Symptomatic Radiographic Knee Osteoarthritis Research Articles

Tick-Borne Disease Infections and Chronic Musculoskeletal Pain

Tick-borne diseases (TBDs) other than Lyme disease, such as spotted fever group rickettsiosis, ehrlichiosis, and galactose-α-1,3-galactose (α-gal) syndrome, are an emerging public health issue. Long-term sequelae secondary to Ehrlichia or Rickettsia infection are uncommon; however, musculoskeletal symptoms are often attributed to prior tick exposure. To evaluate the potential associations between prior exposure to TBDs and musculoskeletal symptoms, including radiographic osteoarthritis. This cross-sectional study analyzed serum samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing longitudinal, population-based study in Johnston County, North Carolina. Biospecimen testing and analysis were performed between May 2022 and November 2023. Participants in the JoCo OA project are noninstitutionalized White and Black Johnston County residents 45 years or older. The primary outcome was seropositivity with Ehrlichia IgG, Rickettsia IgG, and/or α-gal IgE and musculoskeletal symptoms. Secondary outcomes included risk factors associated with elevated α-gal IgE and weighted population point prevalence rates. Participants completed questionnaires, underwent physical assessments, and provided biospecimens for serological testing. Multivariable models were used to estimate associations of interest. Of the 605 participants who completed the fourth visit of the JoCo OA project, 488 (80.7%) had serum samples available for testing. The 488 participants had a median (IQR) age of 72 (68-78) years and included 336 females (68.9%) and 161 Black (33.0%) and 327 White (67.0%) individuals. The overall weighted point prevalence was 8.6% (95% CI, 5.9%-11.3%) for Ehrlichia IgG, 17.1% (95% CI, 12.6%-21.5%) for Rickettsia IgG, and 19.6% (95% CI, 15.3%-23.8%) for α-gal IgE level greater than 0.1 IU/mL. Only α-gal IgE was associated with knee pain, aching or stiffness (mean ratio, 1.30; 95% CI, 1.09-1.56). Antibodies to Rickettsia, Ehrlichia, and α-gal were not associated with symptomatic radiographic knee osteoarthritis. Male sex (odds ratio [OR], 2.63; 95% CI, 1.55-4.47), current smoker status (OR, 3.55; 95% CI, 1.38-9.18), and an attached tick bite in the past 5 years (OR, 3.99; 95% CI, 2.22-7.15) were all risk factors that were associated with α-gal IgE level greater than 0.1 IU/mL. Despite only 84 individuals (17.2%) recalling a tick bite in the past 5 years, 178 (36.5%) had evidence of prior tick-borne exposure, suggesting frequent human-tick interactions. Results of this cross-sectional study indicate no association between Ehrlichia or Rickettsia seropositivity and chronic musculoskeletal symptoms or osteoarthritis. Further investigation is needed into the pathogenesis of α-gal syndrome and interventions to reduce human-tick interactions.

Association between knee osteoarthritis and mortality: a serial propensity score-matched cohort study

Background/Aims: The association between symptomatic knee osteoarthritis (OA) and higher cardiovascular disease (CVD) mortality is established; however, findings from studies that utilized regression analysis were limited, attributed to the strong association between OA and metabolic risk factors. This study aimed to evaluate the association between knee OA and mortality through propensity score matching.Methods: This was a cohort study including Korean National Health and Nutrition Examination Survey (2010–2013) participants aged ≥ 50 years. By linking the survey data to cause of death data (through 2019) from Statistics Korea, mortality and cause-specific mortality data were obtained. Radiographic knee OA (ROA) was defined as bilateral Kellgren–Lawrence grade ≥ 2. Propensity score matching (1:1) was conducted between asymptomatic ROA, knee pain, and symptomatic ROA groups and normal groups, balancing the confounding factors. Time to death was analyzed using Cox proportional hazard modeling.Results: A higher CVD mortality was observed in the symptomatic ROA group, but not in others; the risk estimates were asymptomatic ROA (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.77–1.65), knee pain (HR 0.61; 95% CI 0.27–1.38), and symptomatic ROA (HR 1.39; 95% CI 0.89–2.17). No association was found between the all-cause/cancer mortality and other groups.Conclusions: When propensity score matching controls metabolic risk factor imbalances, the association between symptomatic knee OA and higher CVD mortality was weaker compared to results of prior studies that used regression adjustment. The results may be more precise estimates of the total risk of knee OA for mortality in Koreans.

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

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. 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). 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. 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.

Magnetic Resonance Imaging-Assessed Subchondral Cysts and Incident Knee Pain and Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study.

To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes. We used longitudinal data from the Multicenter Osteoarthritis Study, a community-based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes. Among the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16-3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87-5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit. Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease.

Associations between sagittal plane walking kinematics and femoral cartilage ultrasound echo-intensity in individuals with symptomatic radiographic knee osteoarthritis

Purpose: Ultrasound (US) has recently emerged as a valid and reliable tool for assessing femoral articular cartilage. Previous US studies have demonstrated that individuals with knee OA exhibit thinner cartilage with greater irregularities on the cartilage borders and more irregular femoral cartilage compared to healthy age-matched controls. Similarly, US echo-intensity (EI) values for cartilage are higher in individuals with knee OA compared to healthy controls, which may reflect alterations in femoral articular cartilage, such as an increase in the relative water content of the tissue.

An interpretable deep learning model to predict symptomatic knee osteoarthritis

Purpose: Purpose- Early prediction of knee osteoarthritis may help to initiate potential interventions or treatments sooner, which can result in preventing or delaying knee osteoarthritis development. In this study, we aim to develop a deep learning (DL) prediction model to predict the incident symptomatic radiographic knee osteoarthritis over the next 78 months using radiographs at baseline. Methods: 427 knee radiography images from the Osteoarthritis Initiative (OAI) dataset were used to train and validate our model, with a mean age of 55.7 (SD: 3.2, range: 50 - 62) years and a mean BMI of 31.7 (SD: 3.7, range: 26.1 - 47.1) kg/m2. All subjects had Kellgren-Lawrence (KL) grades of 0 or 1 without symptoms at baseline. Incident symptomatic knee osteoarthritis was defined as knee pain and a definite tibiofemoral osteophyte in the same knee developed at 78-month follow up. Attention scores and probability of symptomatic knee osteoarthritis from radiography images were first extracted using an interpretable hierarchical attention-based convolutional neural network (CNN) model. The proposed model leveraged a transfer learning approach based on VGG-16 architecture. A 5-fold stratified cross-validation was used to evaluate and tune the neural network with 20% of training data as validation set in each fold. Twelve clinical variables including: age, body mass index (BMI), gender, KL grade, varus malalignment, history of knee injury, mild symptoms, presence of Heberden nodes, joint line tenderness, crepitus, morning stiffness and postmenopausal status, along with the attention and probability scores from our trained CNN, were then fed into a logistic regression model to predict the 78-month probability of knee osteoarthritis incident for each individual. The developed model was evaluated using an independent test set of 108 baseline knee radiographs from the OAI dataset (age, BMI, KL distribution, no symptoms at baseline). Results: The developed multi-modal model using radiographs and 12 clinical variables demonstrated an area under the receiver operating characteristic curve (AUC) of 0.91 (Figure 1), which outperforms the results reported in the literature using deep learning based methods. Moreover, the proposed model is interpretable, which can detect the specific location of potential abnormalities within knee images using the learned attention scores (Figure 2). Conclusions: A novel deep learning-based predictive model that takes knee radiographs and clinical variables as inputs was developed. It can predict the risk of symptomatic knee osteoarthritis incident over the next 6.5 years with a high AUC value. The attention maps on knee images confirm that the model predictions at baseline match the knee progression pattern in the course of the disease.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Knee Osteoarthritis, Potential Mediators, and Risk of All‐Cause Mortality: Data From the Osteoarthritis Initiative

To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway. Participants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids). Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use. Participants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

Association of anti-thyroid antibodies with radiographic knee osteoarthritis and chondrocalcinosis: a NHANES III study.

Objectives:To examine the relationships between radiographic knee osteoarthritis (RKOA), symptomatic radiographic knee osteoarthritis (sRKOA), and chondrocalcinosis, as outcome variables, and the autoimmune thyroid disease (AITD) autoantibodies, anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb), in the Third National Health and Nutrition Examination Survey (NHANES III) data source.Methods:NHANES III provided data on 2291 persons over the age of 60 years that included the osteoarthritis variables of interest RKOA, sRKOA and chondrocalcinosis, and the thyroid autoantibodies TPOAb and TgAb. A log-binomial regression model was fit to examine the relationships between anti-thyroid autoantibodies and RKOA. Modified Poisson regression models were employed for the thyroid autoantibodies compared to sRKOA and chondrocalcinosis.Results:Patients with higher levels of TPOAb were more likely to have chondrocalcinosis [prevalence ratio (PR) 1.247, 95% confidence interval (CI) 1.051, 1.479, p = 0.012]. A piecewise regression analysis indicated that this relationship between TPOAb and chondrocalcinosis was only observed when TPOAb was above 35 IU/ml (PR 1.482, 95% CI 1.233, 1.781, p < 0.001). Levels equal to or below 35 IU/ml were not associated with chondrocalcinosis. TPOAb was not associated with RKOA or sRKOA, and TgAb was not significantly related to any of the outcomes.Conclusion:There was no association of AITD autoantibodies TPOAb and TgAb with RKOA or sRKOA. However, there may be an association of TPOAb with the presence of chondrocalcinosis.

Occupation and risk of knee osteoarthritis and knee replacement: A longitudinal, multiple-cohort study

ObjectivesTo examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults. MethodsWe used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded. Participants were followed for up to 19-years (Chingford), 96-months (OAI) and 60-months (MOST) for incident outcomes including radiographic knee OA (RKOA), symptomatic RKOA and TKR. In those with baseline RKOA, progression was defined as the time from RKOA incidence to primary TKR. Occupational job categories and work-place physical activities were assigned to levels of workload. Logistic regression was used to examine the relationship between workload and incident outcomes with survival analyses used to assess progression (reference group: sedentary occupations). ResultsHeavy manual occupations were associated with a 2-fold increased risk (OR: 2.07, 95% CI 1.03 to 4.15) of incident RKOA in the OAI only. Men working in heavy manual occupations in MOST (2.7, 95% CI 1.17 to 6.26) and light manual occupations in OAI (2.00, 95% CI 1.09 to 3.68) had a 2-fold increased risk of incident RKOA. No association was observed among women. Increasing workload was associated with an increased risk of symptomatic RKOA in the OAI and MOST. Light work may be associated with a decreased risk of incident TKR and disease progression. ConclusionHeavy manual work carries an increased risk of incident knee OA; particularly among men. Workload may influence the occurrence of TKR and disease progression.

Sequencing identifies a distinct signature of circulating microRNAs in early radiographic knee osteoarthritis

MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages of OA has yet to be conducted. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective was to sequence the miRNome in plasma from 91 patients with early [Kellgren-Lawrence (KL) grade 0 or 1 (n=41)] or late [KL grade 3 or 4 (n=50)] symptomatic radiographic knee OA to identify unique microRNA signatures in each disease state. MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq 550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs. From 215 differentially expressed microRNAs (FDR<0.01), 97 microRNAs showed an increase or decrease in expression in ≥85% of samples in the early OA group as compared to the median expression in the late OA group. Increasing this threshold to ≥95%, seven microRNAs were identified: hsa-miR-335-3p, hsa-miR-199a-5p, hsa-miR-671-3p, hsa-miR-1260b, hsa-miR-191-3p, hsa-miR-335-5p, and hsa-miR-543. Four novel microRNAs were present in ≥50% of early OA samples and had 27 predicted gene targets in common with the prioritized set of predicted gene targets from the 97 microRNAs, suggesting common underlying mechanisms. Sequencing of well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee OA.

Evaluating the structural effects of intra-articular sprifermin on cartilage and non-cartilaginous tissue alterations, based on sqMRI assessment over 2 years

Sprifermin (recombinant human fibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment. Patients aged 40-85 years with symptomatic radiographic knee OA, Kellgren-Lawrence grade 2 or 3, and medial minimum joint space width ≥2.5mm in the target knee were randomized (1:1:1:1:1) to receive three double-blinded, once-weekly, intra-articular injections of sprifermin 30μg or 100μg or placebo every 6 (q6mo) or 12 months. 1.5- or 3T MRIs were read using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system at baseline and 24 months. Change from baseline at 24 months on compartment and/or whole knee level was assessed for cartilage morphology, bone marrow lesions (BMLs), and osteophytes by delta-subregional and delta-sum (DSM) approaches. Menisci, Hoffa-synovitis, and effusion-synovitis were also evaluated for worsening. 549 patients were included. Dose-dependent treatment effects from baseline to 24 months were observed on cartilage morphology (sprifermin 100μg q6mo vs placebo; mean DSM (95% confidence interval [CI])-0.6 (-1.5, 0.2); less cartilage worsening) in the entire knee and BMLs sprifermin 100μg q6mo vs placebo; mean DSM (95% CI)-0.2 (-0.5, 0.1) in the patellofemoral compartment. No effects over 24 months were observed on osteophytes, menisci, Hoffa-synovitis or effusion-synovitis. Positive effects associated with sprifermin were observed for cartilage morphology changes, and BML improvement. There were no meaningful negative or positive effects associated with sprifermin in the other joint tissues examined.

Predominant lifetime occupation and associations with painful and structural knee osteoarthritis: An international participant-level cohort collaboration

With adults working to older ages, occupation is an important, yet less modifiable domain of physical activity to consider in the risk of knee osteoarthritis (OA). This study aimed to investigate the association between predominant lifetime occupation and prevalent knee OA. Participant-level data were used from five international community-based cohorts: Johnston County Osteoarthritis Project, the Hertfordshire Cohort Study, the Multicenter Osteoarthritis Study, the Tasmanian Cohort Study and Framingham Osteoarthritis Study. Self-reported predominant occupation was categorized into sedentary, light, light manual and heavy manual levels. Cross-sectional associations between predominant lifetime occupation and knee OA outcomes including prevalence of radiographic knee OA (RKOA), symptomatic RKOA and knee pain, were assessed using logistic regression, accounting for cohort clustering. Data for 7391 participants were included. 24.7% reported sedentary lifetime occupation, 30.0% light, 35.9% light manual and 9.4% heavy manual. 43.3% presented with RKOA, 52.1% with knee pain and 29.0% with symptomatic RKOA. There was over a two-fold increase in the odds of having RKOA, knee pain and symptomatic RKOA in those whose with heavy manual compared to sedentary occupations ((odds ratio (OR): 2.14; 95% confidence interval (CI): 1.79, 2.58), (OR: 2.19; 95% CI: 1.78, 2.70), (OR: 2.41; 95% CI: 1.94, 2.99) respectively). This large international multi-cohort study demonstrated an association of heavy manual work with RKOA, symptomatic RKOA and knee pain. Measures that protect workers and are designed to reduce heavy manual related activities remain a priority to reduce the risk of knee OA.

The molecular profile of synovial fluid changes upon joint distraction and is associated with clinical response in knee osteoarthritis

SummaryObjectiveSurgical knee joint distraction (KJD) leads to clinical improvement in knee osteoarthritis (OA) and also apparent cartilage regeneration by magnetic resonance imaging. We investigated if alteration of the joint's mechanical environment during the 6 week period of KJD was associated with a molecular response in synovial fluid, and if any change was associated with clinical response.Method20 individuals undergoing KJD for symptomatic radiographic knee OA had SF sampled at baseline, midpoint and endpoint of distraction (6 weeks). SF supernatants were measured by immunoassay for 10 predefined mechanosensitive molecules identified in our previous pre-clinical studies. The composite Knee injury and OA Outcome Score-4 (KOOS4) was collected at baseline, 3, 6 and 12 months.Results13/20 (65%) were male with mean age 54°±°5yrs. All had Kellgren–Lawrence grade ≥2 knee OA. 6/10 analytes showed statistically significant change in SF over the 6 weeks distraction (activin A; TGFβ-1; MCP-1; IL-6; FGF-2; LTBP2), P < 0.05. Of these, all but activin A increased. Those achieving the minimum clinically important difference of 10 points for KOOS4 over 6 months showed greater increases in FGF-2 and TGFβ-1 than non-responders. An increase in IL-8 during the 6 weeks of KJD was associated with significantly greater improvement in KOOS4 over 12 months.ConclusionDetectable, significant molecular changes are observed in SF following KJD, that are remarkably consistent between individuals. Preliminary findings appear to suggest that increases in some molecules are associated with clinically meaningful responses. Joint distraction may provide a potential opportunity in the future to define regenerative biomarker(s) and identify pathways that drive intrinsic cartilage repair.

Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis

Sprifermin is under investigation as a disease-modifying osteoarthritis drug. To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis. FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported. Participants were randomized to 1 of 5 groups: intra-articular injections of 100 μg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks. The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%). Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 μg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 μg of sprifermin every 12 months; 0.02 mm (95% CI, -0.01 to 0.04 mm) for 30 μg of sprifermin every 6 months; and 0.01 mm (95% CI, -0.01 to 0.03 mm) for 30 μg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 μg of sprifermin administered every 6 months or every 12 months, or for 30 μg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 μg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 μg of sprifermin every 12 months: n = 50 [45.0%]; 30 μg of sprifermin every 6 months: n = 40 [36.0%]; and 30 μg of sprifermin every 12 months: n = 48 [44.0%]). Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 μg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain. ClinicalTrials.gov Identifier: NCT01919164.

The association between asymptomatic hyperuricemia and knee osteoarthritis: data from the third National Health and Nutrition Examination Survey

Invitro and clinical studies suggest that urate may contribute to osteoarthritis (OA) risk. We tested the associations between hyperuricemia and knee OA, and examined the role of obesity, using a cross-sectional, nationally representative dataset. National Health and Nutrition Examination Survey (NHANES) III used a multistage, stratified probability cluster design to select USA civilians from 1988 to 1994. Using NHANES III we studied adults >60 years, with or without hyperuricemia (serum urate>6.8mg/dL), excluding individuals with gout (i.e., limiting to asymptomatic hyperuricemia (AH)). Radiographic knee OA (RKOA) was defined as Kellgren-Lawrence grade≥2 in any knee, and symptomatic radiographic knee osteoarthritis (RKOA) (sRKOA) was defined as RKOA plus knee pain (most days for 6 weeks) in the same knee. AH prevalence was 17.9% (confidence interval (CI) 15.3-20.5). RKOA prevalence was 37.7% overall (CI 35.0-40.3), and was 44.0% for AH vs 36.3% for normouricemic adults (p=0.056). symptomatic radiographic knee osteoarthritis (sRKOA) was more prevalent in AH vs normouricemic adults (17.4% vs 10.9%, p=0.046). In multivariate models adjusting for obesity, model-based associations between AH and knee OA were attenuated (for RKOA, prevalence ratio (PR)=1.14, 95% CI 0.95, 1.36; for sRKOA, PR=1.40, 95% CI 0.98, 2.01). In stratified multivariate analyses, AH was associated with sRKOA in adults without obesity (PR=1.66, 95% CI 1.02, 2.71) but not adults with obesity (PR=1.21, 95% CI 0.66, 2.23). Among adults aged 60 or older, AH is associated with knee OA risk that is more apparent in adults without obesity.

PMS54 - Lack of Association Between Beta Blocker Use and Reduction in Joint Pain and Analgesic Use Among Participants with Symptomatic Radiographic Knee Osteoarthritis

PMS54 - Lack of Association Between Beta Blocker Use and Reduction in Joint Pain and Analgesic Use Among Participants with Symptomatic Radiographic Knee Osteoarthritis

Efficacy and safety of intra-articular Sprifermin in symptomatic radiographic knee osteoarthritis: pre-specified analysis of 3-year data from a 5-year randomized, placebo-controlled, phase II study

Efficacy and safety of intra-articular Sprifermin in symptomatic radiographic knee osteoarthritis: pre-specified analysis of 3-year data from a 5-year randomized, placebo-controlled, phase II study

Longitudinal association between foot and ankle symptoms and worsening of symptomatic radiographic knee osteoarthritis: data from the osteoarthritis initiative.

To assess whether foot and/or ankle symptoms are associated with an increased risk of worsening of knee pain and radiographic change in people with knee osteoarthritis (OA). The presence and laterality of foot/ankle symptoms were recorded at baseline in 1368 participants from the Osteoarthritis Initiative (OAI) with symptomatic radiographic knee OA. Knee pain severity (measured using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width measured on X-ray were assessed yearly over the subsequent 4years. Associations between foot/ankle symptoms and worsening of (1) knee pain, and (2) both knee pain and minJSW (i.e., symptomatic radiographic knee OA) were assessed using logistic regression. Foot/ankle symptoms in either foot/ankle significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI 1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI 1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all associated with knee pain worsening in the follow up period. There was no association between foot/ankle symptoms and worsening of symptomatic radiographic knee OA. The presence of foot/ankle symptoms in people with symptomatic radiographic knee OA was associated with increased risk of knee pain worsening, but not worsening of symptomatic radiographic knee OA, over the subsequent 4years. Future studies should investigate whether treatment of foot/ankle symptoms reduces the risk of knee pain worsening in people with knee OA.

Relationship of Buckling and Knee Injury to Pain Exacerbation in Knee Osteoarthritis: A Web-Based Case-Crossover Study.

BackgroundKnee osteoarthritis (OA) is one of the most frequent causes of limited mobility and diminished quality of life. Pain is the main symptom that drives individuals with knee OA to seek medical care and a recognized antecedent to disability and eventually joint replacement. Evidence shows that patients with symptomatic OA experience fluctuations in pain severity. Mechanical insults to the knee such as injury and buckling may contribute to pain exacerbation.ObjectiveOur objective was to examine whether knee injury and buckling (giving way) are triggers for exacerbation of pain in persons with symptomatic knee OA.MethodsWe conducted a case-crossover study, a novel methodology in which participants with symptomatic radiographic knee OA who have had knee pain exacerbations were used as their own control (self-matched design), with all data collected via the Internet. Participants were asked to log-on to the study website and complete an online questionnaire at baseline and then at regular 10-day intervals for 3 months (control periods)—a total of 10 questionnaires. They were also instructed to go to the website and complete pain exacerbation questionnaires when they experienced an isolated incident of knee pain exacerbation (case periods). A pain exacerbation “case” period was defined as an increase of ≥2 compared to baseline. At each contact the pain exacerbation was designated a case period, and at all other regular 10-day contacts (control periods) participants were asked about knee injuries during the previous 7 days and knee buckling during the previous 2 days. The relationship of knee injury and buckling to the risk of pain exacerbation was examined using conditional logistic regression models.ResultsThe analysis included 157 participants (66% women, mean age: 62 years, mean BMI: 29.5 kg/m2). Sustaining a knee injury was associated with experiencing a pain exacerbation (odds ratio [OR] 10.2, 95% CI 5.4, 19.3) compared with no injury. Knee buckling was associated with experiencing a pain exacerbation (OR 4.0, 95% CI 2.6, 6.2) compared with no buckling and the association increased with a greater number of buckling events (for ≥ 6 buckling events, OR 20.1, 95% CI 3.7, 110).ConclusionsKnee injury and buckling are associated with knee pain exacerbation. Reducing the likelihood of these mechanical events through avoidance of particular activities and/or appropriate rehabilitation programs may decrease the risk of pain exacerbation.

Is waist circumference a better predictor of incident symptomatic radiographic knee osteoarthritis, radiographic knee osteoarthritis and knee pain than body mass index over 10 years?

Is waist circumference a better predictor of incident symptomatic radiographic knee osteoarthritis, radiographic knee osteoarthritis and knee pain than body mass index over 10 years?