outcomes, limited evidence exists regarding FFD changes. The objective of this study was to quantify FFD changes in patients with medial unicompartmental knee arthritis undergoing UKA, and investigate any correlation with clinical outcomes. Methods. This study included 136 patients undergoing robotic arm-assisted medial UKA between January 2018 and December 2022. The study included 75 males (55.1%) and 61 (44.9%) females, with a mean age of 67.1 years (45 to 90). Patients were divided into three study groups based on the degree of preoperative FFD: ≤ 5°, 5° to ≤ 10°, and > 10°. Intraoperative optical motion capture technology was used to assess pre- and postoperative FFD. Clinical FFD was measured pre- and postoperatively at six weeks and one year following surgery. Preoperative and one-year postoperative Oxford Knee Scores (OKS) were collected. Results. Overall, the median preoperative navigated (NAV) FFD measured 6.0° (IQR 3.1 to 8), while the median postoperative NAV FFD was 3.0° (IQR 1° to 4.4°), representing a mean correction of 49.2%. The median preoperative clinical FFD was 5° (IQR 0° to 9.75°) for the entire cohort, which decreased to 3.0° (IQR 0° to 5°) and 2° (IQR 0° to 3°) at six weeks and one year postoperatively, respectively. A statistically significant improvement in PROMs compared with baseline was evident in all groups (p < 0.001). Regression analyses showed that participants who experienced a larger FFD correction, showed greater improvement in PROMs (β = 0.609, p = 0.049; 95% CI 0.002 to 1.216). Conclusion. This study found that UKA was associated with an approximately 50% improvement in preoperative FFD across all three examined groups. Participants with greater correction of FFD also demonstrated larger OKS gains. These findings could prove a useful augment to clinical decision-making regarding candidacy for UKA and anticipated improvements in FFD

Aims. It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth. Methods. C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs. Results. Mechanical stimulation promoted macrophage M2 polarization in vivo and in vitro. The conditioned media from mechanically stimulated BMDMs (MS-CM) enhanced MSC chondrogenic differentiation, and mechanically stimulated BMDMs generated more TGF-β1. Further, neutralizing TGF-β1 in MS-CM can attenuate its pro-chondrogenic effect. In vivo, mechanical stimulation promoted TGF-β1 generation, MSC chondrogenesis, and T-B healing, which were abolished following macrophage depletion. Conclusion. Macrophages subjected to appropriate mechanical stimulation could polarize toward the M2 phenotype and secrete TGF-β1 to promote MSC chondrogenesis, which subsequently augments T-B healing. Cite this article: Bone Joint Res 2023;12(3):219–230

Aims. The first metatarsal pronation deformity of hallux valgus feet is widely recognized. However, its assessment relies mostly on 3D standing CT scans. Two radiological signs, the first metatarsal round head (RH) and inferior tuberosity position (ITP), have been described, but are seldom used to aid in diagnosis. This study was undertaken to determine the reliability and validity of these two signs for a more convenient and affordable preoperative assessment and postoperative comparison. Methods. A total of 200 feet were randomly selected from the radiograph archives of a foot and ankle clinic. An anteroposterior view of both feet was taken while standing on the same x-ray platform. The intermetatarsal angle (IMA), metatarsophalangeal angle (MPA), medial sesamoid position, RH, and ITP signs were assessed for statistical analysis. Results. There were 127 feet with an IMA > 9°. Both RH and ITP severities correlated significantly with IMA severity. RH and ITP were also significantly associated with each other, and the pronation deformities of these feet are probably related to extrinsic factors. There were also feet with discrepancies between their RH and ITP severities, possibly due to intrinsic torsion of the first metatarsal. Conclusion. Both RH and ITP are reliable first metatarsal pronation signs correlating to the metatarsus primus varus deformity of hallux valgus feet. They should be used more for preoperative and postoperative assessment. Cite this article: Bone Jt Open 2024;5(11):1037–1040

Aims. The aims of this study were to report the outcomes of patients with a complex fracture of the lower limb in the five years after they took part in the Wound Healing in Surgery for Trauma (WHIST) trial. Methods. The WHIST trial compared negative pressure wound therapy (NPWT) dressings with standard dressings applied at the end of the first operation for patients undergoing internal fixation of a complex fracture of the lower limb. Complex fractures included periarticular fractures and open fractures when the wound could be closed primarily at the end of the first debridement. A total of 1,548 patients aged ≥ 16 years completed the initial follow-up, six months after injury. In this study we report the pre-planned analysis of outcome data up to five years. Patients reported their Disability Rating Index (DRI) (0 to 100, in which 100 = total disability), and health-related quality of life, chronic pain scores and neuropathic pain scores annually, using a self-reported questionnaire. Complications, including further surgery related to the fracture, were also recorded. Results. A total of 1,015 of the original patients (66%) provided at least one set of outcome data during the five years of follow-up. There was no evidence of a difference in patient-reported disability between the two groups at five years (NPWT group mean DRI 30.0 (SD 26.5), standard dressing group mean DRI 31.5 (SD 28.8), adjusted difference -0.86 (95% CI -4.14 to 2.40; p = 0.609). There was also no evidence of a difference in the complication rates at this time. Conclusion. We found no evidence of a difference in disability ratings between NPWT compared with standard wound dressings in the five years following the surgical treatment of a complex fracture of the lower limb. Patients in both groups reported high levels of persistent disability and reduced quality of life, with little evidence of improvement during this time. Cite this article: Bone Joint J 2024;106-B(8):858–864

Aims. To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design. Methods. Healthcare professionals, clinicians, and/or researchers (HCP/Rs) were surveyed, and the data were presented at a congress workshop. A second and related survey was then developed for people with joint damage caused by knee injury and/or osteoarthritis (PJDs), who were approached by a UK Charity newsletter or Oxford involvement registry. Anonymized data were collected and analyzed in Qualtrics. Results. Survey responses (n = 19 HCP/Rs, 39 PJDs) supported studies testing pharmacological agents preventing PTOA. All HCP/Rs and 30/31 (97%) PJDs supported the development of new treatments that improved or delayed knee symptoms and damage to knee structure. PJDs thought that improving structural knee damage was more important than knee symptoms. Both groups found studies more acceptable as expected future benefit and risk of PTOA increased. All drug delivery routes were acceptable. Workshop participants (around n = 60) reflected survey views. Discussions suggested that stratifying using molecular testing for likely drug response appeared to be more acceptable than using characteristics such as sex, age, and BMI. Conclusion. Our findings supported PTOA drug intervention studies, including situations where there is low risk of disease, no expected benefit of treatment, and frequent treatment administration. PJDs appeared less risk-averse than HCP/Rs. This work reinforces the benefits of consensus and involvement work in the co-creation of PTOA drug trial design. Involvement of key stakeholders, such as PJDs with different risks of OA and regulatory representatives, are critical for trial design success. Cite this article: Bone Joint Res 2024;13(9):513–524

Aims. An objective technological solution for tracking adherence to at-home shoulder physiotherapy is important for improving patient engagement and rehabilitation outcomes, but remains a significant challenge. The aim of this research was to evaluate performance of machine-learning (ML) methodologies for detecting and classifying inertial data collected during in-clinic and at-home shoulder physiotherapy exercise. Methods. A smartwatch was used to collect inertial data from 42 patients performing shoulder physiotherapy exercises for rotator cuff injuries in both in-clinic and at-home settings. A two-stage ML approach was used to detect out-of-distribution (OOD) data (to remove non-exercise data) and subsequently for classification of exercises. We evaluated the performance impact of grouping exercises by motion type, inclusion of non-exercise data for algorithm training, and a patient-specific approach to exercise classification. Algorithm performance was evaluated using both in-clinic and at-home data. Results. The patient-specific approach with engineered features achieved the highest in-clinic performance for differentiating physiotherapy exercise from non-exercise activity (area under the receiver operating characteristic (AUROC) = 0.924). Including non-exercise data in algorithm training further improved classifier performance (random forest, AUROC = 0.985). The highest accuracy achieved for classifying individual in-clinic exercises was 0.903, using a patient-specific method with deep neural network model extracted features. Grouping exercises by motion type improved exercise classification. For at-home data, OOD detection yielded similar performance with the non-exercise data in the algorithm training (fully convolutional network AUROC = 0.919). Conclusion. Including non-exercise data in algorithm training improves detection of exercises. A patient-specific approach leveraging data from earlier patient-supervised sessions should be considered but is highly dependent on per-patient data quality. Cite this article: Bone Joint Res 2023;12(3):165–177

Aims. The rate of day-case total knee arthroplasty (TKA) in the UK is currently approximately 0.5%. Reducing length of stay allows orthopaedic providers to improve efficiency, increase operative throughput, and tackle the rising demand for joint arthroplasty surgery and the COVID-19-related backlog. Here, we report safe delivery of day-case TKA in an NHS trust via inpatient wards with no additional resources. Methods. Day-case TKAs, defined as patients discharged on the same calendar day as surgery, were retrospectively reviewed with a minimum follow-up of six months. Analysis of hospital and primary care records was performed to determine readmission and reattendance rates. Telephone interviews were conducted to determine patient satisfaction. Results. Since 2016, 301/7350 TKAs (4.1%) in 290 patients at our institution were discharged on the day of surgery. Mean follow-up was 31.4 months (6.2 to 70.0). In all, 28 patients (9.3%) attended the emergency department or other acute care settings within 90 days of surgery, most often with wound concerns or leg swelling; six patients (2.0%) were readmitted. No patients underwent a subsequent revision procedure, and there were no periprosthetic infections. Two patients (0.7%) underwent secondary patella resurfacing, and one patient underwent arthroscopic arthrolysis after previous manipulation under anaesthetic (MUA). Three patients (1.0%) underwent MUA alone. Primary care consultation records, available for 206 patients, showed 16 patients (7.8%) contacted their general practitioner within two weeks postoperatively; two (1.0%) were referred to secondary care. Overall, 115/121 patients (95%) telephoned stated they would have day-case TKA again. Conclusion. Day-case TKA can be safely delivered in the NHS with no additional resources. We found low incidence of contact with primary and secondary care in the postoperative period, and high patient satisfaction. Cite this article: Bone Jt Open 2023;4(8):621–627