Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Aims

Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months.

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

Aims. The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma. Cite this article: Bone Joint Res 2024;13(5):214–225

Aims. This study aimed to analyze kinematics and kinetics of the tibiofemoral joint in healthy subjects with valgus, neutral, and varus limb alignment throughout multiple gait activities using dynamic videofluoroscopy. Methods. Five subjects with valgus, 12 with neutral, and ten with varus limb alignment were assessed during multiple complete cycles of level walking, downhill walking, and stair descent using a combination of dynamic videofluoroscopy, ground reaction force plates, and optical motion capture. Following 2D/3D registration, tibiofemoral kinematics and kinetics were compared between the three limb alignment groups. Results. No significant differences for the rotational or translational patterns between the different limb alignment groups were found for level walking, downhill walking, or stair descent. Neutral and varus aligned subjects showed a mean centre of rotation located on the medial condyle for the loaded stance phase of all three gait activities. Valgus alignment, however, resulted in a centrally located centre of rotation for level and downhill walking, but a more medial centre of rotation during stair descent. Knee adduction/abduction moments were significantly influenced by limb alignment, with an increasing knee adduction moment from valgus through neutral to varus. Conclusion. Limb alignment was not reflected in the condylar kinematics, but did significantly affect the knee adduction moment. Variations in frontal plane limb alignment seem not to be a main modulator of condylar kinematics. The presented data provide insights into the influence of anatomical parameters on tibiofemoral kinematics and kinetics towards enhancing clinical decision-making and surgical restoration of natural knee joint motion and loading. Cite this article: Bone Joint Res 2024;13(9):485–496

Aims. Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results. Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (p. discovery GWAS. = 1.21 × 10. -25. , p. replication GWAS. = 1.80 × 10. -12. ), CCDC170 (p. discovery GWAS. = 1.23 × 10. -11. , p. replication GWAS. = 3.22 × 10. -9. ), and SOX6 (p. discovery GWAS. = 4.41 × 10. -15. , p. replication GWAS. = 6.57 × 10. -14. ). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10. -3. ) and positive regulation of chondrocyte differentiation (p = 9.27 × 10. -3. ). Conclusion. We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154

Aims. The aim of this study was to investigate whether anterior pelvic plane-pelvic tilt (APP-PT) is associated with distinct hip pathomorphologies. We asked: is there a difference in APP-PT between young symptomatic patients being evaluated for joint preservation surgery and an asymptomatic control group? Does APP-PT vary among distinct acetabular and femoral pathomorphologies? And does APP-PT differ in symptomatic hips based on demographic factors?. Methods. This was an institutional review board-approved, single-centre, retrospective, case-control, comparative study, which included 388 symptomatic hips in 357 patients who presented to our tertiary centre for joint preservation between January 2011 and December 2015. Their mean age was 26 years (SD 2; 23 to 29) and 50% were female. They were allocated to 12 different morphological subgroups. The study group was compared with a control group of 20 asymptomatic hips in 20 patients. APP-PT was assessed in all patients based on supine anteroposterior pelvic radiographs using validated HipRecon software. Values in the two groups were compared using an independent-samples t-test. Multiple regression analysis was performed to examine the influences of diagnoses and demographic factors on APP-PT. The minimal clinically important difference (MCID) for APP-PT was defined as > 1 SD. Results. There were no significant differences in APP-PT between the control group and the overall group (1.1° (SD 3.0°; -4.9° to 5.9°) vs 1.8° (SD 3.4°; -6.9° to 13.2°); p = 0.323). Acetabular retroversion and overcoverage groups showed higher mean APP-PTs compared with the control group (p = 0.001 and p = 0.014) and were the only diagnoses with a significant influence on APP-PT in the stepwise multiple regression analysis. All differences were below the MCID. The age, sex, height, weight, and BMI showed no influence on APP-PT. Conclusion. APP-PT showed no radiologically significant variation across different pathomorphologies of the hip in patients being assessed for joint-preserving surgery. Cite this article: Bone Joint J 2024;106-B(5 Supple B):3–10

Aims. To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration. Methods. We performed a systematic literature search in MEDLINE, Embase, and Web of Science. The search string included multiple synonyms of the following keywords: "revision TKA", "outcome" and "prognostic factor". We searched for studies assessing the association between at least one prognostic factor and at least one outcome measure after rTKA surgery. Data on sample size, study design, prognostic factors, outcomes, and the direction of the association was extracted and included in an evidence map. Results. After screening of 5,660 articles, we included 166 studies reporting prognostic factors for outcomes after rTKA, with a median sample size of 319 patients (30 to 303,867). Overall, 50% of the studies reported prospectively collected data, and 61% of the studies were performed in a single centre. In some studies, multiple associations were reported; 180 different prognostic factors were reported in these studies. The three most frequently studied prognostic factors were reason for revision (213 times), sex (125 times), and BMI (117 times). Studies focusing on functional scores and patient-reported outcome measures as prognostic factor for the outcome after surgery were limited (n = 42). The studies reported 154 different outcomes. The most commonly reported outcomes after rTKA were: re-revision (155 times), readmission (88 times), and reinfection (85 times). Only five studies included costs as outcome. Conclusion. Outcomes and prognostic factors that are routinely registered as part of clinical practice (e.g. BMI, sex, complications) or in (inter)national registries are studied frequently. Studies on prognostic factors, such as functional and sociodemographic status, and outcomes as healthcare costs, cognitive and mental function, and psychosocial impact are scarce, while they have been shown to be important for patients with osteoarthritis. Cite this article: Bone Jt Open 2023;4(5):338–356

Aims. Psychological status may be an important predictor of outcome after periacetabular osteotomy (PAO). The aim of this study was to investigate the influence of psychological distress on postoperative health-related quality of life, joint function, self-assessed pain, and sports ability in patients undergoing PAO. Methods. In all, 202 consecutive patients who underwent PAO for developmental dysplasia of the hip (DDH) at our institution from 2015 to 2017 were included and followed up at 63 months (SD 10) postoperatively. Of these, 101 with complete data sets entered final analysis. Patients were assessed by questionnaire. Psychological status was measured by Brief Symptom Inventory (BSI-18), health-related quality of life was raised with 36-Item Short Form Survey (SF-36), hip functionality was measured by the short version 0f the International Hip Outcome Tool (iHOT-12), Subjective Hip Value (SHV), and Hip Disability and Outcome Score (HOS). Surgery satisfaction and pain were assessed. Dependent variables (endpoints) were postoperative quality of life (SF-36, HOS quality of life (QoL)), joint function (iHOT-12, SHV, HOS), patient satisfaction, and pain. Psychological distress was assessed by the Global Severity Index (GSI), somatization (BSI Soma), depression (BSI Depr), and anxiety (BSI Anx). Influence of psychological status was assessed by means of univariate and multiple multivariate regression analysis. Results. In multiple multivariate regression, postoperative GSI, BSI Soma, and BSI Depr had a negative effect on postoperative SF-36 (e -2.07, -3.05, and -2.67, respectively; p < 0.001), iHOT-12 (e -1.35 and -4.65, respectively; p < 0.001), SHV (e -1.20 and -2.71, respectively; p < 0.001), HOS QoL (e -2.09 and -4.79, respectively; p < 0.001), HOS Function (e -1.00 and -3.94, respectively; p < 0.001), and HOS Sport (e -1.44 and -5.29, respectively; p < 0.001), and had an effect on postoperative pain (e 0.13 and 0.37, respectively; p < 0.001). Conclusion. Psychological distress, depression, and somatization disorders affect health-related quality of life, perceived joint function, and sports ability. Pain perception is significantly increased by somatization. However, patient satisfaction with surgery is not affected. Cite this article: Bone Jt Open 2023;4(10):758–765

Aims. To describe outcome reporting variation and trends in non-pharmacological randomized clinical trials (RCTs) of distal tibia and/or ankle fractures. Methods. Five electronic databases and three clinical trial registries were searched (January 2000 to February 2022). Trials including patients with distal tibia and/or ankle fractures without concomitant injuries were included. One reviewer conducted all searches, screened titles and abstracts, assessed eligibility, and completed data extraction; a random 10% subset were independently assessed and extracted by a second reviewer at each stage. All extracted outcomes were mapped to a modified version of the International Classification of Functioning, Disability and Health framework. The quality of outcome reporting (reproducibility) was assessed. Results. Overall, 105 trials (n = 16 to 669 participants) from 27 countries were included. Trials compared surgical interventions (n = 62), post-surgical management options (n = 17), rehabilitative interventions (n = 14), surgical versus non-surgical interventions (n = 6), and pre-surgical management strategies (n = 5). In total, 888 outcome assessments were reported across seven domains: 263 assessed body structure or function (85.7% of trials), 136 activities (68.6% of trials), 34 participation (23.8% of trials), 159 health-related quality of life (61.9% of trials), 247 processes of care (80% of trials), 21 patient experiences (15.2% of trials), and 28 economic impact (8.6% of trials). From these, 337 discrete outcomes were described. Outcome reporting was inconsistent across trials. The quality of reporting varied widely (reproducibility ranged 4.8% patient experience to 100% complications). Conclusion. Substantial heterogeneity in outcome selection, assessment methods, and reporting quality were described. Despite the large number of outcomes, few are reported across multiple trials. Most outcomes are clinically focused, with little attention to the long-term consequences important to patients. Poor reporting quality reduces confidence in data quality, inhibiting data synthesis by which to inform care decisions. Outcome reporting guidance and standardization, which captures the outcomes that matter to multiple stakeholders, are urgently required. Cite this article: Bone Jt Open 2022;3(10):832–840

Aims. Navigation devices are designed to improve a surgeon’s accuracy in positioning the acetabular and femoral components in total hip arthroplasty (THA). The purpose of this study was to both evaluate the accuracy of an optical computer-assisted surgery (CAS) navigation system and determine whether preoperative spinopelvic mobility (categorized as hypermobile, normal, or stiff) increased the risk of acetabular component placement error. Methods. A total of 356 patients undergoing primary THA were prospectively enrolled from November 2016 to March 2018. Clinically relevant error using the CAS system was defined as a difference of > 5° between CAS and 3D radiological reconstruction measurements for acetabular component inclination and anteversion. Univariate and multiple logistic regression analyses were conducted to determine whether hypermobile (. Δ. sacral slope(SS). stand-sit. > 30°), or stiff (. ∆. SS. stand-sit. < 10°) spinopelvic mobility contributed to increased error rates. Results. The paired absolute difference between CAS and postoperative imaging measurements was 2.3° (standard deviation (SD) 2.6°) for inclination and 3.1° (SD 4.2°) for anteversion. Using a target zone of 40° (± 10°) (inclination) and 20° (± 10°) (anteversion), postoperative standing radiographs measured 96% of acetabular components within the target zone for both inclination and anteversion. Multiple logistic regression analysis controlling for BMI and sex revealed that hypermobile spinopelvic mobility significantly increased error rates for anteversion (odds ratio (OR) 2.48, p = 0.009) and inclination (OR 2.44, p = 0.016), whereas stiff spinopelvic mobility increased error rates for anteversion (OR 1.97, p = 0.028). There were no dislocations at a minimum three-year follow-up. Conclusion. Despite high reliability in acetabular positioning for inclination in a large patient cohort using an optical CAS system, hypermobile and stiff spinopelvic mobility significantly increased the risk of clinically relevant errors. In patients with abnormal spinopelvic mobility, CAS systems should be adjusted for use to avoid acetabular component misalignment and subsequent risk for long-term dislocation. Cite this article: Bone Jt Open 2022;3(6):475–484

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment. Cite this article: Bone Joint Res 2024;13(12):725–740

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 report patient and clinical outcomes following robotic-assisted total knee arthroplasty (RA-TKA) at multiple institutions with a minimum two-year follow-up. Methods. This was a multicentre registry study from October 2016 to June 2021 that included 861 primary RA-TKA patients who completed at least one pre- and postoperative patient-reported outcome measure (PROM) questionnaire, including Forgotten Joint Score (FJS), Knee Injury and Osteoarthritis Outcomes Score for Joint Replacement (KOOS JR), and pain out of 100 points. The mean age was 67 years (35 to 86), 452 were male (53%), mean BMI was 31.5 kg/m. 2. (19 to 58), and 553 (64%) cemented and 308 (36%) cementless implants. Results. There were significant improvements in PROMs over time between preoperative, one- to two-year, and > two-year follow-up, with a mean FJS of 17.5 (SD 18.2), 70.2 (SD 27.8), and 76.7 (SD 25.8; p < 0.001); mean KOOS JR of 51.6 (SD 11.5), 85.1 (SD 13.8), and 87.9 (SD 13.0; p < 0.001); and mean pain scores of 65.7 (SD 20.4), 13.0 (SD 19.1), and 11.3 (SD 19.9; p < 0.001), respectively. There were eight superficial infections (0.9%) and four revisions (0.5%). Conclusion. RA-TKA demonstrated consistent clinical results across multiple institutions with excellent PROMs that continued to improve over time. With the ability to achieve target alignment in the coronal, axial, and sagittal planes and provide intraoperative real-time data to obtain balanced gaps, RA-TKA demonstrated excellent clinical outcomes and PROMs in this patient population. Cite this article: Bone Jt Open 2022;3(7):589–595

Aims. The aim of this study was to estimate the incremental use of resources, costs, and quality of life outcomes associated with surgical reconstruction compared to rehabilitation for long-standing anterior cruciate ligament (ACL) injury in the NHS, and to estimate its cost-effectiveness. Methods. A total of 316 patients were recruited and randomly assigned to either surgical reconstruction or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment). Healthcare resource use and health-related quality of life data (EuroQol five-dimension five-level health questionnaire) were collected in the trial at six, 12, and 18 months using self-reported questionnaires and medical records. Using intention-to-treat analysis, differences in costs, and quality-adjusted life years (QALYs) between treatment arms were estimated adjusting for baseline differences and following multiple imputation of missing data. The incremental cost-effectiveness ratio (ICER) was estimated as the difference in costs divided by the difference in QALYs between reconstruction and rehabilitation. Results. At 18 months, patients in the surgical reconstruction arm reported higher QALYs (0.052 (95% confidence interval (CI) -0.012 to 0.117); p = 0.177) and higher NHS costs (£1,017 (95% CI 557 to 1,476); p < 0.001) compared to rehabilitation. This resulted in an ICER of £19,346 per QALY with the probability of surgical reconstruction being cost-effective of 51% and 72% at a willingness-to-pay threshold of £20,000 and £30,000 per QALY, respectively. Conclusion. Surgical reconstruction as a management strategy for patients with long-standing ACL injury is more effective, but more expensive, at 18 months compared to rehabilitation management. In the UK setting, surgical reconstruction is cost-effective. Cite this article: Bone Joint J 2024;106-B(1):38–45

Aims. This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Methods. Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures. Results. The JI panel detected microorganisms in 7/48 (14.5%) and 15/67 (22.4%) cases related to UNCs and SPCs, respectively, but not in cases of UPCs. The correlation between JI panel detection and infection classification criteria for early/late acute and chronic PJI was 46.6%, 73%, and 40%, respectively. Overall, the JI panel identified 12.6% additional microorganisms and three new species. The JI panel pathogen identification showed a sensitivity and specificity of 41.4% (95% confidence interval (CI) 33.7 to 49.5) and 91.1% (95% CI 84.7 to 94.9), respectively. In total, 19/195 (9.7%) could have been managed differently and more accurately upon JI panel evaluation. Conclusion. Despite its microbial limitation, JI panel demonstrated clinical usefulness by complementing the traditional methods based on multiple cultures, particularly in PJI with unclear microbiological results. Cite this article: Bone Joint Res 2024;13(7):353–361

Aims. Transfusion after primary total hip arthroplasty (THA) has become rare, and identification of causative factors allows preventive measures. The aim of this study was to determine patient-specific factors that increase the risk of needing a blood transfusion. Methods. All patients who underwent elective THA were analyzed retrospectively in this single-centre study from 2020 to 2021. A total of 2,892 patients were included. Transfusion-related parameters were evaluated. A multiple logistic regression was performed to determine whether age, BMI, American Society of Anesthesiologists (ASA) grade, sex, or preoperative haemoglobin (Hb) could predict the need for transfusion within the examined patient population. Results. The overall transfusion rate was 1.2%. Compared to the group of patients without blood transfusion, the transfused group was on average older (aged 73.8 years (SD 9.7) vs 68.6 years (SD 10.1); p = 0.020) and was mostly female (p = 0.003), but showed no significant differences in terms of BMI (28.3 kg/m. 2. (SD 5.9) vs 28.7 kg/m. 2. (SD 5.2); p = 0.720) or ASA grade (2.2 (SD 0.5) vs 2.1 (SD 0.4); p = 0.378). The regression model identified a cutoff Hb level of < 7.6 mmol/l (< 12.2 g/dl), aged > 73 years, and a BMI of 35.4 kg/m² or higher as the three most reliable predictors associated with postoperative transfusion in THA. Conclusion. The possibility of transfusion is predictable based on preoperatively available parameters. The proposed thresholds for preoperative Hb level, age, and BMI can help identify patients and take preventive measures if necessary. Cite this article: Bone Jt Open 2024;5(7):560–564

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. This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82

Aims. Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA. Methods. A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score. Results. Change in OHS was associated with blood concentrations of tumour necrosis factor (TNF), interleukin-8 (IL-8), interleukin-6 receptor (IL-6R), glycoprotein 130 (gp130), and IL-1β (R. 2. = 0.28, p = 0.006), but not with CSF biomarkers. Baseline pain was associated with blood concentrations of lymphotoxin alpha (LTα), TNFR1, TNFR2, and IL-6R (R. 2. = 0.37, p < 0.001) and CSF concentrations of TNFR1, TNFR2, IL-6, IL-6R, and IL-1Ra (R. 2. = 0.40, p = 0.001). Baseline disability was associated with blood concentrations of TNF, LTα, IL-8, IL-6, and IL-1α (R. 2. = 0.53, p < 0.001) and CSF concentrations of gp130, TNF, and IL-1β (R. 2. = 0.26, p = 0.002). Thus, preoperative systemic low-grade inflammation predicted 12-month postoperative outcome after THA, and was associated with preoperative pain and disability. Conclusion. This study highlights the importance of systemic inflammation in osteoarthritis, and presents a possible path for better patient selection for THA in the future. Preoperative central neuroinflammation was associated with preoperative pain and disability, but not change in OHS after THA. Cite this article: Bone Joint Res 2024;13(12):741–749