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Introduction: Over 200,000 hip and knee total joint arthroplasties (TJAs) are performed annually in England and Wales. UK guidelines recommend regular follow-up because missed early failure can result in complex revision surgery, which places additional burden on overstretched orthopaedic services. This study evaluated the feasibility and acceptability of an expert, consensus-based, standardised virtual clinic (VC) approach for TJA follow-up., Methods: Five UK secondary care orthopaedic centres implemented a standardised VC. Feedback was obtained through patient satisfaction questionnaires and telephone interviews with arthroplasty care practitioners. Key stakeholders subsequently attended an expert discussion forum to achieve consensus on the final VC format and to address obstacles identified during testing., Results: From 19 June 2018 to 11 December 2018, 561 TJA patients [mean age (SD) 70 (9.4) years, 57.8% female, 69.0% hip TJA, 1-28 years postsurgery (median 5 years)] completed a VC. Of these 561 patients, 82.2% were discharged without attending an outpatient appointment and 46 (8.8%) required early face-to-face consultant review. Patient satisfaction with the VC was high (156/188; 83.0%); over 70% of patients indicated a preference for the VC., Discussion: This feasibility study suggested significant resource savings, including time spent by consultant orthopaedic surgeons in outpatient clinics, hospital transport and an estimated saving of up to two-thirds of usual clinic-allotted time. The expert discussion forum provided helpful feedback for supporting more efficient implementation of the VC., Conclusions: A standardised VC is a feasible alternative to outpatient clinics for the follow-up of hip and knee TJA patients, and is acceptable to key stakeholders, including patients.

Objective: We conducted a systematic review in order to understand the relationship between imaging-visualised meniscus pathologies, hyaline cartilage, joint replacement and pain in knee osteoarthritis (OA)., Design: A search of the Medline, Excerpta Medica database (EMBASE) and Cochrane library databases was performed for original publications reporting association between imaging-detected meniscal pathology (extrusion or tear/damage) and longitudinal and cross-sectional assessments of hyaline articular cartilage loss [assessed on magnetic resonance imaging (MRI)], incident joint replacement and pain (longitudinal and cross-sectional) in knee OA. Each association was qualitatively characterised by a synthesis of data from each analysis, based upon study design and quality scoring (including risk of bias assessment and adequacy of covariate adjustment using Cochrane recommended methodology)., Results: In total 4,878 abstracts were screened and 82 publications were included (comprising 72 longitudinal analyses and 49 cross-sectional). Using high quality, well-adjusted data, meniscal extrusion and meniscal tear/damage were associated with longitudinal progression of cartilage loss, cross-sectional cartilage loss severity and joint replacement, independently of age, sex and body mass index (BMI). Medial and lateral meniscal tears were associated with cartilage loss when they occurred in the body and posterior horns, but not the anterior horns. There was a lack of high quality, well-adjusted meniscal pathology and pain publications and no clear independent association between meniscal extrusion or tear/damage with pain severity, progression in pain or incident frequent knee symptoms., Conclusion: Meniscal features have strong associations with cartilage loss and joint replacement in knee OA, but weak associations with knee pain. Systematic review PROSPERO registration number: CRD 42020210910., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Autoantibodies (AutoAbs) have been observed in osteoarthritis (OA) with broad antigenicity, although their prevalence and role remain unclear. Post-translational modification (PTMs) of proteins (oxidation, carbamylation, citrullination) is associated with synovitis and can lead to AutoAb development. Given the prevalence of synovitis, we explored whether AutoAbs to PTM-antigens are common in OA compared with rheumatoid arthritis (RA)., Methods: Serum (n = 895) was obtained from healthy controls, OA and RA patients; and arthritic synovial fluid (SF, n = 290). ELISAs were used to quantify anti-citrullinated peptide (ACPA), anti-carbamylated protein (anti-CarP), anti-oxidized collagen (anti-ROS-CI/CII) antibodies., Results: In sera, positivity for PTM-antigens AutoAbs was observed at a lower frequency in OA with 64.1% (95%CI: 57.2-70.1%) more ACPA+ and 29.8% (21.0-37.3%) more anti-CarP + patients in RA (both P < 0.0001). Levels of ACPA, anti-CarP were also lower in OA (P < 0.0001). Anti-ROS-CII positivity was lower in OA compared to RA (16.6%, 4.8-28.6%) less frequent, P = 0.033) but not anti-native-CII. There was no impact of age/gender on AutoAbs associations with diseases either looking at positivity or levels. In SF, OA patients were often ACPA+ (45.9%) although less frequently than in RA (P = 0.004). Anti-CarP were rarely observed (<5% all samples). All collagen AutoAbs were more frequent in RA compared to OA (all P < 0.010) but only levels of anti-CII and anti-ROS-CII were significantly higher in they RA (P < 0.050)., Conclusion: Although the frequency of AutoAbs for PTM proteins were lower in OA sera compared to RA, a higher proportion of OA SF were positive. The relative retention of AutoAbs in the OA joint requires further investigation., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury., Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors., Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies., Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Bone shape and bone marrow lesions (BMLs) represent different features of Magnetic resonance imaging (MRI)-detected subchondral pathology in osteoarthritis (OA). The aim of this study was to determine how these features are related and how they change in OA progression., Methods: 600 participants from the Osteoarthritis Initiative (OAI) FNIH Biomarkers Initiative were included, having Kellgren-Lawrence grade 1-3, at baseline and MRI data at baseline and 24 months. The associations between 3D quantitative bone shape vectors and presence of (MRI Osteoarthritis Knee Score) MOAKS semi-quantitative BMLs (total BML size ≥1) were analysed for femurs and tibias using linear regression. Responsiveness over 24 months was calculated for both features in four pre-defined progression groups and reported as standardised response means (SRMs). Multilevel models investigated the longitudinal relationship between change in BML size and change in bone shape., Results: Mean age was 61.5, 59% female and mean body mass index (BMI) 30.7. Correlation between baseline femur vector and BML was r = 0.28, P < 0.001. The presence of BMLs was associated with higher bone shape vector; coefficient (95% CI) 0.75 (0.54, 0.96) and 0.57 (0.38, 0.77) for femur and tibia respectively, both P < 0.001. After covariate adjustment, only the femur remained significant [coefficient 0.49, (95% CI 0.30, 0.68)]. Longitudinally bone vector demonstrated more responsiveness to change than BMLs (SRM 0.89 vs 0.13) while multilevel models revealed that increase in BML size was related to a more positive bone shape vector (representing worsening OA)., Conclusion: There is a relationship between bone shape and BMLs, with prevalence of BMLs associated with increasing OA bone shape. Bone shape demonstrated greater responsiveness than semi-quantitative BMLs., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Meniscal pathology is integral to knee osteoarthritis (OA) and its progression; it provides a progression biomarker and a potential treatment target. Magnetic resonance imaging (MRI) demonstrates large heterogeneity in meniscal damage; this structural complexity means measurement is difficult. The aim of this study was to apply novel 3D image analysis to determine which meniscal pathologies demonstrated most change during OA progression., Methods: Knee images were selected from the progression cohort of the Osteoarthritis Initiative choosing participants with risk factors for medial OA progression. Medial and lateral menisci were manually segmented then analysed using a statistical shape model of the tibia as a reference surface. Responsiveness was assessed at 1 year using standardised response means (SRMs) for four constructs: meniscal volume, extrusion volume, thickness and tibial coverage; anatomical sub-regions of these constructs were also explored., Results: Paired images from 86 participants (median age 61.5, 49% female, 56% obese) were included. Reliability of the novel meniscal measurements was very good intraclass correlation coefficients (ICCs all > 0.98). Meniscal volume and extrusion demonstrated no significant change. Moderate responsiveness was observed for medial meniscus thickness (SRM -0.35) and medial tibial coverage (SRM -0.36). No substantial change was seen for the lateral meniscus measures. Sub-region analysis did not improve responsiveness; while greater change was seen in the posterior medial compartment, it was associated with increased variance of the change., Conclusions: The location of meniscal damage was consistently in the posterior medial region, and two measurements (thickness and tibial coverage) were most responsive. Meniscal measures should add to discriminatory power in OA progression assessment., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Radiographic measures of osteoarthritis (OA) are based upon two dimensional projection images. Active appearance modelling (AAM) of knee magnetic resonance imaging (MRI) enables accurate, 3D quantification of joint structures in large cohorts. This cross-sectional study explored the relationship between clinical characteristics, radiographic measures of OA and 3D bone area (tAB)., Methods: Clinical data and baseline paired radiographic and MRI data, from the medial compartment of one knee of 2588 participants were obtained from the NIH Osteoarthritis Initiative (OAI). The medial femur (MF) and tibia (MT) tAB were calculated using AAM. 'OA-attributable' tAB (OA-tAB) was calculated using data from regression models of tAB of knees without OA. Associations between OA-tAB and radiographic measures of OA were investigated using linear regression., Results: In univariable analyses, height, weight, and age in female knees without OA explained 43.1%, 32.1% and 0.1% of the MF tAB variance individually and 54.4% when included simultaneously in a multivariable model. Joint space width (JSW), osteophytes and sclerosis explained just 5.3%, 14.9% and 10.1% of the variance of MF OA-tAB individually and 17.4% when combined. Kellgren Lawrence (KL) grade explained approximately 20% of MF OA-tAB individually. Similar results were seen for MT OA-tAB., Conclusion: Height explained the majority of variance in tAB, confirming an allometric relationship between body and joint size. Radiographic measures of OA, derived from a single radiographic projection, accounted for only a small amount of variation in 3D knee OA-tAB. The additional structural information provided by 3D bone area may explain the lack of a substantive relationship with these radiographic OA measures., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)