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Objective: We evaluated whether patient-reported outcome trajectories (i.e., changes over time) differed by intraoperative compartmental cartilage lesion pattern over 4–6 years following arthroscopic meniscal surgery. Methods: In this ancillary study of the Knee Arthroscopy Cohort Southern Denmark cohort, we intraoperatively categorized cartilage lesions as isolated patellofemoral, isolated tibiofemoral, or combined patellofemoral/tibiofemoral. Participants completed the Knee injury and Osteoarthritis Outcome Score (KOOS) pre-operatively, at 3 and 12 months, and at 4–6 years post-operatively and reported overall satisfaction at final follow-up. Our main outcome was KOOS4 (grand mean of four subscale means). We evaluated whether KOOS4 scores changed over time according to cartilage lesion patterns using adjusted mixed linear regression. We also estimated probability of treatment satisfaction using logistic regression. Results: Of 630 participants with complete cartilage scores, 280 (44%) were women, mean (standard deviation) age was 49 (13) years, and BMI was 27.3 (4.4) kg/m2. KOOS4 scores at baseline were slightly lower in all lesion groups compared to the no lesion group, yet only the combined group was statistically significantly lower. KOOS4 trajectories were similar across cartilage lesion patterns, but by final follow-up, adjusted mean KOOS4 scores were 6.8 (95% CI 2.2, 11.4) to 9.8 (1.1, 18.5) points lower in groups with cartilage lesions compared to the no lesion group. Probability of patient-reported satisfaction did not differ statistically by group. Conclusions: Though KOOS4 scores were slightly lower in groups with arthroscopically assessed cartilage lesions compared to the no lesion group, trajectories were similar across all groups.

Summary Objectives To study bone shape changes as a potential early feature of post-traumatic structural knee OA development, we estimated the association between meniscal status in the anterior cruciate ligament (ACL) injured knee and longitudinal condyle changes in bone surface area. Design We used data from the KANON trial, including 121 young ACL-injured adults. We obtained baseline and 2-year follow-up knee MRIs. Our outcome was change in the bone surface areas (mean mm2, log-transformed) in 4 locations (femur, tibia, patella, and trochlea femur) in the medial and lateral compartment from baseline to 2 years. Meniscal pathology was defined as both present at baseline and newly developed (i.e., incident or progressed) using ACLOAS. We used multilevel linear regression adjusted for baseline bone area, age, sex, body mass index, treatment arm (i.e., early or optional delayed ACL reconstruction), and location. We analyzed medial and lateral compartment separately. We present results as percentage (%) bone area change difference with 95% confidence intervals (CI). Results We analyzed 109 subjects (median 27 (18–36) years, 83% men) due to missing MRI information. The bone surface area increased on average by ∼2% over 2 years. The differences between knees with and without baseline meniscal pathology were 1.1% (95%CI 0.0–2.3%) and 1.4% (95%CI 0.6–2.2%) in the medial and lateral compartment, respectively, and 1.2% (95%CI 0.3–2.0%) and 1.3% (95%CI 0.6–2.0%) for medial and lateral newly developed pathology, respectively. Conclusion Our finding of ∼1% increase bone area in compartment with meniscal pathology suggests a potentially important association between meniscal integrity and early bone surface area changes after ACL injury. Trial registration number ISRCTN 84752559.

Summary: Objective: To investigate to what extent individuals participated in guideline-based first-line treatments before being assigned to a wait list for knee replacement for osteoarthritis (OA), and to what extent they were recommended such treatments once on the list. Factors associated with participation in first-line management were also investigated. Design: All patients on the waiting list ≥ three months for knee replacement due to knee OA (n = 229) at a public hospital in Sweden were invited to participate in this cross-sectional survey study. 136 individuals (mean age 70 ± 9 years, 59% women) answered self-reported questionnaires including demographics, physical activity level, knee function and treatments before and during their time on the waiting list. Results: Before being referred to the waiting list, 40% had participated in guideline-based OA management (Better management of patients with OsteoArthritis (BOA)), 53% in physiotherapy, 67% in either BOA or physiotherapy whilst 23% of those overweight (BMI≥25) had received weight-management advice. Women had participated in BOA and physiotherapy twice as often as men (51% vs. 25%, p = 0.002 and 66% vs. 34%, p

Background: The Hip disability and Osteoarthritis Outcome Score (HOOS) is a self-administered hip-specific questionnaire intended to evaluate symptoms and functional limitations, and it is commonly used to evaluate interventions in individuals with hip dysfunction or hip osteoarthritis. The HOOS consists of 43 questions in five subscales: Pain, Symptoms, Function in daily living, Function in sport and recreation and Hip-Related Quality of Life. This study aimed to establish population-based reference values for the HOOS and to describe the variation of hip-related symptoms in an adult population. Methods: The HOOS questionnaire was mailed to 840 individuals aged 18-84 years randomly retrieved from a national population record for the Skåne region of Southern Sweden. Results: The overall response rate was 67%. Older women and men consistently reported more hip-related complaints than those younger. There were significant differences between the oldest and the youngest age groups in all five subscales in women and men. Conclusions: Hip-related pain, symptoms, activity of daily life and quality of life varied with age and sex in this population-based cohort. Our findings show the importance of using age- and sex-matched reference values for evaluation of outcomes after interventions due to hip-related problems.

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.

Summary Objective To estimate the association between molecular or imaging inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury and patient-reported outcomes at 5 years. Methods For 116 ACL-injured patients, molecular biomarkers of inflammation (synovial fluid and serum cytokines) and Hoffa- and effusion-synovitis as visualized on magnetic resonance imaging (MRI) were assessed 2 years post-injury. Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were assessed at 2 and 5 years. We used multiple imputation to handle biomarker values that were below the level of detection or missing, and linear regression for statistical analyses. Results None of the synovial fluid cytokines or imaging biomarkers of inflammation at 2 years were associated with any of the patient-reported outcomes at 5 years. With each log10 unit higher of serum tumor necrosis factor concentration the knee-related quality of life of KOOS was increased (i.e., better outcome) by 35 (95% confidence interval 7 to 63) points. No other serum biomarker measured at 2 years was associated with patient-reported outcome at 5 years. Conclusion Local joint inflammation assessed by biomarkers in synovial fluid and Hoffa- and effusion-synovitis on MRI at 2 years after an ACL injury did not associate with patient-reported outcomes at 5 years. Thus, chronic inflammation in the ACL-injured knee, as reflected by the biomarkers studied here, seems not to be a key determinant for the long-term patient-reported outcomes.

[Abstract] Objective: To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. Methods: We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. Results: Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. Conclusion: These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.

Purpose: Since 2008 Sweden has had a structured first-line face-to-face knee and hip osteoarthritis (OA) treatment program, BOA (Better management of OsteoArthritis) However, records show that this face-to-face program is underutilized and reaches only a minority of those that would benefit from it The first-line OA management program has been transformed into a digital version, Joint Academy® (JA), to facilitate implementation, scaling, increased accessibility, and improved patient adherence The smartphone application consists of video instructions distributed daily with individualized exercises for participants with knee or hip OA, as well as educational information on OA symptoms and self-management based on current international guidelines for the management of OA Each participant is assigned to a physical therapist available through asynchronous chat and telephone who supervises the participant throughout the whole program To improve chronically ill patients' health and quality of life, long-standing and continuous treatment is needed at an acceptable cost Recent evidence suggests that JA costs 25% compared to the BOA program for three months of treatment Providing patients with equal access to care necessitates availability in urban and rural areas alike This can potentially be achieved by digital delivery, but it is yet unknown if digital delivery of first-line OA treatment, compared with face-to-face, improves equal access to care The purpose of this study was to compare utilization of digital and face-to-face delivered OA treatment in the 21 different county councils of Sweden that are responsible for providing healthcare to the residents Methods: Registered patient participation in the BOA program during 2019 and 2020 was retrieved from the BOA annual reports and live statistics from the BOA website (for 2020, unknown final data retrieval data) Data from digital program participation was retrieved from the JA database (for 2020 until Nov 18th) To be included, a patient needed to have registered for the first visit in the BOA registry or have enrolled in the program by answering the first questionnaire in the JA registry Population density per county and county size were retrieved from Statistics Sweden Results were calculated and presented as users per 100 000 residents Mean and median values as well as standard deviations were calculated separately for registered participants/100 000 for BOA and JA programs, and for regions with more (n=12) or less (n=8) than 20 residents per km2 Results: In total 25652 patients from the BOA registry and 12240 patients from the JA database were included The differences between individual county councils in the number of registered program participants per 100 000 residents varied far more for the face-to-face BOA program than for the digital JA program (Table 1) This is illustrated by the ratio between the highest and lowest participation numbers/100 000 being 13 6 for BOA and 2 6 for JA, and standard deviations of 162 and 27, respectively The variability between county councils was greater for remote regions of the country with a population density below 20 per km2, than for more densely populated regions Conclusions: The results of this preliminary report suggest that digital first-line treatment, compared with the same treatment delivered face-to-face, improves equal access to recommended first-line care of OA of the knee and hip in Sweden Ongoing work aims to explore temporal changes in usage of the different platforms associated with the COVID-19 pandemic [Formula presented] [Formula presented]

Background: Numerous scientific organisations have developed evidence-based recommendations aiming to optimise the management of osteoarthritis (OA). Uptake, however, has been suboptimal. The purpose of this exercise was to harmonize the recent recommendations and develop a user-friendly treatment algorithm to facilitate translation of evidence into practice. Methods: We updated a previous systematic review on clinical practice guidelines (CPGs) for OA management. The guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation for quality and the standards for developing trustworthy CPGs as established by the National Academy of Medicine (NAM). Four case scenarios and algorithms were developed by consensus of a multidisciplinary panel. Results: Sixteen guidelines were included in the systematic review. Most recommendations were directed toward physicians and allied health professionals, and most had multi-disciplinary input. Analysis for trustworthiness suggests that many guidelines still present a lack of transparency. A treatment algorithm was developed for each case scenario advised by recommendations from guidelines and based on panel consensus. Conclusion: Strategies to facilitate the implementation of guidelines in clinical practice are necessary. The algorithms proposed are examples of how to apply recommendations in the clinical context, helping the clinician to visualise the patient flow and timing of different treatment modalities. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

OBJECTIVE: To determine prevalence, incidence and progression of radiographic knee osteoarthritis (OA) in a cohort of subjects with previous meniscectomy.METHODS: We assessed 221 subjects (177 men and 44 women) with weight bearing knee radiography twice (assessment A and B) with a follow-up time ranging from 4 to 10 years. All subjects had undergone meniscectomy 15-22 years before assessment A. At assessment B the mean (SD) age was 60 (11) years. We assessed prevalence and incidence of OA, as well as progression of radiographic features over time. Radiographic OA was defined as approximating Kellgren and Lawrence grade 2 or worse.RESULTS: At assessment A, we found tibiofemoral radiographic OA in 107 subjects' index knee (48%) of which 41 subjects (38%) had bilateral tibiofemoral OA. At assessment B, the corresponding figures were 151 (68%) and 71 (32%). At assessment A, we found patellofemoral OA in 32 subjects' index knee (14%) of which 11 (34%) had bilateral patellofemoral OA. At assessment B, the corresponding figures were 51 (23%) and 19 (37%). There was an increase of the sum of joint space narrowing (JSN) and osteophyte grades in the tibiofemoral joint of 144 subjects' index knee (64%) and in the contralateral tibiofemoral joints of 79 subjects (36%). The corresponding progression in the patellofemoral joint was observed in 66 index knees (30%) and in 41 (19%) contralateral knees.CONCLUSIONS: Overall, some 20-30 years after meniscectomy nearly three out of four persons had developed radiographic tibiofemoral OA and one out of four had developed patellofemoral OA.

Objective: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. Design: Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (>= 70 points, 0-100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study. Results: Seven out of 43 published randomized clinical trials (n = 620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid-and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% Confidence Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. Conclusions: This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Background Trauma-induced cytokine response and local inflammation after knee injury may be important in the development of posttraumatic osteoarthritis (OA). It has been reported that synovial fluid levels of inflammatory markers remain increased up to 5 years after anterior cruciate ligament (ACL) injury, indicative of extended local inflammation in the injured joint.1 Inflammation potentially represents a valid target for treatment in the early and subacute phase after joint trauma in order to prevent or delay onset of post-traumatic knee OA. Objectives To determine the role of inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury for predicting radiographic and magnetic resonance imaging (MRI)-defined knee OA 5 years post injury. Secondary aim was to estimate the concordance of inflammatory biomarkers assessed by MRI and in synovial fluid. Methods We studied 113 patients with acute ACL injury. 1.5 Tesla knee MRIs were read for Hoffa- and effusion-synovitis. Biomarkers of inflammation included IL-6, IL-8, IL-10, TNF-α and IFN-γ in serum and synovial fluid, and IL-12p70 in serum. The outcome was radiographic knee OA (ROA) or MRI-defined OA (MROA) at 5 years. Area under receiver operating characteristic curve (AUC), sensitivity and specificity were evaluated in models including MRI features only (M1), inflammation biomarkers only (serum [M2a] – synovial [M2b]) or both MRI and serum [M3a] or synovial [M3b] markers. Linear regression was used for evaluating association between MRI and synovial biomarkers. Results At 5 years, ROA was present in 26% and MROA was present in 32% of patients’ injured knee. The AUCs (95% CI) for ROA were 0.44 (0.42–0.47;M1), 0.62 (0.59–0.65;M2a), 0.58 (0.55–0.61;M2b), 0.53 (0.50–0.56;M3a) and 0.50 (0.46–0.53;M3b) for each model. The corresponding AUCs for MROA were 0.67 (0.64–0.70), 0.49 (0.47–0.52), 0.65 (0.61–0.68), 0.56 (0.52–0.59) and 0.69 (0.66–0.72) (table 1). The associations between MRI and synovial biomarkers were weak and not statistically significant, apart from effusion–synovitis and IL-8 (log 10 IL8 levels were 0.23 and 0.43 higher in persons with grade 1 or 2/3, respectively). Conclusions Neither MRI-defined inflammation, nor synovial/serum inflammation biomarkers at 2 years as analysed here predicted ROA or MROA at 5 years. The concordance between MRI and synovial inflammatory biomarkers was weak. Additional studies with longer follow-up will be needed to confirm or refute our findings and to more firmly define the role of inflammation for OA development following acute ACL injury. Reference [1] Struglics A, et al. Changes in cytokines and aggrecan ARGS neoepitope in synovial fluid and serum and in C-terminal crosslinking telopeptide of type II collagen and N-terminal crosslinking telopeptide of type I collagen in urine over five years after anterior cruciate ligament rupture: An exploratory analysis in the knee anterior cruciate ligament, nonsurgical versus surgical treatment trial.Arthritis Rheumatol2015;67:1816–25. Acknowledgements We thank the participants of the KANON study without this work would not have been possible. Disclosure of Interest F. Roemer Shareholder of: Boston Imaging Core Lab (BICL), LLC., M. Englund: None declared, A. Turkiewicz: None declared, A. Struglics: None declared, A. Guermazi Shareholder of: Boston Imaging Core Lab (BICL), LLC., Consultant for: Sanofi-Aventis, Merck Serono, OrthoTrophix, AstraZeneca, Pfizer, GE, and TissuGene, L. S. Lohmander: None declared, S. Larsson: None declared, R. Frobell: None declared

Objective: Patients with degenerative or traumatic meniscal tears are at high risk of developing knee osteoarthritis. We investigated if younger (≤40 years) and older (>40 years) patients with preoperative mechanical symptoms (MS) improved more in patient-reported outcomes after meniscal surgery than those without MS. Design: Patients from Knee Arthroscopy Cohort Southern Denmark (KACS) undergoing arthroscopic surgery for a meniscal tear completed online questionnaires before surgery, and at 12 and 52 weeks follow-up. Questionnaires included self-reported presence of MS (i.e., sensation of catching and/or locking) and the Knee injury and Osteoarthritis Outcome Score (KOOS). We analyzed between-group differences in change in KOOS 4 from baseline to 52 weeks, using an adjusted mixed linear model. Results: 150 younger patients (mean age 31 (SD 7), 67% men) and 491 older patients (mean age 54 (SD 9), 53% men) constituted the baseline cohorts. Patients with MS generally had worse self-reported outcomes before surgery. At 52 weeks follow-up, younger patients with preoperative MS had improved more in KOOS 4 scores than younger patients without preoperative MS (adjusted mean difference 10.5, 95% CI: 4.3, 16.6), but did not exceed the absolute postoperative KOOS 4 scores observed for those without MS. No difference in improvement was observed between older patients with or without MS (adjusted mean difference 0.7, 95% CI: −2.6, 3.9). Conclusions: Younger patients (≤40 years) with preoperative MS experienced greater improvements after arthroscopic surgery compared to younger patients without MS. Our observational study result needs to be confirmed in randomized trials.

Summary Objective To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA). Design Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0–4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country. Results In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69–4.97] and 3.30 [2.17–5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32–2.06] and 1.38 [1.15–1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA. Conclusion Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR.

We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of "wet" biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of equine and human OA were reviewed. The participants concluded that new information and studies in equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823-831, 2018.

Objective: To propose draft classification criteria for early stage osteoarthritis (OA) of the knee for use in a primary care setting. Methods: A group of basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists in a workshop setting discussed potential classification criteria for early osteoarthritis of the knee. The workshop was divided into sessions around relevant topics with short state of the art presentations followed by breakout sessions, consensus discussions, and consolidation into a consensus document. Results: Three classes of criteria were agreed: (1) Pain, symptoms/signs, self-reported function, and quality of life using tools such as KOOS: scoring ≤85% in at least 2 out of these 4 categories; (2) Clinical examination: at least 1 present out of joint line tenderness or crepitus; (3) Knee radiographs: Kellgren & Lawrence (KL) grade of 0 or 1. MRI is at present not recommended as an aid to identify or define early OA in routine clinical practice or primary care, in light of the absence of validated consensus criteria and the high population prevalence of structural joint changes detected by this method. Biomarkers may have future utility in early OA classification, but no individual or set of biomarkers is yet robust enough. Conclusion: Based on our consensus proposal, draft classification criteria for early OA of the knee for use in clinical studies should include patient reported outcomes such as pain and function, together with clinical signs and KL grade 0-1 on radiographs.

OBJECTIVE: To explore potential associations between proinflammatory cytokines in synovial fluid and progression of osteoarthritis (OA) in meniscectomized subjects.DESIGN: We studied 132 subjects on average 18 years after meniscectomy, with a second examination 4-10 years later. We measured concentrations of interleukin (IL)-6, -8 and tumor necrosis factor (TNF)-α by multiplex immunoassay, graded radiographic features of tibiofemoral and patellofemoral OA according to the Osteoarthritis Research Society International (OARSI) atlas, scored patient-reported outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and used logistic regression (adjusted for age, gender, body mass index, and time between examinations) for assessment of associations.RESULTS: Higher first examination concentrations of IL-6 and TNF-α were associated with increased risk for subsequent osteophyte progression (odds ratios (OR); 95% confidence intervals 1.05; 1.00-1.09 and 1.35; 1.03-1.75). Higher second examination concentrations of TNF-α were associated with having progressed in loss of joint space (OR 1.70; 1.15-2.52) or having worsened in the activity of daily living subscale of KOOS (OR 1.50; 1.07-2.09) in the preceding years. Subjects with increasing concentrations of IL-6 or TNF-α between examinations were five times more likely to have progressed in joint space narrowing between the same examinations, as compared to those with stable or decreasing concentrations (OR 5.17; 1.54-17.32 and 5.01; 1.32-18.92).CONCLUSIONS: In subjects with previous meniscectomy, higher or over time increasing synovial fluid levels of IL-6 and TNF-α seems to be associated with increased risk for progression of radiographic OA.

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification.

Background The effectiveness of oral glucosamine for symptoms of osteoarthritis (OA) is debated. Individual trials are not powered to show effects within subgroups of patients. Objectives To evaluate the effectiveness of oral glucosamine in clinical relevant subgroups of hip and knee OA patients based on pain severity, BMI, sex, structural abnormalities and inflammation, using individual patient data from published trials. Methods A systematic search for published randomized controlled trials on the effectiveness of any oral glucosamine substance in patients with clinically or radiologically defined knee or hip OA was performed. Additionally, trail registries were searched for ongoing studies. All authors and institutions of all eligible studies were approached and asked to share the trial data. All shared trials were assessed for their risk of bias, using the criteria recommended by the Cochrane. Missing data for covariates and outcome measures were imputed, using multiple imputation methods, within each original study. Subgroup factors were dichotomized, based on consensus of the OA Trial Bank Steering Committee. A multilevel regression analysis was performed to estimate the magnitude of the effect of glucosamine over the control intervention in the different subgroups with the individuals nested within each study. Pain at short-term (3 months) and long-term (24 months) served as primary outcomes measure, function as secondary. Outcome measures measured on different scales were standardized to a 0–100 scale to pool the data. All analyses were performed with and without stratifying for affected joint and type of glucosamine substance. Results Out of 21 eligible studies, six studies (N=1663) shared their trial data with the OA Trial Bank. Only one of these studies (N=40) was industry driven. All six studies had a low risk of bias, of which five trials (all not industry driven) compared glucosamine to placebo. These five studies represented 50% of the total number of randomized subjects in all published trials for this comparison. No main effects of glucosamine were found on pain or function at short-term (mean difference 0.31 95% CI [-2.02 to 2.64] and 1.56 [-0.56 to 3.69], respectively) and at long-term follow-up (0.98 [-1.76 to 3.73] and 1.40 [-1.27 to 4.06], respectively). Also, no significant interactions with treatment were found for subgroups based on pain severity (WOMAC pain 2 vs. ≥27kg/m 2 ), sex (male vs. female) and structural abnormalities (KL-grade 0–2 vs. 3–4), see Table. Stratification for knee OA patients only and for type of glucosamine did not result in any differences in the outcomes. No data was available to adequately form subgroups based on degree of inflammation. Conclusions The majority of industry-led glucosamine studies for osteoarthritis did not wish to share data, challenging optimal use of available data. There is currently no evidence for the use of glucosamine for the treatment of hip or knee osteoarthritis and an absence of support for clinically relevant subgroups of OA patients according to baseline pain severity, BMI, sex, and structural abnormalities. Disclosure of Interest None declared

Experimental findings and previous observational data have suggested lower risk of osteoarthritis (OA) with statin use but results are inconsistent. Large-scale studies with a clinically important outcome are needed. Thus, we aimed to determine whether statin use is associated with a reduced risk of developing clinically-defined hip or knee OA.Pooled analysis based on time-to-event analysis of four population-based large cohorts, encompassing in total 132,607 persons aged 57-91 years resident in southern and central Sweden. We studied the association between statin use and time to consultation or surgery for OA of the hip or knee by time-dependent exposure analysis and Cox regression.During 7.5 years of follow-up, we identified 7468 out- or inpatient treated cases of hip or knee OA. Compared with never use, current use of statins conferred no overall reduction in the risk of OA with an adjusted pooled hazard ratio (HR) of 1.04 (95% confidence intervals [95% CI] 0.99-1.10). We found no dose-response relation between duration of current statin use and the risk of OA, with similar HRs among patients with less than 1 year of use (HR 1.09; 95% CI 0.92-1.32) as in patients with use for 3 years or more (HR 1.05; 0.93-1.16). Results were comparable in those with low, medium and high dose of current statin use, without indications of heterogeneity of study results.Statin use is not associated with reduced risk of consultation or surgery for OA of the hip or knee.

Objectives: To determine socioeconomic inequalities in frequent knee pain (FKP), knee osteoarthritis (OA), and associated health-related quality of life (HRQoL) in Sweden. Method: In 2007 a postal questionnaire about knee pain was sent to a random sample of 10 000 residents of Malmö, Sweden (7402 individuals responded). Subjects reporting pain with duration ≥ 4 weeks in one or both knees in the past 12 months were classified as having FKP. A random sample of 1527 subjects with and without FKP attended a clinical and radiographic knee examination and responded to generic and disease-specific HRQoL questionnaires. We used the individuals’ level of education and occupation as socioeconomic status (SES) measures, and we calculated the relative index of inequality (RII) using Poisson regression with robust standard errors adjusted for age and gender. We applied weighting to account for a possible selection bias that might arise from non-responses in the study. Results: With education, the RIIs for FKP and knee OA were 0.71 [95% confidence interval (CI) 0.61–0.84] and 0.56 (95% CI 0.34–0.93), respectively. With occupation, the corresponding figures were 0.70 (95% CI 0.60–0.82) and 0.59 (95% CI 0.37–0.94), respectively. There were socioeconomic gradients in HRQoL in favour of people with better SES. RIIs for FKP and HRQoL but not knee OA were essentially similar after additional adjustment for mediators. Conclusions: In Sweden there are socioeconomic gradients related to both FKP and knee OA as well as HRQoL in favour of people with better SES. SES should be taken into account in health resource allocation pertaining to knee-related disorders.

Objective. Anterior cruciate ligament (ACL) rupture involves an increased risk of osteoarthritis. The purpose of this study was to explore changes in cartilage thickness over 5 years after ACL rupture. Methods. A total of 121 young active adults (ages 18-35 years; 26% women) from the Knee ACL, Nonsurgical versus Surgical Treatment (KANON) study, who had acute traumatic rupture of the ACL were studied. Sagittal magnetic resonance images were acquired within 4 weeks of ACL rupture (baseline) and at the 2-year and 5-year followup assessments. Medial and lateral femorotibial cartilage was segmented (with blinding to acquisition order), and the mean cartilage thickness was computed across 16 femorotibial subregions. Total femorotibial cartilage thickness change was the primary analytic focus. Maximal subregional mean cartilage thickness loss (ordered value 1 [OV1]) and gain (ordered value 16 [OV16]), independent of its specific location in individual knees, were the secondary analytic focus. Results. Overall femorotibial cartilage thickness increased by 31 mu m/year over 5 years (95% confidence interval 18, 44). The increase was similar in men and women and was significantly greater in those younger, as compared with those older, than the median age (25.3 years). The rate of total cartilage thickness change did not differ significantly between the first 2 years and the later 3 years. However, the maximal annualized subregional cartilage loss (OV1) and gain (OV16) were both significantly greater (P < 0.001 and P < 0.05, respectively) during the earlier interval than during the later interval (-115 versus -54 mu m [OV1] and 116 versus 69 mu m [OV16]). Conclusion. Cartilage thickening was observed over 5 years following ACL injury, particularly in the medial femorotibial compartment and in younger subjects. Major perturbations in cartilage homeostasis were seen over the first 2 years after ACL rupture, with simultaneous subregional thinning and thickening occurring within the same cartilage plate or compartment. (Less)

OBJECTIVE: To validate a modified ligand-binding assay for the detection of aggrecanase generated aggrecan fragments with the ARGS neoepitope in synovial fluid (SF) and blood, and to verify the identity of aggrecan fragments found in blood.DESIGN: An enzyme-linked immunosorbent assay (ELISA) on the Meso Scale Discovery (MSD) platform for detection of ARGS-aggrecan was validated, using a standard made from recombinant human aggrecan. Matched samples of SF, serum, plasma, and urine were obtained from 36 subjects at different time points after knee injury, and analysed for ARGS-aggrecan content. Aggrecan was purified from serum and plasma pools and analysed by Western blot.RESULTS: The limits of quantification for the ARGS-aggrecan assay was between 0.2 and 0.025 pmol ARGS/ml, and the sensitivity of the assay was improved two-fold compared to when using a standard purified from human donors. The ARGS concentrations were highest in SF (mean, range; 3.02, 0.36-30.22 pmol/ml), 20 times lower in the blood samples (0.14, 0.055-0.28 pmol/ml serum and 0.13, 0.053-0.28 pmol/ml plasma), and 80 times lower in urine (0.036, below detection - 0.087 pmol/ml). Serum-ARGS and plasma-ARGS concentrations were similar, and correlated (r(S) = 0.773, P < 0.001). SF concentration correlated with serum concentrations (r(S) = 0.420, P = 0.011). In blood, we identified 129-138 kDa aggrecan fragments containing the ARGS neoepitope.CONCLUSIONS: This novel ARGS-aggrecan assay is highly sensitive and suited for analysis of SF and blood samples. Both SF and blood contains ARGS-aggrecan, and ARGS concentrations in SF and serum are correlated.

Summary Objective To investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA). Methods Data from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into ‘Unloaders' (participants that reduced joint loads) and ‘Loaders' (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period. Results 157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders ( n = 100) or Loaders ( n = 57). The groups showed similar significant changes in symptoms (group difference: −2.4 KOOS points [95% CI −6.8:1.9]) and cartilage loss (group difference: −0.06 BLOKS points [95% CI −0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders. Conclusion For obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads. Clinicaltrials.gov NCT00655941.

Objectives: To assess correlations between Kellgren & Lawrence (KL) gradings, minimum joint space width (mJSW) measurements and the Boston Leeds Osteoarthritis Knee Score (BLOKS) within a cohort of obese patients with knee osteoarthritis (KOA). Methods: 192 Participants were recruited from an outpatient clinic (ClinicalTrials.gov: NCT00655941). Inclusion criteria were age ≥50 years, body mass index (BMI) ≥30 kg/m 2 plus symptomatic and verified KOA. 1.5 T magnetic resonance imaging (MRI) scans were assessed using BLOKS and bi-plane radiography by mJSW and KL. Statistics used were Spearman rank correlation coefficients. Results: The average patient was 63 years of age, female and had a BMI of 37. KL gradings correlated to cartilage damage, bone marrow lesions and meniscus pathology (r = 0.15-0.76) and similar results were found for the relationship between BLOKS and mJSW. BLOKS assessed knee joint pathology co-segregated with compartment and grade specific KL (P < 0.0001). BLOKS variables were statistically significant correlated, particularly in the medial tibiofemoral compartment (r = 0.42-0.80). Adjusting for age, gender and BMI did not alter these associations. Conclusion: Extensive pathological damage is present even in mild radiographic KOA and BLOKS gradings and KL scores increase together. Analyses of compartment specific KL scores revealed differences in their relationship to the assessed MRI variables. Our study displays the segregation of MRI gradings with respect to location and level of radiographic scores, reveals a high inter-dependency of MRI-assessed structures, and describes some redundancy of specific BLOKS variables.

OBJECTIVE: To evaluate the internal consistency and construct validity of the Physical Function short-forms for the Hip and Knee Injury Osteoarthritis Outcome Scores (HOOS-PS/KOOS-PS) and the Intermittent and Constant Osteoarthritis Pain (ICOAP) in a nine country study of patients consulting for total hip or knee replacement (THR or TKR).METHODS: Patients completed HOOS-PS or KOOS-PS, ICOAP and Western Ontario and McMaster Universities' Osteoarthritis Index (WOMAC) pain and physical function subscales at their consultation visit. Internal consistency was calculated using Cronbach's alpha. The association of HOOS-PS/KOOS-PS and ICOAP with WOMAC pain and function subscales was calculated with Spearman correlation coefficients with 95% confidence intervals.RESULTS: HOOS-PS/KOOS-PS and ICOAP demonstrated high internal consistency across countries (alpha 0.75-0.96 (hip) and 0.76-0.95 (knee)). Both HOOS-PS and KOOS-PS demonstrated high correlations (0.76-0.90 and 0.75-0.91, respectively) with WOMAC function in all countries. ICOAP exhibited moderate to high correlations with WOMAC pain and function subscales (0.53-0.84 (hip) and 0.43-0.84 (knee)).CONCLUSION: The psychometric properties of the HOOS-PS/KOOS-PS, and ICOAP were maintained across all countries.

Summary Objective Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years. Design We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA). Results Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated. Conclusions Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines.

Summary Objective Preoperative pain and function is viewed as an important predictor of total knee arthroplasty (TKA) outcomes. We examined whether variations in pain and function outcomes existed at 12 months between two centres in Sweden and Australia, and whether this was explained by variations in patient presentation for TKA. Methods This was a retrospective analysis of prospectively collected data. Patients from one centre in Australia (St. Vincent's Hospital (SVH), N = 516) and in Sweden (Trelleborg (TBG), N = 899) who underwent primary TKA between 2012 and 2013. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was analysed pre- and 12 months' post TKA from which non-response to surgery was determined using the OMERACT-OARSI criteria. Multiple linear regression analysis was used to examine the relationship between change in pain and function and surgery centre, adjusting for preoperative patient characteristics and surgical technique. Results Despite worse preoperative outcomes in all subscales of the WOMAC for the SVH cohort, there were no clinically meaningful differences in 12-month WOMAC subscales nor change in WOMAC subscales between SVH and TBG. Almost identical proportions of patients were considered OMERACT-OARSI responders, 85.7% (SVH) and 85.9% (TBG), however for the SVH cohort 25 (4.9%) were moderate and 417 (80.8%) were high responders, compared to the TBG cohort of which 225 (25%) were moderate and 547 (60.9%) were high responders. Conclusion Despite differences in preoperative presentation between 2 countries, improvements in pain and function and the proportion of individual who responded to TKA surgery at 1 year were similar. Factors related to poor response to TKA surgery require further elucidation.

Summary Objective To investigate whether change in concentrations over time of aggrecanase generated ARGS-aggrecan in synovial fluid (SF ARGS) associates with progression of radiographic knee osteoarthritis (OA) and patient-reported outcome in subjects with previous meniscectomy. Methods We studied 141 subjects at two time points after meniscectomy. Time point A was on average 18years after meniscectomy, time point B was on average 7.5years later; 74 subjects had SF available from both examinations. We measured SF ARGS by an electrochemiluminescence immunoassay, graded radiographic features of tibiofemoral or patellofemoral OA according to the Osteoarthritis Research Society International (OARSI) atlas, and scored patient-reported outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Using logistic regression (adjusted for age, gender, body mass index, time between examinations, and SF ARGS at first examination) we assessed associations between change in SF ARGS between first and second examinations and progression of radiographic OA and KOOS. Results In subjects with decreasing SF ARGS between examinations, the likelihood of loss of joint space and worsening of KOOS pain between examinations was increased 6- and 4-fold respectively compared to those increasing in SF ARGS (odds ratio (OR) 5.72; 95% confidence interval (CI) 1.53–21.4 and 3.66; 1.01–13.2, respectively). No significant associations were seen between decreasing SF ARGS and progression of osteophytes (OR 0.88; 0.28–2.78), or for patient-reported outcomes other than KOOS pain. Conclusion Having decreasing levels of SF ARGS over time was associated with an increased risk of loss of joint space and pain worsening, but showed no association with other patient-reported outcomes or osteophyte progression.

Objective To develop a system for predicting the progression of radiographic knee osteoarthritis (OA) using tibial trabecular bone texture. Methods. We studied 203 knees with (n = 68) or without (n = 135) radiographic tibiofemoral OA in 105 subjects (90 men and 15 women with a mean age of 54 years) in whom 2 sets of knee radiographs were obtained 4 years apart. We determined medial and lateral compartment tibial trabecular bone texture using an automated region selection method. Three texture parameters were calculated: roughness, degree of anisotropy, and direction of anisotropy based on a signature dissimilarity measure method. We evaluated tibiofemoral OA progression using a radiographic semi-quantitative outcome: an increase in the medial joint space narrowing (JSN) grade. We examined the predictive ability of trabecular bone texture in knees with and those without preexisting radiographic OA, with adjustment for age, sex, and body mass index, using logistic regression (generalized estimating equations) and receiver operating characteristic curves. Results. The prediction of increased medial JSN in knees with or without preexisting radiographic OA was the most accurate for medial trabecular bone texture; the area under the curve (AUC) was 0.77 and 0.75, respectively. For lateral trabecular bone texture, the AUC was 0.71 in knees with preexisting OA and 0.72 in knees without preexisting OA. Conclusion. We have developed a system, based on analyzing tibial trabecular bone texture, which yields good prediction of loss of tibiofemoral joint space. The predictive ability of the system needs to be further validated.

Purpose: Meniscal tears, which are longitudinal-vertical tears (e.g. bucket-handle tears) and/or involve all three meniscal sub regions (anterior horn, body and posterior horn), are typically large and assumed to cause patient perceived mechanical knee symptoms (knee grinding or clicking and knee catching or locking). However, whether the presence of such mechanical symptoms is useful for diagnosing these forms of meniscus tears is unknown. Therefore, we investigated the diagnostic values of having mechanical symptoms in diagnosing a bucket-handle tear and/or a tear involving all three meniscal sub regions in middle-aged and older patients undergoing arthroscopic meniscal surgery. Methods: This study is a secondary analysis of Pihl et al. OARSI 2017. The study included patients aged 40 years or older undergoing surgery for a meniscal tear from Knee Arthroscopy Cohort Southern Denmark (KACS) consecutively recruited from February 2013 to January 2014. Within 2 weeks prior to surgery, patients completed online questionnaires self-reporting presence of mechanical symptoms (i.e. knee grinding or clicking and knee catching or locking) assessed by two single items from the Knee Injury and Osteoarthritis Outcome score (KOOS). At arthroscopy, the operating surgeon recorded information about specific meniscal pathology (i.e. tear type and radial location) using a modified version of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) classification of meniscal tears. Sensitivity, specificity, positive predictive value and negative predictive value were calculated separately for experiencing knee grinding and/or clicking, knee catching and/or locking and the two combined in diagnosing a bucket-handle tear and/or a tear involving all three meniscal sub regions (i.e. the anterior horn, mid-body and posterior horn). Results: In total, 398 patients of the 491 KACS cohort patients were aged 40 years or older. Of these, 397 (mean age 54.4 (40-76) years, 54% men) with complete baseline data for the analyses in this study were included. Most patients, 341 (86%), experienced knee grinding and/or clicking, 202 (51%) experienced knee catching and/or locking, and 190 (48%) patients experienced both types of symptoms. The prevalence of having a bucket-handle tear and/or a tear involving all three meniscal sub regions was 15% (n=61). Self-reported knee grinding and/or clicking showed the highest sensitivity, but also the lowest specificity (Table 1), while knee catching and/or locking and the combination of all mechanical symptoms showed very similar values for sensitivity and specificity. The predictive values were virtually the same for all mechanical knee symptoms with low positive predictive values and fairly large negative predictive values (Table 1).Conclusions: In this exploratory study we found a low diagnostic value of experiencing mechanical symptoms for diagnosing large meniscal tears in a population of patients with meniscal tears. The presence of mechanical symptoms only marginally changed the baseline probability of having a bucket-handle tear and/or tear involving all three meniscal sub regions in patients aged 40 years or older with meniscal tears. As predictive diagnostic values are largely driven by prevalence of the outcome, the diagnostic value of mechanical symptoms can be expected to be of even less utility in patients with a suspected but not yet verified meniscal tear. Based on this and the results in this study, presence of patient-reported mechanical symptoms is of questionable value in the diagnosis of patients having a bucket-handle tear and/or a tear involving all three meniscal sub regions in middle-aged and older patients.

summary Objective: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009. Methods: A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence. Results: Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for selfmanagement, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) � 0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES ¼ 0.77, 95% CI 0.36, 1.17) was no longer significant (ES ¼ 0.16, 95% CI � 0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES ¼ 0.10, 95% CI � 0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3 g/day have been published (HR ¼ 1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo. Conclusion: Publication of a large amount of new research evidence has resulted in changes in the calculated risk–benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.