Osteoarthritis Patients Research Articles

Hyperthyroidism increases the risk of osteoarthritis in individuals aged 60–80 years

To elucidate the currently unknown relationship between hyperthyroidism and osteoarthritis (OA). During 2007–2012, 7,433 participants (hyperthyroidism patients = 125; OA patients = 675) were included in the National Health and Nutrition Examination Survey database. We used a weighted multivariable-adjusted logistic regression analysis to assess the association between hyperthyroidism and OA. We also assessed the causality of that relationship using publicly available genome-wide association study data and three Mendelian randomization (MR) analysis methods. The heterogeneity test, pleiotropy test, and leave-one-out tests were used for sensitivity analysis. In this cross-sectional study, after adjusting for potential confounding factors, we found that hyperthyroidism significantly (P = 0.018) increased the risk of OA (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.2–4.17). Age-stratified analysis revealed that hyperthyroidism was associated with a greater risk of OA in the 60–80-year-old age group (OR = 2.86, 95% CI = 1.46–5.59, P = 0.002), with no significant association in the 18–59-year-old age group (all P > 0.05). The results of the inverse-variance weighting (IVW) analysis showed that hyperthyroidism increased the risk of OA (OR = 1.23, 95% CI = 1.04–1.46; P = 0.017). The weighted median estimator (WME) and MR-Egger method also confirmed this causal association (OR = 1.27 and OR = 1.32, respectively). The sensitivity analysis results confirmed the reliability of this conclusion. In addition, IVW-based reverse-MR analysis revealed that OA did not increase the risk of hyperthyroidism (OR = 1.02, 95% CI = 0.97–1.08; P = 0.449). Hyperthyroidism is associated with an increased risk of OA, but the underlying pathological mechanism still needs to be clarified in future research.

CKIP-1-Loaded Cartilage-Affinitive Nanoliposomes Reverse Osteoarthritis by Restoring Chondrocyte Homeostasis.

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage imbalance and disruption of cartilage extracellular matrix secretion. Identifying key genes that regulate cartilage differentiation and developing effective therapeutic strategies to restore their expression is crucial. In a previous study, we observed a significant correlation between the expression of the gene encoding casein kinase-2 interacting protein-1 (CKIP-1) in the cartilage of OA patients and OA severity scores, suggesting its potential involvement in OA development. To test this hypothesis, we synthesized a chondrocyte affinity plasmid, liposomes CKIP-1, to enhance CKIP-1 expression in chondrocytes. Our results demonstrated that injection of CAP-Lipos-CKIP-1 plasmid significantly improved OA joint destruction and restored joint motor function by enhancing cartilage extracellular matrix (ECM) secretion. Histological and cytological analyses confirmed that CKIP-1 maintains altered the phosphorylation of the signal transduction molecule SMAD2/3 of the transforming growth factor-β (TGF-β) pathway by promoting the phosphorylation of the 8T, 416S sit. Taken together, this work highlights a novel approach for the precise modulation of chondrocyte phenotype from an inflammatory to a noninflammatory state for the treatment of OA and may be broadly applicable to patients suffering from other arthritic diseases.

Comprehensive Analysis of Sphingolipid Metabolism-Related Genes in Osteoarthritic Diagnosis and Synovial Immune Dysregulation.

BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the role of sphingolipid metabolism pathway (SMP)-related genes in the occurrence of OA and synovial immune dysregulation remains unclear. MATERIAL AND METHODS In this study, we obtained synovium-related databases from GEO (n=40 for both healthy controls and OA) and analyzed the expression levels of SMP-related genes. Using 2 algorithms, we identified hub genes and developed a diagnostic model incorporating these hub genes to predict the occurrence of OA. Subsequently, the hub genes were further validated in peripheral blood samples from OA patients. Additionally, CIBERSORT and MCP-counter analyses were employed to explore the correlation between hub genes and immune dysregulation in OA synovium. WGCNA was used to determine enriched modules in different clusters. RESULTS Overall, the expression levels of SMP genes were upregulated in OA synovium. We identified 6 hub genes of SMP and constructed an excellent diagnostic model (AUC=0.976). The expression of re-confirmed hub genes showed associations with immune-related cell infiltration and levels of inflammatory cytokines. Furthermore, we observed heterogeneity in the expression patterns of hub genes across different clusters of OA. Notably, older patients displayed increased susceptibility to elevated levels of pain-related inflammatory cytokines and infiltration of immune cells. CONCLUSIONS The SMP-related hub genes have the potential to serve as diagnostic markers for OA patients. Moreover, the 4 hub genes of SMP demonstrate wide participation in immune dysregulation in OA synovium. The activation of different pathways is observed among different populations of patients with OA.

The predictors to self-reported and performance-based physical function in knee osteoarthritis patients: a cross-sectional study.

Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (β = 0.712, p < 0.001), knee flexor muscle strength (β = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: β = -0.428, p < 0.001) and flexor muscle strength (6MGS: β = 0.367, p < 0.001), were the main predictors with performance-based physical function. Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

The development of postoperative pain in patients with late-stage knee osteoarthritis is associated with impaired metabolism and transport of fatty acids in blood cells

Objective: to evaluate differences in the expression of genes associated with β-oxidation and de novo synthesis of fatty acids (FAs) in the blood of patients with the late stage of knee osteoarthritis (OA) before total knee arthroplasty (TA) depending on the development of postoperative pain (POP) in order to determine the molecular mechanisms responsible for the development of chronic POP. Material and methods. Blood of 50 patients with stage III–IV knee OA complaining of constant pain and joint dysfunction was analyzed prior to TA. The control group consisted of 26 healthy individuals. Pain intensity was assessed using a visual analogue scale (VAS) and the BPI questionnaire. In addition, pain, stiffness and physical functioning were assessed using WOMAC index and the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of POP was assessed 3 and 6 months after TA. Total RNA isolated from blood was used to determine the expression of ACLY, ACC1, MLYCD, FASN and CPT1A genes by real-time quantitative reverse transcriptase-polymerase chain reaction. Results and discussion. POP ≥ 30 mm by VAS was detected in 17 patients. Before TA, the expression of most of the analyzed genes was significantly increased compared to controls, while the expression of the FASN gene was comparable in patients with OA and healthy individuals. There were no differences in clinical and functional parameters between the groups of patients with and without POP. Before surgery, patients who subsequently developed POP had significantly higher expression of ACLY and CPT1A genes than patients who were satisfied with the results of TA. At the same time, no differences in the expression of ACC1, MLYCD and FASN were found in the groups analyzed. Conclusion. The development of POP is associated with an increased supply of FAs to the mitochondria caused by overexpression of the CPT1A gene, as well as with the accumulation of acetyl-CoA, a product of high expression of the ACLY gene, which can be measured in the blood of OA patients before TA.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis

Background/purpose(s)The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation.MethodsWe employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples.ResultsOur analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA.ConclusionOur study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.Graphical

Systemic inflammatory biomarkers are novel predictors of all-cause and cardiovascular mortality in individuals with osteoarthritis: a prospective cohort study using data from the NHANES

BackgroundChronic inflammation may contribute to increased mortality risk in individuals with osteoarthritis (OA), but research on the prognostic value of inflammatory biomarkers is limited. We aimed to evaluate the associations of the systemic immune–inflammation index (SII) and systemic inflammation response index (SIRI) with all-cause and cardiovascular mortality among US adults with OA.MethodsThis cohort study included 3545 adults with OA aged ≥ 20 years from the National Health and Nutrition Examination Survey 1999–2020. The SII and SIRI were calculated using complete blood cell count data. Participants were categorized as having a higher or lower SII and SIRI using cutoff points derived by the maximally selected rank statistics method. Cox proportional hazards models, Fine–Gray competing risk regression models and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the associations between the SII/SIRI and mortality in OA patients.ResultsOver a median follow-up of 5.08 (3.42–9.92) years, 636 (17.94%) deaths occurred, including 149 (4.20%) cardiovascular deaths. According to multivariable-adjusted models involving demographic, socioeconomic, and health factors, OA patients with a higher SII had a twofold greater risk of all-cause mortality than patients with a lower SII (HR 2.01; 95% CI: 1.50–2.68). Similarly, a higher SIRI was associated with an 86% increased risk of all-cause mortality relative to a lower SIRI (HR 1.86; 95% CI: 1.46–2.38). Similar to the trend found with all-cause mortality, patients with an elevated SII and SIRI had a 88% and 67% increased risk of cardiovascular mortality, respectively, compared to patients with a lower SII (HR 1.88; 95% CI: 1.16–3.03) and SIRI (HR 1.67; 95% CI: 1.14–2.44). Time-dependent ROC curves showed that both the SII and SIRI have moderate and valid performance in predicting short- and long-term mortality in patients with OA.ConclusionsHigher SII and SIRI values were associated with greater all-cause and cardiovascular mortality among US adults with OA.

Holistic vibrational spectromics assessment of human cartilage for osteoarthritis diagnosis.

Osteoarthritis (OA) is the most common degenerative joint disease, presented as wearing down of articular cartilage and resulting in pain and limited mobility for 1 in 10 adults in the UK [Osteoarthr. Cartil.28(6), 792 (2020)10.1016/j.joca.2020.03.004]. There is an unmet need for patient friendly paradigms for clinical assessment that do not use ionizing radiation (CT), exogenous contrast enhancing dyes (MRI), and biopsy. Hence, techniques that use non-destructive, near- and shortwave infrared light (NIR, SWIR) may be ideal for providing label-free, deep tissue interrogation. This study demonstrates multimodal "spectromics", low-level abstraction data fusion of non-destructive NIR Raman scattering spectroscopy and NIR-SWIR absorption spectroscopy, providing an enhanced, interpretable "fingerprint" for diagnosis of OA in human cartilage. This is proposed as method level innovation applicable to both arthro- or endoscopic (minimally invasive) or potential exoscopic (non-invasive) optical approaches. Samples were excised from femoral heads post hip arthroplasty from OA patients (n = 13) and age-matched control (osteoporosis) patients (n = 14). Under multivariate statistical analysis and supervised machine learning, tissue was classified to high precision: 100% segregation of tissue classes (using 10 principal components), and a classification accuracy of 95% (control) and 80% (OA), using the combined vibrational data. There was a marked performance improvement (5 to 6-fold for multivariate analysis) using the spectromics fingerprint compared to results obtained from solely Raman or NIR-SWIR data. Furthermore, clinically relevant tissue components were identified through discriminatory spectral features - spectromics biomarkers - allowing interpretable feedback from the enhanced fingerprint. In summary, spectromics provides comprehensive information for early OA detection and disease stratification, imperative for effective intervention in treating the degenerative onset disease for an aging demographic. This novel and elegant approach for data fusion is compatible with various NIR-SWIR optical devices that will allow deep non-destructive penetration.

Metformin as adjuvant therapy in obese knee osteoarthritis patients

AimsThis study aimed at investigating the efficacy of metformin as adjuvant therapy for obese knee osteoarthritis (OA) patients, considering its anti-inflammatory and cartilage-protective effects.Patients and methodsIn this randomized, double-blind, placebo-controlled study, 50 obese knee OA patients were assigned randomly to two groups, the metformin group (n = 25) which was treated with metformin 500 mg orally BID plus celecoxib 200 mg orally once daily, and the placebo group (n = 25) which was treated with placebo tablets BID plus celecoxib 200 mg orally once daily for 12 weeks. Cartilage Oligomeric Matrix Protein (COMP), C-terminal cross-linked telopeptide of type I collagen (CTX-1), and Interleukin 1-beta (IL-1β) serum levels were measured, while Western Ontario and McMaster Universities Arthritis Index (WOMAC) score assessed knee pain, stiffness, and physical function at baseline and after 12 weeks.ResultsFollowing a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1β in the serum compared to the placebo group (p = 0.0081, p = 0.0106, and p = 0.0223, respectively). Furthermore, metformin group produced significant improvements in WOMAC total scale (p < 0.0001), specifically in knee pain, stiffness, and physical function compared to placebo group (p < 0.0001, p < 0.0001, and p < 0.0001, respectively).ConclusionMetformin as an adjuvant therapy in obese knee OA patients may have beneficial effects on cartilage degradation and inflammation, as evidenced by the significant decreases in serum COMP, CTX-1, and IL-1β levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores.Clinicaltrials.gov IDNCT05638893/Registered December 6, 2022 — Retrospectively.

Trochlea morphology demonstrates variability but no gender difference in osteoarthritic patients undergoing total knee arthroplasty

BackgroundIn recent years, coronal lower leg alignment has received significant attention. Two classifications recently described the variability in both femoral and tibial morphology, resulting in differing native lower limb alignment.The native trochlea and the variability in morphology has received less attention. MethodsThis is a prospective cohort study of 200 patients undergoing robotically assisted TKA. Preoperative transverse CT scans were used to determine the posterior condylar axis (PCA), transepicondylar axis (TEA), lateral trochlear inclination (LTI), the sulcus angle (SA) and the anterior trochlear line (ATL). Outliers were defined as values > 1.5 IQR from median value. Trochlea dysplasia was defined as LTI < 12°. Gender differences were compared. ResultsIn total, 99 patients were female (49.4%). SA had a median of 137.0° (IQR 12°), ATL 4° (IQR 4), LTI 18° (IQR 7°). Median TEA-PCA was 5° external (IQR 3°). There were 5.0% outliers in SA, 3.0% of outliers in ATL, 3.5% outliers in LTI and 4.5% outliers in the TEA-PCA. Trochlear dysplasia was present in 11.5% of the measurements. There was no difference in any of the angles between the genders. ConclusionThe present study demonstrates no difference in trochlea morphology between the genders, rather a significant number of overall outliers in trochlear morphology. Larger cohorts but also, more investigations, are needed to better understand the trochlear morphology of patients undergoing total knee arthroplasty. The personalized alignment strategies and implants need to account for this variability in the population.

Exploring the Superior Efficacy of Hyaluronic Acid and Platelet-Rich Plasma Co-Administration Over Hyaluronic Acid Alone in Pain Reduction and Functional Status Improvement of Knee Osteoarthritis Patients

Objective: This study aimed to determine whether concurrent injection of hyaluronic acid (HA) with platelet-rich plasma (PRP) would enhance therapeutic effectiveness compared to HA alone in the management of knee osteoarthritis (OA) over a 12-month follow-up. Methodology: A prospective, comparative study was conducted in department of orthopedic Nawaz Sharif Medical College / Aziz Bhatti Shahed Hospital Gujrat from Jan 2023 To Dec 2023 on 100 patients with knee OA (Kellgren-Lawrence grades I-III). The patients were divided into two groups: Group 1, consisting of 50 patients, received intra-articular HA injections, while Group 2, comprising the remaining 50 patients, received a combination of HA and PRP. Pain and functional outcomes were assessed using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at baseline, and at 2, 6, and 12-months post-injection. Results: Assessments at baseline, 2 months, 6 months, and 12 months post-injection revealed significant improvement in both groups compared to baseline. However, patients in Group 2 (HA+PRP) showed significantly greater improvement than those in Group 1 (HA alone), with WOMAC scores at 2-, 6-, and 12-months yielding p-values of 0.001*, 0.001*, and 0.000*, respectively. Conclusions: The study concluded that the combination of PRP and HA is more effective than HA alone in reducing pain and improving joint function in patients with knee OA. The findings suggest that PRP+HA offers superior benefits for managing knee osteoarthritis compared to HA alone.

Syndesmotic fixation in Weber B ankle fractures: A systematic review.

Weber Type B fractures often arise from external rotation with the foot supinated or pronated. Altered tibiofibular joint kinematics in Weber B fractures are responsible for syndesmotic damage seen in Weber B fractures. Weber B fractures are managed using open reduction and internal fixation if displaced. The syndesmosis is injured in up to 40% of cases resulting in an unstable injury with a syndesmotic diastasis. This systematic review aimed to evaluate the current literature on syndesmotic fixation in Weber B fractures, assess the outcomes and complications of syndesmotic fixation and assess the necessity of syndesmotic fixation in Weber B fractures. A search was carried out on the EMBASE, PubMed and CINAHL databases and eight studies assessing the outcomes of syndesmotic fixations versus no syndesmotic fixation with 292 Weber B ankle fractures were included in this systematic review. Results showed significant heterogeneity so a narrative review was conducted. Results of these studies showed that functional, radiological, and quality-of-life outcomes and incidences of post-traumatic osteoarthritis in patients with syndesmotic screws were similar to those of patients not managed with syndesmotic screws. Only one favoured syndesmotic fixation in all cases of diastasis. As such, syndesmotic fixation with screws may not be necessary in the management of Weber B fractures. Screws are also associated with breakage, loosening, local irritation and infections. Suture button devices and antiglide fixation techniques appear to be valid alternatives to syndesmotic screws. It was found that there was no need for routine hardware removal unless the hardware was causing significant side effects for the patient.

Association between progression of knee osteoarthritis pathology and gait changes over two years: Data from the IMI-APPROACH cohort

ObjectiveGait alterations in knee osteoarthritis (OA) patients are potentially related to structural progression of joint tissues, of which some are modifiable. The current objective was to determine whether progression in individual OA pathologies is related to gait kinematic parameters in knee OA patients, and whether these changes are influenced by pain. DesignRange of motion (ROM) during gait, joint tissue pathologies and morphology from index knee radiographs and MRI, and WOMAC pain were collected at baseline and at two-years in the IMI-APPROACH clinical knee OA cohort. Principal component (PC) analysis was performed on two-year change in gait parameters; the resulting (first) PC was compared between progressors and non-progressors for each structural parameter. When the PC indicated differences between groups (p < 0.1), individual gait parameters were compared for that structural outcome. Statistically significant differences in individual gait parameters were corrected for pain change. Results191 patients (age 66.5 ± 6.7; BMI 27.5 ± 4.8; 76 % female; 51 % Kellgren-Lawrence grade ≥2) were analyzed. The gait change PC differed between progressors and non-progressors for meniscal extrusion, bone marrow lesions (BMLs), and patellofemoral cartilage lesions. Further, meniscal extrusion progressors showed significantly more knee ROM and calf ROM decrease, BML progressors worsened more in thigh ROM, and patellofemoral cartilage lesion progressors improved in knee ROM. BML results were no longer significant after pain change adjustment (p = 0.054). ConclusionsMeniscal extrusion and BML progression are associated with gait worsening, though for BMLs the effect might be influenced by pain.

TAK-242 (Resatorvid) inhibits proinflammatory cytokine production through the inhibition of NF-κB signaling pathway in fibroblast-like synoviocytes in osteoarthritis patients

BackgroundFibroblast-like synoviocytes (FLSs) are involved in osteoarthritis (OA) pathogenesis through pro-inflammatory cytokine production. TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-β, IL-6, TNF-α, and TLR4, as well as the phosphorylation of Ikβα, a regulator of the NF-κB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses.Materials and methodsTen OA patients’ synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of IL1-β, IL-6, TNF-α, and TLR4 levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ikβα and pIkβα.ResultsThe results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines IL1-β, IL-6, TNF-α, and TLR4 which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ikβα which was increased by LPS treatment.ConclusionAccording to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-κB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.

Modelling the role of enzymatic pathways in the metabolism of docosahexaenoic acid by monocytes and its association with osteoarthritic pain

Chronic pain is a major cause of disability and suffering in osteoarthritis (OA) patients. Endogenous specialised pro-resolving molecules (SPMs) curtail pro-inflammatory responses. One of the SPM intermediate oxylipins, 17-hydroxydocasahexaenoic acid (17-HDHA, a metabolite of docosahexaenoic acid (DHA)), is significantly associated with OA pain. The aim of this multidisciplinary work is to develop a mathematical model to describe the contributions of enzymatic pathways (and the genes that encode them) to the metabolism of DHA by monocytes and to the levels of the down-stream metabolites, 17-HDHA and 14-hydroxydocasahexaenoic acid (14-HDHA), motivated by novel clinical data from a study involving 30 participants with OA. The data include measurements of oxylipin levels, mRNA levels, measures of OA severity and self-reported pain scores.We propose a system of ordinary differential equations to characterise associations between the different datasets, in order to determine the homeostatic concentrations of DHA, 17-HDHA and 14-HDHA, dependent upon the gene expression of the associated metabolic enzymes. Using parameter-fitting methods, local sensitivity and uncertainty analysis, the model is shown to fit well qualitatively to experimental data.The model suggests that up-regulation of some ALOX genes may lead to the down-regulation of 17-HDHA and that dosing with 17-HDHA increases the production of resolvins, which helps to down-regulate the inflammatory response. More generally, we explore the challenges and limitations of modelling real data, in particular individual variability, and also discuss the value of gathering additional experimental data motivated by the modelling insights.

Thigh muscle composition changes in knee osteoarthritis patients during weight loss: Sex-specific analysis using data from osteoarthritis initiative

ObjectivesSex of patients with knee osteoarthritis (KOA) may impact changes in thigh muscle composition during weight loss, the most well-known disease-modifying intervention. We investigated longitudinal sex-based changes in thigh muscle quality during weight loss in participants with KOA. MethodsUsing Osteoarthritis Initiative (OAI) cohort data, we included females and males with baseline radiographic KOA who experienced >5% reduction in BMI over four years. Using a previously validated deep-learning algorithm, we measured MRI-derived biomarkers of thigh muscles at baseline and year-4. Outcomes were the intra- and inter-muscular adipose tissue (Intra-MAT and Inter-MAT) and contractile percentage of thigh muscles between females and males. The analysis adjusted for potential confounders, such as demographics, risk factors, BMI change, physical activity, diet, and KOA status. ResultsA retrospective selection of available thigh MRIs from KOA participants who also had a 4-year weight loss (>5% of BMI) yielded a sample comprising 313 thighs (192 females and 121 males). Female and male participants exhibited a comparable degree of weight loss (females: -9.72±4.38, males: -8.83±3.64, P-value=0.060). However, the changes in thigh muscle quality were less beneficial for females compared to males, as shown by a less degree of longitudinal decrease in Intra-MAT (change difference,95%CI: 783.44 mm2/4-year, 505.70 to 1061.19, P-value<0.001) and longitudinal increase in contractile percentage (change difference,95%CI: -3.9%/4-year, -6.5 to -1.4, P-value=0.019). ConclusionsIn participants with KOA and 4-year weight loss, the longitudinal changes in thigh muscle quality were overall beneficial but to a less degree in females compared to males. Further research is warranted to investigate the underlying mechanisms and develop sex-specific interventions to optimize muscle quality during weight loss.

Is detection of disease-modifying osteoarthritis drug treatment more effective when performing cartilage morphometry without blinding to MR image acquisition order?

ObjectiveWe here explore whether observed treatment effects of a putative disease modifying osteoarthritis drug (DMOAD) are greater when cartilage morphometry is performed with rather than without knowledge of MRI acquisition order (unblinded/blinded to time point). MethodsIn the FORWARD randomized controlled trial, 549 knee osteoarthritis patients were randomized 1:1:1:1:1 to three once-weekly intra-articular injections of placebo, 30µg sprifermin every 6 or 12 months(M), or 100µg every 6/12M. After year 2, cartilage segmentation of baseline through 24M MRIs was performed, with blinding to acquisition order. After year 5, 24 and 60M MRIs were analyzed together, with unknown relative order, but with segmented BL images as reference (24M unblinded vs. BL), by the same operators. Total femorotibial joint cartilage thickness (TFTJ_ThC) change was obtained for 352 participants analyzed under both conditions. Results24M data read unblinded to order revealed a -35±44 µm lower TFTJ_ThC than blinded analysis (all groups: lower/upper bounds -120/+51µm; correlation r2=97%). With unblinded analysis, the placebo group lost -46±57µm TFTJ_ThC over 24M, whereas 100µg/every 6M lost -2.2±73µm (difference=44µm [95%CI: 22,66]). With blinded analysis, placebo lost -11±53µm, whereas 100µg/every 6M gained 30±62µm (difference=40µm [95%CI: 21,60]). 100µg sprifermin injected every 6M showed statistically significant (p<0.001) treatment effects in TFTJ_ThC, with Cohen D=-0.66 for unblinded and D=-0.69 for blinded analysis. ConclusionsThese results do not reveal that detection of proposed DMOAD treatment is enhanced with MRIs read unblinded to order; rather, the sensitivity is similar to blinded analysis. Choices on blinded vs. unblinded analysis may thus be based on other criteria.

Relationship between hypercholesterolemia and osteoarthritis (preliminary results)

To evaluate the relationship of hypercholesterolemia (HCE) with clinical, instrumental, and laboratory parameters in osteoarthritis (OA) in a multicenter, cross-sectional study. The study included 183 patients aged 40-75 years, with a confirmed diagnosis of stage I-III OA (ACR) of the knee joints, who signed an informed consent. The mean age was 55.6±10.7 years (40 to 75), body mass index was 29.3±6.3 kg/m2, and disease duration was 5 [1; 10] years. For each patient, a case record form was filled out, including anthropometric indicators, medical history, clinical examination data, an assessment of knee joint pain according to VAS, WOMAC, KOOS and comorbidities. All patients underwent standard radiography and ultrasound examination of the knee joints and laboratory tests. HCE was detected in 59% of patients. Depending on its presence or absence, patients were divided into two groups. Patients were comparable in body mass index, waist and hip measurement, and disease duration but differed significantly in age. Individuals with elevated total cholesterol levels had higher VAS pain scores, total WOMAC and its components, an overall assessment of the patient's health, a worse KOOS index, and ultrasound findings (reduced cartilage tissue). HCE patients showed high levels of cholesterol, low-density lipoproteins, triglycerides, STX-II, and COMP (p<0.05). However, after stratification by age, many initial intergroup differences became insignificant, and differences in the WOMAC pain score persisted. The results of the study confirmed the high prevalence of HCE in OA patients (59%). Patients with OA and increased total cholesterol have more intense pain in the knee joints.

Home-based circuit training improves blood lipid profile, liver function, musculoskeletal fitness, and health-related quality of life in overweight/obese older adult patients with knee osteoarthritis and type 2 diabetes: a randomized controlled trial during the COVID-19 pandemic

BackgroundThere is strong evidence showing the association between obesity, type 2 diabetes mellitus (T2DM), and knee pain resulting from osteoarthritis. Regular exercise has been reported as a foundational piece of the preventive therapy puzzle for knee osteoarthritis (KOA) patients. Nonetheless, evidence-based exercise protocols for people with comorbidities, such as obesity, T2DM, and KOA are limited. Therefore, the present trial aimed to assess the effectiveness of a 12-week home-based circuit training (HBCT) protocol on various indices related to cardiometabolic health, musculoskeletal fitness, and health-related quality of life (HRQoL) among overweight/obese older adult patients with KOA and T2DM during the COVID-19 lockdown.MethodsThis is a randomized controlled trial study registered at the National Medical Research Register (ID: RSCH ID-21-01180-KGTNMRR ID-21-02367-FUM) and obtained approval on December 9, 2021. Seventy overweight or obese patients with KOA and T2DM (62.2 ± 6.1 years; 56% female) were randomly assigned to the intervention group (n = 35, HBCT) or the no-exercise control group (n = 35, CON). HBCT performed a 12-week progressive protocol (seven exercises; 15–30 repetitions per exercise, 1 min passive rest between exercises; 2–4 rounds per session; 20–60 min total session duration). Blood samples were collected, and assays were performed to assess the lipid profile, liver function, and fasting blood glucose (FBG). In addition, the 30-s Chair Stand Test (30CST) was used to evaluate lower body muscular strength and endurance while the Timed Up and Go (TUG) test was used to evaluate lower limb function, mobility, and the risk of falls for all the participants. HRQoL was assessed using the Osteoarthritis Knee and Hip Quality of Life (OAKHQoL). All the assessments were conducted at pre-, mid-, and post-training stages during the application or practice of the exercise protocol, rather than during the training sessions themselves.ResultsHBCT significantly reduced total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aminotransferase, alanine aminotransferase, FBG and knee pain (p < 0.05). Furthermore, HBCT induced meaningful increases in high-density lipoprotein (HDL-C), lower body muscular strength, endurance, function, mobility, and HRQoL in overweight/obese older adults with T2DM and KOA (p < 0.05).ConclusionThe present outcomes recommend that an injury-free HBCT program may improve various indicators related to cardiometabolic health, musculoskeletal fitness, and HRQoL in elderly with overweight/obesity, T2DM and KOA. These findings offer valuable insights for clinicians and practitioners seeking evidence-based exercise interventions tailored for patients managing substantial metabolic and musculoskeletal health challenges in clinical practice.

Cartilage oligomeric matrix protein as a potential biomarker for knee osteoarthritis.

This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry. COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner. All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods.