Introduction. Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration, inflammation, and pain. Current treatments provide only symptomatic relief, necessitating novel molecular targets. The caspase family, known for its roles in apoptosis and inflammation regulation, may additionally influence crucial processes for cartilage homeostasis such as differentiation and proliferation. However, the specific roles of individual caspases in OA pathogenesis remain unclear. This study aims to investigate the involvement of the caspase family in OA and as potential targets for therapy, with a focus on caspase-1 and -8. Method. Chondrocytes from both healthy and OA donors were cultured in 2D and 3D culture models and stimulated with TNF-α or IL-1β. The expression and activation of caspase-1 and -8 was assessed using RT-PCR, ELISA. Transcriptome analysis of OA and healthy cartilage samples, along with Mendelian randomization (MR) analysis were conducted to explore the involvement of caspase family in OA and to assess its potential as therapeutic targets. Result. Higher expression levels of caspase-1, -8 were observed in OA cartilage compared to healthy cartilage. TNF-α stimulation increased their expression in both healthy and OA chondrocytes, while IL-1β had limited impact. Caspase-8 expression was causally associated with knee OA in MR analysis, suggesting a potential therapeutic target. The caspase-1 inhibitor VX-765 mildly reduced chondrocyte viability, with no significant effect in the presence of TNF-α. While the caspase-8 inhibitor Z-IETD-FMK exhibited slight enhancements in cell viability, these improvements were not statistically significant. Nevertheless, its effectiveness significantly increased in the presence of TNF-α. Conclusion. This study highlights the involvement of caspase-1 and caspase-8 in OA pathology, with caspase-8 emerging as a potential therapeutic target for knee OA treatment. Further investigation into the roles of caspase-1 and -8 in OA pathophysiology, including the efficacy and potential side effects of their corresponding inhibitors, is warranted. Acknowledgements. Funding Inter-Action/Inter-Excellence project (BTHA-JC-2022-36/LUABA22019)

Introduction. Recent studies suggested that the progression of osteoarthritis (OA), a chronic degenerative joint disease, may be affected by the autonomic nervous system (ANS). Under healthy conditions, the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS are well coordinated to maintain homeostasis. However, pathological conditions are frequently associated with a disturbance of this fine-tuned balance. Therefore, we analyzed whether an autonomic dysfunction occurs in OA patients. Method. 225 participants with early- or late-stage knee OA as well as 40 healthy age-matched probands were included in this study. Autonomic activity was investigated by analyzing heart rate variability (HRV), which decreases under chronic sympathetic overactivity. Time- and frequency-domain HRV indices SDRR, RMSSD, pRR50 and LF were examined. Linear regression analysis was performed to adjust for clinical characteristics, such as age, sex, BMI, or medication. Moreover, perceived chronic stress (PSQ) and pain (WOMAC) were assessed via questionnaires. In addition, the serum stress hormones cortisol, DHEA-S and IL-6 were analyzed via ELISA. Result. SDRR, RMSSD, and pRR50 were slightly reduced in the early stage of OA and showed significant decrease in the later stage of the disease. Also LF decreased significantly with OA progression. HRV was significantly influenced by the grade of OA, but not other patient characteristics. Moreover, late-stage OA patients demonstrated significantly higher PSQ and WOMAC levels compared to healthy controls. In addition, cortisol/DHEA-S ratio and IL-6 serum concentrations were significantly higher in late-stage than in early-stage OA patients and healthy controls. Conclusion. Reduced HRV, increased cortisol/DHEA-S ratio and PSQ level as well as elevated systemic IL-6 concentration indicated an autonomic shift towards a more pronounced SNS activity due to PNS deficiency in OA patients, particularly in the late-stage of the disease. Therefore, modulation of the ANS, for example by vagus nerve stimulation, might be a potential treatment strategy for of knee OA patients

Introduction. Knee osteoarthritis often causes malalignment and altering bone load. This malalignment is corrected during total knee arthroplasty surgery, balancing the ligaments. Nonetheless, preoperative gait patterns may influence postoperative prosthesis load and bone support. Thus, the purpose is to investigate the impact of preoperative gait patterns on postoperative femoral and tibial component migration in total knee arthroplasty. Method. In a prospective cohort study, 66 patients with primary knee osteoarthritis undergoing cemented Persona total knee arthroplasty were assessed. Preoperative knee kinematics was analyzed through dynamic radiostereometry and motion capture, categorizing patients into four homogeneous gait patterns. The four subgroups were labeled as the flexion group (n=20), the abduction (valgus) group (n=17), the anterior drawer group (n=10), and the tibial external rotation group (n=19). The femoral and tibial component migration was measured using static radiostereometry taken supine on the postoperative day (baseline) and 3-, 12-, and 24- months after surgery. Migration was evaluated as maximum total point motion. Result. Of the preoperatively defined four subgroups, the abduction group with a valgus-characterized gait pattern exhibited the highest migration for both the femoral (1.64 mm (CI95% 1.25; 2.03)) and tibial (1.21 mm (CI95% 0.89; 1.53)) components at 24-month follow-up. For the femoral components, the abduction group migrated 0.6 mm (CI95% 0.08; 1.12) more than the external rotation group at 24 months. For the tibial components, the abduction group migrated 0.43 mm (CI95% 0.16; 0.70) more than the external rotation group at 3 months. Furthermore, at 12- and 24-months follow-up the abduction group migrated 0.39 mm (95%CI 0.04; 0.73) and 0.45 mm (95%CI 0.01; 0.89) more than the flexion group, respectively. Conclusion. A preoperative valgus-characterized gait pattern seems to increase femoral and tibial component migration until 2 years of follow-up. This suggests that the implant fixation depends on load distributions originating from specific preoperative gait patterns

Introduction. Knee Osteoarthritis (KOA) is a prevalent joint disease requiring accurate diagnosis and prompt management. The condition occurs due to cartilage deterioration and bone remodeling. Ultrasonography has emerged as a promising modality for diagnosing KOA. Medial meniscus extrusion (MME), characterized by displacement of medial meniscus beyond the joint line has been recognized as a significant marker of KOA progression. This study aimed to explore potentials Ultrasound findings in timely detection of MME and compare it to magnetic resonance imaging (MRI) as a reference standard. Method. A comprehensive literature search was performed in 4 databases from inception to May 1 2024. Two independent reviewers, initiated screening protocols and selected the articles based on inclusion and exclusion criteria and then extracted the data. Meta-analysis was conducted using R 4.3.2 packages mada and metafor. Result. A total of 2500 articles from 4 databases was retrieved; however, following the application of inclusion and exclusion criteria 23 articles were finally extracted. These studies collectively encompassed a total of 777 patients with mean age of 53.2±7.4. The mean BMI calculated for patients was 28.31 ± 2.45. All patients underwent non-weight bearing knee ultrasonography in supine position with 0° flexion. The reported medial meniscus extrusion was 2.58 mm for articles using MRI and 2.65 mm for those using Ultrasound (MD: 0.05 ± 0.12, P= 0.65, I. 2. : 54%). Our meta-analysis revealed insignificant difference between US and MRI. (SMD: 0.03, 95% CI: -0.18 _0.23, P= 0.77, I. 2. : 56%) Meta analysis for diagnostic accuracy measures yielded a pooled sensitivity and specificity of 90.8% and 77% (95% CI: 84.2% – 94.8%, 35.5% – 95.3%, respectively, I. 2. : 44%). Conclusion. Our results indicate a close alignment in the accuracy of measurements obtained using Ultrasound modality. The narrow range suggests a minimal discrepancy in MME values between MRI and ultrasound, highlighting their comparable precision in diagnostic assessments

Introduction. Degenerative meniscal tears are the most common meniscal lesions, representing huge clinical and socio-economic burdens. Their role in knee osteoarthritis (OA) onset and progression is well established and demonstrated by several retrospective studies. Effective preventive measures and non-surgical treatments for degenerative meniscal lesions are still lacking, also because of the lack of specific and accurate animal models in which test them. Thus, we aim to develop and validate an accurate animal model of meniscus degeneration. Method. Three different surgical techniques to induce medial meniscus degenerative changes in ovine model were performed and compared. A total of 32 sheep (stifle joints) were subjected to either one of the following surgical procedures: a) direct arthroscopic mechanical meniscal injury; b) peripheral devascularization and denervation of medial meniscus; c) full thickness medial femoral condyle cartilage lesion. In all the 3 groups, the contralateral joint served as a control. Result. From a visual examination of the knee joint emerged a clear difference between control and operated groups, in the menisci but also in the cartilage, indicating the onset of OA-related cartilage degeneration. The meniscal and cartilaginous lesions were characterized by different severity and location in the different groups. For instance, a direct meniscal injury caused cartilaginous lesions especially in the medial part of the condyles, and the other approaches presented specific signature. Evaluation of scoring scales (e.g. ICRS score) allowed the quantification of the damage and the identification of differences among the four groups. Conclusion. We were effectively able to develop and validate a sheep model of meniscal degeneration which led to the onset of OA. This innovative model will allow to test in a pre-clinical relevant setting innovative approaches to prevent meniscal-related OA. Funding. Project PNRR-MAD-2022-12375978 funded by Italian Ministry of Health

Introduction. Polyacrylamide hydrogel (iPAAG. 1. ), is CE marked for treating symptomatic knee osteoarthritis (OA), meeting the need for an effective, long-lasting, and safe non-surgical option. This study evaluates the efficacy and safety of a single 6 ml intra-articular injection of iPAAG in participants with moderate to severe knee OA over a 5-year post-treatment period, presenting data from the 4-year follow up. Method. This prospective multicentre study (3 sites in Denmark) involved 49 participants (31 females) with an average age of 70 (range 44 – 86 years). They received a single 6 mL iPAAG injection. All participants provided informed consent and re-consented to continue after 1 year. The study followed GCP principles and was approved by Danish health authorities and local Health Research Ethics committees. Twenty-seven participants completed the 4-year follow-up. The study evaluated WOMAC pain, stiffness, function, and Patient Global Assessment (PGA) of disease impact. Changes from baseline were analysed using a mixed model for repeated measurement (MMRM). Sensitivity analyses were applied on the extension data, where the MMRM analysis was repeated only including patients in the extension phase and an ANCOVA model was used, replacing missing values at 4-years with baseline values (BOCF). Results. The planned MMRM analysis (n=49) revealed a statistically significant decrease in WOMAC pain subscale scores (-22.0; 95%CI: -29.5; -14.4) from baseline to 4-years. Analysis of the extension phase (n=27) showed similar results (-21.8; 95%CI: -29.0; -14.6) compared to the initial analysis. Furthermore, BOCF analysis indicated a statistically significant reduction in WOMAC pain subscale scores from baseline (-13.0 units). Four new adverse events were reported between the 3-year and 4-year visits; none were related to treatment. Conclusions. This study shows that single injections of 6 ml intra-articular iPAAG were well tolerated and continued to provide clinically important effectiveness at 4-years after treatment. Acknowledgements. The study was sponsored by Contura International A/S

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.

Aims

The surgical target for optimal implant positioning in robotic-assisted total knee arthroplasty remains the subject of ongoing discussion. One of the proposed targets is to recreate the knee’s functional behaviour as per its pre-diseased state. The aim of this study was to optimize implant positioning, starting from mechanical alignment (MA), toward restoring the pre-diseased status, including ligament strain and kinematic patterns, in a patient population.

Aims

This study examined windswept deformity (WSD) of the knee, comparing prevalence and contributing factors in healthy and osteoarthritic (OA) cohorts.

The October 2024 Knee Roundup. 360. looks at: Managing the unexpected: treatment of intraoperative medial collateral ligament injuries; Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: secondary analysis of data from a randomized controlled trial; Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial; Cartilage regeneration and long-term survival in medial knee osteoarthritis patients treated with high tibial osteotomy and osteochondral autologous transfer system; Treatment of chronic and complex meniscal tears with arthroscopic meniscus repair augmented with collagen matrix wrapping: failure rate and functional outcomes; Long-term outcomes of multiligament knee injuries in American football players

Aims

The prevalence of osteoarthritis (OA) associated with instability of the shoulder ranges between 4% and 60%. Articular cartilage is, however, routinely assessed in these patients using radiographs or scans (2D or 3D), with little opportunity to record early signs of cartilage damage. The aim of this study was to assess the prevalence and localization of chondral lesions and synovial damage in patients undergoing arthroscopic surgery for instablility of the shoulder, in order to classify them and to identify risk factors for the development of glenohumeral OA.

Aims

The influence of metabolic syndrome (MetS) on the outcome after hip and knee arthroplasty is debated. We aimed to investigate the change in patient-reported outcome measure (PROM) scores after hip and knee arthroplasty, comparing patients with and without MetS.

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.

Aims

Patient dissatisfaction following primary total knee arthroplasty (TKA) with manual jig-based instruments has been reported to be as high as 30%. Robotic-assisted total knee arthroplasty (RA-TKA) has been increasingly used in an effort to improve patient outcomes, however there is a paucity of literature examining patient satisfaction after RA-TKA. This study aims to identify the incidence of patients who were not satisfied following RA-TKA and to determine factors associated with higher levels of dissatisfaction.

Aims

The purpose of this study was to determine the association between prior sleeve gastrectomy in patients undergoing primary total hip and knee arthroplasty, and 90-day complications, incidence of revision arthroplasty, and patient-reported outcome scores at final follow-up.

Aims. Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. Methods. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). Results. A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Conclusion. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection. Cite this article: Bone Joint J 2024;106-B(9):907–915

The August 2024 Oncology Roundup³⁶⁰ looks at: What factors are associated with osteoarthritis after cementation for benign aggressive bone tumour of the knee joint: a systematic review and meta-analysis; Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumour resection; Intercalary resection of the tibia for primary bone tumours: are vascularized fibula autografts with or without allografts a durable reconstruction?; 3D-printed modular prostheses for the reconstruction of intercalary bone defects after joint-sparing limb salvage surgery for femoral diaphyseal tumours; Factors influencing the outcome of patients with primary Ewing’s sarcoma of the sacrum; The significance of surveillance imaging in children with Ewing’s sarcoma and osteosarcoma; Resection margin and soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy.

The August 2024 Knee Roundup. 360. looks at: Calcification’s role in knee osteoarthritis: implications for surgical decision-making; Lower complication rates and shorter lengths of hospital stay with technology-assisted total knee arthroplasty; Revision surgery: the hidden burden on surgeons; Are preoperative weight loss interventions worthwhile?; Total knee arthroplasty with or without prior bariatric surgery: a systematic review and meta-analysis; Aspirin triumphs in knee arthroplasty: a decade of evidence; Efficacy of DAIR in unicompartmental knee arthroplasty: a glimpse from Oxford

Aims

Conventional patient-reported surveys, used for patients undergoing total hip arthroplasty (THA), are limited by subjectivity and recall bias. Objective functional evaluation, such as gait analysis, to delineate a patient’s functional capacity and customize surgical interventions, may address these shortcomings. This systematic review endeavours to investigate the application of objective functional assessments in appraising individuals undergoing THA.

Aims

To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.