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Background: Vitamin D is beneficial for musculoskeletal health. Although low levels of vitamin D are linked to increased pain in knee osteoarthritis (OA), their association with functionality remains understudied., Objective: This study aimed to investigate the association between vitamin D deficiency and functional status in elderly individuals with OA and explore the potential correlation between vitamin D deficiency and plasma levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)., Methods: The study included older adults (≥60 years) from an ageing study, encompassing 105 OA patients and 152 controls. OA diagnosis was confirmed radiographically, and the WOMAC questionnaire assessed functional impairment in these patients. Blood samples were collected to measure 25(OH) vitamin D levels by chemiluminescence and TNF-α and IL-6 levels by ELISA., Results: Patients with vitamin D insufficiency/deficiency exhibited more severe cases of OA compared to those with normal vitamin D levels ( p = 0.04). Vitamin D levels were inversely correlated with functional impairment in OA, according to the WOMAC Index (global: rS = -0.25, p = 0.01; pain: rS = -0.21, p = 0.03). Moreover, OA patients with vitamin D deficiency showed significantly higher levels of TNF-α and IL-6 ( p < 0.05, Mann-Whitney test)., Conclusions: Reduced levels of vitamin D are associated with more severe cases of hip and knee osteoarthritis, increased pain, greater functional impairment, and elevated serum levels of TNF-α and IL-6. Further research is required to elucidate the mechanisms underlying the influence of vitamin D on osteoarthritis and to evaluate the potential benefits of vitamin D supplementation for mitigating disease symptoms and progression.

Knee osteoarthritis (KOA) is a prevalent chronic condition characterized by inflammation and oxidative stress, particularly in individuals over 40. Dietary factors, specifically dietary acid load (DAL), may influence these pathological processes. However, the relationship between DAL and inflammatory markers, oxidative stress, and clinical features in patients with KOA remains unexplored. This cross-sectional study involved 147 participants aged 40 and above diagnosed with moderate to severe bilateral primary KOA. Dietary intake was assessed using a validated food frequency questionnaire, and DAL was quantified using Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) indices. Clinical symptoms were evaluated using the WOMAC Index. Biochemical markers of oxidative stress and inflammation were measured from serum samples. Higher PRAL and NEAP scores were associated with increased levels of thiobarbituric acid reactive substances (TBARS) and total oxidant status (TOS), indicating elevated oxidative stress. Additionally, serum levels of inflammatory markers, including TNF-α and hs-CRP, positively correlated with higher DAL scores. Clinical assessments revealed that increased PRAL scores were related to greater severity of symptoms as measured by the WOMAC Index. This study demonstrates a significant association between dietary acid load and markers of inflammation and oxidative stress in KOA patients. These findings suggest that dietary modifications aimed at reducing acid load may serve as a beneficial adjunctive strategy in managing KOA and improving patient outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All experiments were performed in accordance with the declaration of Helsinki and Zabol University of Medical Sciences ethical guidelines and regulations. The research protocol was approved by the Zabol University of Medical Sciences (ethics code number: IR.ZBMU.REC.1402.110). All participants signed a written inform consent before participating in the study., (© 2025. The Author(s).)

Background: Early knee effusion is a common phenomenon after total knee arthroplasty (TKA), with potential clinical implications. Unlike traditional alloy knee prostheses, the polyetheretherketone (PEEK) knee system has radiographic transparency on magnetic resonance (MR) scans, which allows analysis of prosthetic knee effusion. We aimed to identify the distribution and volume of knee effusion after TKA with the PEEK prosthesis with use of MR imaging and to analyze whether dynamic changes in effusion were correlated with serum inflammatory marker changes and knee function recovery., Methods: Nine patients with osteoarthritis who were 59 to 74 years old underwent unilateral TKA with the PEEK prosthesis between June 2021 and August 2021. Dynamic early postoperative changes in the volume and distribution of knee effusion were evaluated with use of 3D MR stereoscopic images. Serum inflammatory markers were measured via blood tests, and joint function was evaluated with use of the subjective functional score of the Knee Society Score (KSS) and knee range of motion (ROM). Linear regression analyses were performed to assess for correlations between knee effusion volume and inflammatory markers and between knee effusion volume and joint function., Results: The mean serum inflammatory marker levels increased significantly at 1 week after TKA with the PEEK prosthesis and then gradually decreased with time from 1 to 6 months. The mean total knee effusion volume gradually decreased over time. Concurrently, the mean KSS subjective functional score and mean knee ROM improved with time. Total knee effusion volume was positively correlated with C-reactive protein level (R2 = 0.16; p = 0.007) and negatively correlated with the change in KSS score between the preoperative and postoperative time points (R2 = 0.19; p = 0.003). Using the 1-week total knee effusion volume as a reference, a positive correlation was observed between the reduction in total knee effusion volume and the actual value of the ROM (R2 = 0.36; p = 0.0001) from 3 to 24 months postoperatively., Conclusions: Through 3D MR imaging, the precise distribution and volume of, and dynamic changes in, knee effusion after TKA with the PEEK prosthesis were confirmed and were found to be correlated with inflammation and joint function in the early postoperative period. The results demonstrate the potential clinical benefit of the PEEK-based knee system for future use., Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This study and the Article Processing Charge for open access publication were supported by grants from the National Key R&D Program of China (2016YFC1101802). Suzhou SinoMed Biomaterials provided the PEEK knee systems for this study.The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I284)., (Copyright © 2024 The Author(s). Published by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Previous observational studies have observed associations between rheumatoid arthritis (RA), knee osteoarthritis (KOA), hip osteoarthritis (HOA), and frailty, but the causal relationships remain unestablished. Objective: This study aimed to evaluate the causal relationships between RA, KOA, HOA, KneeHipOA, and frailty using Mendelian randomization (MR) and bioinformatics analysis. Methods: We performed two-sample MR to test for causality between RA, KOA, HOA, KneeHipOA, and frailty. Subsequently, we combined our results in a meta-analysis and conducted multiple sensitivity analyses (MR-Egger, weighted median, constrained maximum likelihood and model averaging (cML-MA), and Bayesian weighted MR (BWMR)). We further explored the role of circulating immune cells and the effects of RA and OA-related gene expression on frailty. Results: Genetically determined RA, KOA, HOA, and KneeHipOA were correlated with a higher risk of frailty. The results of multivariate MR analyses were consistent with those of two-sample MR. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis indicated that RA and OA-related genes were primarily enriched in various immune responses. Our findings suggested that increases in monocyte cell AC, eosinophil cell AC, and neutrophil cell AC were associated with a higher risk of frailty. Conclusion: This research provides evidence supporting the associations between RA, KOA, HOA, KneeHipOA, and frailty. It also highlights the significant role of circulating immune cells in the development of frailty, indicating the importance of frailty management from an immunological perspective., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Preoperative patients with knee osteoarthritis have a significantly increased risk of venous thromboembolism (VTE). While the Caprini risk assessment model offers some clinical guidance in predicting deep vein thrombosis (DVT), it has a relatively low predictive accuracy. Enhancing the model by integrating biomarkers, such as D-dimers, can potentially improve its accuracy. In this study, we explored the effectiveness of combining the Caprini risk model with D-dimer levels for individualized DVT risk assessment in patients with knee osteoarthritis., Materials and Methods: This retrospective cohort study included 1605 knee osteoarthritis patients scheduled for total knee arthroplasty from Peking Union Medical College Hospital, screened between January 2015 and December 2018. A revised Caprini risk stratification model was developed, and a predictive DVT model was developed based on this revised system. The sensitivity, specificity, and the area under the curve (AUC) were used to determine predictive effectiveness of the model., Results: In the revised Caprini risk stratification, the incidence of DVT increased with higher risk levels: 2.52% in the low-risk group (scores 0-2), 2.88% in the moderate-risk group (score 3), 6.47% in the high-risk group (score 4), and 9.09% in the highest-risk group (score ≥ 5). The incidence of DVT was 3.869-fold higher in the highest-risk group and 2.676-fold higher in the high-risk group compared to the low-risk group (p = 0.013 and p = 0.014, respectively). Combining the revised Caprini risk stratification with D-dimer level demonstrated an improved AUC of 0.792, compared to D-dimer level alone (AUC 0.774) and the revised Caprini model alone (AUC 0.598). Furthermore, applying specific D-dimer thresholds across the four Caprini risk stratifications outperformed the combination of the revised Caprini model and D-dimer level in terms of AUC, specificity, and reduction in unnecessary ultrasonography. Using the Youden index, the AUC for the threshold-based method was slightly higher (0.775 vs 0.754, p = 0.310), with significantly better specificity (76.8% vs 63.6%, p < 0.001) and a greater reduction in ultrasound use (74.1% vs 61.4%). At a sensitivity of 85.5%, the differences were modest but still favored the threshold-based approach. At a sensitivity of 100%, the specificity (36.0% vs 24.7%, p < 0.001) and ultrasound reduction (34.8% vs 23.9%) were significantly better., Conclusion: The revised Caprini risk stratification improves preoperative DVT prediction in patients with knee osteoarthritis. Incorporating specific D-dimer thresholds into the four-level Caprini risk model enhances specificity and reduces unnecessary ultrasonography, outperforming both the use of individual indicators and the combination of the revised Caprini model with D-dimer level., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Numerous circulating proteins are linked to the presence or severity of joint inflammation. However, traditional studies could not explain whether these protein biomarkers are proximate to disease progression., Method: We conducted a study to explore the causal effects of 91 circulating inflammation-related proteins (CIPs) on knee osteoarthritis (KOA) and hip osteoarthritis (HOA), using two-sample Mendelian randomization (MR). The primary analysis utilized the inverse variance weighted (IVW) method, augmented by complementary approaches including weighted median, weighted mode, simple median, MR-Egger, and MR-PRESSO analysis. Sensitivity analysis validated the robustness of the results and ensured the absence of heterogeneity and horizontal pleiotropy., Results: We identified 2 CIPs with a causal effect on KOA, including CXCL9 (OR = 1.249, 95% CI = 1.046-1.492, P = 0.014) and TNF-β (OR = 1.105, 95% CI = 1.014-1.204, P = 0.023). Additionally, 3 CIPs were found to have a causal effect on HOA, including CXCL6 (OR = 1.058, 95% CI = 1.004-1.116, P = 0.035), RANKL (OR = 1.067, 95% CI = 1.002-1.137, P = 0.044), and VEGFA (OR = 1.072, 95% CI = 1.008-1.140, P = 0.027)., Conclusions: In the current study, our findings indicated that CXCL9 and TNF-β had the potential to influence the risk of KOA, while CXCL6, RANKL, and VEGFA could impact the risk of HOA. These discoveries underscored the significance of these proteins as potential targets for intervention in the prevention and treatment of KOA and HOA. Key Points • We presented genetic evidence supporting a causal link between circulating inflammatory proteins associated with joint inflammation using MR methods. • 5 CIPs have demonstrated promotive effects on the occurrence of KOA and HOA., Competing Interests: Compliance with ethical standards. Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: The Intensive Diet and Exercise for Arthritis (IDEA) trial was a randomized trial conducted to evaluate the effects of diet and exercise on osteoarthritis (OA), the most prevalent form of arthritis. Various risk factors, including obesity and sex, contribute to OA's debilitating nature. While diet and exercise are known to improve OA symptoms, cellular and molecular mechanisms underlying these interventions, as well as effects of participant sex, remain elusive., Methods: Serum was obtained at three timepoints from IDEA participants assigned to groups of diet, exercise, or combined diet and exercise (n = 10 per group). A randomly selected subset of serum samples were extracted and analyzed via liquid chromatography-mass spectrometry combined with metabolomic profiling to unveil mechanisms associated with types of intervention and disease. Extracted serum was pooled and fragmentation patterns were analyzed to identify metabolites that statistically differentially regulated between groups., Results: Changes in metabolism across male and female IDEA participants after 18-months of diet, exercise, and combined diet and exercise intervention mapped to lipid, amino acid, carbohydrate, vitamin, and matrix metabolism. The diverse metabolic landscape detected across IDEA participants shows that intervention type differentially impacts the serum metabolome of OA individuals. Moreover, dissimilarities in the serum metabolome corresponded with participant sex., Conclusions: These findings suggest that intensive weight loss among males and females offers potential metabolic benefits for individuals with knee OA. This study provides a deeper understanding of dysregulation occurring during OA development in parallel with various interventions, potentially paving the way for improved interventions, treatments, and quality of life of those impacted by OA., Trial Registration: clinicaltrials.gov Identifier NCT00381290, Registered, 9/25/2006., Competing Interests: Declarations. Ethics approval and consent to participate: The IDEA study was conducted at Wake Forest University, approved by the human subjects committee of Wake Forest Health Sciences, and conducted in accordance with the Declaration of Helsinki. Informed consent was obtained in writing from all participants. Competing interests: Dr. June owns stock in Beartooth Biotech and OpenBioWorks. Neither company was involved in this study. Patient consent for publication: Consent to participate was provided in writing. Consent for publication is not applicable. Conflict of interest: Authors have no conflicts of interest to disclose. Dr. June owns stock in Beartooth Biotech and OpenBioWorks, which were not involved in this study., (© 2024. The Author(s).)

Knee osteoarthritis (OA) is a prevalent degenerative joint disease globally, causing pain, stiffness, and disability. Intravascular laser irradiation of blood (ILIB) has been used for chronic pain and musculoskeletal disease. However, evidence on the clinical benefits and serum biomarkers post-ILIB therapy in knee OA is insufficient. We designed a double-blind randomized controlled trial to evaluate the clinical and biological outcomes of ILIB therapy for knee OA. Seventeen patients with knee OA were randomly assigned to the ILIB and control groups. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Scale, visual analog scale, and biomarker analysis of interleukin (IL)-6, IL-13, IL-1β, epidermal growth factor, macrophage inflammatory protein-1β, and eotaxin. The measurements were performed at baseline and three days, one month, and three months post-intervention. The ILIB group showed a significant improvement in the WOMAC-pain score at one month of follow-up than the control group. IL-1β levels reduced significantly on day three, one month, and three months, and IL-13 levels reduced on day three and three months during follow-up in the ILIB group. ILIB therapy reduced knee OA pain for one month and significantly reduced serum IL-1β and IL-13 levels, suggesting potential for pain management.

Knee osteoarthritis (KOA) is a major cause of disability in the elderly, with its pain primarily driving medical consultations. Despite numerous studies, the role of Vitamin D in managing KOA pain remains inconclusive. This study seeks to explore the association between serum Vitamin D levels and WOMAC pain scores, providing new insights into potential treatment strategies for KOA. Utilizing data from the Osteoarthritis Initiative (OAI) database, we conducted a cross-sectional analysis involving 524 participants. Serum levels of 25-hydroxyvitamin D were measured using liquid chromatography-tandem mass spectrometry. WOMAC pain scores served as the dependent variable. Multivariable linear regression models and restricted cubic splines were employed to assess the relationship between Vitamin D levels and KOA pain, with subgroup analyses stratified by sex. Higher Vitamin D levels were significantly associated with lower WOMAC pain scores in males across all models. For females, no significant associations were observed. The analysis suggests a nonlinear relationship between Vitamin D levels and KOA pain in the general cohort, which becomes non-significant after adjustment for covariates. Our findings indicate that Vitamin D is associated with reduced pain in male patients with KOA, highlighting a potential sex-specific therapeutic approach. The results warrant further investigation through longitudinal studies and randomized controlled trials to substantiate Vitamin D supplementation as a viable treatment for reducing KOA pain in males., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The original survey was approved by the NCHS Research Ethics Review Board and all adult participants provided written informed consent. The present analysis was deemed exempt by the Institutional Review Board at our institution, as the dataset used in the analysis was completely de-identified., (© 2024. The Author(s).)

Objective: The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA., Design: ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported. The primary analysis, adjusted for age, body mass, socioeconomic status, and ethnicity, was to determine any differences in biomarkers between those with/without combat injury, rOA and pain. Secondary analyses were performed to compare post-traumatic/idiopathic OA, painful/painfree rOA and injury patterns., Results: A total of 1145 male participants were recruited, aged 34.1 ± 5.4, 8.9 ± 2.2 years post-injury (n = 579 trauma-exposed, of which, traumatic-amputation n = 161) or deployment (n = 566 matched). Cartilage oligomeric matrix protein (COMP) was significantly higher in the combat-injured group compared to uninjured (p = 0.01). Notably, COMP was significantly lower in the traumatic-amputation group compared to non-amputees (p < 0.001), decreasing relative to number of amputations (p < 0.001). Leptin was higher (p = 0.005) and adiponectin lower (p = 0.017) in those with v without knee pain, associated with an increased risk of 22% and 17% for pain, and 46% and 34% for painful rOA, respectively. There were no significant differences between trauma-exposed and unexposed participants with rOA., Conclusions: The most notable findings of this large, unique study are the similarities between those with rOA regardless of trauma-exposure, the injury-pattern and traumatic-amputation-associated differences in COMP, and the relationship between adipokines and pain., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: Osteoarthritis is a chronic degenerative disorder with rising prevalence. Early detection of structural damage is difficult. Consequently, there is a pressing demand for reliable biomarkers that enable an earlier diagnosis of osteoarthritis. The aim is to investigate the level of serum fibulin-3 in patients with primary knee osteoarthritis and its correlation with disease severity., Subjects and Methods: A case-control study was conducted at the Baqubah Teaching Hospital from November 2023 to January 2024. One hundred twenty persons participated in this study (eighty females with the diagnosis of knee osteoarthritis in its early and late stages, and forty age-matched, apparently healthy control. Serum fibulin-3, ESR, CRP, and calcium levels were measured for all participants. Ethical approval was obtained. SPSS was used for data analysis., Results: Patients with osteoarthritis had considerably higher serum levels of fibulin-3. In patients with late-stage knee osteoarthritis, this rise was greater than in earlier stages. Serum fibulin and ESR are positively correlated. Fibulin's area under the curve is 0.830 for diagnosis and 0.709 for differentiating between osteoarthritis's early and late stages., Conclusion: Serum levels of fibulin-3 can act as diagnostic markers for OA and may be useful in determining the severity of knee osteoarthritis., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background: Osteoarthritis (OA) is characterised by the failure of normal biological processes to repair following damage. Traditionally, OA was considered a "wear and tear" disorder; however, it is now a recognised inflammatory condition, preceded by molecular modifications. The aim of this study was to evaluate inflammatory markers among individuals with early knee OA (eKOA) and well-matched asymptomatic controls., Methods: Twenty six eKOA (females, n = 13; age = 60.2 ± 5.4 yrs, height = 1.73 ± 0.11 m, body mass = 77.8 ± 12.8 kg, body fat = 33.9 ± 8.5%) and twenty-three asymptomatic individuals (females, n = 14; age = 59.9 ± 5.5yrs, height = 1.71 ± 0.09 m, body mass = 72.6 ± 11.3 kg, body fat = 30.4 ± 8.2%) were recruited. The Timed Up and Go, and the 6 Minute Walk Tests evaluated physical function in addition to pain specific questionnaires (KOOS and ICOAP). Serum levels of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8(CXCL8), IL-10, hsCRP and TNF-α were quantified using a multiplex assay via V-plex®Sector Imager 2400., Results: As hypothesised, only KOOS and EQ-5D-5L metrics differed between the groups for non-blood derived measures (p < 0.04). Only IL-6 was higher in eKOA (P = 0.02; 95% CI = 0.202; by 0.197 pg/mL; 34.5%). Among eKOA, IL-6 did not relate to severity of KOOS pain (P = 0.696, r = -0.088), but had a positive relationship with ICOAP consistent (r = 0.469, P = 0.045) rather than intermittent pain. There was a moderate correlation between 6MWD and IL-8 (r = 0.471, P = 0.012)., Conclusion: Our results illustrate the potential for IL-6 as a biomarker for eKOA, and introduce the proposition for particular consideration in those with consistent pain. Further, for the first time the present data showed greater walking distance in eKOA with lower circulating IL-8. Future work should seek to verify these results and further investigate IL-6 and IL-8 related molecular pathways in eKOA, and their potential relationships with consistent knee pain and physical function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To investigate the associations between folate intake and changes in knee pain, inflammation mediators and comorbid conditions over 2 years in patients with symptomatic knee osteoarthritis (OA)., Methods: A post-hoc analysis was performed based on data from the VIDEO study, a multicenter, randomized, double-blind, placebo-controlled clinical trial aimed at assessing the impact of vitamin D supplementation on patients with knee OA who were also vitamin D deficient. The original trial's design and inclusion and exclusion criteria were integrated into this subsequent post-hoc analysis. The average daily folate intake was evaluated using the Dietary Questionnaire for Epidemiological Studies version 2 over two years. The progression of knee symptoms was monitored at the baseline and then at months 3, 6, 12, and 24, utilizing the Western Ontario and McMaster Universities Index alongside a 100-mm visual analog scale. Levels of serum inflammatory mediators were quantified using ELISA techniques. Assessments of knee joint structures, leg muscle strength, depressive symptoms, feet pain, and low back pain were treated at both baseline and follow-up intervals., Results: Folate intake was correlated with reductions in overall knee pain, dysfunction, and stiffness, as well as decreased levels of Leptin and Apelin. Additionally, it was associated with enhanced leg muscle strength and diminished feet and low back pain. However, there is no association between folate intake and alterations in serum cytokine levels or knee joint structural changes. Within the subsets of overall knee pain, a significant relationship was identified between folate intake and the reduction of pain experienced when ascending or descending stairs and standing for two years., Conclusions: Folate intake was linked with reduced knee pain, lower levels of adipokines, and a decreased prevalence of comorbid conditions in individuals with knee OA, implying that folate consumption may be associated with an improvement in knee OA symptoms, but further research is needed to verify this association., Competing Interests: Declarations. Ethics approval and consent to participate: Informed written consent was obtained from each participant, and ethical approval for the study was granted by the Tasmania Health and Human Medical Research Ethics Committee and the Monash University Human Research Ethics Committee, with reference numbers H1040 and CF10/1182-2010000616, respectively. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Considerable studies have demonstrated that osteoarthritis (OA) is a risk factor for dementia. The precise mechanisms underlying the association between OA and increased risk for cognitive dysfunction, however, remain unclear. This study aimed at exploring the associations between pro-inflammatory cytokines/chemokines, biomarkers of Alzheimer's disease (AD), pain intensity, and cognitive decline in knee joint OA patients. A total of 50 patients (26 in OA group and 24 in non-OA control group) were enrolled in this prospective, observational study. The visual analogue scale (VAS) score for pain intensity and Cognitive Abilities Screening Instrument (CASI) score for cognitive functions were examined in both groups. The plasma and cerebrospinal fluid (CSF) levels of pro-inflammatory molecules (IL-1β, IL-6, TNF-α, fractalkine, BDNF, MCP-1, and TGF-β), as well as biomarkers of AD (Aβ 40 , Aβ 42 , total-tau, and phospho-tau), were measured by multiplex immunoassay. Correlations among plasma or CSF biomarkers and questionnaire scores were assessed using Pearson's correlation coefficient and simple linear regressions. There were more patients in the OA group whose CASI cutoff percentiles were 40 , and Aβ 42 in CSF of OA patients. The CSF levels of Aβ 40 and Aβ 42 in OA patients were negatively correlated with attention and abstract scores in CASI. The findings of this study suggest that knee OA is associated with poor cognitive performance, and this association is particularly pronounced in OA patients with chronic pain. Higher levels of brain AD biomarkers, such as Aβ 40 and Aβ 42 , may partially mediate this relationship.

Certain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) progression. We analyzed the mass spectrometry-based proteomic data of plasma EVs and synovial fluid (SF) EVs from knee OA patients (n = 16, 50% female). The identified surface markers of interest were further evaluated in plasma EVs from an independent cohort of knee OA patients (n = 30, 47% female) using flow cytometry. A total of 199 peptides with significant correlation between plasma and SF EVs were identified. Of these, 41.7% were linked to immune system processes, 15.5% to inflammatory responses, and 16.7% to the complement system. Crucially, five previously identified knee rOA severity-indicating surface markers-FGA, FGB, FGG, TLN1, and AMBP-were confirmed on plasma EV subpopulations in an independent cohort. These markers' baseline frequencies on large plasma EVs predicted rOA progression with an AUC of 0.655-0.711. Notably, TLN1 was expressed in OA joint tissue, whereas FGA, FGB, FGG, and AMBP were predominantly liver derived. These surface markers define specific pathogenic EV subpopulations, offering potential OA prognostic biomarkers and novel therapeutic targets for disease modification.

Background: Knee osteoarthritis (KOA) is characterized by mitochondrial damage and increased inflammation. Circulating cell-free mitochondrial DNA (ccf-mtDNA), which originates from damaged mitochondria, is an endogenous damage-associated molecular pattern (DAMPs) molecule that may trigger inflammation and is recognized as a potential biomarker for various diseases. In this study, we investigated the potential association between plasma ccf-mtDNA content and its use as a diagnostic biomarker in patients with KOA., Methods: We collected plasma samples from patients with KOA and healthy controls (HC). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect ccf-mtDNA content in the plasma samples. We used the Kellgren-Lawrence (K-L) classification criteria to classify patients with KOA into four grades: I-IV. Disease severity in patients with KOA was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Next, Spearman analysis was performed to observe the correlation between ccf-mtDNA content and the K-L classification and WOMAC score. Logistic regression analysis was used to evaluate the relationship between ccf-mtDNA and KOA risk., Results: In total, we enrolled 60 patients with KOA and HC who were matched for age, sex, and body mass index (BMI). We found that plasma ccf-mtDNA contents were significantly higher in patients with KOA (median, 2.44; quartile range, 1.10-3.79) than in HC (median, 1.08; quartile range, 0.52-2.12) (P < 0.0001). Plasma ccf-mtDNA content sequentially increased following the KOA class I-IV group (P = 0.040) and positively correlated with the K-L classification (r = 0.369, P = 0.004) and WOMAC scores (r = 0.343, P = 0.007). The ccf-mtDNA content did not significantly differ between patients with bilateral and those with single KOA (P = 0.083). Patients with high levels of ccf-mtDNA had a significantly increased risk of KOA compared with those with low levels of ccf-mtDNA (odds ratio [OR], 4.15, 95% confidence interval [CI], 1.71-10.07; P = 0.002). Quartile analysis revealed a significant dose-dependent association (P trend < 0.001)., Conclusion: Our study's findings showed that plasma ccf-mtDNA was highly expressed in patients with KOA compared with HC. Furthermore, ccf-mtDNA content is significantly associated with the severity and risk of KOA. Therefore, its detection may provide insight into the prevention and treatment of KOA., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted following the principles of the Declaration of Helsinki. This study was approved by the Ethics Committee of the First Affiliated Hospital of Gannan Medical University (approval number: LLSC2023-156) and informed consent was obtained from each participant. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The association between knee osteoarthritis (OA) and miRNAs has been widely reported. However, the utility of miRNAs as predictors of knee osteoarthritis (KOA) progression in longitudinal studies has not been reported. We aimed to identify circulating miRNAs (c-miRNAs) associated with KOA progression in the general population and to examine their potential use as predictors of KOA progression., Methods: In 2012 and 2018, 66 participants (128 knees) took part in a resident health check-up in the Yakumo study. If the KL classification progressed two or more levels, the patient was classified as having progressive OA. Quantitative real-time polymerase chain reaction was used to screen 21 c-miRNAs. The expression levels of those c-miRNAs were compared between the progressive OA group and non-progressive OA group using student-t-test. Logistic analysis was performed in c-miRNAs less than p < 0.10 in univariate analysis., Results: The progressive OA group consisted of 78 knees. The results of the comparison between the progressive OA group and the non-progressive OA group showed that six c-miRNAs as follows; let7d (p = 0.030), c-miRNA-122 (p < 0.001), 150 (p = 0.070), 199 (p = 0.078), 21 (p = 0.016) and 320 (p = 0.093) were extracted as factors related to the progression of knee OA. In addition, logistic regression analysis identified c-miRNA-122 as an independent factor involved in the progression of knee osteoarthritis (odds ratio: 1.510, 95% confidence interval: 1.060-2.140, p = 0.023). The ROC curve showed by c-miRNA-122 for the progression of OA risk had an area under the curve of 0.702 (95% CI: 0.609-0.795). The threshold of c-miRNA-122 was -4.609., Conclusion: The expression level of c-miRNA-122 was associated with the risk of KOA progression in community dwelling Japanese people., Competing Interests: Declaration of competing interest All authors have no conflicts of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the clinical efficacy of autologous platelet rich plasma (PRP) injection in the treatment of knee osteoarthritis (KOA) and its influence on related biomarkers such as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP)., Method: 150 study subjects are randomly selected from KOA patients received treatment in the Third Hospital of Bethune Hospital from January 2022 to January 2023. After enrollment, patients are randomly numbered 1-100. 75 patients with odd and even numbers are included in the control group and the observation group, respectively. The former is cured with etocoxib, while the latter is treated with autologous PRP injection based on this. The clinical efficacy, relevant biomarkers (IL-1β, TNF-α, hs-CRP), and Lysholm knee score scale and Fugl Meyer assessment (FMA) scores are compared and analyzed., Results: The total effective rate of 94.67% (71/75) in the observation group was higher than 84.00% (63/75) in the other one group (P < 0.05). Before treatment, the comparison in IL-1β, TNF-α, hs-CRP, Lysholm knee joint score, and FMA scale score are with P > 0.05. When the treatment period is at 1 and 2 months, the IL-1β, TNF-α, hs-CRP levels within the group were lower than before treatment, while the Lysholm knee joint score and FMA scale score were higher than before treatment (P < 0.05). When the treatment period is at 1 and 2 months, the IL-1β, TNF-α, hs-CRP levels and the Lysholm knee joint and FMA scale scores in the observation group were lower and higher than those in the other one group, respectively (P < 0.05)., Conclusion: The application of autologous PRP injection therapy in KOA patients can significantly improve their levels of related biomarkers, effectively improve knee joint function and motor function, and have good clinical efficacy., (© 2024. The Author(s).)

Background: Total knee arthroplasty (TKA) is an effective treatment for knee osteoarthritis; however, early readmissions due to complications are common. This study assessed the ability of the hemoglobin-to-red cell distribution width ratio (HRR), hemoglobin-to-monocyte ratio (HMR), and hemoglobin-to-leukocyte ratio (HLR) to predict readmission within 14 days after TKA., Methods: Data from the Chang Gung Medical Research Database (CGRD) from 2014 to 2022 were retrospectively analyzed. Patients ≥ 20 years old who underwent primary TKA were eligible for inclusion. Patients with incomplete data on the indices of interest or follow-up < 14 days were excluded. Patient demographic, clinical, and comorbidity data were collected. Logistic regression was utilized to determine the associations between HRR, HMR, and HLR and 14-day readmission., Results: Data from 1,137 patients were analyzed. Multivariable analysis revealed that a higher HMR was significantly associated with lower 14-day readmission risk (adjusted OR [aOR] = 0.72, 95% confidence interval [CI]: 0.51-0.997), an HMR ≥ 2.18 (optimal cutoff value) was predictive of a significantly lower 14-day readmission risk (aOR = 0.61, 95% CI: 0.39-0.96). The composite indicator, HRR-HMR-HLR score, derived from the 3 indices assessed, was significantly associated with a lower 14-day readmission risk (score 2 vs. score 0: aOR = 0.51, 95% CI: 0.27-0.98; score 3 vs. score 0: aOR = 0.37, 95% CI: 0.17-0.82)., Conclusions: High HMR and the HRR-HMR-HLR score are independently associated with a lower 14-day readmission risk after TKA. Implementing these indices into clinical practice may enhance postoperative management., (© 2024. The Author(s).)

Background: The complete circulating long non-coding RNAs (lncRNAs) signature of rheumatoid arthritis (RA) and osteoarthritis (OA) is still uncovered. The lncRNA integrin subunit beta 2 (ITGB2)-anti-sense RNA 1 (ITGB2-AS1) affects ITGB2 expression; however, there is a gap in knowledge regarding its expression and clinical usefulness in RA and OA. This study investigated the potential of serum ITGB2-AS1 as a novel diagnostic biomarker and its correlation with ITGB2 expression and its ligand intercellular adhesion molecule-1 (ICAM-1), disease activity, and severity in RA and primary knee OA patients., Subjects: Forty-three RA patients, 35 knee OA patients, and 22 healthy volunteers were included., Results: Compared with healthy controls, serum ITGB2-AS1 expression was upregulated in RA patients but wasn't significantly altered in knee OA patients, whereas serum ICAM-1 protein levels were elevated in both diseases. ITGB2-AS1 showed discriminative potential for RA versus controls (AUC = 0.772), while ICAM-1 displayed diagnostic potential for both RA and knee OA versus controls (AUC = 0.804, 0.914, respectively) in receiver-operating characteristic analysis. In the multivariate analysis, serum ITGB2-AS1 and ICAM-1 were associated with the risk of developing RA, while only ICAM-1 was associated with the risk of developing knee OA. A panel combining ITGB2-AS1 and ICAM-1 showed profound diagnostic power for RA (AUC = 0.9, sensitivity = 86.05%, and specificity = 91.67%). Interestingly, serum ITGB2-AS1 positively correlated with disease activity (DAS28) in RA patients and with ITGB2 mRNA expression in both diseases, while ICAM-1 positively correlated with ITGB2 expression in knee OA patients., Conclusion: Our study portrays serum ITGB2-AS1 as a novel potential diagnostic biomarker of RA that correlates with disease activity. A predictive panel combining ITGB2-AS1 and ICAM-1 could have clinical utility in RA diagnosis. We also spotlight the association of ICAM-1 with knee OA diagnosis. The correlation of serum ITGB2-AS1 with ITGB2 expression in both diseases may be insightful for further mechanistic studies., (© 2024. The Author(s).)

Background: Persistent pain is a prominent symptom of knee osteoarthritis (KOA) and has been associated with cognitive decline in individuals with KOA. The amygdala, a complex structure consisting of nine subnuclei, and programmed cell death protein-1 (PD-1) levels play crucial roles in pain regulation and cognitive processing. This study aims to investigate the relationships among amygdala subregion volumes, cognitive function, and PD-1 levels to elucidate the underlying mechanism of cognitive decline in KOA., Methods: In this cross-sectional study, we recruited 36 patients with KOA and 25 age/gender-matched healthy controls for neuropsychological tests, structural magnetic resonance imaging scanning, and measurement of serum PD-1 levels. We used the atlas provided by FreeSurfer software to automatically segment the amygdala subnuclei. Subsequently, we compared the volumes of amygdala subregions between groups and explored their correlation with clinical scores and PD-1 levels., Results: Compared to healthy controls, individuals with KOA exhibited significantly lower scores on global cognition tasks, such as long-delay free recall, short-delay free recall, and immediate recall tasks. Moreover, they displayed decreased volumes in lateral nucleus basal nucleus paralaminar nucleus while showing increased volumes in accessory basal nucleus, central nucleus, medial nucleus, and cortical nucleus. Within the KOA group specifically, paralaminar volume was negatively correlated with immediate recall scores; pain scores were negatively correlated with global cognition; basal volume was negatively correlated with PD-1 levels., Conclusion: Our findings highlight those alterations in amygdala subregion volumes along with changes in serum PD-1 levels may contribute to observe cognitive decline among individuals suffering from KOA., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Chemerin and resistin are adipokines studied as potential markers for early diagnosis and disease severity in patients with knee osteoarthritis (KOA) Therefore, we aimed to investigate the associations serum and synovial levels of chemerin and resistin with inflammatory parameters and ultrasonographic scores (US) in KOA individuals. Serum was collected from 28 patients with KOA and synovial fluid was obtained from 16 of them. Another 31 age and sex matched cases with no joint disease were included as healthy controls. Concentrations of chemerin, resistin, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were determined with ELISA. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum uric acid (UA) were measured in the patients group. Participants with KOA underwent US assessment using the Outcome Measures in Rheumatology (OMERACT) scores. Patients with KOA had statistically significant higher level of serum resistin than healthy controls [11.05 (3.78-24.13) ng/mL and 7.23 (3.83-12.19) respectively, p < 0.001]. A strong correlation was found between serum chemerin and ESR (r = 0.434, p = 0.021), uric acid (r = 0.573, p = 0.001) as well as the US (r=-0.872, p < 0.001). Serum resistin demonstrated significant association with TNF-alpha (r = 0.398, p = 0.044). In conclusion, both chemerin and resistin might contribute to inflammatory changes associated with KOA. Further studies are needed to elucidate their potential role in the pathogenesis of the disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We aimed to study, for the first time in the Egyptian population, the relationship between the serum adiponectin level in knee osteoarthritis (KOA) patients and its correlation with clinical, radiological, and ultrasonographic characteristics. Additionally, investigate the relationship between the adiponectin (ADIPOQ) gene rs1501299 (+ 276G/T) polymorphism and KOA susceptibility and severity., Methods: This case-control study enrolled 40 patients with primary KOA and 40 matched controls. All patients underwent physical examination of the knee, pain assessment using the visual analogue scale (VAS), and functional evaluation by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Severity of KOA was assessed by Kellgren Lawrence (KL) grading scale and ultrasonography grading systems. Serum adiponectin levels and adiponectin (ADIPOQ) gene single nucleotide polymorphism (SNP) (rs1501299) genotyping were done for all patients and controls., Results: The study included 40 patients with primary symptomatic KOA and 40 controls with comparable age, sex, and body mass index. The genotype of the rs1501299 (+ 276G/T) polymorphism of the ADIPOQ gene was determined using TaqMan allelic discrimination. An enzyme-linked immunosorbent test was used to measure the level of serum adiponectin. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score was used to assess functional capability, while the visual analogue scale was utilised to assess knee pain. Using the Kellgren-Lawrence (KL) grading method and global femoral cartilage (GFC) ultrasound grading, the severity of KOA was assessed. No significant differences between patients and controls as regards the genotype distributions and allele frequencies (p = 0.400, p = 0.507, respectively) of ADIPOQ gene rs1501299 (+ 276G/T) polymorphism. Furthermore, serum adiponectin level was significantly higher in the patients compared to healthy subjects (p < 0.001). Additionally, adiponectin level had a significant negative correlation with disease severity as evaluated by KL and GFC grading (r=-0.351, p = 0.027 and r=-0.397, p = 0.011, respectively)., Conclusions: The ADIPOQ gene rs1501299 (+ 276G/T) polymorphism was not associated with KOA severity or vulnerability. The level of adiponectin considerably reduced as the severity of KOA rose, indicating that adiponectin may have a preventive effect in KOA., (© 2024. The Author(s).)

Background: Knee osteoarthritis affects the performance of daily activities, independence, and quality of life. The etiopathogenesis of this condition considers the mechanisms of activation of metalloproteinase and reactive oxygen species production pathways. Metalloproteinases-3 (MMP-3) and Glutathione Peroxidase (GPx) may be responsible for cartilage destruction. Aquatic physiotherapy promotes a positive impact on the clinical picture of osteoarthritis, and this study presents an intervention protocol that aims to evaluate the effects of a single session of different aquatic physiotherapy modalities on the biochemical and functional behavior of patients with knee osteoarthritis., Methods: This will be a crossover randomized controlled trial in which 15 individuals will be submitted to three aquatic physiotherapy modalities with a minimum 15-day wash-out period in patients over 50 years old and diagnosed with OA in at least one knee, presence of pain and at least one functional dysfunction for at least 6 months, absence of physical limitation that prevents the exercise protocol from being performed, Kellgren and Lawrence ranking between I and IV, walk independently and without auxiliary device. Variations in the concentrations of MMP-3 and GPx in peripheral blood, pain, edema, and flexibility resulting from the three aquatic physiotherapeutic interventions will be evaluated both pre- and immediate post-intervention. The reference group will be submitted to the same aquatic physiotherapy protocols, however, only the biochemical parameters and the self-perception questionnaires will be evaluated., Registration: ClinicalTrials.gov ( NCT05610696, 18/01/2023)., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Augusto Teixeira C et al.)

Background: Osteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes., Methods: A proteome-wide association study (PWAS) was performed based on OA and its subtypes genome-wide association studies (GWAS) summary datasets and the protein quantitative trait loci (pQTL) data. Subsequently, Mendelian randomization (MR) and colocalization analysis was conducted to estimate the associations between protein and OA risk. The replication analysis was performed in an independent dataset of human plasma pQTL data., Results: The abundance of seven proteins was causally related to OA, two proteins to knee OA and six proteins to hip OA, respectively. We replicated 2 of these proteins using an independent pQTL dataset. With the further support of colocalization, and higher ECM1 level was causally associated with a higher risk of OA and hip OA. Higher PCSK1 level was causally associated with a lower risk of OA. And higher levels of ITIH1, EFEMP1, and ERLEC1 were associated with decreased risk of hip OA., Conclusion: Our study provides new insights into the genetic component of protein abundance in OA and a promising therapeutic target for future drug development., (© 2024. The Author(s).)

Background/objectives: The objective of this study was to test the hypothesis that vitamin D deficiency (i.e., serum 25-hydroxyvitamin D (25(OH)D) ≤ 20 ng/mL) associates with the increased occurrence and shortened time to a knee osteoarthritis (OA) diagnosis after anterior cruciate ligament reconstruction (ACLR)., Methods: This study consisted of a retrospective, case-control design. The inclusion criteria consisted of (1) patients (≥18 y) who underwent arthroscopic ACLR with (cases; n = 28) and without (controls; n = 56) a subsequent knee OA diagnosis (≥90 d from the date of ACLR) and (2) with a documented serum 25(OH)D concentration after ACLR (and before a knee OA diagnosis for the cases). Controls were matched (2:1) to cases based on sex, age at ACLR, date of ACLR, and body mass index. After matching, patients were separated into two groups: (1) vitamin D deficient (serum 25(OH)D ≤ 20 ng/mL) or (2) non-vitamin D deficient (serum 25(OH)D > 20 ng/mL). Data were extracted from the medical records., Results: Thirty-one percent ( n = 26) of patients included were vitamin D deficient. Fifty percent ( n = 13) of the vitamin D deficient and twenty-six percent ( n = 15) of the non-vitamin D deficient patients were subsequently diagnosed with knee OA ( p = 0.03). Time from ACLR to a knee OA diagnosis was significantly ( p = 0.02) decreased in the vitamin D deficient (OA-free interval, 95% confidence interval [CI] = 7.9 to 10.9 y) compared to the non-vitamin D deficient group (OA-free interval, 95% CI = 10.5 to 12.5 y)., Conclusions: Vitamin D deficiency after ACLR may serve as a prognostic biomarker for knee OA following ACLR.

Purpose: This study aimed to investigate the correlation between serum creatinine levels and the presence and severity of radiographic knee osteoarthritis (OA) in individuals aged ≥50 years while adjusting for potential confounders., Materials and Methods: Cross-sectional data from the 2009-2011 Korea National Health and Nutrition Examination Survey comprising 3428 individuals aged ≥50 years were utilized. The Kellgren-Lawrence (K-L) grading scale was used to assess the radiographic presence and severity of knee OA. Logistic regression and receiver operating characteristic analyses were used to investigate the association between serum creatinine levels and the presence of knee OA, whereas ordinal regression was used to assess the impact of creatinine levels on knee OA severity., Results: The presence of radiographic knee OA conferred by low serum creatinine levels was found to be significant in both sexes [odds ratio (OR), 0.118; 95% confidence interval (CI), 0.045-0.314, p <0.001 for men; OR, 0.148; 95% CI, 0.040-0.549, p =0.004 for women]. Low serum creatinine was significantly associated with knee OA-graded K-L severity in each sex-based group [β, -1.923; standard error, 0.478; p <0.001 for men and β, -1.532; SE, 0.575; p =0.008 for women]., Conclusion: Low serum creatinine level was associated with a higher presence of knee OA in both men and women, and was also linked to the severity of the disease. These findings suggest that the serum creatinine level may be a potential biomarker for assessing the presence and severity of knee OA., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Objective: To establish an optimal preoperative HbA1c threshold that enhances surgical outcomes and minimises postoperative complications in diabetic patients undergoing elective total knee arthroplasty (TKA)., Study Design: Prospective cohort study. Place and Duration of the Study: Department of Orthopaedics, First People's Hospital of Lianyungang, China, from January 2021 to March 2024., Methodology: A total of 152 diabetic patients scheduled for elective TKA were included. Data on preoperative HbA1c levels were collected and analysed to assess their impact on postoperative outcomes using the Oxford Knee Score (OKS). Patients were divided into groups based on HbA1c levels and compared for functional and pain recovery one year postoperatively. Statistical analyses included binary and multivariate logistic regression, with an emphasis on the minimum clinically important difference for OKS., Results: Patients with a preoperative HbA1c below 7.35mmol/L exhibited significantly better functional and pain recovery outcomes at one-year post-TKA. The receiver operating characteristic curve (ROC) analysis confirmed the predictive power of HbA1c, with an Area Under the Curve of 0.734 for functional improvement and 0.721 for pain improvement., Conclusion: The study identifies 7.35mmol/L as the optimal preoperative HbA1c threshold for diabetic patients undergoing elective TKA, with lower levels associated with improved functional and pain outcomes. Maintaining HbA1c below this level preoperatively can significantly enhance postoperative recovery and patient satisfaction., Key Words: Diabetes mellitus, Total knee arthroplasty, Haemoglobin A1c, Oxford knee score.

Objectives: To observe the effect of moxibustion at "Zusanli "(ST36) on the plasma amino acid metabolism in rats with knee osteoarthritis (KOA), and to explore the amino acid metabolism mechanism of moxibustion in repairing cartilage injury in KOA., Methods: A total of 30 SD rats were randomly divided into normal, model and moxibustion groups, with 10 rats in each group. Rats in the model and moxibustion groups were injected with the mixture of L-cysteine and papain into bilateral knee joint cavity to make the KOA model. The moxibustion group received moxibustion at bilateral ST36 for 30 min, once daily for 30 days. At the end of the experiment, the swelling degree of knee joint was calculated, the mechanical pain threshold was measured by the Von Frey filament, the cartilage tissue injury was observed by HE staining, the matrix metalloproteinase-13 (MMP-13) content in the synovial tissue was detected by enzyme-linked immunosorbent assay (ELISA), and the differential amino acid metabolites in plasma were detected and screened by liquid chromatography-mass spectrometry (LC-MS)., Results: Compared with the normal group, the model group showed irregular cartilage surface, decreased number of chondrocytes, uneven distribution, and local clusters of chondrocytes；the contour of the tide line was blurred. The degree of joint swelling in the model group was higher than that in the normal group ( P <0.01), the mechanical pain threshold was lower ( P <0.01), and the content of MMP-13 in synovial tissue was higher ( P <0.01). The contents of proline and tryptophan in the model group were down-regulated ( P <0.01, P <0.05). Compared with the model group, the cartilage tissue damage and knee joint swelling were decreased( P <0.05), mechanical pain threshold was increased( P <0.05), MMP-13 content in synovial tissue and levels of glutamate and histidine expression were decreased ( P <0.01, P <0.05)., Conclusions: Moxibustion at ST36 significantly alleviated arthritis-related swelling and pain in KOA model rats, attenuated cartilage damage, and regulated levels of certain plasma amino acid metabolites. Moxibustion may regulate KOA cartilage synthesis and degradation through amino acid metabolic pathways such as proline, tryptophan, glutamate and histidine, exerting anti-inflammatory, analgesic, and protection of cartilage injury effects.

The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K-L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA., (© 2024. The Author(s).)

Objective: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up., Method: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC)., Results: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (β(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (β(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (β(95%CI) = 4.090 (1.92-6.26)) and anandamide (β(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (β(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (β(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (β(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (β(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (β(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (β(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (β(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (β(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82))., Conclusions: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Anterior cruciate ligament injury and anterior cruciate ligament reconstruction (ACLR) are risk factors for symptomatic posttraumatic osteoarthritis (PTOA). After ACLR, individuals demonstrate altered joint tissue metabolism indicative of increased inflammation and cartilage breakdown. Serum biomarker changes have been associated with tibiofemoral cartilage composition indicative of worse knee joint health but not with PTOA-related symptoms., Purpose/hypothesis: The purpose of this study was to determine associations between changes in serum biomarker profiles from the preoperative sample collection to 6 months after ACLR and clinically relevant knee PTOA symptoms at 12 months after ACLR. It was hypothesized that increases in biomarkers of inflammation, cartilage metabolism, and cartilage degradation would be associated with clinically relevant PTOA symptoms after ACLR., Study Design: Case-control study; Level of evidence, 3., Methods: Individuals undergoing primary ACLR were included (N = 30). Serum samples collected preoperatively and 6 months after ACLR were processed to measure markers indicative of changes in inflammation (ie, monocyte chemoattract protein 1 [MCP-1]) and cartilage breakdown (ie, cartilage oligomeric matrix protein [COMP], matrix metalloproteinase 3, ratio of type II collagen breakdown to type II collagen synthesis). Knee injury and Osteoarthritis Outcome Score surveys were completed at 12 months after ACLR and used to identify participants with and without clinically relevant PTOA-related symptoms. K-means cluster analyses were used to determine serum biomarker profiles. One-way analyses of variance and logistic regressions were used to assess differences in Knee injury and Osteoarthritis Outcome Score subscale scores and clinically relevant PTOA-related symptoms between biomarker profiles., Results: Two profiles were identified and characterized based on decreases (profile 1: 67% female; age, 21.4 ± 5.1 years; body mass index, 24.4 ± 2.4) and increases (profile 2: 33% female; age, 21.3 ± 3.2 years; body mass index, 23.4 ± 2.6) in sMCP-1 and sCOMP preoperatively to 6 months after ACLR. Participants with profile 2 did not demonstrate differences in knee pain, symptoms, activities of daily living, sports function, or quality of life at 12 months after ACLR compared to those with profile 1 ( P = .56-.81; η 2 = 0.002-0.012). No statistically significant associations were noted between biomarker profiles and clinically relevant PTOA-related symptoms (odds ratio, 1.30; 95% CI, 0.23-6.33)., Conclusion: Serum biomarker changes in MCP-1 and sCOMP within the first 6 months after ACLR were not associated with clinically relevant PTOA-related symptoms., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Research reported in this manuscript was supported by funding from the University of North Carolina's Department of Orthopaedics Laurence E. Dahners Research Grant, the National Institute of Arthritis and Musculoskeletal and Skin Disease of the National Institutes of Health (1R03 AR066840-01A1 and P30 AR072580), the North Carolina Translational and Clinical Sciences (TraCS) Institute, and the National Athletic Trainers’ Association Research and Education Foundation (14NewINV001). R.A.C. has received consulting fees from Arthrex and support for education from SouthTech Orthopedics. G.K. has received compensation for services other than consulting from Arthrex. J.S. has received support for education from SouthTech Orthopedics. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving the progressive degradation of the cartilage extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological and pathological processes, particularly in protein degradation. Excess cathepsins levels are reported to contribute to the development of OA. However, the causal relationship between the cathepsin family and knee and hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses to explore this causal association. Our results indicated that elevated serum levels of cathepsin O increase the overall risk of knee OA, while increased serum levels of cathepsin H enhance the risk of hip OA. Conversely, the reverse MR analyses did not reveal a reverse causal relationship between them. In summary, OA in different anatomical locations may genetically result from pathological elevations in different serum cathepsin isoforms, which could be utilized as diagnostic and therapeutic targets in clinical practice., (© 2024. The Author(s).)

Background: Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis. This study sought to identify preoperative laboratory values that may serve as predictors of periprosthetic joint infection (PJI) in morbidly obese patients undergoing THA or TKA., Methods: All morbidly obese patients with preoperative laboratory data before undergoing primary elective TKA or THA were identified using the Premier Healthcare Database. Patients who developed PJI within 90 days after surgery were compared with patients without PJI. Laboratory value thresholds were defined by clinical guidelines or primary literature. Univariate and multivariable regression analyses were utilized to assess the association between PJI and preoperative laboratory values, including total lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), albumin level, platelet count, albumin-globulin ratio, hemoglobin level, and hemoglobin A1c., Results: Of the 6,780 patients identified (TKA: 76.67%; THA: 23.33%), 47 (0.69%) developed PJI within 90 days after surgery. The rate of PJI was 1.69% for patients with a hemoglobin level of <12 g/dL (for females) or <13 g/dL (for males), 2.14% for those with a platelet count of <142,000/µL or >417,000/µL, 1.11% for those with an NLR of >3.31, 1.69% for those with a PLR of >182.3, and 1.05% for those with an SII of >776.2. After accounting for potential confounding factors, we observed an association between PJI and an abnormal preoperative NLR (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.04 to 5.44, p = 0.039), PLR (aOR: 4.86, 95% CI: 2.15 to 10.95, p < 0.001), SII (aOR: 2.44, 95% CI: 1.09 to 5.44, p = 0.029), platelet count (aOR: 3.50, 95% CI: 1.11 to 10.99, p = 0.032), and hemoglobin level (aOR: 2.62, 95% CI: 1.06 to 6.50, p = 0.038)., Conclusions: This study identified preoperative anemia, abnormal platelet count, and elevated NLR, PLR, and SII to be associated with an increased risk of PJI among patients with a body mass index of ≥40 kg/m 2 . These findings may help surgeons risk-stratify this high-risk patient population., Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H979 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

This study aimed to examine dietary antioxidant and serum antioxidant capacity in patients with knee osteoarthritis (OA). This case-control study consisted of 47 patients with OA (case group) and 30 healthy subjects (control group). The control and case group were matched age, gender, and body mass index (p > 0.05). A food frequency questionnaire was administered to participants, and dietary total antioxidant capacity (DTAC) was estimated using the ferric reducing antioxidant power method (FRAP). Participants' serum total antioxidant capacity (TAC) and total oxidant capacity (TOC) measurements were performed, and the oxidative stress index (OSI) was calculated. DTAC of case group was found to be lower than the control group (p < 0.05). The daily consumption of red meat and butter of the individuals in the case group was higher than that of the control group, and their fish consumption, dietary vitamin A and carotene intakes were found to be lower (p < 0.05). In addition, OA patients have TAC and OSI was also found to be significantly higher than in control group (p = 0.001 and p < 0.001). Since low dietary total antioxidant capacity and high serum total oxidant capacity, individuals with OA should pay more attention to their diet to increase serum antioxidant status., (© 2024. The Author(s).)

Background: Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA., Methods: We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results., Results: Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013-1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014-1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003-1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018-1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022-1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000-1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014-1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA., Conclusions: Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women., Methods: This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty., Results: Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA., Conclusion: Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Knee osteoarthritis is common in older people. Serum cartilage oligomeric matrix protein (sCOMP) is a biomarker of knee articular cartilage metabolism. The purpose of this study was 2-fold: to (1) determine acute effects of running and swimming on sCOMP concentration in older people; and (2) investigate relationships between sCOMP concentration change due to running and swimming and measures of knee health in older people., Hypotheses: Running would result in greater increase in sCOMP concentration than swimming, and increase in sCOMP concentration due to running and swimming would associate positively with measures of poor knee health., Study Design: Cross-sectional., Level of Evidence: Level 3., Methods: A total of 20 participants ran 5 km and 19 participants swam 1500 m. sCOMP concentration was measured immediately before, immediately after, and 15, 30, and 60 minutes after running or swimming. sCOMP concentration change due to running and swimming was compared. Correlations between sCOMP concentration change due to running and swimming, and other measures of knee health were evaluated, including the Tegner Activity Scale and Knee injury and Osteoarthritis Outcome Score., Results: sCOMP concentration increased 29% immediately after running, relative to baseline, but only 6% immediately after swimming ( P < 0.01). No significant relationship was observed between acute sCOMP change due to running and swimming, and observed measures of knee health ( P > 0.05). Participants with clinically relevant knee symptoms exhibited greater sCOMP concentration before and after running and swimming ( P = 0.03) and had greater body mass ( P = 0.04)., Conclusion: Running results in greater acute articular cartilage metabolism than swimming; however, the chronic effects of this are unclear. Older people with clinically relevant knee symptoms possess greater sCOMP concentration and are heavier, independent of exercise mode and physical activity level., Clinical Relevance: These results describe the effects of exercise (running and swimming) for older physically active persons, with and without knee pain., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Objective: Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA., Methods: We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms., Results: We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes., Conclusion: We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes., (© 2024 American College of Rheumatology.)

Background: The aim of this study was to test the hypothesis that proinflammatory cytokines correlate with knee loading mechanics during gait following a mechanical walking stimulus in subjects 2 years after anterior cruciate ligament reconstruction. Elevated systemic levels of proinflammatory cytokines can be sustained for years after injury. Considering roughly 50% of these patients progress to Osteoarthritis 10-15 years after injury, a better understanding of the role of proinflammatory cytokines such as tumor necrosis factor-α and Interleukin-1β on Osteoarthritis risk is needed., Methods: Serum proinflammatory cytokines concentrations were measured in 21 subjects 2 years after unilateral ACLR from blood drawn at rest and 3.5 h after 30 min of walking. An optoelectronic system and a force plate measured subjects' knee kinetics. Correlations were tested between inflammatory marker response and knee extension and knee adduction moments., Findings: Changes in proinflammatory cytokines due to mechanical stimulus were correlated (R = 0.86) and showed substantial variation between subjects in both cytokines at 3.5 h post-walk. Knee loading correlated with 3.5-h changes in tumor necrosis factor-α concentration (Knee extension moment: R = -0.5, Knee adduction moment: R = -0.5) and Interleukin-1β concentration (Knee extension moment: R = -0.44). However, no significant changes in concentrations were observed in tumor necrosis factor-α and Interleukin-1β when comparing baseline and post walking stimulus conditions., Interpretation: The significant associations between changes in serum proinflammatory markers following a mechanical stimulus and gait metrics in subjects at risk for developing Osteoarthritis underscore the importance of investigating the interaction between biomarkers and biomechanical factors in Osteoarthritis development., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Previously, fragments from Sirtuin 1 (SIRT1) were identified in preclinical and clinical samples to display an increase in serum levels for N-terminal (NT) SIRT1 vs. C-terminal (CT) SIRT1, indicative of early signs of OA. Here we tested NT/CT SIRT1 levels as well as a novel formulated sandwich assay to simultaneously detect both domains of SIRT1 in a manner that may inform us about the levels of full-length SIRT1 in the circulation (flSIRT1) of clinical cohorts undergoing knee joint distraction (KJD)., Methods: We employed an indirect ELISA assay to test NT- and CT-SIRT1 levels and calculated their ratio. Further, to test flSIRT1 we utilized novel antibodies (Ab), which were validated for site specificity and used in a sandwich ELISA method, wherein the CT-reactive served as capture Ab, and its NT-reactive served as primary detection Ab. This method was employed in human serum samples derived from a two-year longitudinal study of KJD patients. Two-year clinical and structural outcomes were correlated with serum levels of flSIRT1 compared to baseline., Results: Assessing the cohort, exhibited a significant increase of NT/CT SIRT1 serum levels with increased osteophytes and PIIANP/CTX-II at baseline, while a contradictory increase in NT/CT SIRT1 was associated with less denuded bone, post-KJD. On the other hand, flSIRT1 exhibited an upward trend in serum level, accompanied by reduced denuded bone for 2-year adjusted values. Moreover, 2 year-adjusted flSIRT1 levels displayed a steeper linear regression for cartilage and bone-related structural improvement than those observed for NT/CT SIRT1., Conclusions: Our data support that increased flSIRT1 serum levels are a potential molecular endotype for cartilage-related structural improvement post-KJD, while NT/CT SIRT1 appears to correlate with osteophyte and PIIANP/CTX-II reduction at baseline, to potentially indicate baseline OA severity., (© 2024. The Author(s).)

Background and Objectives : Knee osteoarthritis (KOA) is a degenerative disease that is continuously targeting people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to analyze specific biomarkers, namely ACRP-30, IL-10, TNF-α, and IL-6, in knee synovial fluid, and correlate them with KOA patients' clinical data, radiographic changes, and functional and pain scores. Materials and Methods : 24 subjects with KOA and over 50 years of age participate in the present study. Synovial fluid was harvested using ultrasound guidance from the target knees of the enrolled KOA patients, and the levels of ACRP-30, IL-10, TNF-α, and IL-6 were measured using enzyme-linked immunosorbent assays (ELISA). All patients underwent a supine X-ray at the target knee and were classified using Kellgren-Lawrence (K-L) grading. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness. Results : The obtained results highlighted a significant correlation between age and adiponectin level ( p = 0.0451, r = -0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced ( p = 0.0405, r = -0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age ( p = 0.0079, r = 0.7993), compared to women ( p = 0.0203, r = 0.6223). In the case of women, the progression of the disease tends to increase more intensively the WOMAC score's total values ( p = 0.00031, r = 0.8342), compared with men ( p = 0.0289, r = 7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions : A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI; in addition, women seem to be more sensitive to pain and stiffness.

Background: This study aimed to quantify the mechanoresponse of 10 blood marker candidates for joint metabolism to a walking stress test in patients with knee osteoarthritis and to determine the association among marker kinetics and with accumulated load and patient reported outcomes., Methods: 24 patients with knee osteoarthritis completed questionnaires, and a 30-minute walking stress test with six blood serum samples and gait analysis. Concentrations of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases (MMP)-1, -3, and -9, epitope resulting from cleavage of type II collagen by collagenases (C2C), type II procollagen (CPII), interleukin (IL)-6, proteoglycan (PRG)-4, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and resistin were determined by enzyme-linked immunosorbent assays, Joint load (moments and compartmental forces) was estimated using musculoskeletal modeling using gait analysis data., Results: COMP and MMP-3 showed an immediate increase after the walking stress followed by a decrease. MMP-9 and resistin showed a delayed decrease below pre-stress levels. ∆COMP correlated with ∆MMP-3 for most time points. ∆MMP-9 correlated with ∆resistin for most time points. The load-induced increase in blood marker levels correlated among blood markers and time points. C2C and resistin correlated positively and C2C/CPII and MMP2 correlated negatively with load during gait. Immediate relative ∆CPII and ∆MMP1 and delayed relative ∆COMP, ∆IL6, ∆C2C, ∆CPII, ∆MMP1 and ∆MMP3 correlated with the load accumulated during the walking stress. Baseline C2C levels correlated with Knee Osteoarthritis Outcome Score (KOOS) subscales and load-induced changes in MMP-3 with KOOS and Short Form 36 quality of life subscores (P<0.05)., Conclusions: The distinct and differentiated physiological response to the walking stress depends on accumulated load and appears relevant for patient reported osteoarthritis outcome and quality of life and warrants further investigation in the context of disease progression.ClinicalTrials.gov registration: NCT02622204., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Mündermann A et al.)

Background: The extent of the association between vitamin D deficiency and knee osteoarthritis remains inadequately understood., Objective: This study aimed to elucidate the relationship between vitamin D levels and knee osteoarthritis through a cross-sectional analysis., Methods: This retrospective study involved an analysis of knee radiographs and serum 25-hydroxyvitamin D3 (25-(OH) vitamin D3) levels in a cohort of 3424 individuals (2901 women and 523 men). Knee osteoarthritis severity was evaluated using the Kellgren-Lawrence radiological scoring system., Results: Of the participants, 49.2% (n= 1,683) were diagnosed with knee osteoarthritis. Among these patients, the levels of adjusted 25-(OH) vitamin D3 were significantly lower (p< 0.001). Regression analysis revealed a significant association between vitamin D deficiency and knee osteoarthritis, with an adjusted odds ratio (OR) of 1.7 (95% CI: 1.5-2.0; p< 0.001). Notably, a stronger association was observed between vitamin D deficiency and knee osteoarthritis in women under 65 compared to those aged 65 and above., Conclusions: The findings of this study indicate a higher prevalence of vitamin D deficiency in patients with knee osteoarthritis. Maintaining adequate serum 25-(OH) vitamin D3 levels may prevent knee osteoarthritis, especially in women below 65.

Objective: To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA., Methods: Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations., Results: Five components explained 78% of the total variance. IL-1β, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs., Conclusion: Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Primary hyperparathyroidism (HPT) is commonly underdiagnosed and undertreated. Joint pain is a nonspecific symptom associated with osteoarthritis or primary HPT. We hypothesize that patients treated for osteoarthritis are underdiagnosed with primary HPT., Methods: Adult patients diagnosed with hip/knee osteoarthritis at the Medical College of Wisconsin from January 2000 to October 2020 were queried. Patients with a calcium level drawn within 1 year of diagnosis of osteoarthritis were included. Patients who had undergone prior parathyroidectomy were excluded. Patients were stratified by serum calcium level, HPT diagnosis, and PTH level. Arthroplasty rates were compared between groups., Results: Of 54,788 patients, 9,967 patients (18.2%) had a high serum calcium level, of whom 1,089 (10.9%) had a diagnosis of HPT. Only 76 (7.0%) patients with HPT underwent parathyroidectomy, 208 (19.1%) underwent knee/hip arthroplasty, and 14 (1.3%) underwent both. Arthroplasty was performed in 1,793 patients without evaluation and/or definitive treatment for HPT. There were higher rates of arthroplasty performed in patients with a high serum calcium level compared with those without (21.2% vs 17.4%, P < .001)., Conclusion: Patients with high serum calcium levels were more likely to undergo arthroplasty than those with normocalcemia. Hypercalcemia in the setting of hip or knee osteoarthritis should prompt a full evaluation for primary HPT., (Published by Elsevier Inc.)

Objective: To investigate the effects of clearing heat and dispelling paralysis soup for osteoarthritis of the knee joint on the motor function of the knee joint and the level of inflammation of the organism in patients., Methods: One hundred and sixteen patients with knee osteoarthritis admitted from January 2020 to May 2021 were selected and randomly divided into 2 groups, 58 cases in the control group were treated with loxoprofen sodium dispersible tablets, and 58 cases in the experimental group were treated with Qinghe dispel paralysis soup on the basis of the control group and the patients' balance ability analysis, gait parameter change analysis, VAS, JOA, AIMS2-SF scale assessment, and serum index. The treatment effects of the two treatment regimens were analyzed by testing., Results: The anterior-posterior axis, left-right axis, A2-A6, A4-A8, and circumferential axis of the experimental group were lower than those of the control group after treatment ( P < 0.05); the step length of the experimental group was higher than that of the control group after treatment ( P < 0.05), and there were no significant differences in step speed, double-support phase, and step width ( P > 0.05), but both groups improved significantly compared with those before treatment ( P < 0.05); the VAS score of the experimental group was lower than that of the control group after treatment. The VAS scores of the experimental group were lower than those of the control group, and the scores of JOA and AIMS2-SF were higher than those of the control group ( P < 0.05); the levels of TIMP-1 in the experimental group were higher than those in the control group, and the levels of TNF- α , TLR4, MMP-3, and IL-1 were lower than those in the control group after treatment ( P < 0.05); there was no significant difference in the incidence of adverse reactions between the two groups during treatment ( P > 0.05), and the efficiency of the experimental group was higher than that of the control group ( P < 0.05)., Conclusion: Combined treatment with Qinghe dispel paralysis soup can better promote the recovery of balance, improve motor ability, and reduce the development of inflammation in the organism, with high safety and effectiveness., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Lihu Xie and Mei Li.)

Objective: Studies suggest an association between elevated total serum cholesterol, particularly low-density lipoprotein (LDL), and osteoarthritis (OA). The present study was undertaken to evaluate the association between total cholesterol, LDL, and high-density lipoprotein (HDL) and risk of knee OA., Methods: We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee radiographs and magnetic resonance images (MRIs) were obtained, and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined 2 sets of patients: those developing radiographic OA, and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of cartilage loss and synovitis on MRI and of knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index scale. We carried out logistic regression adjusting for age, sex, body mass index, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures, and we performed sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL, or low HDL increased risk., Results: We studied 337 patients with incident symptomatic OA and 283 patients with incident radiographic OA. The mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL, nor HDL showed a significant association with radiographic or symptomatic OA. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis, or worsening knee pain., Conclusion: Our data do not support an association between total cholesterol, LDL, or HDL with OA outcomes., (© 2020, American College of Rheumatology.)