Objective To determine the association between joint structure and gait in patients with knee osteoarthritis (OA). Methods IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was... Show moreObjective To determine the association between joint structure and gait in patients with knee osteoarthritis (OA). Methods IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS). Patients were divided into those with/without radiographic OA (ROA). Principal component analyses (PCA) were performed on gait parameters; linear regression models were used to evaluate whether image-based structural and demographic parameters were associated with gait principal components. Results Two hundred seventy-one patients (age median 68.0, BMI 27.0, 77% female) could be analyzed; 149 (55%) had ROA. PCA identifed two components: upper leg (primarily walking speed, stride duration, hip range of motion [ROM], thigh ROM) and lower leg (calf ROM, knee ROM in swing and stance phases). Increased age, BMI, and radiographic subchondral bone density (sclerosis), decreased radiographic varus angle deviation, and female sex were statistically signifcantly associated with worse lower leg gait (i.e. reduced ROM) in patients without ROA (R2=0.24); in ROA patients, increased BMI, radiographic osteophytes, MRI meniscal extrusion and female sex showed signifcantly worse lower leg gait (R2=0.18). Higher BMI was signifcantly associated with reduced upper leg function for non-ROA patients (R2=0.05); ROA patients with male sex, higher BMI and less MRI synovitis showed signifcantly worse upper leg gait (R2=0.12). Conclusion Structural OA pathology was signifcantly associated with gait in patients with clinical knee OA, though BMI may be more important. While associations were not strong, these results provide a signifcant association between OA symptoms (gait) and joint structure. Show less
Objective: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine... Show moreObjective: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort - an exploratory, 5-center, 2-year prospective follow-up cohort. Design: Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 +/- 7.1 years, body mass index (BMI): 28.1 +/- 5.3 kg/m(2), 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test-retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test-retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: similar to 211 mu m) for the quartile with the highest vs the quartile with the lowest s-scores. Results: The test-retest precision was 69 mu m for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached -174 mu m (95% CI: [-207, -141] mu m, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: [0.52, 3.28]). Conclusion: IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score. (c) 2022 The Author(s). 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
Objective: Osteoarthritis (OA) is a highly prevalent chronic condition. The subchondral bone plays an important role in onset and progression of OA making it a potential treatment target for... Show moreObjective: Osteoarthritis (OA) is a highly prevalent chronic condition. The subchondral bone plays an important role in onset and progression of OA making it a potential treatment target for disease-modifying therapeutic approaches. However, little is known about changes of periarticular bone mineral density (BMD) in OA and its relation to meniscal coverage and meniscal extrusion at the knee. Thus, the aim of this study was to describe periarticular BMD in the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort at the knee and to analyze the association with structural disease severity, meniscal coverage and meniscal extrusion. Design: Quantitative CT (QCT), MRI and radiographic examinations were acquired in 275 patients with knee osteoarthritis (OA). QCT was used to assess BMD at the femur and tibia, at the cortical bone plate (Cort) and at the epiphysis at three locations: subchondral (Sub), mid-epiphysis (Mid) and adjacent to the physis (Juxta). BMD was evaluated for the medial and lateral compartment separately and for subregions covered and not covered by the meniscus. Radiographs were used to determine the femorotibial angle and were evaluated according to the Kellgren and Lawrence (KL) system. Meniscal extrusion was assessed from 0 to 3. Results: Mean BMD differed significantly between each anatomic location at both the femur and tibia (p < 0.001) in patients with KL0. Tibial regions assumed to be covered with meniscus in patients with KL0 showed lower BMD at Sub (p < 0.001), equivalent BMD at Mid (p = 0.07) and higher BMD at Juxta (p < 0.001) subregions compared to regions not covered with meniscus. Knees with KL2-4 showed lower Sub (p = 0.03), Mid (p = 0.01) and Juxta (p < 0.05) BMD at the medial femur compared to KL0/1. Meniscal extrusion grade 2 and 3 was associated with greater BMD at the tibial Cort (p < 0.001, p = 0.007). Varus malalignment is associated with significant greater BMD at the medial femur and at the medial tibia at all anatomic locations. Conclusion: BMD within the epiphyses of the tibia and femur decreases with increasing distance from the articular surface. Knees with structural OA (KL2-4) exhibit greater cortical BMD values at the tibia and lower BMD at the femur at the subchondral level and levels beneath compared to KL0/1. BMD at the tibial cortical bone plate is greater in patients with meniscal extrusion grade 2/3. Show less
ObjectiveOsteoarthritis (OA) is a highly prevalent chronic condition. The subchondral bone plays an important role in onset and progression of OA making it a potential treatment target for disease... Show moreObjectiveOsteoarthritis (OA) is a highly prevalent chronic condition. The subchondral bone plays an important role in onset and progression of OA making it a potential treatment target for disease-modifying therapeutic approaches. However, little is known about changes of periarticular bone mineral density (BMD) in OA and its relation to meniscal coverage and meniscal extrusion at the knee. Thus, the aim of this study was to describe periarticular BMD in the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort at the knee and to analyze the association with structural disease severity, meniscal coverage and meniscal extrusion.DesignQuantitative CT (QCT), MRI and radiographic examinations were acquired in 275 patients with knee osteoarthritis (OA). QCT was used to assess BMD at the femur and tibia, at the cortical bone plate (Cort) and at the epiphysis at three locations: subchondral (Sub), mid-epiphysis (Mid) and adjacent to the physis (Juxta). BMD was evaluated for the medial and lateral compartment separately and for subregions covered and not covered by the meniscus. Radiographs were used to determine the femorotibial angle and were evaluated according to the Kellgren and Lawrence (KL) system. Meniscal extrusion was assessed from 0 to 3.ResultsMean BMD differed significantly between each anatomic location at both the femur and tibia (p < 0.001) in patients with KL0. Tibial regions assumed to be covered with meniscus in patients with KL0 showed lower BMD at Sub (p < 0.001), equivalent BMD at Mid (p = 0.07) and higher BMD at Juxta (p < 0.001) subregions compared to regions not covered with meniscus. Knees with KL2–4 showed lower Sub (p = 0.03), Mid (p = 0.01) and Juxta (p < 0.05) BMD at the medial femur compared to KL0/1. Meniscal extrusion grade 2 and 3 was associated with greater BMD at the tibial Cort (p < 0.001, p = 0.007). Varus malalignment is associated with significant greater BMD at the medial femur and at the medial tibia at all anatomic locations.ConclusionBMD within the epiphyses of the tibia and femur decreases with increasing distance from the articular surface. Knees with structural OA (KL2–4) exhibit greater cortical BMD values at the tibia and lower BMD at the femur at the subchondral level and levels beneath compared to KL0/1. BMD at the tibial cortical bone plate is greater in patients with meniscal extrusion grade 2/3. Show less
Roemer, F.W.; Jansen, M.; Marijnissen, A.C.A.; Guermazi, A.; Heiss, R.; Maschek, S.; ... ; Wirth, W. 2022
Background: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI... Show moreBackground: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period.Methods: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition.Results: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 +/- 7.1 years and participants had a mean BMI of 28.1 +/- 5.3 kg/m(2). The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee).Conclusions: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. 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
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
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
Objective: Despite its prevalence, there are few worldwide hand osteoarthritis (HOA) cohorts. The main objective of DIGItal COhort Design (DIGICOD) cohort is to investigate prognostic clinical,... Show moreObjective: Despite its prevalence, there are few worldwide hand osteoarthritis (HOA) cohorts. The main objective of DIGItal COhort Design (DIGICOD) cohort is to investigate prognostic clinical, biological, genetic and imaging factors of clinical worsening after 6 years follow-up.Methods: DIGICOD is a hospital-based prospective cohort including patients > 35 years-old with symptomatic HOA fulfilling: (i) ACR criteria for HOA with > 2 symptomatic joints among proximal/distal interphalangeal joints or 1st interphalangeal joint with Kellgren-Lawrence (KL) > 2; or (ii) symptomatic thumb base OA with KL > 2. Main exclusion criteria were inflammatory arthritis and crystal arthropathies. Annual clinical evaluations were scheduled with imaging (X-rays of the hands and of other OA symptomatic joints) and biological sampling every 3 years. Hand radiographs are scored using KL and anatomical Verbruggen-Veys scores. Follow-up visits are ongoing. Cohort methodology and baseline characteristics are presented.Results: Between April 2013 and June 2017, from the 436 HOA included patients, 426 have been analysed of whom 357 (84%) are women. Mean age +/- standard deviation was 66.7 +/- 7.3 years and mean disease duration was 12.6 +/- 9.6 years. Metabolic syndrome affected 151 (36.5%) patients. Mean Visual Analog Scale (VAS) hand pain (0-100 mm) was 44.4 +/- 26.7 mm at activity. Mean FIHOA (0-100) was 19.9 + 18.6. Elevated serum CRP level (>= 5 mg/L) involved 10% patients. Mean KL score (0-128) was 46.7 +/- 18 and the mean number ofjoint with KL >= 2 was 15.1 +/- 6.3. Erosive HOA (defined as >= 1 Erosive or Remodeling phase joint according to Verbruggen-Veys score) involved 195/426 (45.8%) patients and the median number (interquartile range) of erosive joints in erosive patients was 3.0 (1.0-5.0).Conclusion: DIGICOD is a unique prospective HOA cohort with a long-term 6 years standardized assessment and has included severe radiologically HOA patients with a high prevalence of erosive disease. 2021 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. Show less
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
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
Eyles, J.P.; Hunter, D.J.; Bennell, K.L.; Dziedzic, K.S.; Hinman, R.S.; Esch, M. van der; ... ; Joint Effort Initiative 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
