Changhai H. Ding

There is limited evidence on the comparative effectiveness of different exercise modalities, such as yoga and strengthening exercises, for managing knee osteoarthritis (OA). To compare the effectiveness of yoga vs strengthening exercise for reducing knee pain over 12 weeks in patients with knee OA. This single-center, assessor-blinded (for nonpatient-reported outcomes), parallel-arm, active-controlled, superiority randomized clinical trial included adults aged 40 years or older with knee OA and knee pain levels of 40 or higher on a 100-mm visual analog scale (VAS) in Southern Tasmania, Australia. Participants were recruited from April 2021 to June 2022, and follow-up was completed in December 2022. Data were analyzed from May 2023 to July 2024. Participants were randomized 1:1 to the yoga and strengthening exercise groups. Both groups attended 2 supervised and 1 home-based session per week for 12 weeks followed by 3 unsupervised home-based sessions per week for weeks 13 to 24. The primary outcome was the between-group difference in VAS score over 12 weeks assessed using a range of 0 (no pain) to 100 (worst possible pain) with a prespecified noninferiority margin of 10 mm. Secondary outcomes included knee pain over 24 weeks; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain, function, and stiffness; patient global assessment; Osteoarthritis Research Society International-Outcome Measures in Rheumatology Clinical Trials response; physical performance measures; leg muscle strength; health-related quality of life assessed via the Assessment of Quality of Life-8 Dimensions (AQol-8D) utility score; depression assessed with the Patient Health Questionnaire-9; and neuropathic pain assessment over 12 and 24 weeks. Analyses were based on the intention-to-treat principle. In total, 117 participants were randomized to the yoga (n = 58) or strengthening exercise (n = 59) program. Baseline characteristics of the participants were similar, with a mean (SD) age of 62.5 (8.3) years, and 85 participants (72.6%) were female. The mean (SD) baseline VAS knee pain score of 53.8 (16.0) indicated moderate knee pain. Over 12 weeks, the between-group mean difference in VAS knee pain change was -1.1 mm (95% CI, -7.8 to 5.7 mm), which was not statistically significant but remained within the prespecified noninferiority margin. Of 27 secondary outcomes assessed over 12 and 24 weeks, 7 were statistically significant in favor of yoga. The yoga group showed modestly greater improvements than the strengthening exercise group (between-group differences) over 24 weeks for WOMAC pain (-44.5 mm [95% CI, -70.7 to -18.3 mm]), WOMAC function (-139 mm [95% CI, -228.3 to -49.7 mm]), WOMAC stiffness (-17.6 mm [95% CI, -30.9 to -4.3 mm]), patient global assessment (-7.6 mm [95% CI, -15.1 to -0.2 mm]), and 40-m fast-paced walk test (1.8 [95% CI, 0.4-3.2]). In addition, the yoga group had a modestly greater improvement than the strengthening exercise for depression at 12 weeks (between-group difference in PHQ-9 score, -1.1 [95% CI, -1.9 to -0.2]) and quality of life at 24 weeks (between-group difference in AQoL-8D score, 0.04 [95% CI, 0.0 to 0.07]). Adverse events were similar in both groups and mild. In this randomized clinical trial, yoga did not significantly reduce knee pain compared with strengthening exercises. However, yoga was found to be noninferior to strengthening exercises, suggesting that integrating yoga as an alternative or complementary exercise option in clinical practice may help in managing knee OA. ANZCTR.org Identifier: ACTRN12621000066886.

A recent study reported that methotrexate may reduce joint pain in patients with inflammatory hand osteoarthritis (OA). However, it remains unknown whether methotrexate has similar effects on inflammatory knee OA. To examine whether methotrexate has symptom-relieving and disease-modifying effects for participants with knee OA and effusion-synovitis. This multicenter, placebo-controlled randomized clinical trial was conducted at 11 sites in China between July 18, 2019, and January 15, 2023. Community-dwelling patients with inflammatory knee OA with effusion-synovitis on magnetic resonance imaging were included. Participants were randomly assigned (1:1) to receive methotrexate, up to 15 mg weekly, or placebo using block randomization, stratified by study site. The primary outcomes were knee visual analog scale (VAS) pain change and effusion-synovitis maximal area change, over 52 weeks in the intention-to-treat population. Of 278 participants screened, 215 participants (mean [SD] age, 60.4 [7.4] years; 191 [89%] female) were randomized (108 to the methotrexate group; 107 to the placebo group), and 175 (81%) completed the trial. Changes in VAS pain and effusion-synovitis maximal area were not significantly different between the methotrexate and placebo group over 52 weeks (between-group difference, 0.3 mm [95% CI, -6.7 to 7.3 mm] for VAS pain; 0.1 cm2 [95% CI, -0.8 to 1.0 cm2] for effusion-synovitis maximal area). No significant between-group differences were found for any of the prespecified secondary outcomes. At least 1 adverse event occurred in approximately 32 participants (29.6%) in the methotrexate group and 26 participants (24.3%) in the placebo group. The results of this randomized clinical trial show that, compared to placebo, low-dose methotrexate did not reduce pain or effusion-synovitis over 52 weeks in patients with knee OA and effusion-synovitis. ClinicalTrials.gov Identifier: NCT03815448.

Objective: Classification criteria for early-stage symptomatic knee osteoarthritis (EsSKOA) should discriminate individuals with EsSKOA from those with other causes of knee symptoms. We sought to identify conditions in the differential diagnosis of EsSKOA in adults with knee symptoms. Methods: We conducted an online survey of clinicians. Those consulting monthly on at least five people with undiagnosed knee symptoms were eligible. From qualitative work and clinical experience, we developed three case scenarios representing possible EsSKOA: 1. 40-year-old with 1-month of knee stiffness and swelling; 2. 50-year-old with 8-months of knee discomfort while walking; and 3. 60-year-old with intense knee discomfort getting out of a car 1 week ago. For each scenario, participants indicated conditions on a pre-defined list that they would consider in the differential diagnosis, and the top three diagnoses based on clinical experience. The proportions that considered each condition and among the top three diagnoses for each scenario were summarized overall and by clinical discipline. Results: 127 clinicians responded (43% female, 48% in practice ≤15 years, 50% university-affiliated practice, 7 clinical disciplines). Knee OA and meniscal injuries were among the top three conditions in the differential diagnosis for all three scenarios, followed by immune-mediated and crystal-induced inflammatory arthritis (scenario 1), patellofemoral pain syndrome (scenario 2), and collateral ligament injuries (scenario 3). Conclusions: The differential diagnosis for EsSKOA in adults presenting with undiagnosed knee symptoms includes symptomatic established radiographic knee OA, patellofemoral pain syndrome, meniscal and collateral ligament injuries, and immune-mediated and crystal-induced inflammatory arthritis.

Osteoarthritis (OA), a debilitating disease, has been recognized as a heterogenous disease, with metabolic syndrome-associated osteoarthritis (MetS-OA) emerging as a significant area of interest. Currently, the understanding of MOA remains limited, with a prevailing consensus attributing its etiology to the core components of metabolic syndrome: obesity, hyperglycemia, dyslipidemia, and hypertension. The aim of this review is to summarize the current understanding of the complex relationship between metabolic syndrome and OA from the perspectives of epidemiology and molecular biology, and to explore potential targeting strategies for metabolic syndrome in MetS-OA management. This narrative review evaluated literature (2010-2024) from PubMed, examining clinical and mechanistic evidence linking metabolic syndrome to OA, including therapeutic studies targeting MetS-OA. Metabolic syndrome aggravate the cartilage injury in MetS-OA through metabolic biomarkers (adipokines, advanced glycation end-products and oxidized LDL), metabolic responses (oxidative stress, insulin resistance and ischemic hypoxic injuries), and abnormally activated cells (adipocytes and macrophages). It ultimately lead to the aggravation of synovitis in MetS-OA through inflammatory mediators. The exploration of the relationship between metabolic syndrome and OA could benefit the development of targeting strategies for MetS-OA, including currently FDA-approved drugs for the treatment of metabolic syndrome and potential drugs targeting metabolic factors, which might provide a novel avenue for the future management of MetS-OA.

Circulating proteins in blood are involved in various physiological processes, but their contributions to blood pressure regulation remain partially understood. In traditional observational studies, identifying circulating proteins causally associated with blood pressure is challenging because of potentially unmeasured confounding and possible reverse causality. Two-sample Mendelian randomization analyses were conducted to estimate the causal effects of 2270 circulating proteins (data sourced from 8 genome-wide association studies) on diastolic blood pressure, systolic blood pressure, and pulse pressure. Colocalization analyses were then used to investigate whether the circulating proteins and blood pressure traits shared causal genetic variants. To further verify the findings, we subsequently performed Steiger filtering analyses, annotation of protein-altering variants, assessment of overlap between protein quantitative trait loci and expression quantitative trait loci, protein-protein interaction and functional enrichment analyses, and drug target evaluation. To provide more potential biomarkers, we further evaluated the epidemiological associations of 2923 circulating proteins with blood pressure and hypertension by cross-sectional and longitudinal analyses using individual data in the UK Biobank. Mendelian randomization and colocalization analyses identified 121 circulating proteins with putative causal effects on at least 1 blood pressure trait. Many of the identified proteins are enriched in the pathways relevant to blood pressure regulation, and a majority of these proteins are either known drug targets or druggable candidates. This study has uncovered numerous circulating proteins potentially causally associated with blood pressure, providing insights into the regulatory mechanisms of blood pressure and potential therapeutic targets to facilitate blood pressure management.