Objectives Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.Methods In a cross-sectional multi... Show moreObjectives Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.Methods In a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC).Results Strong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies.Conclusions Differences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups. Show less
Objective: Inflammation and innate immune responses may contribute to development and progression of Osteoarthritis (OA). Chondrocytes are the sole cell type of the articular cartilage and produce... Show moreObjective: Inflammation and innate immune responses may contribute to development and progression of Osteoarthritis (OA). Chondrocytes are the sole cell type of the articular cartilage and produce extracellular-matrix molecules. How inflammatory mediators reach chondrocytes is incompletely understood. Previous studies have shown that chondrocytes express mRNA encoding complement proteins such as C1q, suggesting local protein production, which has not been demonstrated conclusively. The aim of this study is to explore C1q production at the protein level by chondrocytes.Design: We analysed protein expression of C1q in freshly isolated and cultured human articular chondrocytes using Western blot, ELISA and flow cytometry. We examined changes in mRNA expression of collagen, MMP-1 and various complement genes upon stimulation with pro-inflammatory cytokines or C1q. mRNA expression of C1 genes was determined in articular mouse chondrocytes.Results: Primary human articular chondrocytes express genes encoding C1q, C1QA, C1QB, C1QC, and secrete C1q to the extracellular medium. Stimulation of chondrocytes with pro-inflammatory cytokines upregulated C1QA, C1QB, C1QC mRNA expression, although this was not confirmed at the protein level. Extracellular C1q bound to the chondrocyte surface dose dependently. In a pilot study, binding of C1q to chondrocytes resulted in changes in the expression of collagens with a decrease in collagen type 2 and an increase in type 10. Mouse articular chondrocytes also expressed C1QA, C1QB, C1QC, C1R and C1S at the mRNA level.Conclusions: C1q protein can be expressed and secreted by human articular chondrocytes and is able to bind to chondrocytes influencing the relative collagen expression. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Moseng, T.; Dagfinrud, H.; Bodegom-Vos, L. van; Dziedzic, K.; Hagen, K.B.; Natvig, B.; ... ; Osteras, N. 2020
BackgroundTo address the well-documented gap between hip and knee osteoarthritis (OA) treatment recommendations and current clinical practice, a structured model for integrated OA care was... Show moreBackgroundTo address the well-documented gap between hip and knee osteoarthritis (OA) treatment recommendations and current clinical practice, a structured model for integrated OA care was developed and evaluated in a stepped-wedge cluster-randomised controlled trial. The current study used secondary outcomes to evaluate clinically important response to treatment through the Outcome Measures in Rheumatology Clinical Trials clinical responder criteria (OMERACT-OARSI responder criteria) after 3 and 6months between patients receiving the structured OA care model vs. usual care. Secondly, the study aimed to investigate if the proportion of responders in the intervention group was influenced by adherence to the exercise program inherent in the model.MethodsThe study was conducted in primary healthcare in six Norwegian municipalities. General practitioners and physiotherapists received training in OA treatment recommendations and use of the structured model. The intervention group attended a physiotherapist-led OA education program and performed individually tailored exercises for 8-12weeks. The control group received usual care. Patient-reported pain, function and global assessment of disease activity during the last week were evaluated using 11-point numeric rating scales (NRS 0-10). These scores were used to calculate the proportion of OMERACT-OARSI responders. Two-level mixed logistic regression models were fitted to investigate differences in responders between the intervention and control group.ResultsTwo hundred eighty-four intervention and 109 control group participants with hip and knee OA recruited from primary care in six Norwegian municipalities. In total 47% of the intervention and 35% of the control group participants were responders at 3 or 6months combined; showing an uncertain between-group difference (ORadjusted 1.38 (95% CI 0.41, 4.67). In the intervention group, 184 participants completed the exercise programme (exercised >= 2 times/week for >= 8weeks) and 55% of these were classified as responders. In contrast, 28% of the 86 non-completers were classified as responders.ConclusionsThe difference in proportion of OMERACT-OARSI responders at 3 and 6months between the intervention and control group was uncertain. In the intervention group, a larger proportion of responders were seen among the exercise completers compared to the non-completers.Clinical trial registrationClinicaltrials.gov identifier: NCT02333656. Registered 7. January 2015. Show less
Over the past year many studies and clinical trials have been published in the osteoarthritis (OA) field. This review is based on systematic literature review covering the period May 1st, 2018 to... Show moreOver the past year many studies and clinical trials have been published in the osteoarthritis (OA) field. This review is based on systematic literature review covering the period May 1st, 2018 to April 19th , 2019; the final selection of articles was subjective. Specifically those articles considered to be presenting novel insights and of potential importance for clinical practice, are discussed.Further evidence has emerged that OA is a serious disease with increasing impact worldwide. Our understanding of development of pain in OA has increased. Detailed studies investigating widely used pharmacological treatments have shown the benefits to be limited, whereas the risks seem higher than expected, suggesting further studies and reconsideration of currently used guidelines. Promising new pharmacological treatments have been developed and published, however subsequent studies are warranted. While waiting for new treatment modalities to appear joint replacement is an effective alternative; new data have become available on how long they might last. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. Show less
Pelle, T.; Claassen, A.A.O.M.; Meessen, J.M.T.A.; Peter, W.F.; Vlieland, T.P.M.V.; Bevers, K.; ... ; Ende, C.H.M. van den 2020
To compare the amount of physical activity (PA) among patients with different subsets of knee or hip osteoarthritis (OA) and the general population. Secondary analyses of data of subjects >= 50... Show moreTo compare the amount of physical activity (PA) among patients with different subsets of knee or hip osteoarthritis (OA) and the general population. Secondary analyses of data of subjects >= 50 years from four studies: a study on the effectiveness of an educational program for OA patients in primary care (n = 110), a RCT on the effectiveness of a multidisciplinary self-management program for patients with generalized OA in secondary care (n = 131), a survey among patients who underwent total joint arthroplasty (TJA) for end-stage OA (n = 510), and a survey among the general population in the Netherlands (n = 3374). The Short QUestionnaire to ASssess Health-enhancing physical activity (SQUASH) was used to assess PA in all 4 studies. Differences in PA were analysed by multivariable linear regression analyses, adjusted for age, body mass index and sex. In all groups, at least one-third of total time spent on PA was of at least moderate-intensity. Unadjusted mean duration (hours/week) of at least moderate-intensity PA was 15.3, 12.3, 18.1 and 17.8 for patients in primary, secondary care, post TJA, and the general population, respectively. Adjusted analyses showed that patients post TJA spent 5.6 h [95% CI: 1.5; 9.7] more time on PA of at least moderate-intensity than patients in secondary care. The reported amount of PA of at least moderate-intensity was high in different subsets of OA and the general population. Regarding the amount of PA in patients with different subsets of OA, there was a substantial difference between patients in secondary care and post TJA patients. Show less
Loef, M.; Ioan-Facsinay, A.; Mook-Kanamori, D.O.; Dijk, K.W. van; Mutsert, R. de; Kloppenburg, M.; Rosendaal, F.R. 2020
Objective: To investigate the association of postprandial and fasting plasma saturated fatty acid (SFAs), monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) concentrations... Show moreObjective: To investigate the association of postprandial and fasting plasma saturated fatty acid (SFAs), monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) concentrations with hand and knee osteoarthritis (OA).Design: In the population-based NEO study clinical hand and knee OA were defined by the ACR classification criteria. Structural knee OA was defined on MRI. Hand and knee pain was determined by Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and KOOS, respectively. Plasma was sampled fasted and 150 min after a standardized meal, and subsequently analysed using a nuclear magnetic resonance platform. Logistic regression analyses were used to investigate the association of total fatty acid, SFA, MUFA, total PUFA, omega-3 PUFA and omega-6 PUFA concentrations with clinical hand and knee OA, structural knee OA and hand and knee pain. Fatty acid concentrations were standardized (mean 0, SD 1). Analyses were stratified by sex and corrected for age, education, ethnicity and total body fat percentage.Results: Of the 5,328 participants (mean age 56 years, 58% women) 7% was classified with hand OA, 10% with knee OA and 4% with concurrent hand and knee OA. In men, postprandial SFAs (OR (95% CI)) 1.23 (1.00; 1.50), total PUFAs 1.26 (1.00; 1.58) and omega-3 PUFAs 1.24 (1.01; 1.52) were associated with hand OA. SFAs and PUFAs were associated with structural, but not clinical knee OA. Association of fasting fatty acid concentrations were weaker than postprandial concentrations.Conclusion: Plasma postprandial SFA and PUFA levels were positively associated with clinical hand and structural knee OA in men, but not in women. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Kroon, F.P.B.; Veenbrink, A.I.; Mutsert, R. de; Visser, A.W.; Dijk, K.W. van; Cessie, S. le; ... ; Kloppenburg, M. 2019
Objective: The Joint Effort Initiative was endorsed by Osteoarthritis Research Society International (OARSI) in 2018 as a collaboration between international researchers and clinicians with an... Show moreObjective: The Joint Effort Initiative was endorsed by Osteoarthritis Research Society International (OARSI) in 2018 as a collaboration between international researchers and clinicians with an interest in the implementation of osteoarthritis management programs (OAMPs). This study aimed to identify and prioritise activities for future work of the Joint Effort Initiative.Design: A survey was emailed to delegates of the 2018 OARSI World Congress attending a pre-conference workshop or with a known interest in OAMPs (n = 115). Delegates were asked about the most important issues regarding OAMP implementation. The top 20 issues were synthesised into 17 action statements, and respondents were invited to participate in a priority ranking exercise to determine the order of importance of the statements.Results: Survey respondents (n = 51, 44%) were most commonly female (71%), with an allied health background (57%), affiliated with universities (73%) from Oceania (37%), and Europe/UK (45%). The five highest ranked action statements were:i) Establish guidelines for the implementation of different OAMP models to ensure consistency of delivery and adherence to international best practice.ii) Develop and assess training and education programs for health care professionals (HCPs) delivering OAMPs.iii) Develop and evaluate the implementation and outcomes of novel models of OAMPs.iv) Develop and assess core skill sets and resources for HCPs delivering OA care.v) Develop a framework for enhancing the quality of care provided by OAMPs.Conclusion: Prioritising statements will bring focus to the future work of the Joint Effort Initiative in the future and provide a basis for longer-term actions. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Loef, M.; Schoones, J.W.; Kloppenburg, M.; Ioan-Facsinay, A. 2019
Objective: To investigate determinants of decrease and increase in joint pain in symptomatic finger osteoarthritis (OA) on magnetic resonance (MR) imaging over 2 years.Design: Eighty-five patients ... Show moreObjective: To investigate determinants of decrease and increase in joint pain in symptomatic finger osteoarthritis (OA) on magnetic resonance (MR) imaging over 2 years.Design: Eighty-five patients (81.2% women, mean age 59.2 years) with primary hand OA (89.4% fulfilling American College of Rheumatology (ACR) classification criteria) from a rheumatology outpatient clinic received contrast-enhanced MR imaging (1.5T) and physical examination of the right interphalangeal finger joints 2-5 at baseline and at follow-up 2 years later. MR images were scored paired in unknown time order, following the Hand OA MRI scoring system (HOAMRIS). Joint pain upon palpation was assessed by research nurses. Odds ratios (ORs; 95% confidence intervals) were estimated on joint level (n = 680), using generalized estimating equations (GEE) to account for the within patient effects. Additional adjustments were made for change in MR-defined osteophytes, synovitis, and bone marrow lesions (BMLs).Results: Of 116 painful joints at baseline, at follow-up: 76 had less pain, 21 less synovitis, and 13 less BMLs. A decrease in synovitis (OR = 5.9; 1.12-31.0), but not in BMLs (OR = 0.39; 0.10-1.50), was associated with less pain. Of 678 joints without maximum baseline pain, at follow-up: 115 had increased pain, 132 increased synovitis, 96 increased BMLs, and 44 increased osteophytes. Increased synovitis (OR = 1.81; 1.11-2.94), osteophytes (OR = 2.75; 1.59-4.8), but not BMLs (OR = 1.14; 0.81-1.60), was associated with increased pain. Through stratification it became apparent that BMLs were mainly acting as effect modifier of the synovitisepain association.Conclusion: Decrease in MR-defined synovitis is associated with reduced joint pain, identifying synovitis as a possible target for treatment of finger OA. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
BackgroundThis study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).MethodsData from the... Show moreBackgroundThis study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).MethodsData from the European Project on OSteoArthritis were used. At baseline, clinical classification criteria of the American College of Rheumatology were used to diagnose OA in older adults (65-85years). At baseline and 12-18months follow-up, frequency and duration of participation in the activities walking, cycling, gardening, light and heavy household tasks, and sports activities were assessed with the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire. Physical activity was calculated in kcal/day, based on frequency, duration, body weight and the metabolic equivalent of each activity performed. At baseline and 12-18months follow-up, pain severity was assessed using the pain subscales of the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand OA Index. Within-person pain variability was assessed using two-week pain calendars that were completed at baseline, 6months follow-up and 12-18months follow-up.ResultsOf all 669 participants, 70.0% were women. Sex-stratified multiple linear regression analyses showed that greater pain severity at baseline was cross-sectionally associated with less PA in women (Ratio=0.95, 95% CI=0.90-0.99), but not in men (Ratio=0.99, 95% CI=0.85-1.15). The longitudinal analyses showed a statistically significant inverse association between pain severity at baseline and PA at follow-up in women (Ratio=0.94, 95% CI=0.89-0.99), but not in men (Ratio=1.00, 95% CI=0.87-1.11). Greater pain variability over 12-18months was associated with more PA at follow-up in men (Ratio=1.18, 95% CI=1.01-1.38), but not in women (Ratio=0.94, 95% CI=0.86-1.03).ConclusionsGreater pain severity and less pain variability are associated with less PA in older adults with OA. These associations are different for men and women. The observed sex differences in the various associations should be studied in more detail and need replication in future research. Show less
Kroon, F.P.B.; Boersma, A.; Boonen, A.; Beest, S. van; Damman, W.; Heijde, D. van der; ... ; Kloppenburg, M. 2018
This thesis has provided more knowledge on the disease course and its determinants of outcome in hand osteoarthritis. The role of joint-specific factors and coping styles on disability, the... Show moreThis thesis has provided more knowledge on the disease course and its determinants of outcome in hand osteoarthritis. The role of joint-specific factors and coping styles on disability, the prevelance of aesthetic dissatisfaction, its impact on daily life and their determinants were evaluated. Additionally, the association between MR Imaging features with hand pain and the association of MR Imaging features with radiographic progression were investigated. Another part of the thesis focused on the association between osteoarthritis and mortality. Show less
Total hip-and total knee arthroplasties (THA/TKA) are effective treatments for end-stage hip/knee osteoarthritis, leading to satisfactory improvement of pain/function in 80-90% of the patients... Show moreTotal hip-and total knee arthroplasties (THA/TKA) are effective treatments for end-stage hip/knee osteoarthritis, leading to satisfactory improvement of pain/function in 80-90% of the patients within 12-months after surgery. Overall, knowledge regarding clinical outcomes reflecting the process of recovery in patients undergoing THA/TKA over a prolonged period is scarce. First, this thesis addressed the successfull feasibility of collecting a comprehensive set of outcomes relevant for the process of recovery. Second, it was found that the decrease in pain/improvement in function after 1 -year in THA-patients, but not in TKA-patients, was positively associated with more preoperative radiographic severity of OA. Thirdly, most patients’ preoperative expectations of outcomes of THA/TKA regarding functioning were met, unfortunately more frequently not in TKA-patients. Finally, 90%/52% of THA/TKA-patients return after surgery after 12-weeks on average. However, despite high return-to-work rates, a considerable proportion of the patients who return-to-work, worked less hours than preoperatively. Concluding, although overall favourable outcomes were seen, this thesis identified a number of areas for improvement: better identification of subgroups with a likely perceived unsuccessful outcome or recovery process, if not preoperatively then early after surgery. Early identification and subsequent interventions may change the course of recovery of THA/TKA for such patients, leading to added value in this subgroup. Show less
In dit proefschrift worden de moleculaire mechanismen behandeld die onderliggend zijn aan artrose. Specifiek wordt genoomwijd onderzocht welke genen anders tot expressie komen in aangedaan... Show moreIn dit proefschrift worden de moleculaire mechanismen behandeld die onderliggend zijn aan artrose. Specifiek wordt genoomwijd onderzocht welke genen anders tot expressie komen in aangedaan vergeleken met gezond kraakbeen van artrose patienten. Dit in de context van epigenetische regulatie van gen expressie, specifiek door DNA methylatie in het licht van de lokale genetische context in de vorm van puntmutaties. Show less
Immunometabolism focusses on the interplay between immunological and metabolic processes, both at a systemic and a cellular level. This thesis is divided into two parts based on these two... Show moreImmunometabolism focusses on the interplay between immunological and metabolic processes, both at a systemic and a cellular level. This thesis is divided into two parts based on these two levels. The first part focusses on the infrapatellar fat pad (IFP), an adipose tissue located in the knee, and the potential role in the pathophysiology of osteoarthritis. Therefore, we characterized the IFP based on a cellular and molecular level and found that the inflammatory state of the joint does affect the cellular load of the IFP, however, the secretory profile of the IFP does not seem to be affected. Furthermore, obesity-related changes normally found in adipose tissue were not present in the IFP. When characterizing the IFP we found two interesting cell populations, IL-6-secreting T cells and macrophages with an anti-inflammatory phenotype secreting pro-inflammatory cytokines. Both populations could be involved in the pathophysiology of the osteoarthritic joint. Furthermore, in the second part we focussed on cellular metabolism where we determined the mechanism by which fatty acids exert their effect on T cells. We found that fatty acids are not served as energy, however, whether it is used for daughter cells or influencing cell signalling remains to be elucidated. Show less
