Lifetime Cost-Effectiveness of Structured Education and Exercise Therapy for Knee Osteoarthritis in Australia.

Importance: Structured education and exercise therapy programs have been proposed to reduce reliance on total knee replacement (TKR) surgery and improve health care sustainability. The long-term cost-effectiveness of these programs is unclear. Objectives: To estimate the lifetime cost-effectiveness of implementing a national structured education and exercise therapy program for individuals with knee osteoarthritis with the option for future TKR compared with usual care (TKR for all). Design, Setting, and Participants: This economic evaluation used a life table model in combination with a Markov model to compare costs and health outcomes of a national education and exercise therapy program vs usual care in the Australian health care system. Subgroup, deterministic, and probabilistic sensitivity analyses were completed. A hypothetical cohort of adults aged 45 to 84 years who would undergo TKR was created. Exposure: Structured education and exercise therapy intervention provided by physiotherapists. The comparator was usual care where all people undergo TKR without accessing the program in the first year. Main Outcomes and Measures: Incremental net monetary benefit (INMB), with an incremental cost-effectiveness ratio threshold of 28 033 Australian dollars (A$) per quality-adjusted life-year (QALY) gained, was calculated from a health care perspective. Transition probabilities, costs, and utilities were estimated from national registries and a randomized clinical trial. Results: The hypothetical cohort included 61 394 individuals (53.9% female; 93.6% aged ≥55 years). Implementation of an education and exercise therapy program resulted in a lifetime cost savings of A$498 307 942 (US $339 922 227), or A$7970 (US $5537) per individual, and resulted in fewer QALYs (0.43 per individual) compared with usual care. At a population level, education and exercise therapy was not cost-effective at the lifetime horizon (INMB, -A$4090 [-US $2841]). Subgroup analysis revealed that the intervention was cost-effective only for the first 9 years and over a lifetime only in individuals with no or mild pain at baseline (INMB, A$11 [US $8]). Results were robust to uncertainty around model inputs. Conclusions and Relevance: In this economic evaluation of structured education and exercise therapy compared with usual care, the intervention was not cost-effective over the lifetime for all patients but was for the first 9 years and for those with minimal pain. These findings point to opportunities to invest early cost savings in additional care or prevention, including targeted implementation to specific subgroups.

Increased vascular endothelial growth factor expression is associated with cruciate ligament degeneration in patients with osteoarthritis of the knee.

BACKGROUND: This study aimed to investigate the expression of vascular endothelial growth factor (VEGF) in cruciate ligaments from patients with osteoarthritis (OA). It was hypothesized that the expression level of VEGF is associated with the extent of degeneration of the cruciate ligaments. METHODS: Remnants of anterior cruciate ligaments (ACLs) from patients with acute ACL injury due to trauma, and ACLs and posterior cruciate ligaments (PCLs) from patients with primary OA were assessed histologically. Samples were immunohistochemically stained with VEGF and tenomodulin, and immunopositive cells were quantitatively assessed by the histological grades of ligament degeneration. RESULTS: Histological analysis showed significant degeneration of the ACLs from OA patients compared with trauma patients, with increased expression of VEGF correlating with higher grades of degeneration. Conversely, tenomodulin expression was lower in more degenerated cruciate ligaments. The percentage of VEGF-positive cells was correlated inversely with that of tenomodulin-positive cells. CONCLUSIONS: Increased VEGF expression is associated with degeneration of cruciate ligaments in patients with osteoarthritis of the knee.

Incidence of and risk factors for preoperative deep vein thrombosis in elderly patients with end-stage osteoarthritis following total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Deep vein thrombosis (DVT) is a common and serious risk in elderly patients with knee osteoarthritis (OA), making preoperative detection crucial. Despite this, identifying OA patients at high risk for preoperative DVT and appropriately targeting them for venous ultrasound screening remains a challenge. There is limited research-based evidence on the risk factors for preoperative DVT in elderly patients with end-stage OA. We examined the incidence of and risk factors for preoperative DVT in elderly patients with end-stage OA scheduled for total knee arthroplasty. METHODS: We retrospectively analyzed the demographic data (age, sex, body mass index, current smoking, alcohol consumption, walking status, and Barthel index score), medical history, and laboratory test indices of 1411 patients with end-stage OA aged ≥ 60 years scheduled for total knee arthroplasty from January 2015 to December 2018. Risk factors for preoperative DVT were evaluated by univariate and multivariate logistic analyses. Receiver operating characteristic analysis was performed to determine optimal cut-off values. RESULTS: The incidence of preoperative DVT was 4.5% (63 of 1411 patients). Seven independent risk factors were correlated with preoperative DVT in the multivariate logistic regression: age (odds ratio [OR], 1.073; P = 0.002), D-dimer concentration (OR, 1.173; P = 0.003), hyperlipidemia (OR, 2.038; P = 0.045), atrial fibrillation (OR, 4.004; P = 0.033), chronic renal failure (OR, 6.732; P = 0.008), chronic obstructive pulmonary disease (COPD) (OR, 8.721; P = 0.001), and walking status (wheelchair) (OR, 2.697; P = 0.002). The optimal cut-off values for predicting preoperative DVT were 0.585 µg/mL for the D-dimer concentration (area under the curve [AUC], 0.769; P < 0.001) and 72.5 years for age (AUC, 0.668; P < 0.001). CONCLUSION: Among elderly patients with end-stage OA, venous ultrasonography to rule out DVT risk should be prioritized in those with a high D-dimer concentration (> 0.585 µg/mL), high age (> 72.5 years), hyperlipidemia, atrial fibrillation, chronic renal failure, COPD, and walking status (wheelchair).

High expression of transcription factor EGR1 is associated with postoperative muscle atrophy in patients with knee osteoarthritis undergoing total knee arthroplasty.

BACKGROUND: Muscle atrophy is a typical affliction in patients affected by knee Osteoarthritis (KOA). This study aimed to examine the potential pathogenesis and biomarkers that coalesce to induce muscle atrophy, primarily through the utilization of bioinformatics analysis. METHODS: Two distinct public datasets of osteoarthritis and muscle atrophy (GSE82107 and GSE205431) were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA) to probe for common differentially expressed genes (DEGs) and conduct transcription factor (TF) enrichment analysis from such genes. Venn diagrams were used to identify the target TF, followed by the construction of a protein-protein interaction (PPI) network of the common DEGs governed by the target TF. Hub genes were determined through the CytoHubba plug-in whilst their biological functions were assessed using GSEA analysis in the GTEx database. To validate the study, reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry techniques were employed. RESULTS: A total of 138 common DEGs of osteoarthritis and muscle atrophy were identified, with 16 TFs exhibiting notable expression patterns in both datasets. Venn diagram analysis identified early growth response gene-1 (EGR1) as the target TF, enriched in critical pathways such as epithelial mesenchymal transition, tumor necrosis factor-alpha signaling NF-κB, and inflammatory response. PPI analysis revealed five hub genes, including EGR1, FOS, FOSB, KLF2, and JUNB. The reliability of EGR1 was confirmed by validation testing, corroborating bioinformatics analysis trends. CONCLUSIONS: EGR1, FOS, FOSB, KLF2, and JUNB are intricately involved in muscle atrophy development. High EGR1 expression directly regulated these hub genes, significantly influencing postoperative muscle atrophy progression in KOA patients.

[Recommendations regarding arthroscopic surgery in the knee joint and the updated National Guidelines for Musculoskeletal Diseases]. / Att göra eller inte göra ­ kloka val kan ibland vara svåra.

The article discusses the Swedish National Board of Health and Welfare's recommendations regarding arthroscopic surgery in the knee joint and the updated National Guidelines for Musculoskeletal Diseases from 2021. It emphasizes the ongoing discussion within the orthopedic profession and aims to summarize constructive discussions between the National Board of Health and Welfare, the Swedish Orthopedic Association, and the National program board for Musculoskeletal Diseases. The text notes a significant decrease in knee arthroscopies due to knee osteoarthritis and degenerative meniscus injuries over the past decade although 5,000 and 6,000 arthroscopies were performed in 2022 due to knee osteoarthritis or degenerative meniscus rupture. The reasons for the continued performance of the procedure are discussed, including the lack of a precise definition of ¼degenerative meniscus rupture« and interpretation differences within the profession. A recent report from the National Board of Health and Welfare indicates that the profession has largely embraced the recommendations from 2012, but there are significant regional differences in the number of performed arthroscopies. The text emphasizes the need for clearer recommendations, refined data collection, and constructive dialogue to improve the implementation of the National Board of Health and Welfare's recommendations and reduce the use of procedures classified as ¼not recommended.« The authors believe that continuous dialogue and follow-up are necessary to decrease the use of procedures not recommended in the guidelines.

[Total knee replacement in patients under 60 years with high functional demand: functional outcomes and return to sports after an average 2-year follow-up]. / Reemplazo total de rodilla en pacientes menores de 60 años con demanda funcional elevada: resultados funcionales y retorno al deporte después de un promedio de dos años de seguimiento.

INTRODUCTION: a common concern in presurgical medical appointment of total knee replacement medical appointment is return to exercise. The purpose of this study was to analyze functional results and return to sport in patients under 60 years of age after this surgery. MATERIAL AND METHODS: we retrospectively analyzed 41 total knee replacements in 36 athletic patients (average age: 53 years [46-60]). Average follow-up of two years (6 months-5 years). Diagnoses: 37 osteoarthritis, three sequelae of Rheumatoid Arthritis, 1 extra-articular deformity. Functional and radiographic outcomes assessed using modified Knee Society and High Activity Arthroplasty Scores. RESULTS: average improvement from 31.95 to 91.61 in KSS and average from 7.95 to 13.73 in HAAS. Return to sport in 3.5 months average (range 2-6 months). Three patients did not return to sport. CONCLUSIONS: we consider that delaying surgery in these patients will cause progression in their osteoarthritis pathology and cessation of their sports activities. This makes the surgical technique difficult in addition to reducing the patient's physical performance. Analyzing the survival rate of implants in young patients, more than 80% is reported in a 25-year follow-up.

INTRODUCCIÓN: una inquietud frecuente en consultas prequirúrgicas de reemplazo total de rodilla es el regreso al ejercicio. El propósito de este estudio fue analizar resultados funcionales y retorno al deporte en pacientes menores de 60 años posterior a esta cirugía. MATERIAL Y MÉTODOS: analizamos retrospectivamente 41 reemplazos totales de rodilla en 36 pacientes deportistas (edad promedio: 53 años [46-60]). Seguimiento promedio de dos años (6 meses-5 años). Diagnósticos: 37 gonartrosis, tres secuelas de artritis reumatoidea, una deformidad extraarticular. Resultados funcionales y radiográficos evaluados mediante Knee Society modificado y High Activity Arthroplasty Score. RESULTADOS: mejoría promedio de 31.95 a 91.61 en KSS y promedio de 7.95 a 13.73 en HAAS. Retorno al deporte en 3.5 meses promedio (rango: 2-6 meses). Tres pacientes no retornaron al deporte. CONCLUSIONES: consideramos que el retraso de la cirugía en estos pacientes producirá progresión en su patología artrósica y cese de sus actividades deportivas. Esto dificulta la técnica quirúrgica además de disminuir el rendimiento físico del paciente. Analizando la tasa de supervivencia de implantes en pacientes jóvenes, se reporta más de 80% en seguimientos de 25 años.

[Navigated total knee arthroplasty: an alternative surgical technique for patients with gonarthrosis in Mexico]. / Artroplastía total de rodilla navegada: una técnica quirúrgica alternativa para pacientes con gonartrosis en México.

Total knee arthroplasty consists of the artificial replacement of the knee joint in its three compartments. One of its main challenges is the anatomical restoration of the joint line. The relief of inappropriate postoperative pain can lengthen the recovery time and increase the days of intrahospital stay and readmission. Total Navigated Knee Arthroplasty is considered one of the most innovative procedures in the treatment of knee osteoarthritis. It was introduced in the late 90s and there is currently good evidence, that navigation has greater precision in the position of the prosthetic components, compared to a manual instrumentation, especially the reduction of the atypical alignment values of the mechanical axis. The supporters of (TNKA) have argued that this technique can improve the score of functional scales, the alignment of the prosthetic components, revision rates and survival, because it reduces the percentage of atypical radiographic values in the alignment of the coronal and sagittal plane, greater precision in axial rotation of the components, improvement of the flexion gap and the extension gap and the soft tissue balance. In general, experience is gained, learning curves are improved and the complication rate is decreased with acceptable costs.

La artroplastía total de rodilla consiste en el reemplazo artificial de la articulación de la rodilla en sus tres compartimientos. Uno de sus principales desafíos es la restauración anatómica de la línea articular. El alivio de dolor postoperatorio inadecuado puede alargar el tiempo de recuperación y aumentar los días de hospitalización y reingreso. La artroplastía total de rodilla navegada (ATRN) es considerada uno de los procedimientos más novedosos en el tratamiento de la artrosis de rodilla. Se introdujo a finales de los años 90 y actualmente existe una buena evidencia de que la navegación tiene mayor precisión en la colocación de los componentes protésicos, en comparación con la instrumentación manual, especialmente en la reducción de los valores atípicos de alineación del eje mecánico. Los defensores de ATRN han argumentado que esta técnica puede mejorar la puntuación de escalas funcionales, la alineación de los componentes, tasas de revisión y supervivencia, debido a que reduce el porcentaje de valores atípicos radiográficos en la alineación del plano coronal y sagital, mayor precisión en rotación axial de los componentes, mejora de la brecha en flexión y extensión y el balance de ligamentos. Se gana experiencia, se mejoran las curvas de aprendizaje y se disminuyen la tasa de complicaciones, con costos aceptables.

Geographical Differences in the Perspective of Osteoarthritis Care Management: A Cross-Sectional Study in Italy, Sweden and Russia.

BACKGROUND: This study aimed to explore the awareness, experiences, and beliefs of individuals with osteoarthritis (OA) regarding their healthcare management, along with assessing their overall satisfaction levels. METHODS: A cross-sectional online survey was conducted in Italy, Sweden, and Russia, rigorously developed based on OA international guidelines in collaboration with healthcare professionals and individuals with OA. Participants over 40 years of age with self-reported hip and/or knee OA were eligible. The analytical framework included descriptive analysis (assessment of awareness levels for 'recommended', 'optional', and 'not recommended' treatments), analysis of suggested treatments and taken treatments, exploration of beliefs, barriers and satisfaction analysis (0-100 scale). RESULTS: A total of 401 participants (mean age: 59.7, 78.3% female, 28% Italian, 49% Swedish, 23% Russian) contributed to the study. In Sweden, 57%-72% accurately identified recommended treatments, while in Russia, the range was 34%-91%, and in Italy, it was 35%-73%. The predominant suggested and taken treatments were oral anti-inflammatory drugs in Italy (87/81%) and Russia (97/97%) and specific exercise in Sweden (84/79%). Notably, only Sweden reached a consensus on the effectiveness of exercise for everyone, while Russia and Italy insisted on radiographic findings as a prerequisite for exercise. Mean satisfaction levels were 59.7 (Italy), 47.4 (Sweden), and 35.2 (Russia). CONCLUSIONS: This study uncovered variations in awareness, treatment preferences, and beliefs among the three countries, underscoring the necessity for tailored education on OA management that accounts for regional differences across Europe.

Development of a Soft Tissue Knee Clinical Decision-Making Tool for Patients Presenting to Primary Point-of-Care Providers in Alberta, Canada.

Several barriers exist in Alberta, Canada to providing accurate and accessible diagnoses for patients presenting with acute knee injuries and chronic knee problems. In efforts to improve quality of care for these patients, an evidence-informed clinical decision-making tool was developed. Forty-five expert panelists were purposively chosen to represent stakeholder groups, various expertise, and each of Alberta Health Services' 5 geographical health regions. A systematic rapid review and modified Delphi approach were executed with the intention of developing standardized clinical decision-making processes for acute knee injuries, atraumatic/overuse conditions, knee arthritis, and degenerative meniscus. Standardized criteria for screening, history-taking, physical examination, diagnostic imaging, timelines, and treatment were developed. This tool standardizes and optimizes assessment and diagnosis of acute knee injuries and chronic knee problems in Alberta. This project was a highly collaborative, province-wide effort led by Alberta Health Services' Bone and Joint Health Strategic Clinical Network (BJH SCN) and the Alberta Bone and Joint Health Institute (ABJHI).

Translation and Cross-Cultural Adaptation of the Osteoarthritis Knowledge Scale Into Turkish.

BACKGROUND: The Osteoarthritis Knowledge Scale (OAKS) is a validated tool for assessing knowledge about hip and knee osteoarthritis (OA). However, to date, there has been no translation and adaptation of the OAKS for the Turkish population. OBJECTIVES: To translate and cross-culturally adapt the OAKS into Turkish and to assess its psychometric properties in the Turkish population with and without hip or knee OA. METHODS: The OAKS was translated following accepted guidelines. A validation study assessed internal consistency, test-retest reliability and measurement error. An exploratory factor analysis was conducted to assess the factor structure. RESULTS: A total of 278 participants (n = 70 with hip OA, n = 105 with knee OA, and n = 103 without OA) were included. Internal consistency was 0.72, 0.79 and 0.79 for participants with hip OA, knee OA, and no OA, respectively. The test-retest intraclass correlation coefficient was 0.72 (95% CI; 0.45-0.85), 0.89 (95% CI; 0.82-0.93) and 0.88 (95% CI; 0.79-0.93) for participants with hip OA, knee OA and no OA, respectively. It had three principal components accounting for 57.2% of the total variance. CONCLUSIONS: The Turkish version of the OAKS is a reliable and valid tool for measuring OA knowledge in the Turkish population, including those with and without hip and knee OA. Test-retest reliability was below acceptable levels in the population with hip OA only. Therefore, we recommend that the ICC be interpreted with caution when used in this population.

Association between folate intake and radiographic progression, pain function scores in subjects with radiographic knee osteoarthritis: Data from the osteoarthritis initiative.

BACKGROUND: Folate has an important role in the functioning of the musculoskeletal system, including modulation of inflammation, immunity, cartilage regeneration, prevention of osteoporosis, and maintenance of muscle strength, but evidence on the association between folate intake and knee pain, functional scores, and radiographic progression in patients with knee osteoarthritis (OA) is still limited. METHODOLOGY: Our population-based cohort was extracted from the osteoarthritis initiative (OAI), focusing on individuals with prevalent radiographic knee OA (with a Kellgren-Lawrence score ≥2). Folate consumption was determined using the food frequency questionnaire. Data regarding the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and radiographic readings were collected over 48 months. We analyzed the compiled data using generalized additive mixed models. RESULTS: Our cohort consisted of 1472 OA patients (626 men and 846 women, mean [SD] age 62.35 [8.92]). At the 48-month follow-up, we observed a significant correlation between higher folate intake and a slower progression of knee pain and functional scores, as evidenced by a statistically significant decrease in the WOMAC total score, WOMAC pain subscale score, and WOMAC function/disability subscale score (p < .05). The fully adjusted models estimated a reduction of -0.028 points per 50 µg/1000 kcal of daily folate intake on the WOMAC pain subscale, -0.117 points on the WOMAC function subscale, and -0.160 points on the total WOMAC scale. Furthermore, our nonparametric fit analysis suggested that a higher intake of folate might decelerate the radiographic progression of OA. Stratified analyses indicated that an increase in folate consumption might particularly benefit men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake. CONCLUSION: Higher folate intake is correlated with improved knee function and reduced pain in patients with knee OA and might deter the radiographic progression of OA. The benefits appear to be more pronounced in men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake.

Arthroscopic surgery is not superior to conservative treatment in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trails.

BACKGROUND: Studies comparing the effectiveness of arthroscopic knee surgery and conservative treatment on knee osteoarthritis (OA) came up with inconsistent results. Systematic review on this topic still is still lacking. This systematic review and meta-analysis aimed to evaluate the effectiveness of arthroscopic knee surgery on knee OA, compared to conservative treatments. MATERIALS AND METHODS: Literature searches were performed in PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) published before on 1st July 2024. Studies comparing the effectiveness of arthroscopy and conservative treatments only on knee OA were included. Quality of included studies was evaluated by risk of bias 2 (ROB2). Long-term results in terms of pain relief, functional recovery and patients reported satisfaction were meta-analyzed to evaluate the therapeutic effectiveness. RESULTS: Ten studies were included in this review, among which only 1 was considered as low risk of bias. Five studies were involved in meta-analyses and no difference was found in therapeutic effectiveness of arthroscopic surgery and conservative treatment on knee OA, in the evaluation of VAS (p = 0.63), WOMAC (p = 0.38), SF-36 (p = 0.74) and patient satisfaction (p = 0.07). CONCLUSION: The evidence does not support the effectiveness of arthroscopic knee surgery compared to conservative treatments in knee OA.

Effectiveness of whole-body electromyostimulation on knee pain and physical function in knee osteoarthritis: a randomized controlled trial.

In a randomized, controlled study, whole-body electromyostimulation (WB-EMS) was investigated as a promising alternative treatment technique compared to conventional strength training for the management of knee osteoarthritis (OA). Seventy-two overweight participants with symptomatic knee OA were randomly assigned to WB-EMS (n = 36) or a usual care group (UCG, n = 36). For seven months, the WB-EMS group received three times per fortnight a WB-EMS training, while the UCG was prescribed six-times physiotherapeutic treatments. We observed significant effects for the primary outcome "pain", as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS), with more favourable changes in the WB-EMS group vs UCG (between-group difference 9.0 points, 95%CI 2.9-15.1, p = 0.004). Secondary outcomes, including the other KOOS subscales (symptoms, function in daily living, function in sports/recreational activities and quality of life), 7 day pain diary, hip/leg extensor strength and lower limb function (30s sit-to-stand test), were also statistically significant in favour of the WB-EMS group. Overall, WB-EMS was found to be effective in relieving knee pain symptoms and improving physical function in individuals with symptomatic knee OA compared to usual care treatment. WB-EMS could be used as an alternative therapy in the management of knee OA; particularly for patients that cannot be motivated for conventional training.

Combined knee osteoarthritis and diabetes is associated with reduced muscle strength, physical inactivity, and poorer quality of life.

OBJECTIVE: This study delves into the intriguing connection between knee osteoarthritis and diabetes in Malaysia. Specifically, the exacerbation of knee osteoarthritis in the presence of diabetes in terms of symptoms, physical performance, physical activity, psychological status, social participation, and quality of life was discussed. DESIGN: This cross-sectional study recruited adults aged 50 and above by convenient sampling and grouped them into: knee osteoarthritis-diabetes-, knee osteoarthritis+diabetes-, knee osteoarthritis-diabetes+, and knee osteoarthritis+diabetes+. SUBJECTS/PATIENTS: Of 436 recruited participants, 261 (59.8%) participants reported knee osteoarthritis. METHODS: Handgrip strength, Timed Up and Go test, 6 Meter Walk Test, and 5 Times Sit to Stand Test were measured using standardized procedures. Six questionnaires were administered for the remaining parameters. RESULTS: Across groups, there were significant differences: 6 Meter Walk Test (p = 0.024), Timed Up and Go test (p = 0.020), and 5 Times Sit to Stand Test (p < 0.001), quality of life (p = 0.009), and physical activity (p = 0.036). Knee osteoarthritis+diabetes+ was independently associated with reduced handgrip strength, 5 Times Sit to Stand Test, quality of life, and physical inactivity after adjustment. Knee osteoarthritis+diabetes- was independently associated with reduced Timed Up and Go test and social isolation. CONCLUSION: The findings revealed the diabetic knee osteoarthritis subgroup's unique physical and psychosocial features of reduced muscle strength and physical inactivity. Future studies should investigate whether managing metabolic factors, and enhancing physical activity and strength exercises, can reduce knee osteoarthritis symptoms and disease severity.

Effects of transcranial direct current stimulation on pain and physical function in patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

Association between intra-articular hyaluronic acid injections in delaying total knee arthroplasty and safety evaluation in primary knee osteoarthritis: analysis based on Health Insurance Review and Assessment Service (HIRA) claim database in Republic of Korea.

BACKGROUND: The prevalence of knee osteoarthritis (KOA), a progressive degenerative disease, is gradually increasing, and it is a progressive degenerative disease. In patients with mild-to-moderate KOA, intra-articular hyaluronic acid (IA-HA) has been shown to be an effective non-operative treatment option that can provide significant pain relief and symptom improvement by increasing intra-articular viscoelasticity. This study aimed to evaluate the efficacy of IA-HA injections in delaying total knee arthroplasty (TKA) and the safety of IA-HA according to IA-HA type and combination with intra-articular corticosteroid (IA-CS) using a large health insurance claim database. METHODS: For this retrospective cohort study, the study population included patients aged ≥ 50 years with a first diagnosis of KOA between 2009 and 2014, who underwent TKA by 2020, using the Health Insurance Review and Assessment Service claim database in Republic of Korea. IA-HA injections were categorized as single or multiple injection regimen agents. Cox proportional hazard models estimated hazard ratios (HR) for TKA risk, adjusted for covariates. Logistic regression assessed the occurrence of adverse events after IA-HA administration. RESULTS: In all, 36,983 patients were included. Patients who received IA-HA injections had a significantly longer time to TKA compared to those who did not (mean delay of approximately 1 year). The IA-HA group had a significantly lower risk of TKA (HR: 0.61, 95% CI: 0.60-0.62) than non-IA-HA group after adjusting for covariates, which included age, sex, medical history, number of hospital beds, and CS injection. Single injection IA-HA regimen agents showed the longest time to TKA and lowest risk (HR: 0.56, 95% CI: 0.53-0.59). TKA risk decreased with the number of IA-HA cycles. Adverse events occurred in 6.7% of IA-HA cases without CS, with very low incidence of infection. Multiple injection regimen agents (multiple injection regimen 7.0% vs. single injection regimen 3.6%) and concurrent IA-CS use (concurrent IA-CS use 13.9% vs. IA-HA only 6.7%) were associated with higher infection risk. CONCLUSION: IA-HA injections were associated with a significant delay in TKA among patients with KOA. Single-injection regimen agents had the lowest TKA risk. Infection risk increased with multiple injections and concurrent IA-CS use. These findings could suggest the use of IA-HA as an effective non-operative intervention option for managing KOA and delaying TKA. Careful selection of IA-HA type and consideration of concurrent IA-CS use could play a role in delaying the time to TKA and reducing complications.

METTL14-mediated lncRNA-FAS-AS1 promotes osteoarthritis progression by up-regulating ADAM8.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative disease. We explored the role and regulatory mechanisms of lncRNA-FAS-AS1 in OA progression. METHODS: We exposed human immortalized chondrocytes to IL-1ß for 24 h to induce an OA cell model. The target molecule levels were assessed using western blot and quantitative real-time PCR (RT-qPCR). Cell viability and apoptosis were measured using CCK-8 and flow cytometry. The m6A modification of FAS-AS1 was determined using MeRIP. We examined the binding relationships between FAS-AS1, Fragile X mental retardation 1 (FMR1), and A disintegrin and metalloproteinase 8 (ADAM8) using RIP and RNA pull-down. The OA animal model was established by separating the medial collateral ligament and medial meniscus. Safranin-O staining and Mankin's scale were employed to evaluate pathological changes within the cartilage. RESULTS: FAS-AS1, METTL14, and ADAM8 were upregulated, and the JAK/STAT3 signaling pathway was activated in OA mice and IL-1ß-induced chondrocytes. FAS-AS1 knockdown inhibited extracellular matrix degradation in IL-1ß-induced chondrocytes; however, ADAM8 overexpression reversed this effect. FAS-AS1 maintained the stability of ADAM8 mRNA by recruiting FMR1. METTL14 knockdown repressed FAS-AS1 expression in an m6A-dependent manner. FAS-AS1 overexpression reversed the inhibitory effects of METTL14 knockdown on JAK/STAT3 signaling and cartilage damage in the OA model both in vitro and in vivo. CONCLUSION: METTL14-mediated FAS-AS1 promotes OA progression through the FMR1/ADAM8/JAK/STAT3 axis.

The Effectiveness of Alpha-2-Macroglobulin Injections for Osteoarthritis of the Knee.

BACKGROUND: Intra-articular (IA) injections of plateletrich plasma (PRP) have been increasingly used in the nonoperative treatment of knee osteoarthritis (OA) but have considerable heterogeneity in both formulation and clinical results. Alpha-2-macroglobulin (A2M) is a large plasma protein found in PRP that inhibits cartilage-degrading enzymes and could be an efficacious OA treatment independently. The purpose of this study was to compare the short-term clinical efficacy of IA injection of A2M-rich PRP concentrate to conventionally prepared PRP and corticosteroids in the management of symptomatic knee OA. METHODS: This double-blinded, randomized, controlled clinical trial was conducted at a single medical center with enrollment from June 2018 to May 2019. Subjects with symptomatic Kellgren-Lawrence (KL) grade 2 or 3 knee OA were randomized to IA injection with A2M, PRP, or methylprednisolone (MP) and followed for 12 weeks post-injection. Knee pain and function were assessed at pre-treatment baseline and at 6-week and 12-week followup with patient-reported outcome (PRO) surveys including the visual analog scale (VAS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, and Tegner score. RESULTS: Seventy-five subjects were enrolled in the trial, of whom 68 (90.7%) completed the 12-week follow-up. The majority of subjects (73%) were female with a mean age of 59 years (range: 37 to 75 years). There were no significant differences in age (p = 0.30), sex (p = 0.44), or KL grade (p = 0.73) between treatment groups. By 12 weeks postinjection, the A2M group showed significant improvement in VAS, WOMAC, KOOS, and Tegner (p < 0.05), the PRP group showed no significant improvement in any PROs (p > 0.05), and the MP group showed significant improvement in Lysholm only (p = 0.01). However, the changes in PRO scores between baseline and 12-week follow-up did not significantly differ between the three groups (p > 0.05). CONCLUSIONS: Alpha-2-macroglobulin IA injection shows comparable efficacy to PRP and corticosteroids in the treatment of mild-to-moderate knee OA. Alpha-2-macroglobulin treatment resulted in modest improvement in knee pain and function at 6-week follow-up, albeit inconsistently across PRO measures and to a similar degree as PRP and corticosteroids. Given its non-superior short-term efficacy compared to established IA injections, as well as its increased cost of preparation, A2M may not be a justifiable option for routine treatment of knee OA.

Clinical outcomes and radiolucent line analysis in cementless mobile-bearing total knee arthroplasty: a prospective multicentre study in Japan.

The objective of this study was to assess radiolucent lines (RLLs) and to determine their effect on clinical outcomes of the newly introduced cementless mobile-bearing total knee arthroplasty (TKA) system. This was prospective, multicentre study. Seventy-eight patients with knee osteoarthritis who underwent primary TKA were enrolled. Patient-reported outcome measures (PROMs) and radiographic assessments were evaluated at preoperative baseline and at 6 weeks, 1 year, and 2 years after surgery. KOOS, PKIP, 2011KSS, EQ-5D-3L and SKO improved from preoperative baseline to all postoperative timepoints, with no loosening of components. No RLLs were detected at 6 weeks after surgery. However, RLLs ≥ 1 mm developed in 2.8% of the patients for the femur and 9.7% for the tibia at 1 year after surgery, and values were 5.7% and 10.9%, respectively, at 2 years after surgery. RLL incidence was not correlated with PROMs. Age, sex, body mass index, range of motion knee flexion, posterior cruciate ligament treatment and ß angle did not impact the occurrence of RLLs. There were no intraoperative complications, revisions or reoperations. This TKA system improved PROMs and showed less incidence of RLLs compared to the previous reported TKA without implant-related complications.