Incident Symptomatic Knee Osteoarthritis Research Articles

Essential Fatty Acids and Osteoarthritis.

Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA. We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms. We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes. We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes.

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)

Incidence and risk factors of symptomatic knee osteoarthritis among the Chinese population: analysis from a nationwide longitudinal study

BackgroundKnee osteoarthritis (OA) is a common disease condition associated with aging and a frequent cause of primary care consultations. Few longitudinal studies have been conducted to investigate the incidence of symptomatic knee osteoarthritis (OA) and to identify its risk factors among the Chinese population.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) is a nationwide longitudinal survey of persons aged ≥45 years. Symptomatic knee OA was diagnosed when both self-reported knee pain and self-reported physician-diagnosis arthritis existed. Using the national survey data collected from the CHARLS, we estimated the incidence of symptomatic knee OA, taking into account the complex survey design and response rate. We applied weighted logistic regression analysis to identify its risk factors.ResultsIn the 4-year follow-up, the cumulative incidence of symptomatic knee OA among middle-aged and older Chinese adults was 8.5%; the incidence was higher among females (11.2%) than males (5.6%). Female (odds ratio (OR) 1.98 [95% confidence interval (CI) 1.65–2.37]), rural area (OR 1.32 [95% CI 1.08–1.60]), and West region (OR 2.33 [95% CI 1.89–2.87]) were associated with a higher risk of incident symptomatic knee OA. Physical activities (OR 0.47 [95% CI 0.29–0.76]) and high education level (OR 0.60 [95% CI 0.41–0.88]) was associated with a lower risk of incident symptomatic knee OA, while histories of heart disease (OR 1.40 [95% CI 1.07–1.82]), kidney disease (OR 1.80 [95% CI 1.35–2.39]), and digestive disease (OR 1.54 [95% CI 1.30–1.82]) were associated with a higher risk of incident symptomatic knee OA.ConclusionThe cumulative incidence of symptomatic knee OA over 4 years was relatively high, and varied by province and region. Lack of physical activities was confirmed to be risk factors of incident symptomatic knee OA. The presence of heart disease, kidney disease, and digestive disease may be associated with a higher risk of incident symptomatic knee OA, further research need to confirm these findings.

Inflammatory potential of diet and risk of knee osteoarthritis: data from the osteoarthritis initiative

Purpose: Diet plays a fundamental role in prevention of many chronic diseases by regulating inflammation and body weight. The evidence of diet in OA development is accumulating. We aimed to examine the relation of inflammatory potential of diet, a modifiable risk factor, to incident knee osteoarthritis (OA) and the role of BMI in the association of interest. Methods: We used data from the Osteoarthritis Initiative. Dietary inflammatory index®(DII®) was calculated based on theBlock Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. DII® is a literature-derived population-based scoring algorithm to assess the inflammatory potential of diet as a whole and was evaluated for validity and shown to predict inflammatory markers. A higher score of DII® indicates a greater inflammatory potential of diet (i.e., pro-inflammatory effect of diet). Outcomes were incident radiographic knee OA (ROA) (i.e., a KL grade ≥2) and incident symptomatic knee OA (SxOA) (i.e., a combination of a frequent knee pain and ROA). We examined the association of DII® with the risk of knee ROA (or SxOA) by comparing a higher quartile (Q2, Q3 and Q4) with the lowest quartile (Q1: reference category) using generalized estimating equations to account for the correlation between two knees for each participant. In the base model (model 1), we adjusted for age, sex (men vs. women), race (white vs. non-white) and total energy intake (kcal/day). In model 2, we further adjusted for educational attainment (below college vs college or above), annual income (<50,000 US$ vs ≥50,000 US$), tobacco use (non-smoker vs former and current smoker) and PASE score. We tested linear trends using the median value of each quartile of DII®as a continuous variable in the regression model. We conducted sensitivity analyses by including knee replacement due to knee OAduring the follow-up period as incident knee ROA or SxOA, respectively. We performed mediation analyses to assess mediation effect of BMI in DII®-OA relation. Results: We included 1786 and 2940 eligible participants in the final analyses for the association of DII®with incident knee ROA and SxOA, respectively (Figure 1). We identified 232 and 978 knees developed ROA and SxOA among eligible participants over 48-month follow-up period, respectively. Compared with the lowest quartile of DII®, odds ratio (OR) of incident ROA for the highest quartile of DII®was 1.73 (95% confidence interval (CI): 1.15 to 2.62, P for trend= 0.007) (Table 1). The corresponding OR of SxOA was 1.43 (95% CI: 1.16 to 1.76, P for trend = 0.001) (Table 1). When total knee replacement due to knee OA was counted as an incident case of either ROA or SxOA, the results did not change materially.The DII®-OA association was significantly mediated via BMI with an indirect effect of 1.05 (95% CI: 1.02,1.08) for ROA and 1.05 (95% CI: 1.05, 1.11) for SxOA, accounting for 15.6% and 36.0% of total effect, respectively (Table 2). Conclusions: A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. A role of inflammatory potential in dietary strategy for OA was indicated.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Subjective Crepitus as a Risk Factor for Incident Symptomatic Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

Subjective crepitus is the reporting of hearing grating, cracking, or popping sounds in and/or around a joint. We aimed to evaluate whether there is an association between crepitus and incident symptomatic knee osteoarthritis (OA) in the Osteoarthritis Initiative (OAI), a multicenter longitudinal US cohort. Knees without baseline symptomatic OA were included. Crepitus frequency was assessed using a question from the Knee Injury and Osteoarthritis Outcome Score at baseline and at 12, 24, and 36 months. Frequent knee pain and radiographs were assessed at baseline and at annual visits up to 48 months. Radiographic OA was defined as a tibiofemoral Kellgren/Lawrence grade ≥2. Symptomatic OA was defined as a knee with both frequent symptoms and radiographic OA. We performed a repeated-measures analysis with a predictor of crepitus and outcome of incident symptomatic OA, adjusting for age, sex, and body mass index (BMI), with those never reporting crepitus as the referent group. There were a total of 3,495 participants (42.2% male), with mean ± SD age of 61.1 ± 9.2 years and a mean ± SD BMI of 28.2 ± 4.7 kg/m². The odds of incident symptomatic OA were higher with greater frequency of crepitus (never, rarely, sometimes, often, and always, with adjusted odds ratios of (referent), 1.5, 1.8, 2.2, and 3.0, respectively; P < 0.0001 for trend). The group with radiographic OA at OAI baseline but without symptoms contributed 26% of the observations but more than 75% of the incident symptomatic OA cases. In those without symptomatic OA, subjective knee crepitus predicts incident symptomatic OA longitudinally, with most cases occurring in those with preexisting tibiofemoral radiographic OA but without frequent knee pain. However, an important limitation is that patellofemoral OA was not systematically evaluated within the OAI. Subjective crepitus offers utility for the identification of at-risk individuals, predictive modeling, and future research.

Projecting Lifetime Risk of Symptomatic Knee Osteoarthritis and Total Knee Replacement in Individuals Sustaining a Complete Anterior Cruciate Ligament Tear in Early Adulthood

To estimate the lifetime risk of knee osteoarthritis (OA) and total knee replacement (TKR) in persons sustaining anterior cruciate ligament (ACL) tear by age 25 years. We used the Osteoarthritis Policy Model to project the cumulative incidence of symptomatic knee OA requiring TKR in varying situations: no prevalent or incident injury; isolated ACL tear, surgically treated; isolated ACL tear, nonoperatively treated; or a prevalent history or surgically treated ACL and meniscal tear (MT). We estimated MT prevalence and incidence and increased risk of knee OA associated with ACL injury and MT from published literature. We conducted a range of sensitivity analyses to examine the impact of uncertainty in input parameters. Estimated lifetime risk of symptomatic knee OA was 34% for the cohort with ACL injury and MT, compared to 14% for the no-injury cohort. ACL injury without MT was associated with a lifetime risk of knee OA between 16% and 17%, depending on ACL treatment modality. Estimated lifetime risk of TKR ranged from 6% in the no-injury cohort to 22% for the ACL injury and MT cohort. Subjects in the ACL injury and MT cohort developed OA approximately 1.5 years earlier (55.7 versus 57.1) and underwent TKR approximately 2 years earlier (66 versus 68) than the cohort without knee injuries. Sustaining ACL injury early in adulthood leads to greater lifetime risk and earlier onset of knee OA and TKR; concomitant MTs compound this risk. These data provide insight into the impact of sustainable injury prevention interventions in young adults.

Effect of Knee Extensor Strength on Incident Radiographic and Symptomatic Knee Osteoarthritis in Individuals With Meniscal Pathology: Data From the Multicenter Osteoarthritis Study.

High knee extensor strength may be important to protect against the development of knee osteoarthritis (OA) in populations at elevated risk, such as individuals with meniscal pathology. We investigated the extent to which high knee extensor muscle strength was associated with a decreased risk of developing radiographic or symptomatic knee OA in individuals with medial meniscal pathology. We studied knees that at the baseline visit of the Multicenter Osteoarthritis Study had medial meniscal pathology but did not have radiographic knee OA (373 knees in 373 participants) or symptomatic knee OA (combination of radiographic knee OA and frequent knee symptoms; 531 knees in 531 participants). Isokinetic knee extensor strength was measured at baseline, and participants were followed for development of incident radiographic knee OA or incident symptomatic knee OA at 84 months. Separate binomial regression analyses with robust SEs adjusted for age, history of knee surgery, physical activity level, and clinic site were conducted for men and women. High knee extensor strength (normalized by allometric scaling) was associated with a reduced risk of radiographic knee OA in women (relative risk [RR] 0.52, 95% confidence interval [95% CI] 0.29-0.94) but not in men (RR 0.56, 95% CI 0.27-1.16). High knee extensor strength did not protect against the development of symptomatic knee OA, either in women or men. The results only partly confirm the hypothesis that high knee extensor muscle strength protects against later development of knee OA in individuals with medial meniscal pathology.

Longitudinal Course of Physical Function in People With Symptomatic Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative.

Pain and functional decline are hallmarks of knee osteoarthritis (OA). Nevertheless, longitudinal studies unexpectedly reveal stable or improved physical function. The aim of this study was to impute missing and pre-total knee replacement (TKR) values to describe physical function over time among people with symptomatic knee OA. We included participants from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) with incident symptomatic knee OA, observed during the first 30 months in MOST and 36 months in OAI. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function (WOMAC-PF), the 5-times sit-to-stand test, and the 20-meter-walk test were assessed at 4 and 5 years in MOST and at 6 years in OAI. We used a multiple imputation method for missing visits, and estimated pre-TKR values close to the time of TKR, using a fitted local regression smoothing curve. In mixed-effect models, we investigated the physical function change over time, using data before and after imputation and calculation of pre-TKR values. In MOST, 225 (8%) had incident knee OA, with corresponding 577 (12.7%) in OAI. After adjusting for pre-TKR values and imputing missing values, we found that WOMAC-PF values remained stable or slightly declined over time, and the 20-meter-walk test results changed from stable in nonimputed analyses to worsening using imputed data. Data from MOST and OAI showed stable to worsening physical function over time in people with incident symptomatic knee OA after imputing missing values and adjusting pre-TKR values.

Is Quadriceps Muscle Weakness a Risk Factor for Incident or Progressive Knee Osteoarthritis?

The role of the quadriceps muscle in mediating risk for knee osteoarthritis (OA) is a common subject of investigation. The quadriceps muscle is a principal contributor to knee joint stability and provides shock absorption for the knee during ambulation. Clinically, weakness of the quadriceps muscle is consistently found in patients with knee OA. Research has shown that higher quadriceps muscle strength is associated with a reduced risk for incident symptomatic knee OA. However, there is limited evidence to suggest that quadriceps muscle plays a significant role in the incidence of radiographic knee OA. In addition, greater quadriceps muscle strength is associated with a lower risk for progression of tibiofemoral joint space narrowing and cartilage loss in women. This article summarizes knowledge of the relationship between quadriceps muscle strength and risk for knee OA.

Nottingham knee osteoarthritis risk prediction models

Objectives(1) To develop risk prediction models for knee osteoarthritis (OA) and (2) to estimate the risk reduction that results from modification of potential risk factors.MethodThis was a 12-year retrospective cohort...

Effect of Quadriceps Strength and Proprioception on Risk for Knee Osteoarthritis

Impaired quadriceps strength and joint position sense (JPS) have been linked with knee osteoarthritis (OA) cross-sectionally. Although neither has been independently associated with incident radiographic OA, their combination may mediate risk. The purpose of this study was to determine whether better sensorimotor function protects against the development of incident radiographic or symptomatic knee OA. The Multicenter Osteoarthritis study is a longitudinal study of adults aged 50–79 yr at high risk for knee OA. Participants underwent bilateral, weight-bearing, fixed-flexion radiographs, JPS acuity tests, and isokinetic quadriceps strength tests. The relationships between combinations of the tertiles of sex-specific baseline peak strength and mean JPS and development of incident radiographic (Kellgren–Lawrence (KL) grade Q2) or symptomatic knee OA (KL grade Q2 and frequent knee pain or stiffness) at a 30-month follow-up were evaluated. Secondary analyses defined JPS as the variance during the 10 JPS trials and also assessed the interaction of strength and JPS in predicting each outcome. The study of incident radiographic knee OA included 1390 participants (age = 61.2 ± 7 .9 yr and body mass index = 29.4 ± 5.1 kg·m−²), and the study of incident symptomatic knee OA included 1829 participants (age = 62.2 ± 8.0 yr and body mass index = 30.0 ± 5.4 kg·m−²). Greater strength at baseline protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile. There was no significant relationship between the strength–JPS interaction and the development of radiographic or symptomatic knee OA. The finding that quadriceps strength protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile suggests that strength may be more important than JPS in mediating risk for knee OA.

Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal cohort

To assess whether knee extensor strength or hamstring:quadriceps (H:Q) ratio predicts risk for incident radiographic tibiofemoral and incident symptomatic whole knee osteoarthritis (OA) in adults ages 50-79 years. We followed 1,617 participants (2,519 knees) who, at the baseline visit of the Multicenter Osteoarthritis (MOST) Study, did not have radiographic tibiofemoral OA and 2,078 participants (3,392 knees) who did not have symptomatic whole knee OA (i.e., did not have the combination of radiographic OA and frequent knee symptoms). Isokinetic strength was measured at baseline, and participants were followed for development of incident radiographic tibiofemoral OA, or incident symptomatic whole knee OA at 30 months. Generalized estimating equations accounted for 2 knees per subject, and multivariable models adjusted for age, body mass index (BMI), hip bone mineral density, knee surgery or pain, and physical activity score. In the studies of incident radiographic and incident symptomatic knee OA, mean +/- SD ages were 62.4 +/- 8.0 years and 62.3 +/- 8.0 years, respectively, and mean +/- SD BMI scores were 30.6 +/- 5.8 kg/m(2) and 30.2 +/- 5.5 kg/m(2), respectively. Knee extensor strength and H:Q ratio at baseline significantly differed between men and women. Neither knee extensor strength nor the H:Q ratio was predictive of incident radiographic tibiofemoral OA. Compared with the lowest tertile, the highest tertile of knee extensor strength protected against development of incident symptomatic whole knee OA in both sexes (adjusted odds ratio 0.5-0.6). H:Q ratio was not predictive of incident symptomatic whole knee OA in either sex. Thigh muscle strength does not appear to predict incident radiographic OA, but does seem to predict incident symptomatic knee OA.