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To identify and synthesise the content of knee bracing interventions in randomised controlled trials (RCTs) of knee osteoarthritis (OA). In this scoping review, three electronic databases (PubMed, Web of Science, Cochrane) were searched up to 10th June 2024. Nineteen previous systematic reviews of knee bracing for knee OA and four recent international clinical practice guidelines were also hand searched. Identified studies were screened for eligibility by two independent reviewers. Information on bracing interventions was extracted from included RCT reports, informed by Template for Intervention Description and Replication (TIDieR) guidelines. Data were synthesised narratively. Thirty-one RCTs testing 47 different bracing interventions were included. Braces were broadly grouped as valgus/varus, patellofemoral, sleeve, neutral hinged, or control/placebo knee braces. Brace manufacturer and models varied, as did amount of recommended brace use. Only three interventions specifically targeted brace adherence. Information on brace providers, setting, number of treatment sessions, and intervention modification over time was poorly reported. Adherence to brace use was described for 32 (68%) interventions, most commonly via self-report. Several mechanisms of action for knee braces were proposed, broadly grouped as biomechanical, neuromuscular, and psychological. Many different knee brace interventions have been tested for knee OA, with several proposed mechanisms of action, a lack of focus on adherence, and a lack of full reporting. These issues may be contributing to the heterogeneous findings and inconsistent guideline recommendations about the clinical effectiveness of knee bracing for knee OA to date. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) drug development is hampered by a number of challenges. One of the main challenges is the apparent discordance between pain and structure, which has had a significant impact on drug development programs and has led to hesitance among stakeholders. Since 2017, the Clinical Trials Symposium (CTS) has been hosted under the Osteoarthritis Research Society International (OARSI) leadership. OARSI and the CTS steering committee yearly invite and encourage discussions on selected special subject matter between regulators, drug developers, clinicians, clinical researchers, biomarker specialists, and basic scientists to progress drug development in the OA field. The main topic for the 2022 OARSI CTS was to elucidate the many facets of pain in OA and to enable a discussion between regulators (Food and Drug Administration (FDA) and the European Medicines Agency (EMA)) and drug developers to clarify outcomes and study designs for OA drug development. Signs or symptoms indicative of nociceptive pain occur in 50–70% of OA patients, neuropathic-like pain in 15–30% of patients, and nociplastic pain in 15–50% of patients. Weight-bearing knee pain is associated with bone marrow lesions and effusions. There are currently no simple objective functional tests whose improvements correlate with patient perceptions. The CTS participants, in collaboration with the FDA and EMA, raised several suggestions that they consider key to future clinical trials in OA including the need for more precise differentiation of pain symptoms and mechanisms, and methods to reduce placebo responses in OA trials. [ABSTRACT FROM AUTHOR]

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 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 OSTeoArthritis in Secondary care (HOSTAS) cohort were studied. Severity of morning stiffness were examined with Australian/Canadian hand OA index (AUSCAN) and presence and duration of morning stiffness was 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. [ABSTRACT FROM AUTHOR]

Introduction: Higher intake of fiber has been associated with lower risk of incident symptomatic osteoarthritis (OA). We examined whether levels of alkylresorcinol (AR), a marker of whole grain intake, were associated with OA in subjects in The Multicenter Osteoarthritis (MOST) Study.Method: Knee x-rays and knee pain were assessed at baseline and through 60-months. Stored baseline fasting plasma samples were analyzed for AR homologues (C17:0, C19:0, C21:0, C23:0, C25:0) and total AR levels (AR sum). Two nested case-control studies, one for incident radiographic OA and one for incident symptomatic OA were performed with participants re-assessed at 15, 30 and 60 months. Multivariable conditional logistic regression with baseline covariates including age, sex, BMI, physical activity, quadriceps strength, race, smoking, depressive symptoms, diabetes and knee injury tested the association of log transformed AR levels with OA outcomes.Results: Seven hundred seventy-seven subjects were, on average, in their 60's, and most were women. For 60-month cumulative incidence, there was no significant association between quartiles of AR concentration and incident radiographic (e.g., for incident radiographic OA, highest vs lowest quartile of AR sum showed RR = 0.93 (95% CI 0.59, 1.47), and for symptomatic OA RR was 1.22 (95% CI 0.76, 1.94). In secondary analyses examining 30-month incidence, high AR levels were associated with a reduced risk of X-ray OA (RR = 0.31 (95% CI 0.15, 0.64).Conclusion: In primary analyses, AR levels were not associated with risk of OA, but secondary analyses left open the possibility that high AR levels may protect against OA. [ABSTRACT FROM AUTHOR]

Objectives: To determine how many persons with knee pain have subsequent pain resolution and what factors are associated with resolution, focusing especially on types of physical activity.Methods: Using data from MOST, an NIH funded longitudinal cohort study of persons with or at risk of knee osteoarthritis, we studied participants who at baseline reported knee pain on most days at both a telephone interview and clinic visit. We defined pain resolution if at 30 and 60 month exams, they reported no knee pain on most days and compared these participants to those who reported persistent pain later. In logistic regression analyses, we examined the association of baseline risk factors including demographic factors, BMI, depressive symptoms, isokinetic quadriceps strength and both overall physical activity (using the PASE survey) and specific activities including walking, gardening, and different intensities of recreational activities with pain resolution.Results: Of 1,304 participants with knee pain on most days at baseline, 265 (20.3%) reported no knee pain at 30 and 60 months. Lower BMI and stronger quadriceps were associated with higher odds of pain resolution while overall physical activity was not. Of activities, walking decreased the odds of pain resolution (adjOR = 0.86 (95% CI 0.76, 0.98)), but gardening (adjOR = 1.59 (1.16, 2.18)) and moderate intensity recreational activities ((adjOR = 1.24 (1.05, 1.46)) increased it.Conclusion: Pain resolution is common in those with knee pain. Factors increasing the odds of pain resolution include lower BMI, greater quadriceps strength and gardening and moderately intensive recreational activities. [ABSTRACT FROM AUTHOR]

Objective: Intra-articular (IA) injections of glucocorticoids (GCs) have been shown to decrease pain, increase mobility, and improve quality of life in patients with osteoarthritis (OA) of the knee. Concerns about cartilage loss with IA GCs have prompted reconsideration of their use in knee OA. This review has three objectives: 1) critically review the clinical, molecular, and structural effects of IA GCs in knee OA; 2) provide a design for a clinical trial aimed at improving our understanding of the long-term consequences of IA GCs; and 3) provide practical guidance on the use of IA GCs in patients with knee OA based on current information.Design: A narrative review of current literature on the use of IA GCs for OA of the knee.Results: Important questions remain to be fully answered with respect to IA GCs, including long-term effects on all aspects of the structural and molecular environment of the knee, and identification of factors that can reliably predict a positive or negative response to IA GCs.Conclusions: While awaiting results from an appropriately designed study, several provisional statements regarding IA GCs can be put forward: 1) IA GCs appear to be a relatively safe option that is effective in specific patients with symptomatic knee OA; 2) there is no definitive evidence that IA GCs accelerate joint deterioration to an important extent or hastens the requirement for knee replacement; and 3) there are few contraindications to IA GCs and injection-associated complications are rare when IA GCs are delivered with proper technique. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later.Method: Individuals from a prospective cohort of individuals aged 50-79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA.Results: Relative to knees without lateral meniscal pathology at baseline, those with grades 3-4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 [95% CI: 1.1-2.7) and (1.7 [1.2-2.5]), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1-2 (0.6 [0.4-0.9]) and 3-4 (0.7 [0.5-1.0]) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later.Conclusion: Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ. [ABSTRACT FROM AUTHOR]

Objective: To investigate associations between lower levels of muscle strength, physical performance and physical activity and the risk of knee replacement (KR) in older adults with frequent knee pain.Method: Participants from the Multicenter Osteoarthritis Study (MOST) with knee pain on most of the past 30 days at baseline were included (n = 1257; mean (SD) age of 62.2 (8.2)). We examined the association between (1) baseline peak isokinetic knee extensor strength, (60°/sec, maximum out of four trials), (2) best time to stand in timed chair stand (2 trials of five repetitions), and (3) baseline Physical Activity Scale for the Elderly score (PASE) with incident KR between baseline and the 84-month follow-up.Results: 1252 (99.6%) participants (1682 knees) completed the follow-up visits. 331 participants (394 knees) underwent a KR during the 84 months (229 women and 102 men). The crude analysis demonstrated a decreased risk of KR in women (P < 0.0001) with higher knee extensor strength (Hazard Ratio (HR; 95% CI) 0.99 (0.98-0.99)). The risk remained significant (P = 0.03) when adjusting for age, BMI, race, clinic site, education, occupation, previous knee injury, previous knee surgery, and WOMAC pain (HR (95% CI) 0.99 (0.99-1.00)), but not when adjusting for Kellgren-Lawrence grade (P = 0.97).Conclusion: Lower levels of chair stand performance and self-reported physical activity are not associated with an increased risk of KR within 7 years, while the independent effect of knee extensor strength on risk for KR in women is non-significant after adjusting for radiographic severity. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that quantitative measures of meniscus extrusion predict incident radiographic knee osteoarthritis (KOA), prior to the advent of radiographic disease.Methods: 206 knees with incident radiographic KOA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline, developing KLG 2 or greater with a definite osteophyte and joint space narrowing (JSN) grade ≥1 by year 4) were matched to 232 control knees not developing incident KOA. Manual segmentation of the central five slices of the medial and lateral meniscus was performed on coronal 3T DESS MRI and quantitative meniscus position was determined. Cases and controls were compared using conditional logistic regression adjusting for age, sex, BMI, race and clinical site. Sensitivity analyses of early (year [Y] 1/2) and late (Y3/4) incidence was performed.Results: Mean medial extrusion distance was significantly greater for incident compared to non-incident knees (1.56 mean ± 1.12 mm SD vs 1.29 ± 0.99 mm; +21%, P < 0.01), so was the percent extrusion area of the medial meniscus (25.8 ± 15.8% vs 22.0 ± 13.5%; +17%, P < 0.05). This finding was consistent for knees restricted to medial incidence. No significant differences were observed for the lateral meniscus in incident medial KOA, or for the tibial plateau coverage between incident and non-incident knees. Restricting the analysis to medial incident KOA at Y1/2 differences were attenuated, but reached significance for extrusion distance, whereas no significant differences were observed at incident KOA in Y3/4.Conclusion: Greater medial meniscus extrusion predicts incident radiographic KOA. Early onset KOA showed greater differences for meniscus position between incident and non-incident knees than late onset KOA. [ABSTRACT FROM AUTHOR]

Objective: To determine what MRI-detectable osteoarthritis features that are not visualized on radiography demonstrate progression longitudinally in Kellgren and Lawrence (KL) grade 4 knees.Methods: We studied subjects from the Multicenter Osteoarthritis Study who had KL grade 4 knees at baseline and had baseline and 30-month MRI. Cartilage damage, bone marrow lesions (BMLs), meniscal damage, synovitis (signal changes in Hoffa fat pad), and effusion (fluid equivalent signal in the joint cavity) were semiquantitatively scored using the Whole Organ MRI Score (WORMS) system in five subregions of the medial and lateral tibiofemoral (TF) compartments. Analysis was performed for the compartment showing bone-on-bone appearance ("index") on radiograph and also for the other TF compartment of the same knee. Synovitis and effusion were assessed for the whole knee. Changes in scores at follow-up were noted for each feature. For cartilage and BML, within-grade changes were also recorded.Results: 140 subjects (164 knees) were included (50% women, mean age 66.0 ± 8.6 years, mean BMI 30.4 ± 5.1 kg/m(2)). Longitudinally, 51 index compartments (34%) showed an increase in the sum of cartilage scores from all subregions. In the other compartment, 25% showed an increase in the sum score for cartilage damage. For BMLs in the index compartment, 50 knees (33%) showed an increase in maximum score and 32 (21%) showed a decrease. Meniscal status mostly remained stable. Effusion worsened in 36 knees (25%) and improved in 13 knees (9%). Synovitis worsened in 14 knees (10%) and improved in six knees (4%).Conclusion: In KL grade 4 knees, MRI-detected cartilage loss and fluctuation of BMLs, effusion, and synovitis occurred frequently over a 30-month period. [ABSTRACT FROM AUTHOR]

Purpose: To determine the association of MRI-assessed worsening of tibiofemoral cartilage damage, meniscal damage, meniscal extrusion, separately and together, with progression of radiographic joint space narrowing (JSN).Method and Materials: The Multicenter Osteoarthitis Study (MOST) Study is a cohort study of subjects with or at risk for knee osteoarthritis (OA). Knees with radiographic OA Kellgren-Lawrence grade 2 at baseline and with baseline and 30-month 1.0 T MRIs were selected for reading using the WORMS system for cartilage damage, meniscal damage, and meniscal extrusion. The association of worsening of cartilage damage, meniscal damage, and/or meniscal extrusion with increases in the JSN was performed using logistic regression.Results: A total of 276 knees (one per subject) were included (women 68.5%, mean age 62.9 ± 7.8, mean body mass index (BMI) 30.2 ± 5.0). Worsening of each MRI feature was associated with any increase in JSN (P < 0.01). Worsening of cartilage damage was more frequently observed than worsening of meniscal damage and extrusion, and was significantly associated with both slow and fast progression of JSN. An increasing risk of JSN worsening was associated with increasing number of worsening MRI features (P for trend < 0.0001).Conclusion: Worsening of tibiofemoral cartilage damage, meniscal damage, and meniscal extrusion are independent predictors of JSN progression in the same compartment. Worsening of cartilage damage is more frequently observed in JSN when compared to meniscal worsening. A strong cumulative effect on JSN progression is observed for worsening of more than one MRI feature. [ABSTRACT FROM AUTHOR]

Objective To determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA). Design and methods A cross-sectional analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren-Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA). Results Women reported higher VAS pain at all KL grades in unadjusted analyses (d = 0.21-0.31, P < 0.0001-0.0038) and in analyses adjusted for all covariates except WSP (d = 0.16-0.22, P < 0.0001-0.0472). Pain severity differences further decreased with adjustment for WSP (d = 0.10-0.18) and were significant for KL grade ≤2 (P = 0.0015) and 2 (P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades (d = 0.32-0.52, P < 0.0001-0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade (d = 0.45-0.62, P = 0.0006-0.0030) and remained significant for all KL grades in adjusted analyses (d = 0.31-0.57, P = 0.0013-0.0361). Results using WOMAC were similar. Conclusions Women reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences. [ABSTRACT FROM AUTHOR]

Summary: Background: Previous studies suggest that the antioxidants vitamins C and E may protect against development of knee osteoarthritis (OA). We examined the association of circulating levels of vitamin C and E with incident whole knee radiographic OA (WKROA). Methods: We performed a nested case–control study of incident WKROA in MOST, a cohort of 3,026 men and women aged 50–79 years with, or at high risk of, knee OA. Incident cases were knees without either tibiofemoral (TF) or patellofemoral (PF) OA at baseline that developed TF and/or PF OA by 30-month follow-up. Two control knees per case were selected from those eligible for WKROA that did not develop it. Vitamin C and E (alpha-tocopherol) assays were done on baseline supernatant plasma (PCA) and serum samples, respectively. We examined the association of gender-specific tertiles of vitamin C and E with incident WKROA using logistic regression with GEE, adjusting for age, gender, and obesity. Results: Subjects without WKROA at baseline who were in the highest tertile of vitamin C had a higher incidence of WKROA [adjusted OR = 2.20 (95% CI: 1.12–4.33); P-value = 0.021], with similar results for the highest tertile of vitamin E [adjusted OR = 1.89 (1.02–3.50); P-value = 0.042], compared to those in the lowest tertiles. P-values for the trend of vitamin C and E tertiles and incident WKROA were 0.019 and 0.030, respectively. Conclusions: Higher levels of circulating vitamin C and E did not provide protection against incident radiographic knee OA, and may be associated with an increased risk of knee OA. [Copyright &y& Elsevier]

Objective: To determine which subregions of the knee joint have a high prevalence of pre-radiographic osteoarthritic changes, i.e., cartilage damage and osteophytes that can only be detected by magnetic resonance imaging (MRI), in radiographically normal knees.Methods: Institutional Review Board approval and written informed consent from all participants was obtained. Data was collected from a community cohort in Framingham, MA, involving people aged 50-79. Participants underwent weight-bearing posteroanterior and lateral knee radiography with the fixed-flexion protocol, and 1.5 T MRI. Knees without radiographic osteoarthritis (Kellgren Lawrence grade 0 for the tibiofemoral joint and absence of any osteophytes or joint space narrowing in the patellofemoral joint) were included. The knee joint was divided into 14 subregions for cartilage and 16 subregions for osteophytes, and prevalence and severity of cartilage damage (grade 0-6) and osteophytes (grade 0-7) were semiquantitatively assessed using the Whole Organ Magnetic Resonance Imaging Score (WORMS).Results: The mean age of 696 participants was 62.3 ± 8.4 years, and the mean body mass index was 27.9 ± 5.1 kg/m2. Women comprised 55.2% of the study sample (384/696). Prevalence of cartilage damage (grade ≥2) was 47.7% (332/696) in the medial patellar and 29.9% (208/696) in patellar lateral (PL) subregions, and 24.0% (167/696) in femoral medial anterior (FMA) and 26.5% (184/696) in femoral medial central (FMC) subregions. Prevalence of osteophytes (grade ≥2) was highest at 60.8% (423/696) in the medial femoral posterior subregion, followed by 34.0% (237/696) in PL and 24.6% (171/696) in patellar medial (PM) subregions. For all other subregions, prevalence of these lesions was lower than the aforementioned percentages.Conclusion: MRI-detected cartilage damage and osteophytes are highly prevalent in the medial patellofemoral and medial posterior tibiofemoral joints in radiographically normal knees in persons aged 50-79. [ABSTRACT FROM AUTHOR]

Objectives: Knee osteoarthritis (OA) is thought to be a slowly evolving disease with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years with evidence that over 6 months change in cartilage is not detectable. In contrast to cartilage, bone has the capacity to adapt rapidly, such as after fracture. We tested whether bone marrow lesions (BMLs) change in volume in 6 and 12 weeks, suggesting they may provide evidence of short term fluctuations of joint damage.Methods: In 62 patients with patellofemoral knee OA (mean age 55.7 years, 59.7% women, mean BMI 31.0), we obtained baseline, 6 and 12 week knee MRIs with contrast enhancement. Of those with BMLs at baseline, we assessed BML volume on the axial proton density fat saturated (FS) images and postcontrast sagittal T1 weighted FS images. We manually segmented BML volumes, testing repeatability of BML volumes in knees remeasured. Using the standard deviation of the difference between repeated measurements to calculate Bland-Altman Limits of Agreement, we determined how much BML volume change represented a change greater than due to chance.Results: Fifty-two patients had BMLs at baseline. Test-retest reliability for BML volume was high (ICC 0.89, 95% CI 0.80-0.97). All knees showed at least some change in BML volume by 6 and 12 weeks. On the axial view at 6 weeks, 20/49 (40.8%) knees showed BML volume changes greater than the limits of agreement with similar results at 12 weeks. BML changes were evenly divided among knees with enlarging and shrinking BMLs. 63.3% of the knees had more than 50% change in BML volume at either 6 or 12 weeks on the axial view and 48.7% on the sagittal view.Conclusions: Knee BML volumes change in several weeks in many persons with knee OA. To the extent that they could be regarded as treatment targets, trials testing BML effects could avoid the usual prolonged structure modification trials. [ABSTRACT FROM AUTHOR]

Objective: In order to increase sensitivity to detect longitudinal change, recording of within-grade changes was introduced for cartilage morphology and bone marrow lesion (BML) assessment in semiquantitative magnetic resonance imaging (MRI) scoring of knee osteoarthritis (OA). The aim of this study was to examine the validity provided by within-grade scoring.Design: The Multicenter Osteoarthritis (MOST) study is a longitudinal study of subjects with or at risk of knee OA. Baseline and 30 months MRIs were read according to the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system including within-grade changes for cartilage and BMLs. We tested the validity of within-grade changes by whether the 30-month changes in cartilage and BML assessment were predicted by baseline ipsi-compartmental meniscal damage and malalignment, factors known to affect cartilage loss and BMLs, using ordinal logistic regression.Results: 1867 Knees (from 1411 participants) were included. Severe medial meniscal damage predicted partial grade (adjusted odds ratio (aOR) 4.4, 95% confidence interval (95% CI) 2.2, 8.7) but not ≥full grade (aOR 1.3, 95% CI 0.8, 2.2) worsening of cartilage loss and predicted both, partial grade (aOR 9.6, 95% CI 3.6, 25.1) and ≥full grade (aOR 5.1, 95% CI 3.2, 8.2) worsening of BMLs. Severe, but not moderate, malalignment predicted ipsi-compartmental within-grade (medial cartilage damage: aOR 5.5, 95% CI 2.6, 11.6; medial worsening of BMLs: aOR 4.9, 95% CI 2.0, 12.3) but not full grade worsening of BMLs and cartilage damage.Conclusions: Within-grade changes in semiquantitative MRI assessment of cartilage and BMLs are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures. [ABSTRACT FROM AUTHOR]

Summary: Purpose: The number of effective knee osteoarthritis (OA) interventions, especially those tailored to specific compartmental involvement, are small. The objective of this study was to determine the efficacy of a realigning patellofemoral (PF) brace in improving pain and function among persons with symptomatic lateral PF OA. Method: We conducted a double blind, randomized crossover trial of a realigning PF brace for persons with lateral PF OA. Participants had lateral PF OA with anterior knee symptoms on most days of the month, lateral PF joint space narrowing, and radiographic evidence of a definite osteophyte in the PF joint. We compared two treatments: (1) Control treatment consisting of a BioSkin Q Brace with patellar realigning strap removed; and (2) Active treatment consisting of a realigning BioSkin Q Brace with the strap applied. For each participant, the trial lasted 18 weeks, including 6 weeks each of active and control treatment period separated by a 6-week washout period. The order of treatments was randomized. The primary outcome was change in knee pain on the visual analog scale (VAS). Secondary outcomes included WOMAC pain, function, and stiffness. An unstructured correlation matrix for observations within participants was used in generalized estimating equation fitting to derive a linear regression model that expressed the relation between the intervention and change in VAS pain. Results: 80 participants (63 F) with a mean age and body mass index of 61 years and 28kg/m2, respectively, were randomized by order of treatment. A model examining the main effects for change in VAS knee pain (0–100) demonstrated no significant treatment effect (−0.68 VAS units, 95% CI: −6.2, 4.8 units, P =0.81) and no differential carryover effect. There was also no significant difference between active and control treatments for WOMAC pain, function, or stiffness outcomes. Conclusion: The effects of a specific realigning PF brace are not of clinical or statistical significance. NIH Clinical Trials Registry NCT00381563 [Copyright &y& Elsevier]

Summary: 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 =3×10−9). 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. [Copyright &y& Elsevier]

Summary: Objective: Researchers commonly use the femoral shaft–tibial shaft angle (FS–TS) from knee radiographs to estimate the hip-knee-ankle angle (HKA) in studies examining risk factors for knee osteoarthritis (OA) incidence and progression. The objective of this study was to determine the relationship between HKA and FS–TS, depending on the method of calculating FS–TS and the direction and degree of knee deformity. Methods: 120 full-length digital radiographs were assigned, with 30 in each of four alignment groups (0.0°–4.9°, and ≥5.0° of varus and valgus), from a large cohort of persons with and at risk of knee OA. HKA and five measures of FS–TS (using progressively shorter shaft lengths) were obtained using Horizons Analysis Software, Orthopaedic Alignment & Imaging Systems Inc. (OAISYS). The offsets between HKA and the different versions of FS–TS were calculated, with 95% confidence intervals (CIs). Pearson correlations were calculated. Results: In varus limbs use of a shorter shaft length increased the offset between HKA and FS–TS from 5.1° to 7.0°. The opposite occurred with valgus limbs (from 5.0° to 3.7°). Correlations between HKA and FS–TS for the whole sample of 120 individuals were excellent (r range 1.00–0.88). However, correlations for individual alignment groups were low to moderate, especially for the shortest-shaft FS–TS (r range 0.41–0.66). Conclusions: The offsets obtained using the shorter FS–TS measurements vary depending on direction and degree of knee deformity, and therefore may not provide reliable predictions for HKA We recommend that full-length radiographs be used whenever an accurate estimation of HKA is required, although broad categories of alignment can be estimated with FS–TS. [ABSTRACT FROM AUTHOR]

Objective: To establish sex-specific (subregional) reference values of cartilage thickness and potential maximal Z-scores in the femorotibial joint.Methods: The mean cartilage thickness (ThCtAB.Me) in femorotibial compartments, plates and subregions was determined on coronal magnetic resonance imaging (MRI) from a population-based sample (Framingham) and from a healthy reference sample of the Osteoarthritis Initiative (OAI).Results: 686 Framingham participants (309 men, 377 women, age 62 ± 8 years) had no radiographic femorotibial osteoarthritis (OA) ("normals") and 376 (156 men, 220 women) additionally had no MRI features of cartilage lesions ("supernormals"). The Framingham "normals" had thinner cartilage in the medial (3.59 mm) than in the lateral femorotibial compartment (3.86 mm). Medially, the femur displayed thicker cartilage (1.86 mm) than the tibia (1.73 mm), and laterally the tibia thicker cartilage (2.09 mm) than the femur (1.77 mm). The thickest cartilage was observed in central, and the thinnest in external femorotibial subregions. Potential maximal Z-scores ranged from 5.6 to 9.8 throughout the subregions; men displayed thicker cartilage but similar potential maximal Z-scores as women. Mean values and potential maximal Z-scores in Framingham "supernormals" and non-exposed OAI reference participants (112 participants without symptoms or risk factors of knee OA) were similar to Framingham "normals".Conclusions: We provide reference values and potential maximal Z-scores of cartilage thickness in middle aged to elderly non-diseased populations without radiographic OA. Results were similar for "supernormal" participants without MRI features of cartilage lesions, and in a cohort without OA symptoms or risk factors. A cartilage thickness loss of around 27% is required for attaining a Z-score of -2. [ABSTRACT FROM AUTHOR]

Summary: Objective: Magnetic resonance imaging (MRI) has greater sensitivity to detect osteoarthritis (OA) damage than radiographs but it is uncertain which MRI findings in early OA are clinically important. We examined MRI abnormalities detected in knees without radiographic OA and their association with incident knee symptoms. Method: Participants from the Multicenter Osteoarthritis Study (MOST) without frequent knee symptoms (FKS) at baseline were eligible if they also lacked radiographic features of OA at baseline. At 15 months, knees that developed FKS were defined as cases while control knees were drawn from those that remained without FKS. Baseline MRIs were scored at each subregion for cartilage lesions (CARTs); osteophytes (OST); bone marrow lesions (BML) and cysts. We compared cases and controls using marginal logistic regression models, adjusting for age, gender, race, body mass index (BMI), previous injury and clinic site. Results: 36 case knees and 128 control knees were analyzed. MRI damage was common in both cases and controls. The presence of a severe CART (P =0.03), BML (P =0.02) or OST (P =0.02) in the whole knee joint was more common in cases while subchondral cysts did not differ significantly between cases and controls (P >0.1). Case status at 15 months was predicted by baseline damage at only two locations; a BML in the lateral patella (P =0.047) and at the tibial subspinous subregions (P =0.01). Conclusion: In knees without significant symptoms or radiographic features of OA, MRI lesions of OA in only a few specific locations preceded onset of clinical symptoms and suggest that changes in bone play a role in the early development of knee pain. Confirmation of these findings in other prospective studies of knee OA is warranted. [Copyright &y& Elsevier]

Objective: To date semiquantitative whole-organ scoring of knee osteoarthritis (OA) relies on 1.5 Tesla (T) Magnetic resonance imaging (MRI) systems. Less costly 1.0 T extremity systems have been introduced that offer superior patient comfort, but may have limitations concerning field-of-view and image quality. The aim of this study was to compare semi-quantitative (SQ) scoring on a 1.0 T system using 1.5 T MRI as the standard of reference.Methods: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of individuals who have or are at high risk for knee OA. A sample of 53 knees was selected in which MRI was performed on a 1.0 T extremity system as well as on a 1.5 T scanner applying a comparable sequence protocol. MRIs were read according to the Whole Organ Magnetic Resonance Imaging Score (WORMS) score. Agreement was determined using weighted kappa statistics. Sensitivity, specificity and accuracy were assessed using the 1.5 T readings as the reference standard. In addition the number of non-readable features was assessed.Results: Agreement (w-kappa) for seven main WORMS features (cartilage, bone marrow lesions (BMLs), osteophytes, meniscal damage and extrusion, synovitis, effusion) ranged between 0.54 (synovitis) and 0.75 (cartilage). Sensitivity ranged between 68.1% (meniscal damage) and 88.1% (effusion). Specificity ranged between 63.6% (effusion) and 96.4% (BMLs). Although the overall rate of non-readable features was very low, it was higher for the 1.0 T system (1.9% vs 0.2%).Conclusions: Semiquantitative whole organ scoring can be performed using a 1.0 T peripheral scanner with a moderate to high degree of agreement and accuracy compared to SQ assessment using a 1.5 T whole body scanner. Our results are comparable to the published inter- and intra observer exercises obtained from 1.5 T systems. Sensitivity to change of longitudinal scoring was not evaluated in this cross-sectional design and should be investigated in future validation studies. [ABSTRACT FROM AUTHOR]

Objective: Magnetic resonance imaging (MRI) of articular cartilage has evolved to be an important tool in research on cartilage (patho)physiology and osteoarthritis (OA). MRI provides a wealth of novel and quantitative information, but there exists no commonly accepted terminology for reporting these metrics. The objective of this initiative was to propose a nomenclature for definitions and names to be used in scientific communications and to give recommendations as to which minimal methodological information should be provided when reporting MRI-based measures of articular cartilage in OA.Methods: An international group of experts with direct experience in MRI measurement of cartilage morphology or composition reviewed the existing literature. Through an iterative process that included a meeting with a larger group of scientists and clinicians (December 2nd, 2004, Chicago, IL, USA), they discussed, refined, and proposed a nomenclature for MRI-based measures of articular cartilage in OA.Results: The group proposes a nomenclature that describes: (1) the anatomical location and (2) the structural feature being measured, each name consisting of a metric variable combined with a tissue label. In addition, the group recommends minimal methodological information that should be described.Conclusions: Utilization of this nomenclature should facilitate communication within the scientific community. Further, the uniform adoption of comprehensive nomenclature to describe quantitative MRI- features of articular cartilage should strengthen epidemiological, clinical, and pharmacological studies in OA. [ABSTRACT FROM AUTHOR]

Objective: Osteoarthritis (OA) biomarkers are needed by researchers and clinicians to assist in disease diagnosis and assessment of disease severity, risk of onset, and progression. As effective agents for OA are developed and tested in clinical studies, biomarkers that reliably mirror or predict the progression or amelioration of OA will also be needed.Methods: The NIH-funded OA Biomarkers Network is a multidisciplinary group interested in the development and validation of OA biomarkers. This review summarizes our efforts to characterize and classify OA biomarkers.Results: We propose the "BIPED" biomarker classification (which stands for Burden of Disease, Investigative, Prognostic, Efficacy of Intervention and Diagnostic), and offer suggestions on optimal study design and analytic methods for use in OA investigations.Conclusion: The BIPED classification provides specific biomarker definitions with the goal of improving our ability to develop and analyze OA biomarkers, and to communicate these advances within a common framework. [ABSTRACT FROM AUTHOR]

Summary: Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)–Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy. [Copyright &y& Elsevier]