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- Kerkhof, H. J. M., et al.
(author)
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Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
- 2011
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264
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Journal article (peer-reviewed)abstract
- Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 9. |
- Leyland, K. M., et al.
(author)
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Harmonising measures of knee and hip osteoarthritis in population-based cohort studies : an international study
- 2018
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 26:7, s. 872-879
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Journal article (peer-reviewed)abstract
- Objective: Population-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses. Method: International OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI). Results: OA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0–20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question. Conclusion: This research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts.
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| 11. |
- Fawole, H. O., et al.
(author)
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Is the association between physical activity and fatigue mediated by physical function or depressive symptoms in symptomatic knee osteoarthritis? The Multicenter Osteoarthritis Study
- 2021
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 50:5, s. 372-380
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Journal article (peer-reviewed)abstract
- Objectives: To examine whether physical activity (PA) was associated with fatigue, and quantify the extent of potential mediation through depressive symptoms or physical function (PF) on the relationship between PA and fatigue in symptomatic knee osteoarthritis (KOA). Method: This longitudinal study used data from the Multicenter Osteoarthritis Study (n = 484), comprising subjects aged ≥ 50 years. Baseline PA was quantified via an ankle-worn accelerometer. The outcome was fatigue, measured using a 0–10 rating scale at 2 year follow-up. Mediators included gait speed as a measure of PF and depressive symptoms at 2 year follow-up. Mediation analysis was carried out after adjustment for baseline confounders. Stratified analysis by baseline fatigue status [no/low (< 4) and high (≥ 4) fatigue] was performed. Results: A significant direct association was found between PA and fatigue at 2 years [unstandardized coefficient (B) = −0.054; 95% confidence interval (CI) −0.107, −0.002, p = 0.041]. The PA–fatigue relationship was not mediated by gait speed (B = −0.006; 95% CI −0.018, 0.001) or depressive symptoms (B = 0.009; 95% CI 0.009, 0.028). In the subgroup with high baseline fatigue, direct associations were found between PA and fatigue (gait speed model:, B = −0.107; 95% CI −0.212, −0.002, p = 0.046; depressive symptoms model: B = −0.110; 95% CI −0.120, −0.020, p = 0.017); but in the no/low baseline fatigue group, no significant association was found between PA and fatigue. Conclusion: In the symptomatic KOA population, higher baseline PA was directly associated with reduced fatigue 2 years later, especially in those with high baseline fatigue. However, this relationship was not mediated by depressive symptoms or PF.
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| 12. |
- Hayashi, D., et al.
(author)
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Knee malalignment is associated with an increased risk for incident and enlarging bone marrow lesions in the more loaded compartments: the MOST study
- 2012
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 20:11, s. 1227-1233
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Journal article (peer-reviewed)abstract
- Objective: To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs. Methods: Subjects from the Multicenter Osteoarthritis Study aged 50-79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and 30-month magnetic resonance imaging (MRI) of knees (n = 1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form 'more loaded' compartment, while lateral compartment in valgus and medial compartment in varus were combined to form 'less loaded' compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline. Results: Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment [adjusted RRs (95%CI): 1.5 (1.2-1.9)] and valgus alignment in the lateral compartment [1.4 (1.0-2.1)]. Increase in BML score was more likely in the more loaded compartments [1.7 (1.4-2.0)] in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees [0.8 (0.7-1.0)]. Conclusion: Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 13. |
- Podsiadlo, P., et al.
(author)
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Baseline trabecular bone and its relation to incident radiographic knee osteoarthritis and increase in joint space narrowing score : directional fractal signature analysis in the MOST study
- 2016
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 24:10, s. 1736-1744
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Journal article (peer-reviewed)abstract
- Purpose To explore the association of baseline trabecular bone structure with incident tibiofemoral (TF) osteoarthritis (OA) and with increase in joint space narrowing (JSN) score. Methods The Multicenter Osteoarthritis Study (MOST) includes subjects with or at risk for knee OA. Knee radiographs were scored for Kellgren–Lawrence (KL) grade and JSN at baseline, 30, 60 and 84 months. Knees (KL ≤ 1) at baseline were assessed for incident OA (KL ≥ 2) and increases in JSN score. For each knee image at baseline, a variance orientation transform method (VOT) was applied to subchondral tibial bone regions of medial and lateral compartments. Seventeen fractal parameters were calculated per region. Associations of each parameter with OA incidence and with medial and lateral JSN increases were explored using logistic regression. Analyses were stratified by digitized film (DF) vs computer radiography (CR) and adjusted for confounders. Results Of 894 knees with CR and 1158 knees with DF, 195 (22%) and 303 (26%) developed incident OA. Higher medial bone roughness was associated with increased odds of OA incidence at 60 and 84 months and also, medial and lateral JSN increases (primarily vertical). Lower medial and lateral anisotropy was associated with increased odds of medial and lateral JSN increase. Compared to DF, CR had more associations and also, similar results at overlapping scales. Conclusion Baseline trabecular bone texture was associated with incident radiographic OA and increase of JSN scores independently of risk factors for knee OA. Higher roughness and lower anisotropy were associated with increased odds for radiographic OA change.
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| 15. |
- Roemer, F. W., et al.
(author)
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The association of meniscal damage with joint effusion in persons without radiographic osteoarthritis: the Framingham and MOST osteoarthritis studies
- 2009
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 17:6, s. 748-753
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Journal article (peer-reviewed)abstract
- Objective: To assess the cross-sectional association between meniscal status and joint effusion on magnetic resonance imaging (MRI) in knees without radiographic osteoarthritis (OA). Design: Knees without OA (Kellgren/Lawrence grade 0) from the Framingham and MOST studies were examined by MRI. Meniscal status was assessed with a score of 0-4 in the anterior horn/body/posterior horn of the medial/lateral meniscus and effusion was assessed using a score of 0-3. The odds ratios (ORs) of joint effusion in those with meniscal damage were estimated using a logistic regression model. A sub-analysis was performed for knees without MRI-detected cartilage damage. Results: Of 1368 knees, 296 (21.6%) showed meniscal pathology in at least one subregion. Effusion was present in 133 (44.9%) of knees with meniscal damage vs 328 (30.6%) in those without meniscal damage. The adjusted OR of effusion in a knee with meniscal damage was 1.8, 95% confidence intervals (CI) [1.4, 2.4]. The OR of effusion for the group with meniscal pathology in two compartments was 5.4, 95% CI [2.1, 14.3]. For knees without any cartilage lesions but with meniscal damage in any compartment the OR was 2.3, 95% CI [1.1, 4.5]. Conclusions: Knees without OA but with meniscal pathology exhibit joint effusion to a significantly higher degree than knees without meniscal damage. The association persists for knees without cartilage damage. The prevalence of effusion is further increased when present in two compartments. Concomitant occurrence of synovial activation and meniscal damage contributes to understanding the pathophysiology of early degenerative joint disease. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 16. |
- Englund, Martin, et al.
(author)
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Effect of meniscal damage on the development of frequent knee pain, aching, or stiffness
- 2007
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 56:12, s. 4048-4054
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the effect of meniscal damage on the development of frequent knee pain, aching, or stiffness in middle-aged and older adults. METHODS: The Multicenter Osteoarthritis Study is a prospective study of 3,026 individuals 50 years of age or older who have or are at high risk of developing knee osteoarthritis (OA). We investigated knees at baseline and at 15 months. Case knees (n = 110) were those with no pain, aching, or stiffness on most days at baseline, but that had developed frequent pain, aching, or stiffness at 15 months. Control knees (n = 220) were drawn randomly from knees with no frequent symptoms at baseline that did not become case knees. Using 1.0T magnetic resonance imaging performed at baseline and at followup, 2 musculoskeletal radiologists blinded to the case-control status assessed the meniscal damage using the following scale: 0 = intact, 1 = minor tear, 2 = nondisplaced tear or prior surgical repair, and 3 = displaced tear, resection, maceration, or destruction. The effect of meniscal damage was analyzed by contingency tables and logistic regression. RESULTS: Meniscal damage was common at baseline both in case knees (38%) and in control knees (29%). Although there was a modest association between the meniscal damage score (range 0-3) and the development of frequent knee pain, aching, or stiffness (odds ratio [OR] 1.21, 95% confidence interval [95% CI] 0.96-1.51, adjusted for age, sex, and body mass index), meniscal damage was mostly present in knees with OA. When considering the co-occurrence of OA, we found no independent association between meniscal damage and the development of frequent knee symptoms (OR 1.05, 95% CI 0.80-1.37). CONCLUSION: In middle-aged and older adults, any association between meniscal damage and the development of frequent knee pain seems to be present because both pain and meniscal damage are related to OA and not because of a direct link between the two.
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| 17. |
- Evangelou, Evangelos, et al.
(author)
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A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
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Journal article (peer-reviewed)abstract
- Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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| 18. |
- Fawole, Henrietta O., et al.
(author)
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Determinants of generalized fatigue in individuals with symptomatic knee osteoarthritis : The MOST Study
- 2020
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In: International Journal of Rheumatic Diseases. - 1756-1841. ; 23:4, s. 559-568
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Journal article (peer-reviewed)abstract
- Aim: The aim of the study was to identify sociodemographic, disease-related, physical and mental health-related determinants of fatigue at 2-year follow-up in individuals with symptomatic knee osteoarthritis (OA). Methods: A longitudinal analysis of participants with symptomatic knee OA from the Multicenter Osteoarthritis Study (MOST) was conducted to identify predictors of fatigue at 2-year follow-up. Participants self-reported fatigue at baseline for the first time in the MOST cohort and at follow-up using a 0-10 visual analog scale. At baseline, questionnaires on sociodemographics, disease-related symptoms, physical and mental health factors were completed. Data were analyzed using linear regressions with a backwards elimination approach. Results: Of the 2330 individuals in the MOST cohort at baseline, 576 had symptomatic knee OA and of these, 449 with complete fatigue values at baseline and follow-up were included in this analysis. Minimally important fatigue change (ie, worsening [≥1.13], no change [<0.82 or <1.13] and improvement [≥−0.82]) from baseline to follow-up were unequal within the population (34.5%, 26.9%, 38.5%; χ2 [2, N = 449] = 9.32, P =.009). The multiple linear regression showed that baseline fatigue (unstandardized coefficient [Β] = 0.435; 95% confidence interval [CI] 0.348-0.523, P <.001), slow gait speed (Β = −1.124; 95% CI −1.962 to −0.285, P =.009), depressive symptoms (Β = 0.049; 95% CI 0.024-0.075, P <.001) and higher numbers of comorbidities (Β = 0.242; 95% CI 0.045-0.439, P =.016) were significant predictors of greater fatigue at follow-up. Conclusion: Fatigue is strongly associated with physical- and mental-related health factors. Individualized treatments that include combined psychological and physical function rehabilitation might be modalities for fatigue management.
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| 19. |
- Felson, David T., et al.
(author)
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Valgus Malalignment Is a Risk Factor for Lateral Knee Osteoarthritis Incidence and Progression Findings From the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative
- 2013
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 65:2, s. 355-362
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Journal article (peer-reviewed)abstract
- Objective. To study the effect of valgus malalignment on knee osteoarthritis (OA) incidence and progression. Methods. We measured the mechanical axis from long limb radiographs from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) to define limbs with valgus malalignment (mechanical axis of >= 1.1 degrees valgus) and examined the effect of valgus alignment versus neutral alignment (neither varus nor valgus) on OA structural outcomes. Posteroanterior radiographs and knee magnetic resonance (MR) images were obtained at the time of the long limb radiograph and at followup examinations. Lateral progression was defined as an increase in joint space narrowing (on a semiquantitative scale) in knees with OA, and incidence was defined as new lateral narrowing in knees without radiographic OA. We defined lateral cartilage damage and progressive meniscal damage as increases in cartilage or meniscus scores at followup on the Whole-Organ Magnetic Resonance Imaging Score scale (for the MOST) or the Boston Leeds Osteoarthritis Knee Score scale (for the OAI). We used logistic regression with adjustment for age, sex, body mass index, and Kellgren/Lawrence grade, as well as generalized estimating equations, to evaluate the effect of valgus alignment versus neutral alignment on disease outcomes. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). Results. We studied 5,053 knees (881 valgus) of subjects in the MOST cohort and 5,953 knees (1,358 valgus) of subjects in the OAI cohort. In both studies, all strata of valgus malalignment, including 1.1 degrees to 3 degrees valgus, were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment >3 degrees was associated with incidence (e. g., in the MOST, adjusted OR 2.5 [95% CI 1.0-5.9]). Valgus alignment >3 degrees was also associated with cartilage damage on MR imaging in knees without OA (e. g., in the OAI, adjusted OR 5.9 [95% CI 1.1-30.3]). We found a strong relationship of valgus malalignment with progressive lateral meniscal damage. Conclusion. Valgus malalignment increases the risk of knee OA radiographic progression and incidence as well as the risk of lateral cartilage damage. It may cause these effects, in part, by increasing the risk of meniscal damage.
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| 21. |
- Cotofana, S., et al.
(author)
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Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI
- 2013
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:9, s. 1214-1222
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Journal article (peer-reviewed)abstract
- Objective: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. Methods: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 +/- 9.6 yrs, BMI 29.4 +/- 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. Results: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% Cl 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 135-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. Conclusion: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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