Osteoarthritis and Cartilage Open

Objective To determine reliability among four experienced and calibrated readers in cross-sectional and longitudinal semi-quantitative MRI assessments of knee osteoarthritis (OA) in the Multicenter Osteoarthritis (MOST) study. Design From all MOST participants with at least one knee with readable 60-month and 84-month paired knee MRIs (1.0 T extremity systems), we selected 10 subjects having a spectrum of baseline disease severity of cartilage, bone marrow lesions, and meniscal damage and a spectrum of longitudinal changes in severity at 24 months follow-up. MRIs were independently assessed using the WORMS grading system by four musculoskeletal radiologists with the chronological sequence known to the readers. Kappa statistics were used to determine agreement between each pair of readers and Kendall's coefficient of concordance to determine average agreement across readers. Results For most features, cross-sectional reliability was substantial to almost perfect. Regarding longitudinal reliability (detection of longitudinal change), inter-reader reliability as weighted kappa values ranged from 0.62 to 0.78 for cartilage damage, 0.75–0.88 for bone marrow lesions, 0.75–0.92 for meniscal tears, 0.67–0.95 for meniscal extrusion, 0.51–0.77 for bone attrition, 0.43–0.76 for osteophytes, 0.31–0.70 for Hoffa-synovitis, and 0.47–0.85 for effusion-synovitis. Kendall's coefficient ranged from 0.65 to 0.98. Conclusion High levels of cross-sectional reliability and moderate to high longitudinal reliability was achieved using four experienced readers in semiquantitative MRI-assessment of most knee OA features.

Objective EP-104IAR is a novel, sustained-release, intra-articular (IA) formulation of the corticosteroid fluticasone propionate (FP), in development for the treatment of osteoarthritis (OA) pain. This study evaluated the safety, pharmacokinetics (PK) and efficacy of a single dose of EP-104IAR in patients with OA of the knee. Design This was a multi-center, randomized, double-blind, placebo-controlled trial performed at 3 sites in Canada. Subjects with moderate to severe pain received either a single dose of the investigational product EP-104IAR (15 mg) or placebo (vehicle) and were evaluated for up to 42 weeks. The primary outcome measures were safety and PK. The study was not powered to assess efficacy, however patient reported outcome measures were analyzed to evaluate pain and symptom relief. Results Thirty-two subjects were randomized (21 women, 11 men, mean age: 64.8 years). EP-104IAR was well tolerated. Average serum cortisol levels showed no clinically significant deviations compared to placebo and remained within the normal range of cortisol variation. Plasma PK concentrations were within acceptable safety margins, compared to marketed FP products. Synovial fluid FP levels were approximately 2 orders of magnitude higher and at efficacious concentrations for most subjects. Efficacy evaluations indicated that EP-104IAR provided an immediate improvement of OA symptoms and these effects persisted for 8 to 12 weeks consistently across all measures. Conclusions This study provides evidence that 15 mg of EP-104IAR is well tolerated and has the potential for efficacy in OA patients. These data support further examination of EP-104IAR in larger clinical studies.

Objective The adamalysin metalloproteinase 15 (ADAM15) has been shown to protect against development of osteoarthritis in mice. Here, we have investigated factors that control ADAM15 levels in cartilage. Design Secretomes from wild-type and Adam15−/− chondrocytes were compared by label-free quantitative mass spectrometry. mRNA was isolated from murine knee joints, either with or without surgical induction of osteoarthritis on male C57BL/6 mice, and the expression of Adam15 and other related genes quantified by RT-qPCR. ADAM15 in human normal and osteoarthritic cartilage was investigated similarly and by fluorescent immunohistochemistry. Cultured HTB94 chondrosarcoma cells were treated with various anabolic and catabolic stimuli, and ADAM15 mRNA and protein levels evaluated. Results There were no significant differences in the secretomes of chondrocytes from WT and Adam15−/− cartilage. Expression of ADAM15 was not altered in either human or murine osteoarthritic cartilage relative to disease-free controls. However, expression of ADAM15 was markedly reduced upon aging in both species, to the extent that expression in joints of 18-month-old mice was 45-fold lower than in that 4.5-month-old animals. IL-13 increased expression of ADAM15 in HTB94 cells by 2.5-fold, while modulators of senescence and autophagy pathways had no effect. Expression of Il13 in the joint was reduced with aging, suggesting this cytokine may control ADAM15 levels in the joint. Conclusion Expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging human and murine joints, possibly due to a concomitant reduction in IL-13 expression. We thus propose IL-13 as a novel factor contributing to increased osteoarthritis risk upon aging.

Objective MicroRNA-140-3p is the most prevalent form of canonical miR-140 in native chondrocytes. IsomiRs are sequence variants of microRNAs with potentially distinct functionalities. Here we present functional studies of canonical microRNA-140-3p and two of its most prevelant isomiRs, a 5' isomiR and a 3' isomiR, in an inflammation-induced model of osteoarthritis (OA). Method Canonical miR-140-3p, the 5' isomiR and the 3' isomiR were overexpressed seperately in chondrocytes from three donors and subsequently subjected to an inflammatory milieu mediated by interleukin 1 beta and tumor necrosis factor alpha. RNA sequencing was performed on the cells to investigate the altered transcriptomes, RT-qPCR was performed to validate important observations, and western blot analysis was carried out to further study key inflammatory molecules. Results The three microRNAs downregulated many of the same genes. However, the 5' isomiR showed a much greater target spectrum compared to the other two miRNAs, and downregulated cascades of genes downstream of interferon beta, interferon gamma and interleukin 1 beta as well as genes involved in several other inflammatory and antiviral pathways. In addition the 5' isomiR downregulated practically all HLA class II and class I genes. Conclusion Introduction of the 5’ isomiR led to downregulation of genes essential for some of the most important inflammation cascades and virtual silencing of genes responsible for antigen presentation. These observations may indicate a very promising therapeutic potential for the 5' isomiR for OA and several inflammatory conditions, particularliy HLA associated immune conditions including many arthritic diseases.

Objective To investigate whether the first wave of the COVID-19 pandemic impacted healthcare consultations (HCC) and hospitalization among people with and without osteoarthritis (OA). Methods Using register data, we included individuals aged ≥35 years residing in Skåne region, Sweden, during 2009–2019 with (n = 123,523) and without (n = 552,412) a diagnosis of OA during January 1, 2009–December 31, 2019. We collected bi-weekly individual data on HCC/hospitalization between January and May for years 2017–2020. Treating the year 2020 as intervention and 2017–2019 as control as well as dividing data to pre– (January–February) and post–pandemic (March–May), we applied event study design to measure the dynamic effects of the COVID-19 pandemic on HCC/hospitalization. We used fixed-effect Poisson regressions for estimation and subgroup analyses by sex, age, and comorbidity were conducted among OA patients. Results The impact of the pandemic on healthcare use was evident from mid-March 2020 (34–45%/12–25% reductions in in-person HCC/hospitalization) among people with OA relative to 2017–2019. Smaller reductions were seen in those without OA with 25–34%/8–16% reductions in in-person HCC/hospitalization. On contrary, there were increases in remote HCC following the pandemic (5–25% and 11–31% in people with and without OA, respectively). Among persons with OA, there were variations in the pandemic's effects by sex, age and comorbidity. Conclusion Despite no lockdown in Sweden there were substantial reductions in in-person healthcare use during the first wave of COVID-19 pandemic with greater reductions among people with than without OA.

Objective To describe the point prevalence of hip symptoms, radiographic hip osteoarthritis (rHOA), severe rHOA, and symptomatic rHOA (sxHOA) at five time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCoOA). Design Data were from 3068 JoCoOA participants who attended up to five study visits (1991–2018). Standardized supine pelvis radiographs were read by a single, expert musculoskeletal radiologist with high reliability. The four outcomes were: 1) self-reported hip symptoms: “On most days, do you have pain, aching, or stiffness in your right/left hip?“; 2) rHOA: Kellgren-Lawrence grade (KLG) of 2–4; 3) severe rHOA: KLG of 3–4; and 4) sxHOA: both symptoms and rHOA in the same joint. Weighted point prevalence and 95% confidence intervals (CI) were generated overall and by age group (45–54, 55–64, 65–74, 75+ years), sex, race (Black/White), and body mass index (BMI; 18.5–24.9; 25–29.9; 30+ kg/m²). Results At the most recent follow-up (2017–2018), the point prevalence (%) of hip symptoms, rHOA, severe rHOA, and sxHOA were 30% (95% CI 25%, 35%), 53% (95% CI 48%, 58%), 9% (95% CI 6%, 12%), and 15% (95% CI 11%, 19%), respectively. RHOA and severe rHOA were most prevalent in those 75+ years. Women were more likely than men to have hip symptoms and sxHOA. No consistent trends were noted by race or BMI. Conclusion These updated point prevalence estimates demonstrate a large and increasing burden of HOA in the general population, particularly with aging. Black and White individuals were affected similarly in this cohort.

Objective We aimed to evaluate the association between inflammatory biomarkers in peripheral blood and severity of knee osteoarthritis (OA). Methods We performed a cross-sectional study in participants with frequent knee pain, evaluated radiographic and clinical severity. We measured inflammatory biomarkers: plasma (p) IL-1Ra, IL-1β, IL-18, serum (s) CD14, hsCRP and bone and cartilage biomarkers: urine (u) CTX-II, (s) HA, COMP, CTX-I, PIIANP. We assessed radiographic severity by Kellgren-Lawrence (KL) grading and Osteoarthritis Research Society International (OARSI) standardized scoring atlas; and clinical severity by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results 139 participants (82% women, mean ± SD age: 55.5 ± 7.8 years) were included. (p) IL-1Ra was negatively associated with radiographic severity by KL grading (Spearman rho= -0.197, P= 0.021), osteophytes (Spearman rho= -0.217, P= 0.011), and joint space narrowing of index knee (Spearman rho= -0.172, P= 0.045); and KL sum score of both knees (Spearman rho= -0.180, P= 0.035), after adjustment for age, gender and body mass index (BMI). Other inflammatory markers were not associated with radiographic severity. Cartilage degradation markers (u) CTXII and (s) COMP were modestly associated with radiographic severity after adjustment. In multivariate models, (s) hsCRP and the bone and cartilage biomarkers, but not the inflammatory biomarkers, were associated with radiographic severity. Conclusion Among the inflammatory biomarkers in peripheral blood, IL-1Ra was negatively associated with radiographic severity in this early knee OA cohort.

Objective Compare a telemedical treatment (distant working) with an onsite treatment. Telemedical services have been used frequently in non-surgical disciplines. It remains unclear if orthopaedic outpatients can be treated via telemedicine. We evaluated the diagnostic accuracy and recommended therapy of a mobile healthcare communication app. Design We conducted a prospective, double-blind, anonymized clinical study of consecutive outpatients at an orthopaedic department at a university hospital. Patients were treated by an onsite doctor, who then uploaded each patient’s variables (e.g. personal history, clinical findings, radiograph) for evaluation by a telemedical doctor. The telemedical doctor received the information only via app and did not see the patient physically. Both the onsite and telemedical doctors then uploaded their respective diagnosis and suggested therapy, blinded to each other. The patient received treatment from the onsite doctor only: virtual treatment was solely for scientific purposes and had no therapeutic impact. Results Among 280 consecutive orthopaedic outpatients (57% female and 43% male), the mean age was 63 years. In 83% of cases, the telemedical diagnosis matched the onsite diagnosis, and in 98% of cases, the telemedical treatment did no harm. In 75% of cases, the onsite and telemedical doctors proposed the same therapy. In 2% of cases, the telemedical therapeutic regimen differed from the onsite treatment and could possibly harm the patient. Conclusion The results suggest that diagnosis and treatment via telemedicine seems feasible in the field of orthopaedic surgery and could be an option for telemedical patient interactions (via work from home or virtual interactions).

Objective To gain insight into Treg interactions with synovial tissues in early OA, an equine tri-culture model of OA was used to test the hypothesis that Tregs, in the absence of T Helper 17 cells, are sufficient to resolve inflammation elicited by IL-1β. Methods To model normal and OA joints, synoviocytes were co-cultured with chondrocytes in a transwell system and +/- stimulated with IL-1β. Tregs were activated and enriched, then added to co-cultures, creating tri-cultures. At culture end, synoviocytes and chondrocytes were analyzed for gene expression, Treg Foxp3 expression was reexamined by flow cytometry, and conditioned media were evaluated by ELISA. Results Tregs increased IL-10 and IL-4 in tri-culture media and increased TIMP1 gene expression in synoviocytes and chondrocytes. Tregs increased IL-6 in conditioned media and Il6 gene expression in synoviocytes, which was additive with IL-1β. In chondrocytes, addition of Tregs decreased Col2b gene expression while Acan gene expression was decreased by IL-1β and addition of Tregs. IL-17A was detected in tri-cultures. CCL2 and CCL5 were increased in tri-cultures. Conclusions In a tri-culture model of OA, addition of Tregs resulted in conditions conducive to chondroprotection including increased concentration of IL-10 and IL-4 in conditioned media and increased gene expression of TIMP1 in both chondrocytes and synoviocytes. However, there was increased concentration of the catabolic cytokine IL-6, and decreased gene expression of Col2b and Acan in IL-1β-stimulated chondrocytes. These results suggest that blocking IL-6 could enhance Treg function in mitigating OA progression.

Objective The trends in prevalence of hip osteoarthritis (OA) over a 10-year period among Japanese men and women were investigated using the data from the Research on Osteoarthritis/osteoporosis Against Disability study. Design We analyzed the data of 2924 baseline survey participants (1026 men, 1898 women) aged 40–89 years (mean 70.7 years) residing in urban, mountainous, and coastal communities who were surveyed in 2005–2007. We compared these data with that of 2347 participants (726 men, 1621 women) aged 40–89 years (mean 69.2 years) from the fourth survey in 2015–2016. The fourth survey invited participants to attend follow-ups for baseline survey and recruited new participants. After scoring the radiographs using the Kellgren/Lawrence (K/L) grading system, hip OA was defined as a K/L score ≥2. Results The prevalence of radiographic hip OA was 18.4% and 14.4% in the baseline survey, and 16.0% and 10.7% in the fourth survey among men and women, respectively. Among the participants aged 40–69 years, the prevalence of radiographic hip OA was significantly lower during the fourth survey than during the baseline survey. Whereas, among elderly men aged 70–79 years, radiographic hip OA was significantly less prevalent during the baseline survey than during the fourth survey. From the logistic regression analysis results, radiographic hip OA was significantly less prevalent during the fourth survey than during the baseline survey (odds ratio: 0.55, 95% confidence interval: 0.46–0.65). Conclusion At a 10-year interval, the prevalence of radiographic hip OA shows an improving trend.

Objective To assess the extent and trends in registration of Orthopaedic randomized clinical trials (RCTs) between 2015 – 2020. Design Epidemiological study. Primary publications of RCTs published in top Orthopaedic journals (ISI Journal Citation Reports 2019 rankings) between 2015 – 2020 were included in this meta-epidemiological study with no restrictions on patient population, intervention/control groups or outcome type. Independent reviewers in pairs were involved in RCT selection and data extraction. The proportion of RCTs published that were registered (prospectively or retrospectively) or not registered were reported using counts and percentages stratified by years for each journal. Results A total of 474 primary RCTs were considered eligible. We identified 157 out of 474 RCTs (33% of RCTs across journals) that were reported to have been registered prospectively. The proportion of prospective RCT registrations had increased by 40% (10% to 50%) between 2015 – 2020. On the other hand, the proportion of RCTs with no registrations were reduced by 29% (50% to 21%) between 2015 – 2020. Conclusion Prospective RCT registration in the past 5 years in the field of orthopaedic has increased, but 2/3 of published RCTs still failed to report prospective registration.

Objective To describe the frequency and severity of magnetic resonance imaging (MRI) based peripheral osteoarthritis (OA) in athletes during the Rio de Janeiro 2016 Olympic Games. Methods All MRIs of the peripheral joints in Olympic athletes, performed at the centralized imaging facility, either following acute trauma or for non-traumatic joint pain, were included. All MRIs were retrospectively reviewed for presence and severity of MRI-based OA using an adapted Outerbridge classification for cartilage and adapted classifications for other tissues. Scoring of MRI abnormalities was independently and retrospectively performed without reference to the on-site clinical reports. The frequencies of MRI-detected OA were tabulated and grouped into sports categories, athletes’ age (<25; 25-29; and ≥30 years of age), and sex. Results 11,274 athletes participated in the Games. 320 athletes underwent MRI of the peripheral joints. One hundred sixty (50.0%) were female, 109 (34.1%) were <25 years, 132 (41.3%) between the ages of 25 and 29 years old, and 79 (24.7%) ≥30 years old. 53 (16.6%) had MRI-based OA, with slightly more than half having severe OA. In every age category, severe OA was the most frequent finding and there was a linear trend for increased likelihood of having OA with increasing age (Cochran-Armitage test, p=0.009). Frequencies of OA were similar in male and female athletes. The wrist (29.2%) and the knee (23.3%) were the most commonly affected joints. Conclusions MRI-defined OA was not uncommon among elite athletes in this selected sample.

Objective To stimulate future research directions that seek solutions for osteoarthritis (OA) at the interface between diverse disciplines and address osteoarthritis (OA) as a serious disease with a complexity that has presented a barrier to finding safe effective solutions. Methods Sessions were conducted at the 2019 meetings of the Orthopaedic Research Society (ORS) and Osteoarthritis Research Society International (OARSI) that included presentations and questions/comments submitted from leading OA researchers representing imaging, mechanics, biomarkers, phenotyping, clinical, epidemiology, inflammation and exercise. Results Solutions for OA require a paradigm shift in research and clinical methods in which OA is contextualized as a complex whole-body/person disease. New OA definition(s)/phenotype(s) and OA markers/signals are needed to address the interplay between genetic and environmental factors of the disease as well as capture the mechanosensitivity of the disease. The term “Mechanokines” was proposed to highlight the importance of incorporating whole body mechanics as a marker of early OA. New interventions and apparent paradoxical observations/questions (e.g. exercise vs. load modification) were also discussed in the context of considering OA as a complex system. Conclusion To advance new OA treatments that are safe and effective, OA should be considered as a “Whole Person” disease. This approach requires a concerted effort to bridge disciplines and include interactions across scales from the molecule to the whole body, including psychosocial aspects.

Background and objectives Osteoarthritis (OA) is the most common form of arthritis and is associated with significant morbidity and mortality. There are several available recently updated guidelines for the management of hip and knee OA. Herein, we describe the similarities and differences among the 2019 American College of Rheumatology/Arthritis Foundation (ACR/AF), the 2019 Osteoarthritis Research Society International (OARSI), and the 2020 Veterans Affairs and Department of Defense (VA/DoD) treatment guidelines. Results In all the three guidelines, patient education, weight loss encouragement for overweight patients, exercise, and self-efficacy and self-management programs were considered core treatments for hip and knee OA. Topical NSAIDs are strongly recommended for knee OA, oral NSAIDs and intraarticular steroid injections are also recommended among all three guidelines. The ACR/AF and VA/DoD recommend the use of paracetamol and topical capsaicin in contrast to the OARSI guidelines. Intra-articular hyaluronic acid is not recommended by the ACR/AF in contrast to the OARSI and VA/DoD. Another difference is the use of tramadol in patients with persistent knee or hip OA pain, which is recommended by ACR/AF as opposed to VA/DoD and OARSI who recommend against the use of opioid analgesics without exceptions. Conclusion All three guidelines are mostly consistent in their recommendations.

Objective To provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions. Methods The Mine the Gap online workshop was hosted on October 14th and 15th, 2020. Five international panels, each comprised of a clinician, clinical researcher and basic scientist, presented gaps and proposed solutions for the themes of biomechanics, pain, biological measurements, phenotypes and imaging. This was followed by an interactive panel discussion with consumer insights. Results A number of translational gaps and proposed solutions across each of the five themes were identified. A consumer panel provided constructive feedback highlighting the need for improved resources, communication and shared decision making, and treatment individualisation. Conclusion This brief report provides a greater understanding of the diverse work and gaps relevant to fundamental/discovery scientists, clinical researchers and clinicians working across the musculoskeletal field. The numerous translational gaps highlight the need to improve communication and collaboration across the musculoskeletal field.

Objective Osteoarthritis (OA) is heterogeneous disease, for which drug development has proven to be challenging, both facilitated and hampered by changing guidelines. This is evident by the current lack of approved treatments, which improve joint function and delay joint failure. There is a need to bring together key stakeholders to discuss, align and enhance the processes for OA drug development to benefit patients. Design To facilitate drug development, the Osteoarthritis Research Society International (OARSI) initiated a series of annual clinical trials symposia (CTS). The aim of these symposia was to bring together academics, translational and clinical scientists, regulators, drug developers, and patient advocacy groups to share, refine and enhance the drug development process for the benefit of patients. Results OARSI is now considered the leading organization to facilitate open dialogue between all these stakeholders, in the intersection of understanding of the pathologies and drug development. Clearly, such a pivotal task needs an annual forum to allow stakeholders to share and discuss information, as possible solutions are joint efforts rather than a single stakeholder contribution. Conclusions The main topic of the 2021 CTS was how to improve clinical studies to help patients through overcoming barriers to development of new disease modifying treatments for OA. One key aspect was the focus on definitions of disease activity, status and the definitions of “illness vs disease”. There is a clear medical need to couple a given disease activity with the optimal intervention for the right patient.

Objective To identify post-operative risk factors for the development of chronic pain after knee replacement. Design Primary knee replacements in persons aged ≥18 years between April 2008 and December 2016 from the National Joint Registry, linked with English Hospital Episode Statistics data, and Patient Reported Outcome Measures. The outcome was chronic pain 6-months after surgery (Oxford Knee pain score). Logistic regression modelling identified risk factors for chronic pain outcome. Results 258,386 patients; 56.7% women; average age 70.1 years (SD ±8.8 years). 43,702 (16.9%) were identified as having chronic pain 6-months post-surgery. Within 3 months of surgery complications were uncommon: intra-operative complications 1,224 (0.5%); ≥1 medical complication 6,073 (2.4%)); 32,930 (12.7%) hospital readmissions; 3,848 (1.5%) re-operation; 835 (0.3%) revision. Post-surgical risk factors of chronic pain were: mechanical complication of prosthesis odds ratio (OR) 1.56 (95% Confidence Interval 1.35, 1.80); surgical site infection OR 1.13 (0.99, 1.29); readmission OR 1.47 (1.42, 1.52); re-operation OR 1.39 (1.27, 1.51); revision OR 1.92 (1.64, 2.25); length of stay e.g. 6+ vs. <2 days OR 1.48 (1.35, 1.63), blood transfusion OR 0.47 (0.26, 0.86) and myocardial infarction OR 0.69 (0.49, 0.97). Discriminatory ability of the model was only fair (c-statistic 0.71) indicating that post-surgical predictors explain a limited amount of variability in chronic pain. Conclusions We identified a number of post-operative factors relating to the operation and early recovery that are associated with chronic pain following primary knee replacement. The model had weak discriminatory ability indicating that there remains considerable unexplained variability in chronic pain outcome.

Objective Due to the complexity and heterogeneity of osteoarthritis (OA) pathophysiology, studying the interaction between intrinsic molecular changes in chondrocytes after hyper-physiological mechanical stress (MS) and aberrant signalling of OA risk genes remains a challenge. In this study we set out to set up an in vitro 3D neo cartilage pellet model that enables us to explore the responses of OA risk genes to hyper-physiological MS. Design Human primary chondrocyte neo-cartilage pellets were exposed for 2 days to 2 × 10 min of hyper-physiological dynamic MS attained by a 20% strain and a frequency of 5 Hz. In order to assess cartilage damage, sulphated glycosaminoglycan (sGAG) content in the neo-cartilage was quantified using Alcian blue staining and a dimethyl methylene blue (DMMB) assay, while cleavage of aggrecan was visualized by immunohistochemical staining of aggrecan neo-epitope NITEGE. In addition, changes in expression levels of catabolic, anabolic and hypertrophic genes, and of three OA risk genes; IL11, MGP and TGFA were determined. Results Hyper-physiological MS induced cartilage damage, as reflected by decreased sGAG content. mRNA levels of aggrecanase ADAMTS5 were increased, while hypertrophic gene RUNX2 was downregulated. MS increased expression of pro-apoptotic marker NOXA. Furthermore, 20% MS led to increased expression of all three OA risk genes IL11, MGP and TGFA. Conclusions We established a human in vitro model in which hyper-physiological MS induced cartilage damage and catabolic signalling. Next, we demonstrated its usage to study OA risk genes and their response to the mechanical aspects of OA pathophysiology.

Objectives Weakness of upper leg muscles has a negative impact on future disease and functional status in subjects with knee osteoarthritis (OA). The aims of the present study were to (i) describe the course of muscle strength over 48 months and (ii) identify baseline predictors for a decline in upper leg muscle strength over time in subjects with knee OA. Methods Data were obtained from the Osteoarthritis Initiative (OAI) database, a multicenter, observational study of knee OA. Upper leg muscle strength (in N/kg) was measured at baseline, 24 and 48 months. Potential baseline predictors included demographics, OA-specific and health and lifestyle related factors. Linear mixed model analyses were performed. Results A total of 1390 subjects with knee osteoarthritis were included. A statistically significant decline of muscle strength was found between baseline and 24 months (B = −0.186, 95%CI [-0.358,-0.014], p = 0.03), but not between other time points (24–48 months p = 0.89, and baseline and 48 months p = 0.058). Predictors of a decline in muscle strength over time included demographic predictors (older age, being female, higher body mass index (BMI)), one lifestyle predictor (lower dietary protein intake) and one OA-specific predictor (radiographic severity). Conclusions Muscle strength declined over time in subjects with knee OA. The identified predictors may help clinicians to select and treat subjects with knee OA at risk of a decline in muscle strength.

Objective People with knee or hip osteoarthritis (OA) can experience comorbid lumbar spinal stenosis (LSS), but the impact on treatment outcomes is unknown. The aim of this study was to investigate associations between comorbid LSS symptoms and changes in pain, function, and quality of life following a patient education and exercise therapy program. Design This was a longitudinal analysis of 6,813 participants in the Good Life with osteoArthritis in Denmark (GLA:D®) program; a structured patient education and exercise therapy program for knee and hip OA. Participants were classified as having comorbid LSS symptoms based on self-report symptom items. Linear mixed models were used to assess differences in change in pain, function, and quality of life outcomes (0 worst to 100 best) at 3- and 12-month follow-up. Results 15% and 23% of knee and hip OA participants had comorbid LSS symptoms, respectively. Knee participants with comorbid LSS symptoms had smaller improvement in pain at 3-months (-1.7, 95% CI -3.3 to -0.1) and hip participants with comorbid LSS symptoms had greater improvement in function at 3- (2.5, 95% CI 0.5 to 5.0) and 12-months (3.8, 95% CI 0.9 to 6.6), when compared to those without LSS symptoms. These differences were not clinically significant and no differences in other outcomes were observed. Conclusion Knee or hip OA patients with comorbid LSS symptoms should expect similar improvements in knee- or hip-related pain, function, and quality of life outcomes when undergoing a patient education and exercise therapy program compared to those without LSS symptoms.

Objective To demonstrate an ultra-high field (UHF) 7 T delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) protocol for quantitative post-traumatic osteoarthritis (PTOA) detection and monitoring in a rabbit anterior cruciate ligament transection (ACLT) model. Design ACL transections were performed unilaterally in 5 rabbits (33-weeks-old, 3.5 ± 0.5 kg) to induce PTOA. MRI exams were performed at 7 T prior to and 2, 4, 7 and 10-weeks after ACLT using a modified dGEMRIC protocol. Voxel-based T1 and T2 maps were created over manually drawn femoral cartilage ROIs from the center of the tibial plateau to the posterior meniscus. Femoral, tibial, and patellar epiphyses were harvested 10-weeks post-surgery and processed for μCT imaging and histology. Results Quantitative analysis revealed a 35% and 39% decrease in dGEMRIC index in the medial ACLT knee compartment 7- and 10-weeks post-surgery, respectively (p = 0.009 and p = 0.006) when compared to baseline. There was no significant change in the lateral ACLT compartment or in either compartment of the control knees. Visual inspection of histology confirmed PTOA in the ACLT knees. Osteophytes were found only in ACLT knees (osteophyte volume in femur: 94.53 ± 44.08 mm³, tibia: 29.35 ± 13.79 mm³, and patella: 3.84 ± 0.92 mm³) and were significantly larger in the medial compartments of the femur than lateral (p = 0.0312). Conclusion The dGEMRIC technique quantitatively applied at 7 T UHF-MRI demonstrates site-specific cartilage degeneration in a large animal PTOA model. This should encourage further investigation, with potential applications in drug and therapeutic animal trials as well as human studies.

Objective Our primary objective was to identify the prevalence of spin — misleading reporting practices that overemphasize benefit or underemphasize harm — within the abstracts of systematic reviews and meta-analyses focused on surgical management of osteoarthritis of the knee. Methods A search string was developed to search Ovid MEDLINE and Ovid Embase for articles pertaining to surgical management, or quality of life after surgical management, of osteoarthritis of the knee. Titles and abstracts were screened according to our protocol, developed a priori, followed by full-text evaluation for spin in included articles. Study characteristics were simultaneously extracted with spin data and each included study received an AMSTAR-2 quality appraisal. All procedures were performed by two examiners in a masked, duplicate fashion. Results Of the 1419 articles returned, 96 systematic reviews qualified for inclusion. 35.4% of the included abstracts (34/96) contained at least one type of spin with a total of 36 occurrences (two abstracts contained two types of spin). Selective reporting favoring benefit (type 3; 15/36, 41.7%) was the most prevalent followed by selective reporting of harms (type 6; 7/36, 19.4%). None of the abstracts contained spin types 2, 4, or 8. We found no significant association between spin and either AMSTAR-2 rating or extracted study characteristics. Conclusion Of the included systematic reviews and meta-analyses, 35.4% contained spin in their abstract. To improve the reliability of systematic reviews and meta-analyses, researchers should act to minimize spin in future abstracts.