In the Innovative Medicine's Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee osteoarthritis (OA) study, machine learning models were trained... Show moreIn the Innovative Medicine's Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee osteoarthritis (OA) study, machine learning models were trained to predict the probability of structural progression (s-score), predefined as >0.3 mm/year joint space width (JSW) decrease and used as inclusion criterion. The current objective was to evaluate predicted and observed structural progression over 2 years according to different radiographic and magnetic resonance imaging (MRI)-based structural parameters. Radiographs and MRI scans were acquired at baseline and 2-year follow-up. Radiographic (JSW, subchondral bone density, osteophytes), MRI quantitative (cartilage thickness), and MRI semiquantitative [SQ; cartilage damage, bone marrow lesions (BMLs), osteophytes] measurements were obtained. The number of progressors was calculated based on a change exceeding the smallest detectable change (SDC) for quantitative measures or a full SQ-score increase in any feature. Prediction of structural progression based on baseline s-scores and Kellgren-Lawrence (KL) grades was analyzed using logistic regression. Among 237 participants, around 1 in 6 participants was a structural progressor based on the predefined JSW-threshold. The highest progression rate was seen for radiographic bone density (39%), MRI cartilage thickness (38%), and radiographic osteophyte size (35%). Baseline s-scores could only predict JSW progression parameters (most P>0.05), while KL grades could predict progression of most MRI-based and radiographic parameters (P<0.05). In conclusion, between 1/6 and 1/3 of participants showed structural progression during 2-year follow-up. KL scores were observed to outperform the machine-learning-based s-scores as progression predictor. The large amount of data collected, and the wide range of disease stage, can be used for further development of more sensitive and successful (whole joint) prediction models. Trial Registration: Clinicaltrials.gov number NCT03883568. Show less
Osteoarthritis is one of the most common musculoskeletal disorders. Despite its high prevalence, the pathogenesis of osteoarthritis is incompletely understood. A major risk factor for... Show moreOsteoarthritis is one of the most common musculoskeletal disorders. Despite its high prevalence, the pathogenesis of osteoarthritis is incompletely understood. A major risk factor for osteoarthritis is obesity. Not only due to increased mechanical stress, but also due to systemic factors such as lipids. Our knowledge on how lipids are involved in osteoarthritis is limited. Therefore, this thesis focusses on the association of lipids with hand and knee osteoarthritis. Firstly, we investigated the reproducibility of lipid measurements to guide future lipidomic research. Subsequently, comparison of the lipid profile of osteoarthritis patients in different disease stages showed that the lipid profile explained disease severity to a limited extent. We observed the strongest association of the lipid profile with hand pain, and no association with knee osteoarthritis. This suggests that lipotoxicity may play a larger role in the hand, while in the knee mechanical stress is more relevant. In addition, treatment with anti-inflammatory medication resulted in a change in lipid concentrations in patients with hand osteoarthritis, suggesting that lipids are involved in inflammation and/or pain processes. These insights may increase our understanding of osteoarthritis pathophysiology and lead to new targets for future development of disease modifying osteoarthritis medication. Show less
Loef, M.; Stadt, L. van de; Bohringer, S.; Bay-Jensen, A.C.; Mobasheri, A.; Larkin, J.; ... ; Kloppenburg, M. 2022
Objective: To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function. Design: We used... Show moreObjective: To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function. Design: We used baseline data from the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort, comprising persons with knee OA fulfilling the clinical American College of Rheumatology classification criteria. Radiographic knee and hand OA severity was quantified with Kellgren-Lawrence sum scores. Knee and hand pain and function were assessed with validated questionnaires. We quantified fasted plasma higher order lipids and oxylipins with liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based platforms. Using penalised linear regression, we assessed the variance in OA severity explained by lipidomics, with adjustment for clinical covariates (age, sex, body mass index (BMI) and lipid lowering medication), measurement batch and clinical centre. Results: In 216 participants (mean age 66 years, mean BMI 27.3 kg/m2, 75% women) we quantified 603 higher order lipids (triacylglycerols, diacylglycerols, cholesteryl esters, ceramides, free fatty acids, sphingomyelins, phospholipids) and 28 oxylipins. Lipidomics explained 3% and 2% of the variance in radiographic knee and hand OA severity, respectively. Lipids were not associated with knee pain or function. Lipidomics accounted for 12% and 6% of variance in hand pain and function, respectively. The investigated OA severity outcomes were associated with the lipidomic fraction of bound and free arachidonic acid, bound palmitoleic acid, oleic acid, linoleic acid and docosapentaenoic acid. Conclusions: Within the APPROACH cohort lipidomics explained a minor portion of the variation in OA severity, which was most evident for the outcome hand pain. Our results suggest that eicosanoids may be involved in OA severity. (c) 2022 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. Show less
Helvoort, E.M. van; Welsing, P.M.J.; Jansen, M.P.; Gielis, W.P.; Loef, M.; Kloppenburg, M.; ... ; Mastbergen, S. 2021
Objectives Osteoarthritis (OA) patients with a neuropathic pain (NP) component may represent a specific phenotype. This study compares joint damage, pain and functional disability between knee OA... Show moreObjectives Osteoarthritis (OA) patients with a neuropathic pain (NP) component may represent a specific phenotype. This study compares joint damage, pain and functional disability between knee OA patients with a likely NP component, and those without a likely NP component.Methods Baseline data from the Innovative Medicines Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway knee OA cohort study were used. Patients with a painDETECT score >= 9 (with likely NP component, n=24) were matched on a 1:2 ratio to patients with a painDETECT score <= 12 (without likely NP component), and similar knee and general pain (Knee Injury and Osteoarthritis Outcome Score pain and Short Form 36 pain). Pain, physical function and radiographic joint damage of multiple joints were determined and compared between OA patients with and without a likely NP component.Results OA patients with painDETECT scores >= 19 had statistically significant less radiographic joint damage (p <= 0.04 for Knee Images Digital Analysis parameters and Kellgren and Lawrence grade), but an impaired physical function (p < 0.003 for all tests) compared with patients with a painDETECT score <= 12. In addition, more severe pain was found in joints other than the index knee (p <= 0.001 for hips and hands), while joint damage throughout the body was not different.Conclusions OA patients with a likely NP component, as determined with the painDETECT questionnaire, may represent a specific OA phenotype, where local and overall joint damage is not the main cause of pain and disability. Patients with this NP component will likely not benefit from general pain medication and/or disease-modifying OA drug (DMOAD) therapy. Reserved inclusion of these patients in DMOAD trials is advised in the quest for successful OA treatments. Show less
Terpstra, S.E.S.; Velde, J.H.P.M. van der; Mutsert, R. de; Schiphof, D.; Reijnierse, M.; Rosendaal, F.R.; ... ; Loef, M. 2021
Objective: To investigate if knee osteoarthritis (OA) is associated with lower physical activity in the general middle-aged Dutch population, and if physical activity is associated with patient... Show moreObjective: To investigate if knee osteoarthritis (OA) is associated with lower physical activity in the general middle-aged Dutch population, and if physical activity is associated with patient-reported outcomes in knee OA. Design: Clinical knee OA was defined in the Netherlands Epidemiology of Obesity population using the ACR criteria, and structural knee OA on MRI. We assessed knee pain and function with the Knee Injury and Osteoarthritis Score (KOOS), health-related quality of life (HRQoL) with the Short Form-36, and physical activity (in Metabolic Equivalent of Task (MET) hours) with the Short Questionnaire to Assess Health-enhancing physical activity. We analysed the associations of knee OA with physical activity, and of physical activity with knee pain, function, and HRQoL in knee OA with linear regression adjusted for potential confounders. Results: Clinical knee OA was present in 14% of 6,212 participants, (mean age 56 years, mean BMI 27 kg/m(2), 55% women, 24% having any comorbidity) and structural knee OA in 12%. Clinical knee OA was associated with 9.60 (95% CI 3.70; 15.50) MET hours per week more physical activity, vs no clinical knee OA. Structural knee OA was associated with 3.97 (-7.82; 15.76) MET hours per week more physical activity, vs no structural knee OA. In clinical knee OA, physical activity was not associated with knee pain, function or HRQoL. Conclusions: Knee OA was not associated with lower physical activity, and in knee OA physical activity was not associated with patient-reported outcomes. Future research should indicate the optimal treatment advice regarding physical activity for individual knee OA patients. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Objectives. To assess underlying domains measured by GaitSmart (TM) parameters and whether these are additional to established OA markers including patient reported outcome measures (PROMs) and... Show moreObjectives. To assess underlying domains measured by GaitSmart (TM) parameters and whether these are additional to established OA markers including patient reported outcome measures (PROMs) and radiographic parameters, and to evaluate if GaitSmart analysis is related to the presence and severity of radiographic knee OA.Methods. GaitSmart analysis was performed during baseline visits of participants of the APPROACH cohort (n = 297). Principal component analyses (PCA) were performed to explore structure in relationships between GaitSmart parameters alone and in addition to radiographic parameters and PROMs. Logistic and linear regression analyses were performed to analyse the relationship of GaitSmart with the presence (Kellgren and Lawrence grade >= 2 in at least one knee) and severity of radiographic OA (ROA).Results. Two hundred and eighty-four successful GaitSmart analyses were performed. The PCA identified five underlying GaitSmart domains. Radiographic parameters and PROMs formed additional domains indicating that GaitSmart largely measures separate concepts. Several GaitSmart domains were related to the presence of ROA as well as the severity of joint damage in addition to demographics and PROMs with an area under the receiver operating characteristic curve of 0.724 and explained variances (adjusted R-2) of 0.107, 0.132 and 0.147 for minimum joint space width, osteophyte area and mean subchondral bone density, respectively.Conclusions. GaitSmart analysis provides additional information over established OA outcomes. GaitSmart parameters are also associated with the presence of ROA and extent of radiographic severity over demographics and PROMS. These results indicate that Gaitsmart (TM) may be an additional outcome measure for the evaluation of OA. Show less
Loef, M.; Gademan, M.G.J.; Latijnhouwers, D.A.J.M.; Kroon, H.M.; Kaptijn, H.H.; Marijnissen, W.J.C.M.; ... ; LOAS Study Grp 2021
Background: We aimed to investigate the application of the Knee Injury and Osteoarthritis Outcome Score (KOOS) percentile curves, using preoperative and postoperative data of patients with knee... Show moreBackground: We aimed to investigate the application of the Knee Injury and Osteoarthritis Outcome Score (KOOS) percentile curves, using preoperative and postoperative data of patients with knee osteoarthritis undergoing total knee arthroplasty (TKA).Methods: We used Longitudinal Leiden Orthopedics Outcomes of Osteo-Arthritis study data of patients between 45 and 65 years and undergoing primary TKA. KOOS scores (0-100) were obtained preoperatively and 6, 12, and 24 months after TKA. Preoperative knee radiographs were assessed according to Kellgren-Lawrence (KL) in a subset (37%) of patients. Comorbidities were self-reported using a standardized questionnaire. The median (interquartile range) population-level KOOS scores were plotted on previously developed population-based KOOS percentile curves. In addition, we assessed the application of the curves on patient level and investigated differences in scores between patients with preoperative KL scores <= 2 and >= 3 and presence (vs absence) of comorbidities.Results: The study population consisted of 853 patients (62% women, mean age 59 years, body mass index 30 kg/m(2)) with knee osteoarthritis undergoing primary TKA. Preoperatively, median KOOS scores of all subscales were at or below the 2.5th percentile. Scores increased to approximately the 25th percentile 12 months postoperatively. Greater improvements were observed in pain and less improvements in sport and recreational function and quality of life. Patients with higher preoperative KL scores and without comorbidities showed greater improvements.Conclusion: The KOOS percentile curves provided visual insights in knee complaints of patients relative to the general population. Furthermore, the KOOS percentile curves give insight in how preoperative patient characteristics are correlated with postoperative results. (C) 2021 The Author(s). Published by Elsevier Inc. Show less
Objectives. To assess underlying domains measured by GaitSmart (TM) parameters and whether these are additional to established OA markers including patient reported outcome measures (PROMs) and... Show moreObjectives. To assess underlying domains measured by GaitSmart (TM) parameters and whether these are additional to established OA markers including patient reported outcome measures (PROMs) and radiographic parameters, and to evaluate if GaitSmart analysis is related to the presence and severity of radiographic knee OA.Methods. GaitSmart analysis was performed during baseline visits of participants of the APPROACH cohort (n = 297) . Principal component analyses (PCA) were performed to explore structure in relationships between GaitSmart parameters alone and in addition to radiographic parameters and PROMs. Logistic and linear regression analyses were performed to analyse the relationship of GaitSmart with the presence (Kellgren and Lawrence grade >= 2 in at least one knee) and severity of radiographic OA (ROA).Results. Two hundred and eighty-four successful GaitSmart analyses were performed. The PCA identified five underlying GaitSmart domains. Radiographic parameters and PROMs formed additional domains indicating that GaitSmart largely measures separate concepts. Several GaitSmart domains were related to the presence of ROA as well as the severity of joint damage in addition to demographics and PROMs with an area under the receiver operating characteristic curve of 0.724 and explained variances (adjusted R-2) of 0.107, 0.132 and 0.147 for minimum joint space width, osteophyte area and mean subchondral bone density, respectively.Conclusions. GaitSmart analysis provides additional information over established OA outcomes. GaitSmart parameters are also associated with the presence of ROA and extent of radiographic severity over demographics and PROMS. These results indicate that Gaitsmart (TM) may be an additional outcome measure for the evaluation of OA. Show less
Loef, M.; Geest, R.J. van der; Lamb, H.J.; Mutsert, R. de; Cessie, S. le; Rosendaal, F.R.; Kloppenburg, M. 2021
Objective. We investigated the role of blood pressure, vessel wall stiffness [pulse wave velocity (PWV)] and subclinical atherosclerosis markers [carotid intima-media thickness (cIMT), popliteal... Show moreObjective. We investigated the role of blood pressure, vessel wall stiffness [pulse wave velocity (PWV)] and subclinical atherosclerosis markers [carotid intima-media thickness (cIMT), popliteal vessel wall thickness (pVWT)] as mediators of the association of obesity with OA.Methods. We used cross-sectional data from a subset of the population-based NEO study (n = 6334). We classified clinical hand and knee OA by the ACR criteria, and structural knee OA, effusion and bone marrow lesions on MRI (n = 1285). cIMT was assessed with ultrasonography. pVWT was estimated on knee MRI (n = 1285), and PWV by abdominal velocity-encoded MRIs (n = 2580), in subpopulations. Associations between BMI and OA were assessed with logistic regression analyses, adjusted for age, sex and education. Blood pressure, cIMT, pVWT and PWV were added to the model to estimate mediation.Results. The population consisted of 55% women, with a mean (S.D.) age of 56(6) years. Clinical hand OA was present in 8%, clinical knee OA in 10%, and structural knee OA in 12% of participants. BMI was positively associated with all OA outcomes. cIMT partially mediated the association of BMI with clinical hand OA [10.6 (6.2; 30.5)%], structural knee OA [3.1 (1.9; 7.3)%] and effusion [10.8 (6.0; 37.6)%]. Diastolic blood pressure [2.1 (1.6; 3.0)%] minimally mediated the association between BMI and clinical knee OA. PWV and pVWT did not mediate the association between BMI and OA.Conclusions. cIMT and diastolic blood pressure minimally mediated the association of BMI with OA. This suggests that such mediation is trivial in the middle-aged population. Show less
Loef, M.; Hegedus, J.H. von; Ghorasaini, M.; Kroon, F.P.B.; Giera, M.; Ioan-Facsinay, A.; Kloppenburg, M. 2021
It is essential to measure lipid biomarkers with a high reproducibility to prevent biased results. We compared the lipid composition and inter-day reproducibility of lipid measurements in plasma... Show moreIt is essential to measure lipid biomarkers with a high reproducibility to prevent biased results. We compared the lipid composition and inter-day reproducibility of lipid measurements in plasma and erythrocytes. Samples from 42 individuals (77% women, mean age 65 years, mean body mass index (BMI) 27 kg/m(2)), obtained non-fasted at baseline and after 6 weeks, were used for quantification of up to 1000 lipid species across 13 lipid classes with the Lipidyzer platform. Intraclass correlation coefficients (ICCs) were calculated to investigate the variability of lipid concentrations between timepoints. The ICC distribution of lipids in plasma and erythrocytes were compared using Wilcoxon tests. After data processing, the analyses included 630 lipids in plasma and 286 in erythrocytes. From these, 230 lipids overlapped between sample types. In plasma, 78% of lipid measurements were reproduced well to excellently, compared to 37% in erythrocytes. The ICC score distribution in plasma (median ICC 0.69) was significantly better than in erythrocytes (median ICC 0.51) (p-value < 0.001). At the class level, reproducibility in plasma was superior for triacylglycerols and cholesteryl esters while ceramides, diacylglycerols, (lyso)phosphatidylethanolamines, and sphingomyelins showed better reproducibility in erythrocytes. Although in plasma overall reproducibility was superior, differences at individual and class levels may favor the use of erythrocytes. Show less
Loef, M.; Damman, W.; Mutsert, R. de; Rosendaal, F.R.; Kloppenburg, M. 2020
Objective. To investigate the association of hand osteoarthritis (OA) and concurrent hand and knee OA with health-related quality of life (HRQOL) in the general population, and in patients... Show moreObjective. To investigate the association of hand osteoarthritis (OA) and concurrent hand and knee OA with health-related quality of life (HRQOL) in the general population, and in patients consulting a rheumatology outpatient clinic.Methods. In the population-based Netherlands Epidemiology of Obesity (NEO) study, participants were recruited from the greater area of Leiden, the Netherlands. In the Hand OSTeoArthritis in Secondary care (HOSTAS) study, patients with a rheumatologist's diagnosis of hand OA were recruited from a Leiden-based hospital. In both cohorts, hand and knee OA were defined by the American College of Rheumatology clinical criteria. In NEO, self-reported hospital-based specialist consultation for OA was recorded. Physical and mental HRQOL was assessed with normalized Medical Outcomes Study Short Form-36 scores. Associations were analyzed using linear regression, adjusted for age, sex, education, ethnicity, and body mass index.Results. Hand OA alone and concurrent hand and knee OA was present in 8% and 4% of 6334 NEO participants, and in 57% and 32% of 538 HOSTAS patients. In NEO, hand OA alone, and concurrent hand and knee OA, were associated with lower physical component summary (PCS) scores [mean difference -2.4 (95% CI -3.6, -1.3) and -7.7 (95% CI -9.3, -6.2), respectively] compared with no OA. Consulting a specialist was associated with worse PCS scores. In the HOSTAS cohort, mean PCS scores were lower than norm values (-3.5 and -7.9 for hand OA and combined OA, respectively). Mental HRQOL was not clinically relevantly associated in either cohort.Conclusion. Hand OA was associated with reduced physical, but not mental, HRQOL in the general population and hospital patients. Physical HRQOL was further reduced in hospital care, and with concurrent knee OA. Show less
Loef, M.; Kroon, F.P.B.; Bohringer, S.; Roos, E.M.; Rosendaal, F.R.; Kloppenburg, M. 2020
Objective: To improve the interpretation of the Knee injury and Osteoarthritis Outcome Score (KOOS) in individual patients, we explored associations with age, sex, BMI, history of knee injury and... Show moreObjective: To improve the interpretation of the Knee injury and Osteoarthritis Outcome Score (KOOS) in individual patients, we explored associations with age, sex, BMI, history of knee injury and presence of clinical knee osteoarthritis, and developed percentile curves.Methods: We used cross-sectional data of middle-aged individuals from the population-based Netherlands Epidemiology of Obesity (NEO) study. Clinical knee osteoarthritis was defined using the ACR classification criteria. KOOS scores were handled according to the manual (zero = extreme problems, 100 = no problems). Patient characteristics associated with KOOS were explored using ordered logistic regression, and sex and body mass index (BMI)-specific percentile curves were developed using quantile regression with fractional polynomials. The curves were applied as a benchmark for comparison of KOOS scores of participants with knee osteoarthritis and comorbidities.Results: The population consisted of 6,643 participants (56% women, mean (SD) age 56(6) years). Population-based KOOS subscale scores (median; interquartile range) near optimum: pain (100;94-100), symptoms (96;86-100), ADL function (100;96-100), sport/recreation function (100;80-100), quality of life (100;75-100). Worse KOOS scores were observed in women and in participants with higher BMI. Clinical knee osteoarthritis was defined in 15% of participants, and was, in comparison to other patient characteristics, associated with the highest odds of worse KOOS scores. Furthermore, presence of any comorbidity and cardiovascular disease specifically, was associated with worse KOOS scores, particularly in women.Conclusions: In the middle-aged Dutch population KOOS scores were generally good, but worse in women and with higher BMI. These percentile curves may be used as benchmarks in research and clinical practice. (c) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. 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
Helvoort, E.M. van; Spil, W.E. van; Jansen, M.P.; Welsing, P.M.J.; Kloppenburg, M.; Loef, M.; ... ; Lafeber, F.P.J.G. 2020
Purpose The Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) consortium intends to prospectively describe in detail, preselected patients with knee osteoarthritis... Show morePurpose The Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) consortium intends to prospectively describe in detail, preselected patients with knee osteoarthritis (OA), using conventional and novel clinical, imaging, and biochemical markers, to support OA drug development.Participants APPROACH is a prospective cohort study including 297 patients with tibiofemoral OA, according to the American College of Rheumatology classification criteria. Patients were (pre)selected from existing cohorts using machine learning models, developed on data from the CHECK cohort, to display a high likelihood of radiographic joint space width (JSW) loss and/or knee pain progression.Findings to date Selection appeared logistically feasible and baseline characteristics of the cohort demonstrated an OA population with more severe disease: age 66.5 (SD 7.1) vs 68.1 (7.7) years, min-JSW 2.5 (1.3) vs 2.1 (1.0) mm and Knee injury and Osteoarthritis Outcome Score pain 31.3 (19.7) vs 17.7 (14.6), except for age, all: p<0.001, for selected versus excluded patients, respectively. Based on the selection model, this cohort has a predicted higher chance of progression.Future plans Patients will visit the hospital again at 6, 12 and 24 months for physical examination, pain and general health questionnaires, collection of blood and urine, MRI scans, radiographs of knees and hands, CT scan of the knee, low radiation whole-body CT, HandScan, motion analysis and performance-based tests.After two years, data will show whether those patients with the highest probabilities for progression experienced disease progression as compared to those wit lower probabilities (model validation) and whether phenotypes/endotypes can be identified and predicted to facilitate targeted drug therapy. Show less
Loef, M.; Schoones, J.W.; Kloppenburg, M.; Ioan-Facsinay, A. 2019
