PLOD2 gene expression in infrapatellar fat pad is correlated with fat mass in obese patients with end-stage knee osteoarthritis.

Objective: To investigate associations between obesity-linked systemic factors and gene expression indicative for the inflammatory and fibrotic processes in the infrapatellar fat pad (IFP), in a population of obese patients with end-stage knee osteoarthritis (KOA). Methods: We collected human IFPs from 48 patients with a mean body mass index (BMI) of 35.44 â€‹kg/m2 during total knee replacement procedures. These patients were part of a randomized controlled trial and met the criteria of having OA and a BMI of ≥30 â€‹kg/m2. Blood samples were collected to assess serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and leptin. Total body composition was measured using dual-energy X-ray absorptiometry. Gene expressions of IL6, TNFA, COL1A1, IL1B, ASMA, PLOD2 in the IFP were analyzed. Results: Univariate analysis resulted in a positive correlation between BMI and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression (r2 â€‹= â€‹0.13). In univariate analyses of obesity-linked systemic factors and PLOD2, significant correlations were found for lean mass (r2 â€‹= â€‹0.20), fat mass (r2 â€‹= â€‹0.20), serum cholesterol (r2 â€‹= â€‹0.17), serum triglycerides (r2 â€‹= â€‹0.19) and serum leptin (r2 â€‹= â€‹0.10). A multiple linear regression model indicated fat mass to be a strong predictor of PLOD2 production in the IFP (r2 â€‹= â€‹0.22, P â€‹= â€‹0.003). Conclusion: Our study demonstrates the positive association between fat mass and PLOD2 expression in the IFP of obese end-stage knee OA patients. This may indicate that within this patient population the fibrotic process in the IFP is influenced by systemic adipose tissue, next to local inflammatory processes.

"You don't put it down to arthritis": A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis.

Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n â€‹= â€‹17 groups) and one-on-one interviews (n â€‹= â€‹3) conducted in 91 individuals living with knee OA as part of an international study to better understand the OA pain experience. In each focus group or interview, participants were asked to describe their first symptoms of knee OA. We inductively coded these transcripts and conducted thematic analysis. Results: Mean age of participants was 70 years (range 47-92) and 68 â€‹% were female. We developed four overarching themes: Insidious and Episodic Onset, Diverse Early Symptoms, Must be Something Else, and Adjustments. Participants described the gradual and intermittent way in which symptoms of knee OA developed over many years; many could not identify a specific starting point. Participants described diverse initial knee symptoms, including activity-exacerbated joint pain, stiffness and crepitus. Most participants dismissed early symptoms or rationalized their presence, employing various strategies to enable continued participation in recreational and daily activities. Few sought medical attention until physical functioning was demonstrably impacted. Conclusions: The earliest symptoms of knee OA are frequently insidious in onset, episodic and present long before individuals present to health professionals. These results highlight challenges to identifying people with knee OA early and support the development of specific classification criteria for EsSKOA to capture individuals at an early stage.

Platelet-Rich Plasma Injections for the Treatment of Ankle Osteoarthritis.

BACKGROUND: Ankle osteoarthritis is debilitating and usually affects relatively young people, often as a result of previous ankle traumas, frequently occurring in sports. Platelet-rich plasma (PRP) injections for ankle osteoarthritis have shown no evidence of benefit over the course of 26 weeks. Previous studies on PRP for knee osteoarthritis showed that clinically significant improvements with PRP occurred between 6 to 12 months in the absence of initial benefit. No studies have evaluated the effect of PRP from 6 to 12 months in ankle osteoarthritis. PURPOSE: To assess the efficacy of PRP injections in ankle osteoarthritis over the course of 52 weeks. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In this 52-week follow-up trial, 100 patients with ankle osteoarthritis were randomized to a PRP group or placebo (saline) group. Patients received 2 intra-articular talocrural injections: at inclusion and after 6 weeks. Patient-reported outcome measures were used to assess pain, function, quality of life, and indirect costs over 52 weeks. RESULTS: Two patients (2%) were lost to follow-up. The adjusted between-group difference for the patient-reported American Orthopaedic Foot & Ankle Society score over 52 weeks was -2 points (95% CI, -5 to 2; P = .31) in favor of the placebo group. No significant between-group differences were observed for any of the secondary outcome measures. CONCLUSION: For patients with ankle osteoarthritis, PRP injections did not improve ankle symptoms and function over 52 weeks compared with placebo injections. REGISTRATION: NTR7261 (Netherlands Trial Register).

Acetabular dysplasia and the risk of developing hip osteoarthritis at 2,5,8, and 10 years follow-up in a prospective nationwide cohort study (CHECK).

OBJECTIVE: To assess the relationship between acetabular dysplasia (AD) and the risk of incident and end-stage radiographic hip osteoarthritis (RHOA) over 2,5,8 and 10 years. DESIGN: Individuals (n = 1002) aged between 45 and 65 from the prospective Cohort Hip and Cohort Knee (CHECK) were studied. Anteroposterior pelvic radiographs were obtained at baseline and 2,5,8, and 10-years follow-up. False profile radiographs were obtained at baseline. AD was defined as a lateral center edge angle, an anterior center edge angle, or both <25° at baseline. The risk of developing RHOA was determined at each follow-up moment. Incident RHOA was defined by Kellgren & Lawrence (KL) grade ≥2 or total hip replacement (THR), end-stage RHOA by a KL grade ≥3 or THR. Associations were expressed in odds ratios (OR) using logistic regression with generalized estimating equations. RESULTS: AD was associated with the development of incident RHOA at 2 years follow-up (OR 2.46, 95% CI 1.00-6.04), 5 years follow-up (OR 2.28, 95% CI 1.20-4.31), and 8 years follow-up (OR 1.86, 95%CI 1.22-2.83). AD was only associated with end-stage RHOA at 5 years follow-up (OR 3.75, 95% CI 1.02-13.77). No statistically significant associations were observed between AD and RHOA at 10-years follow-up. CONCLUSION: Baseline AD in individuals between 45 and 65 years is associated with an increased risk of developing RHOA within 2- and 5 years. However, this association seems to weaken after 8 years and disappears after 10 years.

Changes to consultations and diagnosis of osteoarthritis in primary care during the COVID-19 pandemic.

OBJECTIVE: General practitioners (GP) are often the first medical professionals to treat musculoskeletal complaints. Yet the impact of COVID-19 on primary care utilisation for musculoskeletal complaints is largely unknown. This study quantifies the impact of the pandemic on primary care utilisation for musculoskeletal complaints and specifically osteoarthritis (OA) in the Netherlands. DESIGN: We extracted data on GP consultations in 2015-2020 from 118,756 patients over 45 years of age and estimated reductions in consultations in 2020 as compared to 5-year average. Outcomes were GP consultations for: any musculoskeletal complaints, knee and hip OA, knee and hip complaints, and newly diagnosed knee and hip OA/complaints. RESULTS: The relative reductions in consultations ranged from 46.7% (95% confidence intervals (CI): 43.9-49.3%) (all musculoskeletal consultations) to 61.6% (95% CI: 44.7-73.3%) (hip complaints) at the peak of the first wave, and from 9.3% (95% CI: 5.7-12.7%) (all musculoskeletal consultations) to 26.6% (95% CI: 11.5-39.1%) (knee OA) at the peak of the second wave. The reductions for new diagnoses were 87.0% (95% CI: 71.5-94.1%) for knee OA/complaints, and 70.5% (95% CI: 37.7-86.0%) for hip OA/complaints at the peak of the first wave, and not statistically significant at the peak of the second wave. CONCLUSION: We observed 47% reduction in GP consultations for musculoskeletal disorders during the first wave and 9% during the second wave. For hip and knee OA/complaints, the reductions were over 50% during the first, and 10% during the second wave. This disruption may lead to accumulation of patients with severe OA symptoms and more requests for arthroplasty surgery.

Medical students' perception of general practice: a cross-sectional survey.

BACKGROUND: An increase in the demand for general practitioners is expected in many countries, but only a minority of medical students consider a career in general practice. More detailed and up-to-date knowledge about medical student's perception of general practice would be helpful for efforts to encourage medical students to consider a career in general practice. METHODS: We performed a cross-sectional single center survey among Dutch medical students to evaluate their perception of general practice at three different stages in their study: Ba1: first-year bachelor students; Ba3: third-year bachelor students; Ma3: third-year master students. The impact of different factors on their attitudes and perceptions was quantified. A multivariate logistic regression was performed with 'interest in general practice' as the outcome variable. RESULTS: The median age for Ba1 was 18 (IQR: 18-19) and 71.5% were female, for Ba3 the median age was 20 (IQR: 20-21) and 70.6% were female and for Ma3 the median age was 25 years (IQR: 24-26) and 73.3% were female. On average, 31.2% of the respondents had a migration background. The mean response rate for this study was 77.1%. Of the participating Ba1 students (n = 340) only 22.4% considered working as a GP after medical school; for Ba3 students (n = 231) this percentage was 33.8%, and for Ma3 students (n = 210) it was significantly higher at 70.5%; in the final multivariate model this corresponded to an odds ratio (OR) of 4.3 (95%-CI:2.6-6.9) compared to Ba1 students. The strongest predictor in the final model was the opinion that general practice provides a pleasant working environment (OR 9.5; 95%-CI: 6.2-14.5). CONCLUSION: This study showed that multiple factors are significantly related to medical students' interest in general practice. Although students believed that general practice does not have a high status within the medical profession, they acknowledged the social importance and the pleasant working environment of general practice. Knowledge obtained in this study can be used when designing a medical curriculum or a general practice course.

Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis.

OBJECTIVE: To study potential surrogate outcomes for osteoarthritis (OA) incidence by evaluating the association of short-term changes in clinical and imaging biomarkers with long-term clinical knee OA incidence. DESIGN: Middle-aged women with overweight/obesity, but free of knee symptoms were recruited through their general practitioners. At baseline, after 2.5 years, and after 6.5 years, questionnaires, physical examination, radiographs, and Magnetic resonance imaging (MRI) scans were obtained. The percentage of knees with a minimal clinically important difference for knee pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/stiffness/function, and joint space narrowing, and of those with progression/regression of medial knee alignment, chronic knee pain, radiographic osteophytes, and cartilage defects, bone marrow lesions, osteophytes, and effusion/synovitis on MRI were determined. For each of these potential surrogate outcomes with ≥10% improvement or progression in the population over 2.5 years, the association with incident clinical knee OA, defined using the combined ACR-criteria, after 6.5 years was determined. RESULTS: Most pre-defined potential surrogate outcomes showed ≥10% change in the population over 2.5 years, but only worsening of TF cartilage defects, worsening of TF osteophytes on MRI, and an increase in pain severity were significantly associated with greater clinical knee OA incidence after 6.5 years. These potential surrogate outcomes had high specificity and negative predictive value (89-91%) and low sensitivity and positive predictive value (20-28%) CONCLUSIONS: Worsening of TF cartilage defects and TF osteophytes on MRI, and increased pain severity could be seen as surrogate outcomes for long-term OA incidence. However, higher positive predictive values seem warranted for the applicability of these factors in future preventive trials.

Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the Netherlands.

OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR < 1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA. CONCLUSION: This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions.

The KNee OsteoArthritis Prediction (KNOAP2020) challenge: An image analysis challenge to predict incident symptomatic radiographic knee osteoarthritis from MRI and X-ray images.

OBJECTIVES: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth. DESIGN: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC). RESULTS: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables. CONCLUSION: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation.

Associations between biomarkers of matrix metabolism and inflammation with pain and fatigue in participants suspected of early hip and or knee osteoarthritis: data from the CHECK study.

OBJECTIVES: To assess the associations of biomarkers in serum [highsensitivity C-reactive protein (hs-CRP), serum cartilage oligomeric protein (sCOMP), serum propeptide of type I procollagen (sPINP) and serum osteocalcin (sOC)] and urine [urinary type II collagen telopeptide (uCTX-2)] with the extent and progression of nocturnal pain, pain while walking, and fatigue in participants with hip and/or knee pain suspected to be early stage osteoarthritis (OA). METHODS: hs-CRP, uCTX-2, sCOMP, sPINP and sOC were measured at baseline in 1,002 participants of the Cohort Hip and Cohort Knee (CHECK). Nocturnal pain, pain while walking and fatigue were assessed by self-reported questionnaires at baseline and 2-year follow-up. Associations between these biomarkers and symptoms were examined using logistic and linear regression analyses. RESULTS: hs-CRP was significantly associated with mild nocturnal pain (OR 1.18 95% CI 1.01-1.37), with mild and moderate pain while walking (OR 1.17 95% CI 1.01-1.35 and OR 1.56 95% CI 1.29-1.90, respectively) and with progression of nocturnal pain (OR 1.25 95% CI 1.07-1.46). uCTX-2 was associated with mild nocturnal pain (OR 1.40 95% CI 1.05-1.85) and with mild and severe-extreme pain while walking (OR 1.35 95% CI 1.04-1.75 and OR 2.55 95% CI 1.03-6.34, respectively). sPINP was associated with severe-extreme nocturnal pain (OR 0.45 95% CI 0.25-0.82). No significant associations were found for sCOMP and sOC, nor for any of the biomarkers and fatigue. CONCLUSION: This study of biomarkers in a large cohort of participants with hip and/or knee pain suspected to reflect early stage hip and/or knee OA suggests that inflammation and cartilage matrix degeneration play a role in pain, but not in fatigue.

How does hip osteoarthritis differ from knee osteoarthritis?

Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management.

A lifespan approach to osteoarthritis prevention.

Prevention is an attractive solution for the staggering and increasingly unmanageable burden of osteoarthritis. Despite this, the field of osteoarthritis prevention is relatively immature. To date, most of what is known about preventing osteoarthritis and risk factors for osteoarthritis is relative to the disease (underlying biology and pathophysiology) of osteoarthritis, with few studies considering risk factors for osteoarthritis illness, the force driving the personal, financial and societal burden. In this narrative review we will discuss what is known about osteoarthritis prevention, propose actionable prevention strategies related to obesity and joint injury which have emerged as important modifiable risk factors, identify where evidence is lacking, and give insight into what might be possible in terms of prevention by focussing on a lifespan approach to the illness of osteoarthritis, as opposed to a structural disease of the elderly. By targeting a non-specialist audience including scientists, clinicians, students, industry employees and others that are interested in osteoarthritis but who do not necessarily focus on osteoarthritis, the goal is to generate discourse and motivate inquiry which propel the field of osteoarthritis prevention into the mainstream.

Are changes in meniscus volume and extrusion associated to knee osteoarthritis development? A structural equation model.

OBJECTIVE: To explore the interplay between (changes in) medial meniscus volume, meniscus extrusion and radiographic knee osteoarthritis (OA) development over 30 months follow-up (FU). METHODS: Data from the PRevention of knee Osteoarthritis in Overweight Females study were used. This cohort included 407 middle-aged women with a body mass index ≥27 kg/m2, who were free of knee OA at baseline. Demographics were collected by questionnaires at baseline. All menisci at both baseline and FU were automatically segmented from MRI scans to obtain the meniscus volume and the change over time (delta volume). Baseline and FU meniscus body extrusion was quantitatively measured on mid-coronal proton density MR images. A structural equation model was created to assess the interplay between both medial meniscus volume and central extrusion at baseline, delta volume, delta extrusion, and incident radiographic knee OA at FU. RESULTS: The structural equation modeling yielded a fair to good fit of the data. The direct effects of both medial meniscus volume and extrusion at baseline on incident OA were statistically significant (Estimate = 0.124, p = 0.029, and Estimate = 0.194, p < 0.001, respectively). Additional indirect effects on incident radiographic OA through delta meniscus volume or delta meniscus extrusion were not statistically significant. CONCLUSION: Baseline medial meniscus volume and extrusion were associated to incidence of radiographic knee OA at FU in middle-aged overweight and obese women, while their changes were not involved in these effects. To prevent knee OA, interventions might need to target the onset of meniscal pathologies rather than their progression.

Prevalence of small osteophytes on knee MRI in several large clinical and population-based studies of various age groups and OA risk factors.

Objective: Osteophytes, also small ones, are an important imaging feature of OA. However, due to their high prevalence on MR, the question has arisen whether these are truly pathophysiologic features of early OA, a result of physiologic aging, or rather a merely transient phenomenon. The aim of this study was to explore the prevalence of osteophytes on MR in various locations of the knee, with special emphasis on small osteophytes, across multiple large studies conducted in our institution comprising a wide range of subjects at different ages. Method: Retrospective explorative study of the prevalence of osteophytes, particularly grade 1 according to MOAKS, among four studies with a wide variety in age and OA risk factors. Results: A large number of grade 1 osteophytes were found in all four studies. The largest number of osteophytes were present in the youngest age group of <30 years (69.6%) compared to 36.8% in the age group of ≥30 â€‹< â€‹50 years and 54,3% when aged ≥50 years, of which most were grade 1 osteophytes. Conclusion: Small osteophytes are highly prevalent among populations with varying age and OA risk factors, in particular among young subjects without other OA features. This might suggest that these "osteophytes" do not necessarily represent early OA, but rather indicate a transient physiologic phenomenon.

Towards developing diagnostic criteria for early knee osteoarthritis: data from the CHECK study.

OBJECTIVES: There is a general consensus that a shift in focus towards early diagnosis and treatment of knee OA is warranted. However, there are no validated and widely accepted diagnostic criteria for early knee OA available. The current study aimed to take the first steps towards developing diagnostic criteria for early knee OA. METHODS: Data of 761 individuals with 1185 symptomatic knees at baseline were selected from the CHECK study. For CHECK, individuals with pain/stiffness of the knee, aged 45-65 years, who had no prior consultation or a first consultation with the general practitioner for these symptoms in the past 6 months were recruited and followed for 10 years. A group of 36 experts (17 general practitioners and 19 secondary care physicians) evaluated the medical records in pairs to diagnose the presence of clinically relevant knee OA 5-10 years after enrolment. A backward selection methods was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing, using the experts' diagnoses as gold standard outcome. RESULTS: Prevalence of clinically relevant knee OA during follow-up was 37%. Created models contained 7-11 baseline factors and obtained an area under the curve between 0.746 (0.002) and 0.764 (0.002). CONCLUSION: The obtained diagnostic models for early knee OA had 'fair' predictive ability in individuals presenting with knee pain in primary care. Further modelling and validation of the identified predictive factors is required to obtain clinically feasible and relevant diagnostic criteria for early knee OA.

Reasons why Dutch novice nurses leave nursing: A qualitative approach.

Shortages in the nursing profession are increasing. It is, therefore, imperative to understand why novice nurses are leaving the profession. This qualitative study explores Dutch novice nurses' motives for leaving the profession. Individual semi-structured interviews were held with seventeen former novice nurses who had decided to leave nursing within two years after graduation. Data was collected and analysed following the principles of Thematic Analysis, leading to six themes; 1) Lack of challenge; ambitious to progress further in management or research roles. 2) Lack of passion; no feeling of passion for patient care. 3) Lack of perceived competence; not feeling "up to the challenge". 4) Lack of job satisfaction due to heavy workload; work-life imbalance and inability to deliver high-quality care. 5) Lack of work capacity due to non-work-related health conditions; unmet requirements for job or work environment adjustment. 6) Lack of feeling of belonging; suffering from a negative attitude of colleagues to one another. To prevent novice nurse professional turnover, measures such as capacity building, supervisor support and a tailored personal development plan could be taken. To make novice nurses feel safe and reassured, support from colleagues and supervisors is important. Such measures require thoughtful implementation and evaluation.

Moderators of the effects of therapeutic exercise for people with knee and hip osteoarthritis: A systematic review of sub-group analyses from randomised controlled trials.

Objective: 1) To identify potential moderators of the effect of therapeutic exercise explored in randomised controlled trials (RCTs) of knee and hip osteoarthritis (OA); 2) summarise the extent, strength and quality of evidence reported for moderators. Design: Systematic review (PROSPERO CRD42019148074). Inclusion criteria: a) RCTs with sub-group analyses investigating potential moderator variables; b) participants with knee and/or hip OA; c) therapeutic exercise interventions compared to either no exercise control or alternative exercise intervention(s), and; d) measuring pain or physical function outcomes. Included RCTs' risk of bias and sub-group analysis quality were assessed. Data were extracted on sub-group analyses (methods and potential moderators), outcomes (pain and function) and sub-group findings (associated statistics of potential moderator∗intervention effects). Findings were analysed using narrative synthesis. Results: 14 RCTs were included; 13 knee OA RCTs (n = 2743 participants) explored 23 potential moderators and 1 hip OA RCT (n = 203) explored 6 potential moderators. Sub-group analysis quality was mixed. Knee varus malalignment was the only moderator of therapeutic exercise compared to non-exercise control in 1 RCT (WOMAC-pain adjusted difference 12.7 in the neutral alignment sub-group and 1.8 in the malaligned sub-group, interaction term: p = 0.02). Varus thrust, knee laxity/instability, obesity and cardiac problems all moderated the effect of therapeutic exercise on pain or function compared to different comparison exercise. Conclusions: Therapeutic exercise may be effective for reducing pain in people with knee OA and neutral alignment but not for those with varus malalignment. The exercise moderator literature is limited. More robust evidence is required to inform sub-group exercise selection.

The clinical and radiographic course of early knee and hip osteoarthritis over 10 years in CHECK (Cohort Hip and Cohort Knee).

OBJECTIVE: To describe the radiographic and symptomatic course in subjects with hip or knee complaints suspected of early osteoarthritis (OA). DESIGN: CHECK (Cohort Hip and Cohort Knee) is a multicenter, prospective observational cohort study of 1,002 subjects with first complaints in knee(s) and/or hip(s) (age 56 ± 5 years; 79% female; body mass index (BMI) 26 ± 4 kg/m2). Visits took place at baseline and at 2, 5, 8, and 10 year follow-up. At each visit, questionnaires were administered, physical examination performed, and X-ray images obtained. Clinical OA was defined according to the clinical American College of Rheumatism (ACR) criteria. Radiographic OA (ROA) was defined as Kellgren and Lawrence score (K&L) ≥2. RESULTS: 83% of the subjects reported knee pain, 59% hip pain, and 42% reported both hip and knee pain at baseline. 85% of the subjects completed 10-year follow-up. Pain scores remained rather stable over time, although individual scores fluctuated. A total of 138 subjects never fulfilled the clinical American College of Rheumatology (ACR) criteria. 60% (n = 601) had ROA in one or both knees, and 51% (n = 513) had ROA in one or both hips at 10 years. Only 13.5% of the subjects did not develop ROA after 10 years. Most joint replacements (n = 52 (57%)) took place in subjects with multiple affected joints. CONCLUSIONS: The symptomatic course in subjects with hip or knee complaints suspected of OA remained fairly stable on population level, though individual scores fluctuated. The radiological course was progressive, with joint replacements particularly in subjects with both hip and knee OA.

Do we need another trial on exercise in patients with knee osteoarthritis?: No new trials on exercise in knee OA.

OBJECTIVE: We aim to investigate if we need additional trials on exercise in knee osteoarthritis (OA) to accept a certain effect size to be a 'true' effect size, and new studies are not needed anymore. DESIGN: We performed a secondary analyses of a meta-analysis of studies on patients with knee osteoarthritis, on pain immediately post treatment. We performed five different analysis: a) we evaluated publication bias, b) we performed subgroup analysis, c) a sensitivity analysis based on the overall risk of bias (RoB) score, d) a cumulative meta-analysis and e) we developed an extended funnel plot to explore the potential impact of a new study on the summary effect estimate. RESULTS: We included 42 studies with in total 6863 patients. The analyses showed that a) there is no clear publication bias, b) subgrouping did not affect the overall effect estimate, c) the effect estimate of exercise is more consistent (no heterogeneity) in the studies of low RoB, d) the benefit of exercise was clear since 2010 and e) the extended funnel plot suggests that an additional study has a none or very limited impact to change the current effect estimate. CONCLUSION: Exercise is effective and clinically worthwhile in reducing pain immediately post treatment compared to no or minimal interventions in patients with knee OA and adding new data will unlikely change this conclusion.