| 1. |
- Evangelou, Evangelos, et al.
(author)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Journal article (peer-reviewed)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 2. |
- Emery, Carolyn A, et al.
(author)
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Establishing outcome measures in early knee osteoarthritis
- 2019
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In: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4804 .- 1759-4790. ; 15:7, s. 438-448
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Research review (peer-reviewed)abstract
- The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting.
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| 3. |
- Mahmoudian, Armaghan, et al.
(author)
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Early-stage symptomatic osteoarthritis of the knee — time for action
- 2021
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In: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4790 .- 1759-4804. ; 17:10, s. 621-632
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Research review (peer-reviewed)abstract
- Osteoarthritis (OA) remains the most challenging arthritic disorder, with a high burden of disease and no available disease-modifying treatments. Symptomatic early-stage OA of the knee (the focus of this Review) urgently needs to be identified and defined, as efficient early-stage case finding and diagnosis in primary care would enable health-care providers to proactively and substantially reduce the burden of disease through proper management including structured education, exercise and weight management (when needed) and addressing lifestyle-related risk factors for disease progression. Efforts to define patient populations with symptomatic early-stage knee OA on the basis of validated classification criteria are ongoing. Such criteria, as well as the identification of molecular and imaging biomarkers of disease risk and/or progression, would enable well-designed clinical studies, facilitate interventional trials, and aid the discovery and validation of cellular and molecular targets for novel therapies. Treatment strategies, relevant outcomes and ethical issues also need to be considered in the context of the cost-effective management of symptomatic early-stage knee OA. To move forwards, a multidisciplinary and sustained international effort involving all major stakeholders is required.
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| 4. |
- Mahmoudian, Armaghan, et al.
(author)
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Towards classification criteria for early-stage knee osteoarthritis : A population-based study to enrich for progressors
- 2021
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 51:1, s. 285-291
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Journal article (peer-reviewed)abstract
- Objective: To facilitate a greater likelihood of favorable response to new disease-modifying therapies, recruitment of patients at an earlier stage of their disease into clinical trials may be an attractive strategy. Hence, there is a need to develop widely accepted classification criteria for early-stage knee osteoarthritis (OA). We have proposed a set of classification criteria for early-stage knee OA (2018 classification criteria) now being further refined. Here, we test the draft criteria for enrichment for clinical and structural progression. Design: Performance of the 2018 classification criteria for early stage knee OA was tested using data from the Osteoarthritis Initiative (OAI). The OAI comprises data of 4796 men and women aged 45–79 years with or at risk for knee OA at baseline. Based on the 2018 classification criteria, a knee with Kellgren & Lawrence (K&L) grade of 0-I, two out of four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales equal or less than 85, and presence of at least one of joint line tenderness or crepitus, was considered as early-stage knee OA. Knees with K&L grade 0-I that did not fulfill the 2018 criteria, were considered as controls. Logistic regression analysis was used to evaluate the predictive performance of the criteria set for structural as well as clinical progression. We further explored the discriminatory capability of criteria by including the average KOOS4 score, and relevant clinical examination findings such as the presence of effusion and/or Heberden's nodes. Results: We identified 1315 (27%) knees from OAI fulfilling the 2018 early-stage knee OA classification criteria. The female to male ratio was higher in the early knee OA group compared to controls. The early-stage knee OA group were on average slightly younger and had higher body mass index vs controls (mean [SD] age: 59.2 [8.9] years vs. 60.2 [9.1] and mean [SD] BMI 28.3 [7.0] vs. 26.8 [6.0]). By applying the 2018 criteria, there was a substantial enrichment compared to controls at 48 and 96 months for both structural (OR=1.1–1.4, and AUC=0.72–0.74) and clinical progressors (OR=2.1–2.5, 95% and AUC=0.66). Expanding the clinical examination findings by including joint effusion and/or Heberden's nodes improved the enrichment for both structural and clinical progressors (OR=4.2, 95% confidence interval=3.2–5.5 and OR=3.3, 95% confidence interval=2.8–3.5, respectively). Replacing scoring of the 4 separate KOOS domains by a KOOS4 score performed comparably. Conclusions: The proposed 2018 early-stage knee OA classification criteria showed encouraging performance characteristics with regard to an enrichment for structural and clinical progression using longitudinal OAI data. Our results indicate that the addition of clinical findings improves the performance of previous criteria to define early-stage disease and risk for progression.
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