Objective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically... Show moreObjective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors’ effect was explored in meta-regression and stratified models with pain as the dependent variable. Results: 84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of −0.51 (95% confidence interval −0.61 to −0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias. Conclusion: The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials. PROSPERO registration ID: CRD42022298984 Show less
Runhaar, J.; Özbulut, Ö; Kloppenburg, M.; Boers, M.; Bijlsma, J.W.J.; Bierma-Zeinstra, S.; CREDO expert group 2024
Objective To provide a set of diagnostic criteria for early-stage hip osteoarthritis (OA) in primary care, using signs and symptoms monitored over 2 years in individuals with hip pain and/or... Show moreObjective To provide a set of diagnostic criteria for early-stage hip osteoarthritis (OA) in primary care, using signs and symptoms monitored over 2 years in individuals with hip pain and/or stiffness. Additionally, the study aimed to see whether these factors were additive to factors based on baseline signs and symptoms only.Methods Data of the 543 persons with 735 symptomatic hips were collected from the prospective Cohort Hip and Cohort Knee cohort study. Using data from 5 to 10 years of follow-up, 24 experts (13 general practitioners, 11 secondary care physicians (6 rheumatologists and 5 orthopaedic surgeons)) inspected individuals’ medical data on the presence of clinically relevant hip OA. Their diagnoses are used as reference standards. Backward selection method was used to provide models using the factors from baseline to 2 years of follow-up. Additionally, new models were combined with previously published models, using same selection method. Area under the curve (AUC) was calculated after each removal of factors in the final combined models.Results Radiographic factors and high-sensitive C reactive protein did not end up in any model with change factors only. AUC value (SD) of the final obtained model of change factors was 0.70 (0.01). Adding newly defined factors to previously published models significantly (p<0.0001) increased the AUC value to 0.75 (0.01).Conclusion Final diagnostic criteria, consisting only of the factors obtained through history taking and physical examination, were able to detect early-stage hip OA associated with clinically relevant hip OA 5–10 years later, with ‘moderate’ precision. Show less
Objectives The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on selfreported data and radiographic... Show moreObjectives The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on selfreported data and radiographic features. Methods The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. Results In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0–15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. Conclusions International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology. Show less
Background Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stifness, pain, and a signifcant decrease in... Show moreBackground Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stifness, pain, and a signifcant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (Guilak in Best Pract Res Clin Rheumatol 25:815–823, 2011). It has been shown that postmitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state. Results We showed that hyper-physiological loading evokes consistent changes in CpGs associated with expression changes (ML-tCpGs) in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology (OA-tCpGs), we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity Show less
Jansen, M.P.; Hodgins, D.; Mastbergen, S.C.; Kloppenburg, M.; Blanco, F.J.; Haugen, I.K.; ... ; Wirth, W. 2024
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
Boone, I.; Tuerlings, M.; Almeida, R.C. de; Lehmann, J.; Ramos, Y.; Nelissen, R.; ... ; Meulenbelt, I. 2023
Heterogeneous accumulation of senescent cells expressing the senescence-associated secretory phenotype (SASP) affects tissue homeostasis which leads to diseases, such as osteoarthritis (OA). In... Show moreHeterogeneous accumulation of senescent cells expressing the senescence-associated secretory phenotype (SASP) affects tissue homeostasis which leads to diseases, such as osteoarthritis (OA). In this study, we set out to characterize heterogeneity of cellular senescence within aged articular cartilage and explored the presence of corresponding metabolic profiles in blood that could function as representative biomarkers. Hereto, we set out to perform cluster analyses, using a gene-set of 131 senescence genes (N = 57) in a previously established RNA sequencing dataset of aged articular cartilage and a generated metabolic dataset in overlapping blood samples. Using unsupervised hierarchical clustering and pathway analysis, we identified two robust cellular senescent endotypes. Endotype-1 was enriched for cell proliferating pathways, expressing forkhead box protein O4 (FOXO4), RB transcriptional corepressor like 2 (RBL2), and cyclin-dependent kinase inhibitor 1B (CDKN1B); the FOXO mediated cell cycle was identified as possible target for endotype-1 patients. Endotype-2 showed enriched inflammation-associated pathways, expressed by interleukin 6 (IL6), matrix metallopeptidase (MMP)1/3, and vascular endothelial growth factor (VEGF)C and SASP pathways were identified as possible targets for endotype-2 patients. Notably, plasma-based metabolic profiles in overlapping blood samples (N = 21) showed two corresponding metabolic clusters in blood. These non-invasive metabolic profiles could function as biomarkers for patient-tailored targeting of senescence in OA. Show less
Osteoarthritis (OA) is a prevalent age-related joint disease, determined by diverse changes in pathways maintaining articular cartilage and subchondral bone. This thesis aimed to identify and study... Show moreOsteoarthritis (OA) is a prevalent age-related joint disease, determined by diverse changes in pathways maintaining articular cartilage and subchondral bone. This thesis aimed to identify and study gene networks driving interacting etiopathophysiological OA processes in cartilage and subchondral bone. Hereto, characterization of the molecular landscape of bone and cartilage of OA patients showed 305 genes with similar direction of effect, including IL11 and CHADL. Moreover, to capture biological complexity and decipher underlying OA disease mechanisms a variety of human 3D cartilage and bone organoids models were exploited and a human osteochondral construct-on-a-chip was developed. Herein, we showed that the robust OA risk gene WWP2 may initiate OA, via aberrant responses in hypoxia-associated genes and a decrease in anabolic markers. Additionally we showed, as reflected by upregulation of SPP1 and downregulation of WNT16 in cartilage, that treatment of ex vivo human osteochondral explants with human recombinant IL11 does not necessarily has a beneficial outcome. Finally, to allow implementation of knowledge on diverse OA pathophysiological processes, the potency of circulating miRNAs to report on ongoing OA pathophysiological process in joint tissues was established. Such insights are crucial to stratify respective OA patients that require different therapeutic mode of action, towards precision medicine. Show less
Stadt, L.A. van de; Haugen, I.K.; Felson, D.; Kloppenburg, M. 2023
Objective: Prolonged morning stiffness (>60 min) is considered a symptom of inflammatory arthritis, but has a poor discriminative ability. Knowledge about morning stiffness in patients with hand... Show moreObjective: Prolonged morning stiffness (>60 min) is considered a symptom of inflammatory arthritis, but has a poor discriminative ability. Knowledge about morning stiffness in patients with hand osteoarthritis (OA) is lacking. We therefore studied morning stiffness in patients with hand OA. Design: Patients with primary hand OA according to their treating rheumatologist in the Hand OSTeo-Arthritis in Secondary care (HOSTAS) cohort were studied. Severity of morning stiffness was examined with Australian/Canadian hand OA index (AUSCAN) and presence and duration of morning stiffness were examined with a standardized questionnaire. Association of patient and disease characteristics with prolonged morning stiffness (>60 min) were analyzed with logistic regression. Results: In total 519 of 538 patients had available data about duration of morning stiffness, of whom 89 (17%) had prolonged morning stiffness. Severity of stiffness was mild in 158 of 525 (30%), intermediate in 194 (37%), severe in 97 (18%) and extreme in 19 (4%) patients. Patients with prolonged morning stiffness reported more pain, worse physical function and had a reduced mental and physical quality of life. Patients with prolonged morning stiffness also had more severe radiographic disease, although the association did not reach statistical significance. Conclusions: Prolonged and severe morning stiffness are frequently present in patients with hand OA. Patients with these symptoms report more pain in general and have a lower quality of life than patients that do not report these symptoms. Prolonged morning stiffness does not preclude a diagnosis of hand OA. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Objectives: Erosive hand osteoarthritis (EHOA) is a severe subset of hand osteoarthritis (OA). It is unclear if EHOA is genetically different from other forms of OA. Sequence variants at ten loci... Show moreObjectives: Erosive hand osteoarthritis (EHOA) is a severe subset of hand osteoarthritis (OA). It is unclear if EHOA is genetically different from other forms of OA. Sequence variants at ten loci have been associated with hand OA but none with EHOA. Methods: We performed meta-analysis of EHOA in 1484 cases and 550 680 controls, from 5 populations. To identify causal genes, we performed eQTL and plasma pQTL analyses, and developed one zebrafish mutant. We analysed associations of variants with other traits and estimated shared genetics between EHOA and other traits. Results: Four common sequence variants associated with EHOA, all with relatively high effect. Rs17013495 (SPP1/MEPE, OR=1.40, p=8.4x10(-14)) and rs11243284 (6p24.3, OR=1.35, p=4.2x10(-11)) have not been associated with OA, whereas rs11631127 (ALDH1A2, OR=1.46, p=7.1x10(-18)), and rs1800801 (MGP, OR=1.37, p=3.6x10(-13)) have previously been associated with hand OA. The association of rs1800801 (MGP) was consistent with a recessive mode of inheritance in contrast to its additive association with hand OA (OR homozygotes vs non-carriers=2.01, 95% CI 1.71 to 2.37). All four variants associated nominally with finger OA, although with substantially lower effect. We found shared genetic components between EHOA and other OA measures, grip strength, urate levels and gout, but not rheumatoid arthritis. We identified ALDH1A2, MGP and BMP6 as causal genes for EHOA, with loss-of-function Bmp6 zebrafish mutants displaying EHOA-like phenotypes. Conclusions: We report on significant genetic associations with EHOA. The results support the view of EHOA as a form of severe hand OA and partly separate it from OA in larger joints. Show less
ObjectivesIn osteoarthritis, methylation of lysine 79 on histone H3 (H3K79me), a protective epigenetic mechanism, is reduced. Histone methylation levels are dynamically regulated by histone... Show moreObjectivesIn osteoarthritis, methylation of lysine 79 on histone H3 (H3K79me), a protective epigenetic mechanism, is reduced. Histone methylation levels are dynamically regulated by histone methyltransferases and demethylases. Here, we aimed to identify which histone demethylases regulate H3K79me in cartilage and investigate whether their targeting protects against osteoarthritis. MethodsWe determined histone demethylase expression in human non-osteoarthritis and osteoarthritis cartilage using qPCR. The role of histone demethylase families and subfamilies on H3K79me was interrogated by treatment of human C28/I2 chondrocytes with pharmacological inhibitors, followed by western blot and immunofluorescence. We performed C28/I2 micromasses to evaluate effects on glycosaminoglycans by Alcian blue staining. Changes in H3K79me after destabilisation of the medial meniscus (DMM) in mice were determined by immunohistochemistry. Daminozide, a KDM2/7 subfamily inhibitor, was intra-articularly injected in mice upon DMM. Histone demethylases targeted by daminozide were individually silenced in chondrocytes to dissect their role on H3K79me and osteoarthritis. ResultsWe documented the expression signature of histone demethylases in human non-osteoarthritis and osteoarthritis articular cartilage. Inhibition of Jumonji-C demethylase family increased H3K79me in human chondrocytes. Blockade of KDM2/7 histone demethylases with daminozide increased H3K79me and glycosaminoglycans. In mouse articular cartilage, H3K79me decayed rapidly upon induction of joint injury. Early and sustained intra-articular treatment with daminozide enhanced H3K79me and exerted protective effects in mice upon DMM. Individual silencing of KDM7A/B demethylases in human chondrocytes demonstrated that KDM7A/B mediate protective effects of daminozide on H3K79me and osteoarthritis. ConclusionTargeting KDM7A/B histone demethylases could be an attractive strategy to protect joints against osteoarthritis. 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
Terpstra, S.E.S.; Stadt, L.A. van de; Kloppenburg, M. 2023
Hand osteoarthritis (OA) is treated by several medical professionals. In this review the rheumatologist's perspective will be conveyed. The rheumatologist tasks are to diagnose hand OA, exclude... Show moreHand osteoarthritis (OA) is treated by several medical professionals. In this review the rheumatologist's perspective will be conveyed. The rheumatologist tasks are to diagnose hand OA, exclude other causes of patient's complaints, and provide treatment. The rheumatologist therefore has a distinctive and important role in hand OA treatment. Although no disease modifying treatment exists, there are multiple options for managing hand OA in rheumatology practice, with the goal of achieving symptom relief and optimizing hand function. These treatments can be non-pharmacological or pharmacological. In this review we will provide a summary of evidence-based management options based on existing guidelines. Furthermore, we will describe common practice among rheumatologists for hand OA management. In order to do so, we performed a literature review of studies addressing treatment modality usage for hand OA. The review comprised 25 studies, which were heterogeneous in terms of treatment modality usage. In addition, a detailed description of care usage by patients in a Rheumatology outpatient clinic is given, based on data of our Hand OSTeoArthritis in Secondary care primary hand OA cohort. The large majority of these patients used any form of hand OA treatment (83%). Non-pharmacological treatment was less frequently used (47%) than pharmacological treatment (77%).(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Terpstra, S.E.S.; Stadt, L.A. van de; Kloppenburg, M. 2023
Hand osteoarthritis (OA) is treated by several medical professionals. In this review the rheumatologist's perspective will be conveyed. The rheumatologist tasks are to diagnose hand OA, exclude... Show moreHand osteoarthritis (OA) is treated by several medical professionals. In this review the rheumatologist's perspective will be conveyed. The rheumatologist tasks are to diagnose hand OA, exclude other causes of patient's complaints, and provide treatment. The rheumatologist therefore has a distinctive and important role in hand OA treatment. Although no disease modifying treatment exists, there are multiple options for managing hand OA in rheumatology practice, with the goal of achieving symptom relief and optimizing hand function. These treatments can be non-pharmacological or pharmacological. In this review we will provide a summary of evidence-based management options based on existing guidelines. Furthermore, we will describe common practice among rheumatologists for hand OA management. In order to do so, we performed a literature review of studies addressing treatment modality usage for hand OA. The review comprised 25 studies, which were heterogeneous in terms of treatment modality usage. In addition, a detailed description of care usage by patients in a Rheumatology outpatient clinic is given, based on data of our Hand OSTeoArthritis in Secondary care primary hand OA cohort. The large majority of these patients used any form of hand OA treatment (83%). Non-pharmacological treatment was less frequently used (47%) than pharmacological treatment (77%).(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Tuerlings, M.; Janssen, G.M.C.; Boone, I.; Hoolwerff, M. van; Ruiz, A.R.; Houtman, E.; ... ; Meulenbelt, I. 2023
Objective: To explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and study cartilage characteristics when mimicking the effect of OA risk allele... Show moreObjective: To explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and study cartilage characteristics when mimicking the effect of OA risk allele rs1052429-A on WWP2 expression in a human 3D in vitro model of cartilage. Method: Co-expression behavior of WWP2 with genes expressed in lesioned OA articular cartilage (N = 35 samples) was explored. By applying lentiviral particle mediated WWP2 upregulation in 3D in vitro pellet cultures of human primary chondrocytes (N = 8 donors) the effects of upregulation on cartilage matrix deposition was evaluated. Finally, we transfected primary chondrocytes with miR-140 mimics to evaluate whether miR-140 and WWP2 are involved in similar pathways. Results: Upon performing Spearman correlations in lesioned OA cartilage, 98 highly correlating genes (| r| > 0.7) were identified. Among these genes, we identified GJA1, GDF10, STC2, WDR1, and WNK4. Sub-sequent upregulation of WWP2 on 3D chondrocyte pellet cultures resulted in a decreased expression of COL2A1 and ACAN and an increase in EPAS1 expression. Additionally, we observed a decreased expression of GDF10, STC2, and GJA1. Proteomics analysis identified 42 proteins being differentially expressed with WWP2 upregulation, which were enriched for ubiquitin conjugating enzyme activity. Finally, upregu-lation of miR-140 in 2D chondrocytes resulted in significant upregulation of WWP2 and WDR1. Conclusions: Mimicking the effect of OA risk allele rs1052429-A on WWP2 expression initiates detri-mental processes in the cartilage shown by a response in hypoxia associated genes EPAS1, GDF10, and GJA1 and a decrease in anabolic markers, COL2A1 and ACAN.(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
Bone and joint disorders have an enormous personal- and societal impact. Diagnosis and treatment of these disorders are most efficient if targeted screening, accurate diagnosis, and targeted... Show moreBone and joint disorders have an enormous personal- and societal impact. Diagnosis and treatment of these disorders are most efficient if targeted screening, accurate diagnosis, and targeted treatment are available. To enable targeted screening, the population at risk must be well-defined, and categorized if required. Subsequently, screening- and diagnostic methods must have good, or excellent predictive value and finally, treatment must target the disease, thus spare healthy tissues and processes and thereby avoid adverse events.The aim of this thesis is to gain new insights about the diagnostic process- and treatment of pathological conditions of the bone and joints, namely male urological cancer-induced bone loss and inflammatory arthritis. Show less
Wissen, M.A.T. van; Berger, M.A.M.; Schoones, J.W.; Gademan, M.G.J.; Ende, C.H.M. van den; Vlieland, T.P.M.V.; Weely, S.F.E. van 2022
To assess the reporting quality of interventions aiming at promoting physical activity (PA) using a wearable activity tracker (WAT) in patients with inflammatory arthritis (IA) or hip/knee... Show moreTo assess the reporting quality of interventions aiming at promoting physical activity (PA) using a wearable activity tracker (WAT) in patients with inflammatory arthritis (IA) or hip/knee osteoarthritis (OA). A systematic search was performed in eight databases (including PubMed, Embase and Cochrane Library) for studies published between 2000 and 2022. Two reviewers independently selected studies and extracted data on study characteristics and the reporting of the PA intervention using a WAT using the Consensus on Exercise Reporting Template (CERT) (12 items) and Consolidated Standards of Reporting Trials (CONSORT) E-Health checklist (16 items). The reporting quality of each study was expressed as a percentage of reported items of the total CERT and CONSORT E-Health (50% or less = poor; 51-79% = moderate; and 80-100% = good reporting quality). Sixteen studies were included; three involved patients with IA and 13 with OA. Reporting quality was poor in 6/16 studies and moderate in 10/16 studies, according to the CERT and poor in 8/16 and moderate in 8/16 studies following the CONSORT E-Health checklist. Poorly reported checklist items included: the description of decision rule(s) for determining progression and the starting level, the number of adverse events and how adherence or fidelity was assessed. In clinical trials on PA interventions using a WAT in patients with IA or OA, the reporting quality of delivery process is moderate to poor. The poor reporting quality of the progression and tailoring of the PA programs makes replication difficult. Improvements in reporting quality are necessary. 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
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
