Aims. The aim of this study was to further evaluate the accuracy of ten promising synovial biomarkers (bactericidal/permeability-increasing protein (BPI), lactoferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil elastase 2 (ELA-2), α-defensin, cathelicidin LL-37 (LL-37), human β-defensin (HBD-2), human β-defensin 3 (HBD-3), D-dimer, and procalcitonin (PCT)) for the diagnosis of periprosthetic joint infection (PJI), and to investigate whether inflammatory joint disease (IJD) activity affects their concentration in synovial fluid. Methods. We included 50 synovial fluid samples from patients with (n = 25) and without (n = 25) confirmed PJI from an institutional tissue bank collected between May 2015 and December 2016. We also included 22 synovial fluid samples aspirated from patients with active IJD presenting to Department of Rheumatology, the first Medical Centre, Chinese PLA General Hospital. Concentrations of the ten candidate biomarkers were measured in the synovial fluid samples using standard enzyme-linked immunosorbent assays (ELISA). The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves. Results. BPI, LTF, NGAL, ELA-2, and α-defensin were well-performing biomarkers for detecting PJI, with areas under the curve (AUCs) of 1.000 (95% confidence interval, 1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), and 0.998 (0.994 to 1.000), respectively. The other markers (LL-37, HBD-2, D-dimer, PCT, and HBD-3) had limited diagnostic value. For the five well-performing biomarkers, elevated concentrations were observed in patients with active IJD. The original best thresholds determined by the Youden index, which discriminated PJI cases from non-PJI cases could not discriminate PJI cases from active IJD cases, while elevated thresholds resulted in good performance. Conclusion. BPI, LTF, NGAL, ELA-2, and α-defensin demonstrated excellent performance for diagnosing PJI. However, all five markers showed elevated concentrations in patients with IJD activity. For patients with IJD, elevated thresholds should be considered to accurately diagnose PJI. Cite this article: Bone Joint J 2021;103-B(1):32–38

Little is known about the long-term outcome of mobile-bearing total ankle replacement (TAR) in the treatment of end-stage arthritis of the ankle, and in particular for patients with inflammatory joint disease. The aim of this study was to assess the minimum ten-year outcome of TAR in this group of patients. We prospectively followed 76 patients (93 TARs) who underwent surgery between 1988 and 1999. No patients were lost to follow-up. At latest follow-up at a mean of 14.8 years (10.7 to 22.8), 30 patients (39 TARs) had died and the original TAR remained in situ in 28 patients (31 TARs). The cumulative incidence of failure at 15 years was 20% (95% confidence interval (CI) 11 to 28). The mean American Orthopaedic Foot and Ankle Society (AOFAS) ankle–hindfoot score of the surviving patients at latest follow-up was 80.4 (95% CI 72 to 88). In total, 21 patients (23 TARs) underwent subsequent surgery: three implant exchanges, three bearing exchanges and 17 arthrodeses. Neither design of TAR described in this study, the LCS and the Buechel–Pappas, remains currently available. However, based both on this study and on other reports, we believe that TAR using current mobile-bearing designs for patients with end-stage arthritis of the ankle due to inflammatory joint disease remains justified. Cite this article: Bone Joint J 2013;95-B:1656–61

Introduction and Aims: We undertook this study to detemine the results of acetabular fixation using the Duraloc 300 uncemented acetabular component in patients with inflammatory joint disease and poor bone stock. Method: Fifty consecutive total hip replacements using a Duraloc 300 cup in patients with imflammatory joint disease were reviewed at an average of 8.2 years. Postoperative x-rays were analysed for cup placement and interface gaps. Follow-up films were analysed for lucent lines, osteolysis, wear and migration. Kaplan-Meier survivorship analysis was performed. Results: All components were found to be stable with no evidence of loosening or migration. One patient developed sepsis seven years post-surgery. There was no evidence of excessive wear or osteolysis. Conclusion: The Duraloc 300 cementless acetabular component has excellent fixation with no cases of loosening at an average of 8.2 years in patients with inflammatory joint disease. The low rate of wear and pelvic osteolysis may be indicative of the decreased demands placed on the prosthesis in this cohort of patients. The poor bone stock has not however adversely effected acetabular fixation

Aims. Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials. Methods. A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures. Results. Out of 1,160 studies initially identified, 39 were included. Most studies (85%) were published between 2020 and 2024, with 82% using publicly available datasets, primarily the Osteoarthritis Initiative. ML methods were predominantly supervised, with significant variability in the definitions of OA progression: most studies focused on structural changes (59%), while fewer addressed pain progression or both. Deep learning was used in 44% of studies, while automated ML was used in 5%. There was a lack of standardization in evaluation metrics and limited external validation. Interpretability was explored in 54% of studies, primarily using SHapley Additive exPlanations. Conclusion. Our systematic review demonstrates the feasibility of ML models in predicting OA progression, but also uncovers critical limitations that currently restrict their clinical applicability. Future priorities should include diversifying data sources, standardizing outcome measures, enforcing rigorous validation, and integrating more sophisticated algorithms. This paradigm shift from predictive modelling to actionable clinical tools has the potential to transform patient care and disease management in orthopaedic practice. Cite this article: Bone Joint J 2024;106-B(11):1216–1222

Objective: To study the incidence of joint replacement procedure, arthrodesis, and synovectomy among patients with chronic inflammatory joint disease during the period 1994 to 2004. Methods: Data from the Norwegian Arthroplasty Register was used to find the number of joint replacement procedures performed in Norway 1994 – 2004. The incidences of arthrodeses and synovectomies were obtained from the Norwegian Patient Register. Incidence rates were calculated based on age, year, and gender specific population rates for the Norwegian population, obtained from Statistics Norway. Results: There were 8268 primary joint replacements, 3554 arthrodeses, and 5012 synovectomies performed in patients with inflammatory arthritis (IA) during the study period. A reduction in joint replacement procedures and synovectomies took place during the period 1994 to 2004, in patients with IA. For the oldest patients (80 years and older), no such trend was found. During the same time period, the incidence of joint replacements due to osteoarthritis increased. A significant reduction in the incidence of arthrodesis procedures was also found for the total study group, but not for the different subgroups. Conclusion: The incidence of joint replacements and synovectomies among patients with chronic inflammatory joint disease decreased from 1994 to 2004. This may be the result of improved medical treatment of these patients

In-vitro models of disease are valuable tools for studying disease and analysing response to therapeutics. Recently, advances in patient-derived organoid (PDO) models have been shown to faithfully recapitulate structure, function, and therapeutic response for a wide range of tissues. Frozen shoulder is a rare example of a chronic inflammatory fibrotic disease which is self-limiting, unlike many other soft tissue fibrotic disorders. As no in-vitro 3D models or in-vivo animal models exist for frozen shoulder, establishing an organoid model which recapitulates core diseases features may give insight into fibrosis resolution. Consequently, using biocompatible hydrogels, primary capsular fibroblasts, monocyte-derived macrophages and HUVEC cells, we generated stable PDO cultures which exhibited key disease phenotypes, including vascularization, increased stiffness, and an expanded lining layer over 21 days of culture. Through further investigation of cell-matrix and cell-cell interactions in the organoid model, we intend to unpack the differences between resolving and non-resolving fibrotic disease and uncover clinically relevant therapeutic targets for fibrosis.

Purpose: Arthodesis is the conventional treatment for the rheumatoid wrist. In the event of severe bilateral disease, bilateral arthrodesis can be discussed as an alternative to unilateral arthrodesis an contralateral prosthesis. We wanted to know the functional outcomes after bilateral arthrodesis. Material and methods: This retrospective analysis involved seven patients (one man and six women), mean age 46 years (28–69) who underwent total bilateral arthrodesis of the wrist for inflammatory joint disease (six rheumatoid, one chronic juvenile arthritis). Mean follow-up was five years. The patients were reviewed clinically and radiographically. We noted goniometric measurements of the upper limbs, the Jebsen hand function test (for activities of daily life), force (wrist and grip), and the Buck-Gramcko-Lohmann evaluation. Results: On average, the position achieved after arthrodesis was 2° flexion (−5° to +10°) with 6° ulnar inclination (−5° to +20°). Radiological fusion was achieved in all cases. At last follow-up, we noted that three patients had resumed their occupational activities, one had been reclassified as handicapped, and one as disabled. One patient was a housewife and one other woman was retired. The Jebsen hand test showed that our patients could perform 32 of the 49 daily activities (65%). Daily activity was noted excellent in three patients, good in two and fair in two. The Buck-Gramcko-Lohmann score was fair 6.8/10 (2–10) corresponding to good outcome. All patients were satisfied with the outcome. Discussion: Daily life activities could be performed readily after bilateral arthrodesis of the wrist. Perineal hygiene was possible for five of our patients. The only problems concerned activities requiring force and fine movements, because of the apprehension and the lack of fine dexterity. Poor results could be attributed to metacarpophalangeal deformations and decreased grip force. We observed an 80% reduction in force compared with a representative population of non-operated patients with rheumatoid disease. Bilateral arthrodesis is a valid alternative to bilateral arthroplasty or combined arthrodesis prosthesis implantation. It does not expose the patients to the risk of mechanical arthroplasty

Aims

The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA).

Aims

Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes.

Osteoarthritis (OA) is one of the most prevalent diseases of the elderly, affecting greater than 50% of the population over 60 years of age. Many factors are implicated in the development of OA but currently no mechanism has been described that provides an explanation for age as the major risk factor for OA. The present studies were designed to investigate the hypothesis that age-related accumulation of advanced glycation endproducts (AGEs) provides a molecular mechanism that explains (at least in part) the age-related increase in the incidence of OA.

To gain insight in the diversity of AGEs present in articular cartilage, several AGE measures were determined in a wide age-range of normal human articular cartilage samples: all demonstrated increased AGE levels with increasing age. The level of these AGEs was high in cartilage compared to other tissues such as skin, which is mainly caused by the very low turnover of the cartilage matrix proteins. The t1/2 of collagen in articular cartilage is ~117 years (compared to t1/2 of skin collagen of ~15 years).

Accumulation of AGEs in cartilage affected biomechanical, biochemical and cellular characteristics of the tissue. At the biomechanical level, increased AGE levels were accompanied by increased stiffness and brittleness, indicating that AGE accumulation leads to increased susceptibility of articular cartilage to mechanical damage. On the cellular level, accumulation of AGEs decreased the synthesis and degradation (= turnover) of the cartilage matrix. Such decreased cartilage turnover is likely to result in decreased repair capacity of the tissue.

In combination, the AGE-related increase in tissue brittleness and decrease in extracellular matrix turnover, results in articular cartilage that is more prone to damage. This concept, that AGE accumulation predisposes to the development of OA was tested in the canine anterior cruciate ligament transection (ACLT) model for osteoarthritis. Selectively enhancing AGE levels in articular cartilage of young animals (in the absence of other age-related changes) resulted in more severe OA.

Altogether, AGE accumulation in articular cartilage presents a molecular mechanism by which ageing predisposes to the development of OA, and it provides new possibilities for prevention and/or therapy via the inhibition and/or reversal of cartilage AGE formation.

Aims: The purpose of this presentation is to discuss what population interventions are effective, what the evidence for the different interventions for the different conditions is and how one can identify those who will benefit most. Methods: Evidence of effective interventions for primary, secondary and tertiary prevention of the individual conditions has been identified from systematic reviews and guidelines through literature review. From this and expert opinion, recommendations have been developed which follow a template to enable common themes appropriate to the different musculo-skeletal conditions to emerge. Results: Common factors with an effect on the population level on different musculoskeletal conditions include exercise, body weight, diet, smoking, alcohol and occupational factors. One specific factor is injury prevention including falls to prevent osteoporotic fractures. One recommendation supported by evidence that applies to all conditions considered is the need for early appropriate intervention for those at highest risk or with early features of the condition. Evidence for the different interventions for the conditions will be presented Conclusions: Prevention of musculoskeletal conditions on a population level is possible. If risk factors for the different conditions are identified, development of effective interventions is necessary.

Aims: The purpose of this presentation is to discuss what population interventions are effective, what the evidence for the different interventions for the different conditions is and how one can identify those who will benefit most. Methods: Evidence of effective interventions for primary, secondary and tertiary prevention of the individual conditions has been identified from systematic reviews and guidelines through literature review. From this and expert opinion, recommendations have been developed which follow a template to enable common themes appropriate to the different musculoskeletal conditions to emerge. Results: Common factors with an effect on the population level on different musculoskeletal conditions include exercise, body weight, diet, smoking, alcohol and occupational factors. One specific factor is injury prevention including falls to prevent osteoporotic fractures. One recommendation supported by evidence that applies to all conditions considered is the need for early appropriate intervention for those at highest risk or with early features of the condition. Evidence for the different interventions for the conditions will be presented Conclusions: Prevention of musculoskeletal conditions on a population level is possible. If risk factors for the different conditions are identified, development of effective interventions is necessary.

The decision to undertake total hip replacement (THA) in a child is complex and daunting. This is augmented by the paucity of data on potential quality of life (QoL) improvement and functional outcomes. Therefore, the aim of this study was to ascertain whether outcomes after surgery are influenced by the nature of the primary diagnosis. This was a prospective, consecutive cohort study of patients under the age of 18 years undergoing THA by a single arthroplasty surgeon in collaboration with colleagues at a regional paediatric hospital. Patient electronic notes, radiographs and PROMS (EQ5D-Y, Oxford Hip Score (OHS) and modified Harris Hip Score(mHHS)) were reviewed. Twenty-two THAs were performed in patients less than 18 years (median 15 (range 10.7–17.9), with 7 patients undergoing bilateral surgery. Mean follow-up was 2 years. Thirteen of the THAs were undertaken for systemic conditions effecting multiple joints (Mucopolysaccharidoses, Mucolipidosis and Scwachman-Diamond syndrome) with the hip the worst affected joint and 9 for single joint disease (AVN, Perthes, dysplasia and idiopathic chondrolysis). PROMS scores showed reliable improvements with no differences between the two groups. Health related QoL was calculated from EQ5D-Y and indicated an overall improvement of 1.06(0.879–1.25). 6 patients were wheelchair users preop. All patients were independent walkers at follow-up. One patient underwent successful revision surgery for aseptic acetabular loosening. There were no other complications. THA in children leads to a significant positive impact on QoL as measured with validated PROMS scores. Patients with systemic conditions can benefit just as much as those with single joint disease. Further follow-up is required to understand the long-term outcomes

Aims. Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273

Osteoarthritis (OA) is the most common joint disease, affecting approximately 16% of the adult population worldwide. The chronic inflammation in the joint leads to the breakdown of cartilage, which leads to permanent pain and limitations in everyday life at an early stage of the disease. To date, there is no therapy that can interrupt the inflammatory state or reverse cartilage damage. The PROTO consortium (funded by the EU Horizon Europe program, Grant 101095635) aims to prevent the development of OA by correcting a pathological biomechanical pattern by a digital training intervention and to treat early stage OA with an innovative allogeneic cell therapy

Aims. Hereditary haemochromatosis is a genetic disorder that is caused by several known mutations in the human homeostatic iron regulator protein (HFE) gene. Abnormal accumulation of iron causes a joint disease that resembles osteoarthritis (OA), but appears at a relatively younger age and is accompanied by cirrhosis, diabetes, and injury to other organs. Increased serum transferrin saturation and ferritin levels are known markers of haemochromatosis with high positive predictive values. Methods. We have retrospectively analyzed the iron studies of a cohort of 2,035 patients undergoing knee joint arthroplasty due to OA. Results. No patients had HFE gene C282Y, S65C, or H63D mutations testing. In total, 18 patients (2.96%) of the male cohort and 51 (3.58%) of the female cohort had pathologically increased ferritin levels that may be indicative of haemochromatosis. Seven patients (0.34%) had serum transferrin saturation above 45%. Conclusion. The awareness for the diagnosis of this disorder in Orthopaedics is low and needs improvement. Osteoarthritic patients undergoing knee arthroplasty should be routinely screened for haemochromatosis by iron studies and referred to genetic testing when needed. Level of evidence: Level III - Retrospective cohort study. Cite this article: Bone Jt Open 2021;2(12):1062–1066