Intersection of inflammation and herbal medicine in the treatment of osteoarthritis

Herbal remedies and dietary supplements have become an important area of research and clinical practice in orthopaedics and rheumatology. Understanding the risks and benefits of using herbal medicines in the treatment of arthritis, rheumatic diseases, and musculoskeletal complaints is a key priority of physicians and their patients. This review discusses the latest advances in the use of herbal medicines for treating osteoarthritis (OA) by focusing on the most significant trends and developments. This paper sets the scene by providing a brief introduction to ethnopharmacology, Ayurvedic medicine, and nutrigenomics before discussing the scientific and mechanistic rationale for targeting inflammatory signalling pathways in OA by use of herbal medicines. Special attention is drawn to the conceptual and practical difficulties associated with translating data from in-vitro experiments to in-vivo studies. Issues relating to the low bioavailability of active ingredients in herbal medicines are discussed, as also is the need for large-scale, randomized clinical trial

Depressive symptoms in women's midlife in relation to their body weight before, during and after childbearing years

OBJECTIVE: This study aimed to examine how weight and weight changes related to pregnancy were associated with depressive symptoms 11–16 years after childbirth. METHOD: We followed 16,998 first‐time mothers from the Danish National Birth Cohort up till 16 years after birth and estimated associations between depressive symptoms and pre‐pregnancy body mass index (BMI) (kg m(−2)), weight changes in different time periods, and BMI‐adjusted waist circumference 7 years after birth (WC(BMI), cm). Depressive symptoms were estimated by the Center for Epidemiologic Studies Depression 10‐item scale. Multiple logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals. RESULTS: Compared with normal‐weight, we found that underweight, overweight and obesity were associated with greater odds of depressive symptoms (1.29, 1.24 and 1.73, respectively). Compared with weight change ±1 BMI unit during the total follow‐up period, greater odds for depressive symptoms were observed with weight loss (OR 1.14, 0.96–1.36) or gain of 2–2.99 kg m(−2) (OR 1.11, 0.92–1.33) or gain of ≥3 kg m(−2) (OR 1.68, 1.46–1.94). WC(BMI) > 2.2 cm was associated with greater odds of depressive symptoms (OR 1.16, 0.99–1.36) than waist circumference as predicted by BMI. CONCLUSION: Low and high pre‐pregnancy BMI, weight changes and WC(BMI) larger than predicted were associated with more depressive symptoms in midlife

Effectiveness and safety of polyacrylamide hydrogel injection for knee osteoarthritis: results from a 12-month follow up of an open-label study

Objective: There are few effective osteoarthritis (OA) therapies. A novel injectable polyacrylamide hydrogel (iPAAG) previously demonstrated efficacy and safety up to week 26 in an open-label study of knee OA. Here we report longer-term effectiveness and safety data. Methods: This multi-centre, open-label study included patients with symptomatic and radiographic knee OA. Primary outcome was WOMAC pain (0–100 scale) at 13 weeks, and patients continued to 26 weeks before entering a further 26-week extension phase. Secondary efficacy outcomes included WOMAC stiffness and function subscales, Patient Global Assessment (PGA) and proportion of OMERACT-OARSI responders. Safety outcomes were adverse events (AEs). Results: 49 participants (31 women, mean age 70) received an ultrasound-guided, intra-articular injection of 6 ml iPAAG; 46 completed the extension phase to 52 weeks. There was a significant reduction in the WOMAC pain score from baseline to 52 weeks (− 17.7 points (95% CI − 23.1; − 12.4); p < 0.0001). Similar sustained improvements were observed for WOMAC stiffness (11.0 points; 95% CI − 17.0; − 4.9), physical function (18.0 points; 95% CI − 19.1; − 10.6), and PGA (16.3 points; 95% CI − 23.1; − 9.4). At 52 weeks 62.2% of patients were OMERACT-OARSI responders. From 26 to 52 weeks, 8 adverse effects (AE), including 1 serious AE (cerebrovascular accident) were reported in 5 subjects. None of the new adverse events were thought to be device related. Conclusion: This open-label study suggests persistent benefits and safety of iPAAG through 52 weeks after a single injection. Trial registration: Clinicaltrials.gov NCT04179552

Exercise and education vs intra-articular saline for knee osteoarthritis:a 1-year follow-up of a randomized trial

Objective: To assess the longer-term effect of the Good Life with osteoarthritis in Denmark (GLAD) exercise and education program relative to open-label placebo (OLP) on changes from baseline in core outcomes in individuals with knee osteoarthritis (OA). Methods: In this 1-year follow-up of an open-label, randomized trial, patients with symptomatic and radiographically confirmed knee OA were monitored after being randomized to either the 8-week GLAD program or OLP given as 4 intra-articular saline injections over 8 weeks. The primary outcome was the change from baseline in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale after 1 year in the intention-to-treat population. Key secondary outcomes were the KOOS function and quality of life subscales, and Patients' Global Assessment of disease impact. Results: 206 adults were randomly assigned: 102 to GLAD and 104 to OLP, of which only 137 (63/74 GLAD/OLP) provided data at 1 year. At one year the mean changes in KOOS pain were 8.4 for GLAD and 7.0 for OLP (Difference: 1.5 points; 95% CI −2.6 to 5.5). There were no between-group differences in any of the secondary outcomes. Conclusions: In this 1-year follow-up of individuals with knee OA, the 8-week GLAD program and OLP both provided minor longer-term benefits with no group difference. These results require confirmation given the significant loss to follow-up. Trial registration number: NCT03843931.</p

Patients with rheumatoid arthritis acquire sustainable skills for home monitoring: a prospective dual-country cohort study (ELECTOR clinical trial I)

Objective: In an eHealth setting, to investigate intra- and interrater reliability and agreement of joint assessments and Disease Activity Score using C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA) and test the effect of repeated joint assessment training. Methods: Patients with DAS28-CRP ≤ 5.1 were included in a prospective cohort study (clinicaltrials.gov: NCT02317939). Intrarater reliability and agreement of patient-performed joint counts were assessed through completion of 5 joint assessments over a 2-month period. All patients received training on joint assessment at baseline; only half of the patients received repeated training. A subset of patients was included in an appraisal of interrater reliability and agreement comparing joint assessments completed by patients, healthcare professionals (HCP), and ultrasonography. Cohen’s κ coefficients and intraclass correlation coefficients (ICC) were used for quantifying of reliability of joint assessments and DAS28-CRP. Agreement was assessed using Bland-Altman plots. Results: Intrarater reliability was excellent with ICC of 0.87 (95% CI 0.83–0.90) and minimal detectable change of 1.13. ICC for interrater reliability ranged between 0.69 and 0.90 (good to excellent). Patients tended to rate DAS28-CRP slightly higher than HCP. In patients receiving repeated training, a mean difference in DAS28-CRP of –0.08 was observed (limits of agreements of –1.06 and 0.90). After 2 months, reliability between patients and HCP was similar between groups receiving single or repeated training. Conclusion: Patient-performed assessments of joints and DAS28-CRP in an eHealth home-monitoring solution were reliable and comparable with HCP. Patients can acquire the necessary skills to conduct a correct joint assessment after initial and thorough training. [clinicaltrials.gov (NCT02317939)

Polyacrylamide Hydrogel Injection for Knee Osteoarthritis: A 6 Months Prospective Study

Objective: Intra-Articular (IA) injection of polyacrylamide hydrogel (PAAG) is a possible treatment for symptomatic Osteoarthritis (OA) of the knee. This study evaluated the efficacy and safety of a single injection of 6 ml intra-articular PAAG over 26 weeks. Methods: Open-label study in patients with symptomatic and radiographically confirmed knee OA . Primary outcome was change in WOMAC pain after 13 weeks. Secondary outcomes were WOMAC stiffness and function subscales, Patient Global Assessment of disease impact (PGA) and proportion of OMERACT-OARSI responders. Follow-up time points were 4, 13 and 26 weeks. Results: 49 patients (31 females) received PAAG, with 48 patients completing the 13 and 46 the 26 weeks assessments. Mean change in WOMAC pain after 13 weeks was -18.3 points [95% CI-23.4 to -13.3]; P<.0001 and at 26 weeks -20.8 points [95% CI -26.3 to -15.3]; P<0.0001 with similar benefits for WOMAC stiffness, physical function, and PGA. After 13 weeks 64.6% were OMERACT-OARSI responders and this was maintained at 26 weeks.. During the 13 weeks, 18 patients reported 23 adverse events, 13 of which were related to PAAG, none severe. Two serious adverse events, atrial fibrillation and gastrointestinal pain, were assessed as ‘not related’ to PAAG. Conclusions: PAAG can be delivered in a single 6 ml injection and this non-randomized trial in patients with knee OA demonstrated beneficial clinical effects at 13 and 26 weeks. No serious adverse events were seen with PAAG. These encouraging results need to be confirmed in controlled studies

Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial

Objective: To identify contextual factors that modify the treatment effect of the ‘Good Life with osteoArthritis in Denmark’ (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). Methods: Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n = 102) or OLP given as 4 intra-articular saline injections over 8 weeks (n = 104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. Results: Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). Conclusions: These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. Trial registration: ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71.</p

Metformin treatment for patients with hand osteoarthritis:protocol for the multicentre, randomised, placebo-controlled METRO trial

Introduction Hand osteoarthritis (OA) is a prevalent joint disorder with limited treatment options. Accumulating evidence suggests that the antidiabetic drug metformin has beneficial effects on knee OA and may likewise be beneficial for hand OA. The objective of this randomised, double-blinded, placebo-controlled trial is to investigate the effect of metformin 1000 mg two times a day, or maximum tolerated dose, compared with placebo on reducing finger joint pain after 16 weeks of treatment. Methods and analysis The participants will be enrolled from the OA clinic at the Parker Institute at Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark and from the Department of Rheumatology, Hospitalsenhed Midt, Silkeborg, Denmark. 150 participants with painful hand OA according to the American College of Rheumatology criteria will be randomly allocated in a 1:1 ratio to receive either metformin or a matching placebo for 16 weeks. The initial dose of 500 mg of metformin or placebo once daily is increased by 500 mg every week until the target dose of 1000 mg two times a day, or the maximum tolerated dose, is reached. The participants will have clinical visits every 4 weeks, except the week 12 visit, which is by telephone. The primary endpoint is the between-group difference in least squares means for the change in the Visual Analogue Scale (VAS) finger joint pain scores between the metformin and placebo groups at 16 weeks. The main analysis will be conducted on the intention-to-treat population, comprising all participants assessed and randomly assigned at baseline. Least squares means and the differences between them, along with their respective 95% CIs, will be derived from a mixed-effects model for repeated measurements (outcomes collected at baseline and at weeks 4, 8, 12 and 16). Adverse events will be registered systematically. Ethics and dissemination Approval has been obtained from the European Medicines Agency (EudraCT: 2023-509181-38-00), which also includes approval from the local health research ethics committee. Written informed consent will be obtained from all participants. Study findings will be published in international peer-reviewed journals and will be presented in relevant media and at international scientific conferences.</p

Polyautoimmunity in patients with cutaneous lupus erythematosus:A nationwide sex- and age-matched cohort study from Denmark

BACKGROUND: Polyautoimmunity is defined as having 2 or more autoimmune diseases. Little is known about polyautoimmunity in patients with cutaneous lupus erythematosus (CLE).OBJECTIVES: To estimate prevalence and 5-year incidence of non-lupus erythematosus (LE) autoimmune diseases in patients with CLE.METHODS: Patients with CLE were identified In the Danish National Patient Registry and each patient was age- and sex-matched with 10 general population controls. Outcome information on non-LE autoimmune diseases was obtained by register-linkage between Danish National Patient Registry and the National Prescription Register. The risk ratio (RR) for prevalent non-LE autoimmune disease at time of CLE diagnosis was calculated in modified Poisson regression; and hazard ratios (HRs) for incident non-LE autoimmune disease were estimated in Cox regression analyses.RESULTS: Overall, 1674 patients with CLE had a higher prevalence of a non-LE autoimmune disease than the comparators (18.5 vs 7.9%; RR 2.4; 95% CI, 2.1 to 2.6). Correspondingly, the cumulative incidence of a non-LE autoimmune disease during 5 years of follow-up was increased for the patients with CLE: HR 3.5 (95% CI, 3.0 to 4.0).LIMITATIONS: Risk of detection and misclassification bias, mainly pertaining to the CLE group.CONCLUSION: Patients with CLE had higher prevalence and 5-year cumulative incidence of a non-LE autoimmune disease than the general population.</p