OA is a painful joint disease that predominantly affects the elderly. Pain is the primary symptom of OA, and it can present as either intermittent or constant. OA pain mechanisms are complex and have only recently been determined. Both peripheral and central processes are involved in creating the OA pain experience, making targeted therapy problematic. Nociceptive, inflammatory and neuropathic pains are all known to occur in OA, but to varying degrees in a patient- and time-specific manner. A better understanding of these multifactorial components of OA pain will lead to the development of more effective and safer pain treatments.

Objective.: To investigate the associations of Outcome Measures in Rheumatology (OMERACT) ultrasound scores for knee osteoarthritis (OA) with pain severity, other symptoms, and OA severity on radiographs and magnetic resonance imaging (MRI).Methods.: Participants with symptomatic and mild to moderate radiographic knee OA underwent baseline dynamic ultrasound (US) assessment according to standardized OMERACT scanning protocol. Using the published US image atlas, a physician operator obtained semiquantitative or binary scores for US pathologies. Clinical severity was measured on numerical rating scale (NRS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms and pain subscores. OA severity was assessed using the Kellgren-Lawrence (KL) grade on radiographs and MRI Osteoarthritis Knee Score (MOAKS) on noncontrast-enhanced MRI. Separate linear regression models were used to determine associations of US OA pathologies with pain and KOOS subscores, and Spearman correlations were used for US scores with KL grade and MOAKS.Results.: Eighty-nine participants were included. Greater synovial hypertrophy, power Doppler (PD), and meniscal extrusion scores were associated with worse NRS pain [β 0.92 (95% CI 0.25–1.58), β 0.73 (95% CI 0.11–1.35), and β 1.01 (95% CI 0.22–1.80), respectively]. All greater US scores, except for cartilage grade, demonstrated significant associations with worse KOOS symptoms, whereas only PD and meniscal extrusion were associated with worse KOOS pain. All US scores, except for PD, were significantly correlated with KL grade. US pathologies, except for cartilage, revealed moderate to good correlation with their MOAKS counterparts, with US synovitis having the greatest correlation (0.69, 95% CI 0.60–0.78).Conclusion.: OMERACT US scores revealed significant associations with pain severity, KL grade, and MOAKS.

Osteoarthritis is a leading cause of disability, and disease-modifying osteoarthritis drugs (DMOADs) could represent a pivotal advancement in treatment. Identifying the potential of antidiabetic medications as DMOADs could impact patient care significantly. We designed a comprehensive analysis pipeline involving two-sample Mendelian Randomization (MR) (genetic proxies for antidiabetic drug targets), summary-based MR (SMR) (for mRNA), and colocalisation (for drug-target genes) to assess their causal relationship with 12 osteoarthritis phenotypes. Summary statistics from the largest genome-wide association meta-analysis (GWAS) of osteoarthritis and gene expression data from the eQTLGen consortium were utilised. Seven out of eight major types of clinical antidiabetic medications were identified, resulting in fourteen potential drug targets. Sulfonylurea targets ABCC8/KCNJ11 were associated with increased osteoarthritis risk at any site (odds ratio (OR): 2.07, 95% confidence interval (CI): 1.50-2.84, P < 3 × 10^-4), while PPARG, influenced by thiazolidinediones (TZDs), was associated with decreased risk of hand (OR: 0.61, 95% CI: 0.48-0.76, P < 3 × 10^-4), finger (OR: 0.50, 95% CI: 0.35-0.73, P < 3 × 10^-4), and thumb (OR: 0.49, 95% CI: 0.34-0.71, P < 3 × 10^-4) osteoarthritis. Metformin and GLP1-RA, targeting GPD1 and GLP1R respectively, were associated with reduced risk of knee and finger osteoarthritis. In the SMR analyses, gene expression of KCNJ11, GANAB, ABCA1, and GSTP1, targeted by antidiabetic drugs, was significantly linked to at least one osteoarthritis phenotype and was replicated across at least two gene expression datasets. Additionally, increased KCNJ11 expression was related to decreased osteoarthritis risk and co-localised with at least one osteoarthritis phenotype. Our findings suggest a potential therapeutic role for antidiabetic drugs in treating osteoarthritis. The results indicate that certain antidiabetic drug targets may modify disease progression, with implications for developing targeted DMOADs. This study was funded by the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (2022), the Shanghai Municipal Health Commission Health Industry Clinical Research Project (Grant No. 20224Y0139), Beijing Natural Science Foundation (Grant No. 7244458), and the Postdoctoral Fellowship Program (Grade C) of China Postdoctoral Science Foundation (Grant No. GZC20230130).

Objective.: To evaluate the association of sleep quality, sleep duration, and fatigue with hip pain exacerbations in persons with symptomatic hip osteoarthritis (OA).Methods.: Participants (n = 252) were followed for 90 days and asked to complete online questionnaires at 10-day intervals (control periods). A hip pain exacerbation (case periods) was defined as an increase of 2 points in pain intensity compared with baseline on a numeric rating scale (0–10). Subjective sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index, and fatigue was measured by Multidimensional Assessment of Fatigue in both periods. Univariable and multivariable conditional logistic regressions were used to assess the association.Results.: Of the 252 participants, 130 (52%) were included in the final analysis. Univariate association analysis showed that both poor sleep quality and greater fatigue were associated with increased odds of pain exacerbations (OR 1.72, 95% CI 1.04–2.86; OR 1.92, 95% CI 1.21–3.05, respectively). Short sleep duration was not associated with pain exacerbations. Poor sleep quality and greater fatigue remained associated with pain exacerbations after adjustment for physical activity and night pain levels in multivariable analysis. There was no significant interaction between sleep quality and fatigue (p = 0.21).Conclusion.: Poor sleep quality and greater fatigue were related to pain exacerbation in persons with symptomatic hip OA. Sleep disorders and fatigue should be considered when dealing with pain exacerbations.

Thumb-base osteoarthritis (OA) is a common cause of pain and disability This study aimed to investigate the associations of musculoskeletal ultrasound OA pathologies with the extent of pain, function, radiographic scores, and muscle strength in symptomatic thumb-base osteoarthritis. This is a cross-sectional study of an ongoing clinical trial with eligibility criteria including thumb-base pain on Visual Analogue Scale (VAS) ≥40 (0 to 100 mm), Functional Index for Hand OA (FIHOA) ≥ 6 (0 to 30) and Kellgren Lawrence (KL) grade ≥ 2. The most symptomatic side was scanned to measure synovitis and osteophyte severity using a 0–3 semi-quantitative score, power Doppler and erosion in binary score. A linear regression model was used for associations of ultrasound findings with VAS pain, FIHOA and hand grip and pinch strength tests after adjusting for age, gender, body mass index, disease duration and KL grade as appropriate. For correlation of ultrasound features with KL grade, OARSI ((Osteoarthritis Research Society International) osteophyte and JSN scores, Eaton grades, Spearman coefficients were calculated, and a significant test defined as a p-value less than 0.05. The study included 93 participants (mean age of 67.04 years, 78.5% females). Presence of power Doppler has a significant association with VAS pain [adjusted β coefficient = 11.29, P = 0.02] while other ultrasound pathologies revealed no significant associations with all clinical outcomes. In comparison to radiograph, ultrasonographic osteophyte score was significantly associated with KL grade [rs = 0.44 (P < 0.001)], OARSI osteophyte grade [rs = 0.35 (P = 0.001)], OARSI JSN grade [rs = 0.43 (P < 0.001)] and Eaton grade [rs = 0.30 (P < 0.01)]. Ultrasonographic erosion was significantly related with radiographic erosion [rs = − 0.49 (P = 0.001)]. From a clinical perspective the significant relationship of power Doppler with pain severity in thumb base OA suggests this might be a useful tool in understanding pain aetiology. It is important to recognise that power Doppler activity was only detected in 14% of the study so this might be an important subgroup of persons to monitor more closely. Registered at Australian New Zealand Clinical Trials Registry (ANZCTR), http://www.anzctr.org.au/ , ACTRN12616000353493.