Risk Of Knee Osteoarthritis Progression Research Articles

Circulating miRNA-122 is associated with knee osteoarthritis progression: A 6-year longitudinal cohort study in the Yakumo study

ObjectiveThe association between knee osteoarthritis (OA) and miRNAs has been widely reported. However, the utility of miRNAs as predictors of knee osteoarthritis (KOA) progression in longitudinal studies has not been reported. We aimed to identify circulating miRNAs (c-miRNAs) associated with KOA progression in the general population and to examine their potential use as predictors of KOA progression. MethodsIn 2012 and 2018, 66 participants (128 knees) took part in a resident health check-up in the Yakumo study. If the KL classification progressed two or more levels, the patient was classified as having progressive OA. Quantitative real-time polymerase chain reaction was used to screen 21 c-miRNAs. The expression levels of those c-miRNAs were compared between the progressive OA group and non-progressive OA group using student-t-test. Logistic analysis was performed in c-miRNAs less than p < 0.10 in univariate analysis. ResultsThe progressive OA group consisted of 78 knees. The results of the comparison between the progressive OA group and the non-progressive OA group showed that six c-miRNAs as follows; let7d (p = 0.030), c-miRNA-122 (p < 0.001), 150 (p = 0.070), 199 (p = 0.078), 21 (p = 0.016) and 320 (p = 0.093) were extracted as factors related to the progression of knee OA. In addition, logistic regression analysis identified c-miRNA-122 as an independent factor involved in the progression of knee osteoarthritis (odds ratio: 1.510, 95% confidence interval: 1.060–2.140, p = 0.023). The ROC curve showed by c-miRNA-122 for the progression of OA risk had an area under the curve of 0.702 (95% CI: 0.609–0.795). The threshold of c-miRNA-122 was −4.609. ConclusionThe expression level of c-miRNA-122 was associated with the risk of KOA progression in community dwelling Japanese people.

Do Glucocorticoid Injections Increase the Risk of Knee Osteoarthritis Progression Over 5 Years?

Recent findings have demonstrated that intraarticular (IA) glucocorticoid injections can be deleterious for knees with osteoarthritis (OA). This study was undertaken to assess, in a real-life setting, the risk of knee OA progression in patients who received IA glucocorticoid injections over a 5-year follow-up period. We used marginal structural modeling with inverse probability of treatment weighting to determine the causal association between IA glucocorticoid injections and the 5-year risk of disease progression in patients with symptomatic knee OA from the Knee and Hip Osteoarthritis Long-term Assessment cohort. OA progression was defined as an incident total knee replacement (TKR) and/or radiographic worsening (Kellgren/Lawrence [K/L] grade or joint space narrowing [JSN]). We also examined these outcomes in knees that received IA hyaluronan (IAHA) injections. Among the 564 patients with knee OA included in the study sample, 51 (9.0%) and 99 (17.5%) received IA glucocorticoid or IAHA injections, respectively, and 414 (63.1%) did not receive any injection during follow-up. Compared to untreated knees, those treated with IA glucocorticoid injections had a similar risk of incident TKR (hazard ratio [HR] 0.92 [95% confidence interval (95% CI) 0.20, 4.14]; P = 0.91) or K/L grade worsening (HR 1.33 [95% CI 0.64, 2.79]; P = 0.44). IAHA injections had no effect on the risk of TKR (HR 0.81 [95% CI 0.14, 4.63]; P = 0.81) or K/L grade worsening (HR 1.36 [95% CI 0.85, 2.17]; P = 0.20). Similar results were obtained for JSN, and when TKR and radiographic outcomes were combined. In this study, IA glucocorticoid injections for symptomatic knee OA did not significantly increase the 5-year risk of incident TKR or radiographic worsening. These findings should be interpreted cautiously and replicated in other cohorts.

Association between Iron Intake and Progression of Knee Osteoarthritis.

Background: Iron overload is drawing attention in the development of knee osteoarthritis (OA). To identify the modifiable risk factors for iron-related pathological conditions, we examined the association between iron intake and the risk of knee OA progression. Methods: A total of 1912 participants in the Osteoarthritis Initiative (OAI), aged 45–79 years and with at least one knee radiographic OA at baseline, were identified and were followed up to 6 years. The iron and other nutrient intake was measured by the validated Block Brief 2000 Food Frequency Questionnaire. The outcome measures were by radiographic progression on the basis of the Kellgren–Lawrence (KL) grade and the joint-space-narrowing (JSN) score. The association between the iron intake and the knee OA progression was examined by Cox proportional hazards models and restricted cubic spline (RCS) regression. Results: Among the study participants, 409 participants experienced KL-grade progression, and 684 participants experienced JSN-score progression within 6 years. Overall, the association between iron intake and the risk of KL-grade progression followed a U shape (p for nonlinearity < 0.001). The risk of KL-grade progression was significantly lower in participants with iron intakes of <16.5 mg/day (per mg/day: adjusted hazard ratio (HR), 0.75; 95% CI (confidence interval), 0.64–0.89), and it was higher in those with iron intakes ≥16.5 mg/day (per mg/day: HR, 1.20; 95% CI, 1.04–1.38). Consistently, when the iron intake was assessed as deciles, compared to those in Deciles 3–5 (10.9–23.3 mg/day), the risk of KL-grade progression was higher for Deciles 1–2 (≤10.9 mg/day: HR, 1.57; 95% CI, 1.17–2.10) and for Deciles 6–10 (>23.3 mg/day: adjusted HR, 1.60; 95% CI, 1.19–2.16). Similar U-shaped relations were found for iron intake with the risk of JSN-score progression (p for nonlinearity = 0.035). Conclusions: There was a U-shaped association between the iron intake and the progression of knee OA, with an inflection point at about 16.5 mg/day, and minimal risk from 10.9 to 23.3 mg/day of iron intake. An appropriate iron intake was advisable for knee OA, whereas excessive or deficient iron intake increased the risk of knee OA progression.

Metabolic obesity and the risk of knee osteoarthritis progression in elderly community residents: A 3-year longitudinal cohort study.

Metabolic syndrome is a major health problem worldwide associated with obesity, thus drawing attention to its relation to osteoarthritis (OA). However, it is still uncertain whether metabolic syndrome or body fat distribution is associated with knee OA. The aim of this longitudinal study was to elucidate the association between metabolic obesity and adverse structural changes of knee OA assessed by magnetic resonance imaging (MRI). Participants were recruited from the Hallym Aging Study cohort in Korea. Knee MRI scans, along with dual-energy X-ray absorptiometry, were assessed in 226 participants at baseline and after 3years. The structural progression in the tibiofemoral joint was evaluated using the semi-quantitative Whole-Organ MRI Score (WORMS) for cartilage morphology and bone marrow lesions (BML). Logistic regression with generalized estimating equation was performed for associations of metabolic risk factors with worsening of WORMS scores at the subregional level. In the medial compartment, fat mass in women was associated with cartilage loss, but the statistical significance disappeared after adjusting for body mass index. Metabolic syndrome and each of its components were not associated with cartilage loss or increase of BML. On the other hand, the interaction effects of metabolic syndrome on the association between obesity and knee OA progression were not significant. In this cohort, metabolic effects of obesity on knee cartilage damage and BML were not demonstrated. Further large-scale studies are required to prove the causal relationship between metabolic obesity and knee OA.

Do non-steroidal anti-inflammatory drugs cause osteoarthritis progression, a systematic review and meta analysis

Do non-steroidal anti-inflammatory drugs cause osteoarthritis progression, a systematic review and meta analysis

Metabolic syndrome, diabetes and osteoarthritis progression: the Rotterdam study

Purpose: Osteoarthritis (OA) is a degenerative musculoskeletal disorder, characterized by cartilage degradation, synovitis and sclerosis of subchondral bone. Results from observational studies have suggested the existence of a distinct form of OA linked to obesity related factors such as type 2 diabetes (T2D) and dyslipidaemia, also known as metabolic OA. However, conclusive evidence for the existence of such a separate form of OA is still lacking. Recently there has been an increase of interest in the relation between metabolic factors and OA, in particular the metabolic syndrome and its components. In this study, we aimed to investigate the relation between several metabolic factors and conditions (diabetes mellitus, metabolic syndrome, and its components) and progression of radiographic osteoarthritis (OA) in knee, hip and hand joints. Methods: We used data from the Rotterdam Study, a large population-based longitudinal cohort aimed at identifying risk factors for cardiovascular, neurological, endocrine and musculoskeletal diseases in the elderly. The present study included 6,191 individuals with up to 12 years of follow-up data for OA (knee, hip and hand) and data on metabolic factors. Progression of radiographic OA in knee and hip joints was defined as a combination of incident OA (i.e. Kellgren/Lawrence (KL) grade <2 at baseline and ≥2 at follow-up) and progression (increase in KL grade starting from 2 or above). An increase of ≥2 in KL sum score in distal Interphalangeal (DIP)/proximal interphalangeal (PIP) joints was defined as progression in hand OA. We analysed the associations of (components of) the metabolic syndrome with progression of radiographic knee and hip OA stratified for sex using multivariate regression models with generalised estimating equations. In the first model we adjusted for age, smoking, alcohol use, education, subcohort, baseline K/L grade and months between radiographs, while in model 2 we additionally adjusted for BMI. In addition, quartiles of each metabolic factor were analysed for risk of OA progression. Results: Metabolic syndrome and two of its components, abdominal obesity and elevated blood pressure, were associated with higher odds of knee OA progression. However, after additional adjustment for BMI (models 2), the association with metabolic syndrome showed a protective and significant association only in women and the ORs for the elevated blood pressure were attenuated and no longer significant (see Table 1), while the association of abdominal obesity disappeared suggesting that it can be explained by BMI. Diabetes and high fasting glucose, another metabolic component, showed significant protective associations only after adjusting for BMI as shown in Table 1. In additional analyses, the upper 3 quartiles of systolic blood pressure had an increased odds of radiographic knee OA progression before (OR 1.44, 95% CI 1.20 - 1.73) and after BMI adjustment (OR 1.27, 95% CI 1.06 - 1.53) when women and men were analysed together. Figure 1 shows the sex stratified analysis, where the effect sizes attenuated slightly after adjustment for BMI and results did not reach significance level anymore. No associations with hip and hand OA progression were found for the metabolic syndrome components that were tested. Furthermore, secondary survival analyses suggested that the protective effects seen for the metabolic syndrome and diabetes were due to competing risks. Conclusions: Metabolic syndrome and its component were not associated with higher risk of progression in hip, knee or hand OA independently from BMI, suggesting that the associations are mainly driven by obesity and high BMI. For diabetes, high fasting glucose and metabolic syndrome (only in women) an apparent protection against knee OA progression was observed in both non-stratified and stratified analysis. However, the apparent protective effect of diabetes and metabolic syndrome against knee OA progression is most probably due to competing risks. The only factor that seems associated with an increased risk for knee OA progression is higher systolic blood pressure.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Intra-articular corticosteroids and the risk of knee osteoarthritis progression: results from the Osteoarthritis Initiative

A recent randomized clinical trial reported that repeated intra-articular corticosteroids (IACs) were associated with a greater cartilage loss. This study aimed to examine the relation of IACs to knee radiographic osteoarthritis (ROA) progression in a real-world setting. A cohort that initiated IACs and a comparison cohort without IACs from participants with mild to moderate knee ROA in the Osteoarthritis Initiative (OAI) were assembled (from 0-month to 48-month). Two measures of knee ROA progression were assessed during the follow-up period: (1) an increase in Kellgren and Lawrence (KL) grade by ≥1 grade or having a knee replacement (i.e., KL grade worsening); and (2) a decrease in joint space width (JSW) by ≥0.7mm or having a knee replacement (i.e., JSW worsening). The associations of IACs initiation using a propensity-score matched cohort study and continuous IACs using marginal structural models with the risk of knee ROA progression were examined. Among 684 propensity-score matched participants at baseline (148 IACs initiators, 536 comparators), 65 knees (21.7/100 person-years) in the IACs initiation cohort and 90 knees (7.1/100 person-years) in the comparison cohort experienced KL worsening. The hazard ratios (HRs) of KL worsening from IACs initiation and continuous IACs were 3.02 (95% confidence interval [CI], 2.19-4.16) and 4.67 (95% CI, 2.92-7.47), respectively. The corresponding HRs of JSW worsening were 2.93 (95% CI, 2.13-4.02) and 3.26 (95% CI, 1.78-5.96), respectively. All HRs for continuous use of IACs were further away from the null. IACs, especially continuous IACs, may be associated with an increased risk of knee ROA progression.

The effect of knee joint effusion on gait mechanics and muscle activations in individuals with moderate knee osteoarthritis

Purpose: Knee osteoarthritis (OA) is the most common joint disease and is often characterized by pain, stiffness, swelling and limited tolerance to weight-bearing activities. It has been shown to be associated with biological inflammatory processes in the synovium, synovitis, and mechanical insults that lead to the deterioration of the joint structures. Synovitis is usually characterized by knee joint swelling and the mechanical knee joint environment during a loading stimulus can be studied in vivo using state-of-the-art gait analyses. The study objective is to compare knee mechanics and muscle activation patterns during gait in individuals with knee OA who have and do not have knee joint swelling. Methods: 45 patients diagnosed with moderate medial compartment knee OA were recruited. Knee swelling was measured at three locations (mid, medial, lateral) of the supra-patellar recess (SRD) using ultrasound imaging. A maximum depth, regardless of the location was determined. Effusion presence was defined as a SRD depth >4 mm. Knee joint motion was calculated from skin markers and net external moments calculated through inverse dynamics during walking on a dual-belt instrumented treadmill at self-selected speed. Electromyography (EMG) from vastus medialis (VM) and lateralis (VL), medial (MH) and lateral hamstrings (LH), medial (MG) and lateral gastrocnemius (LG) was recorded using standardized procedures. Two-sample unpaired t-tests were used to test for significant differences in sagittal plane knee joint angles, sagittal and frontal external moments, pain, Knee Osteoarthritis Outcome Scores, age, body mass index, stride characteristics, and knee extensor and flexor strength. Principal component analysis (PCA) was performed on the EMG waveforms to capture amplitude and temporal based features. Principal Pattern (PP)-scores were calculated from principal patterns that together explained >90% of the waveform variability. Two-way mixed-model Analysis of Variance models were performed on the PP-scores to identify muscle, group and interaction effects. Bonferroni corrected pairwise post-hoc comparisons were made. A P-value of 0.05 was used to determine statistical significance. Results: Of the 45 participants, 25 had effusion (SRD > 4mm). No significant differences were found between groups in subject demographic and anthropometrics, questionnaire outcomes, and knee strength (P > 0.05). Both groups had a similar radiographic grade distribution. No biomechanical differences existed between both groups, however the effusion group had greater overall amplitudes of VM and VL (PP1-scores) and greater early stance activation of the gastrocnemius muscles (PP2-scores). No other group differences or group by muscle interactions existed. Conclusions: These results, as shown in Figure 1, indicate that specific amplitude knee joint muscle activation patterns are altered in the presence of knee effusion during gait in individuals with knee OA. Greater stance phase amplitudes in the quadriceps and gastrocnemius muscles are consistent with responses aimed at providing neuromuscular knee joint support and increasing early stance active stiffness, respectively, in order to preserve knee function when effusion is present. These muscular adaptations have been previously reported with increased OA severity suggesting a possible link between gait mechanics and knee swelling as knee OA progresses. The 4 mm SRD threshold has previously been linked to a higher risk of knee OA progression, supporting findings of this study. Future studies can investigate different cut-off values for the detection of effusion sonographically to establish whether biomechanical subgroups may exist.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Systemic Lipopolysaccharide Burden May Increase the Risk of Knee Osteoarthritis Progression

Systemic Lipopolysaccharide Burden May Increase the Risk of Knee Osteoarthritis Progression

Knee osteoarthritis active living assistant side force measurements as potential means for assessing knee osteoarthritis

Purpose: The lifetime risk of developing symptomatic knee osteoarthritis (KOA) has been estimated to be 45%. Knee abduction/adduction moment (KAM) is recognized as a primary marker of KOA progression. A 1% increase in peak external KAM has been linked to a greater than 6-fold increase in the risk of KOA progression. Due to high costs, and limited measurement granularity, established KAM measurement techniques are an impractical means for tracking KOA progression. Measurement of KAM is currently limited to gait laboratories, which utilize motion capture systems to determine knee moments. KOA often takes decades to develop. Identifying statistically significant changes in KAM on a year over year (or more frequent) basis therefore requires a higher degree of granularity than current techniques offer. Other attempts at measuring KAM during free ambulation have neither achieved complete independence from lab measurements, nor generated significantly greater granularity. In this work, a novel means of measuring a KAM proxy during free ambulation is presented, offering high measurement accuracy and granularity. We have developed an orthotic leg brace containing pressure sensors located on the inner and outer shank and thigh regions that measure side forces. From these side forces, we have measured the forces generated by the knee that are balanced by the legbrace. The purpose of this particular study was to assess the potential for this KAM proxy to differentiate between knees with diagnosed KOA and knees without KOA. We performed a preliminary test with a passive variant of a Knee OsteoArthritis Active Living Assistant (KOAALA) prototype (Figure 1) on a 75- year old male test subject with a differential KOA diagnosis between his left and right knee, and a young control subject in good health. Sessions were for 50 strides on a treadmill at 1m/s. The test subject walked one session with the sensorized legbrace on his left (afflicted) leg, then one session with the sensorized legbrace on his right (unafflicted) leg. The control subject walked one session with the sensorized legbrace on his left leg. Legbrace side force sensors were sampled at 4,608 samples per second and data was logged to a micro-secure-digital-card with a granularity of 4g. Additional Gait measures logged included: knee angle, shank tilt angle, shank lean angle, heel pressure, ball-of-foot pressure, foot angle and heel strike timing. After testing, data were processed using Wolfram’s Mathematica; processed data was compared. View Large Image Figure ViewerDownload Hi-res image Download (PPT) Results: The left/right panels of Figure 2 shows the data logged by KOAALA for average heel force (purple), ball-of-foot force (red) and average side force (blue) along with the minimum side force (gold) and maximum side force (green) versus percent of gait cycle of the test subject’s left and right legs respectively. Figure 3 shows the analogous data for the control subject. The side forces began in the lateral direction prior to heel strike and peaked immediately following heel strike and again peaked in the lateral direction prior to toe off. The left leg graph, however, has dramatically different characteristics from both the test subject’s right leg and the control subject. Specifically, in the healthy and in the unafflicted knee the pressure in the period between the peaks was nominal, while the test subject’s left leg (afflicted) side force measurements showed a substantial spike in the medial direction during the transition of support from heel to ball-of-foot. Conclusions: Our novel method for measuring a KAM proxy measures the primary discernable side forces exerted by the legbrace. Sensor calibration has not been established preventing analysis of relative pressures between the brace and traditional KAM measurement methods, but the series of spikes is not generally discernable in traditional methods. Further testing will be required to ascertain if these peaks are anomalous; peculiar to the brace/test; or are simply not detected by traditional methods. The high accuracy and fine granularity side force measurements our method provides has the potential of creating a novel means of tracking/managing KOA. The peak in the medial direction of the afflicted leg during the transitional support phase shows potential for this KAM proxy as a biomarker for KOA.

Vitamin D Deficiency Is Associated with Progression of Knee Osteoarthritis

Background: Knee osteoarthritis causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee osteoarthritis. The metabolism of vitamin D is regulated by parathyroid hormone (PTH).Objective: The objective was to investigate whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH, individually and jointly, predict the progression of knee osteoarthritis.Methods: Serum 25(OH)D and PTH were measured at the 30- or 36-mo visit in 418 participants enrolled in the Osteoarthritis Initiative (OAI) who had ≥1 knee with both symptomatic and radiographic osteoarthritis. Progression of knee osteoarthritis was defined as any increase in the radiographic joint space narrowing (JSN) score between the 24- and 48-mo OAI visits.Results: The mean concentrations of serum 25(OH)D and PTH were 26.2 μg/L and 54.5 pg/mL, respectively. Approximately 16% of the population had serum 25(OH)D < 15 μg/L. Between the baseline and follow-up visits, 14% progressed in JSN score. Participants with low vitamin D [25(OH)D < 15 μg/L] had >2-fold elevated risk of knee osteoarthritis progression compared with those with greater vitamin D concentrations (≥15 μg/L; OR: 2.3; 95% CI: 1.1, 4.5). High serum PTH (≥73 pg/mL) was not associated with a significant increase in JSN score. However, participants with both low vitamin D and high PTH had >3-fold increased risk of progression (OR: 3.2; 95%CI: 1.2, 8.4).Conclusion: Our results suggest that individuals deficient in vitamin D have an increased risk of knee osteoarthritis progression.

Hyaluronan molecular weight distribution is associated with the risk of knee osteoarthritis progression

We investigated the relationship between the molecular weight (MW) distribution of hyaluronan (HA) in synovial fluid (SF) and risk of knee osteoarthritis (OA) progression. HA MW was analyzed for 65 baseline knee SFs. At 3-year follow-up, knees were scored for change in joint space narrowing (JSN), osteophyte (OST) progression, or occurrence of total knee arthroplasty (TKA). HA MW distribution was analyzed using agarose gel electrophoresis (AGE), and its relationship to OA progression was evaluated using logistic regression. The association between HA MW and self-reported baseline knee pain was analyzed using Pearson's correlation coefficients. Knee OA was categorized as non-progressing (OST-/JSN-, 26 knees, 40%), or progressing based on OST (OST+/JSN-, 24 knees, 37%), OST and JSN (OST+/JSN+, 7 knees, 11%) or total knee arthroplasty (TKA, 8 knees, 12%). The MW distribution of HA in baseline SFs was significantly associated with the odds of OA progression, particularly for index knees. After adjusting for age, gender, BMI, baseline X-ray grade and pain, each increase of one percentage point in %HA below 1 million significantly increased the odds of JSN (odds ratios (OR)=1.45, 95% CI 1.02-2.07), TKA or JSN (OR=1.24, 95%CI 1.01-1.53) and the odds of any progression (OR=1.16, 95% CI 1.01-1.32). HA MW distribution significantly correlated with pain. These data suggest that the odds of knee OA progression increases as HA MW distribution shifts lower and highlight the value of reporting MW distribution rather than just average MW values for HA.

SAT0417 Insight into the Role of Meniscal Extrusion and Bone Marrow Lesions in Knee Osteoarthritis Progression and their Impact on Response to Strontium Ranelate Treatment in A Subset of Patients from the SEKOIA Study

BackgroundKnee osteoarthritis (OA) structural changes are complex and comprise cartilage volume loss as well as meniscal lesions, which were shown to promote cartilage loss. Recently, strontium ranelate (SrRan) was demonstrated...

A Kinetic and Kinematic Analysis of the Effect of Stochastic Resonance Electrical Stimulation and Knee Sleeve During Gait in Osteoarthritis of the Knee

Extended use of knee sleeves in populations at risk for knee osteoarthritis progression has shown functional and quality of life benefits; however, additional comprehensive kinematic and kinetic analyses are needed to determine possible physical mechanisms of these benefits which may be due to the sleeve's ability to enhance knee proprioception. A novel means of extending these enhancements may be through stochastic resonance stimulation. Our goal was to determine whether the use of a knee sleeve alone or combined with stochastic resonance electrical stimulation improves knee mechanics in knee osteoarthritis. Gait kinetics and kinematics were assessed in subjects with medial knee osteoarthritis when presented with four conditions: control1, no electrical stimulation/sleeve, 75% threshold stimulation/sleeve, and control2. An increase in knee flexion angle throughout stance and a decrease in flexion moment occurring immediately after initial contact were seen in the stimulation/sleeve and sleeve alone conditions; however, these treatment conditions did not affect the knee adduction angle and internal knee abduction moment during weight acceptance. No differences were found between the sleeve alone and the stochastic resonance with sleeve conditions. A knee sleeve can improve sagittal-plane knee kinematics and kinetics, although adding the current configuration of stochastic resonance did not enhance these effects.

Does hip implant positioning affect the peak external adduction moments of the healthy knees of subjects with total hip replacements?

After unilateral total hip replacement (THR) for hip osteoarthritis (OA), knee OA incidence or progression is common. The contralateral knee is at particular risk, and some have speculated that abnormal THR-hip biomechanics contributes to this asymmetry. We investigated the relationships between operated-hip joint geometry or gait variables and the peak external knee adduction moments-an indicator of knee OA risk-in 21 subjects with unilateral THRs. We found that the peak adduction moment was 14% higher on the contralateral versus the ipsilateral knee (p = 0.131). The best predictors of ipsilateral knee adduction moments were superior-inferior joint center position and operated-hip peak adduction moment (adj R(2) = 0.291, p = 0.017). The sole predictor of the contralateral knee adduction moment was the medial-lateral hip center position (adj R(2) = 0.266, p = 0.010). A postoperative medial shift of the hip center was significantly correlated with a lower postoperative contralateral/ipsilateral knee adduction moment ratio (R = 0.462, p = 0.035). Based on these relationships, we concluded that implant positioning could influence the biomechanical risk of knee OA progression after THR. Although implant positioning decisions are necessarily driven by other factors, it may be appropriate to assess individual THR candidate's knee OA risk and adjust perioperative management accordingly.

371 MRI-BASED CARTILAGE THICKNESS LOSS AND JOINT SPACE NARROWING IN AN OAI CORE PROGRESSION SAMPLE, AND THEIR RELATIONSHIP WITH AGE, SEX, AND BMI

Purpose: Recent evidence suggests that peri-articular bone changes are integral to knee osteoarthritis (OA) pathophysiology. Peri-articular trabecular morphology changes have been associated with radiographic knee OA severity and may identify individuals at risk for knee OA progression. However, it is unclear how patient characteristics are associated with peri-articular trabecular morphology in knees with OA. The purpose of this study was to evaluate the association between patient characteristics and trabecular morphology in knees with OA. Methods: The sample comprised a convenience sample of 337 participants in the Osteoarthritis Initiative (OAI) progression cohort who at the 30or 36-month OAI visit had 3-tesla magnetic resonance imaging that included coronal 3D Fast Imaging with Steady State Precession (FISP) trabecular morphometry sequences. We used a trabecular morphometry program with a modified algorithm (calcDCN, University of CaliforniaSan Francisco) to evaluate 4 peri-articular trabecular morphology measures: bone volume fraction (BVF), trabecular number (tb.n), spacing (tb.sp), and thickness (tb.th). The four measures were calculated for 20 consecutive central slices within a 15mm x 3.75mm region of interest placed in the peri-articular medial tibia and then averaged. Intratester reproducibility was high (ICC = 0.99). The association between demographic data or knee-specific data (from the 24-month OAI visit) and trabecular morphometry were evaluated with independent sample t-tests or Wilcoxon rank-sum tests (when applicable) and Spearman correlations. Among a subset of 285 patients with 24-month joint space narrowing (JSN) scores, four forward-selection multiple linear regression models were used to further evaluate the associations between patient characteristics and each trabecular morphometry measure. Results: Participants were 66±9 years of age, body mass index 29.6±4.8 kg/m, and 50% female. Peri-articular trabecular morphometry was averaged (± standard deviation) for the cohort: BVF = 0.12±0.08, tb.sp = 1.53±1.25mm, tb.n = 0.86±0.39mm−1, and tb.th = 0.13±0.03mm. Peri-articular trabecular morphometry was not significantly different (p > 0.05) between participants with or without college degrees (n = 208, n = 127; respectively), with or without history of smoking (n =147, n = 188; respectively), and with or without knee symptoms at the 24month OAI visit (n = 191, n = 145; respectively). Many variables were associated with trabecular morphometry (see table). Age correlated with BVF (r = −0.16), tb.n (r = −0.18), and tb.sp (r = 0.17), but not tb.th (r = −0.08). Body mass index also correlated with BVF (r = 0.12), tb.n (r = 0.14), and tb.sp (r = −0.14), but not tb.th (r = 0.07). The 400-meter walk time (24-month visit) was related to tb.sp (r = 0.12). In multiple linear regression models, the presence of medial JSN and female gender were associated with all 4 trabecular morphometry measures. Three patient characteristics were associated with select measures: age (associated with tb.sp, tb.n), history of knee injury/surgery (associated with BVF, tb.th), and race (associated with tb.th).

The relationship between meniscal tears and meniscal position

To investigate how different types of meniscal tears predispose to different patterns of meniscal position in subjects with and without symptomatic knee osteoarthritis (OA). A cross-sectional analysis of 161 women participating in an observational study to evaluate knee OA progression was performed using baseline MRI data. Meniscal morphologic features were scored in three separate locations. Meniscal position measures were determined for extrusion and proportion of coverage. Analysis was performed using multiple linear regression models treating each tear type as an individual variable with a binary response. Complex tears, cysts and maceration of the medial meniscus were associated with more medial (p=0.0004, p=0.004, p <0.0001, respectively) and anterior extrusion (p =0.03, p=0.03, p<0.0001, respectively) than normal menisci. Horizontal tears of the lateral meniscus had more lateral (p=0.005) and anterior extrusion (p<0.0001) than normal menisci. Anterior and body tears of the medial meniscus were associated with more anterior extrusion (p=0.0006, p=0.01, respectively), whereas meniscal body tears alone had more medial extrusion than normal menisci (p= 0.0002). Meniscal body tears of the lateral meniscus had more lateral extrusion than normal menisci (p=0.01). Anterior horn and meniscal body tears and the more severe macerated and complex tear types predisposed to more medial meniscal extrusion. Laterally, only meniscal body and horizontal tears significantly affected extrusion, potentially reflecting a lower overall prevalence of lateral meniscal tears. These results may have important implications in identifying tear types associated with more meniscal dysfunction, with the ultimate goal of identifying those at greatest risk for knee OA progression.

A genome‐wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22

To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and approximately 39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values <1 x 10(-7) considered genome-wide significant. The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14-fold increased risk (95% confidence interval 1.09-1.19) of knee and/or hand OA (P = 8 x 10(-8)) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03-1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 x 10(-12)). Immunohistochemistry experiments revealed that G protein-coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22-positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged with in vivo papain treatment or methylated bovine serum albumin treatment. GPR22-positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. Our findings identify a novel common variant on chromosome 7q22 that influences susceptibility to prevalence and progression of OA. Since the GPR22 gene encodes a G protein-coupled receptor, this is potentially an interesting therapeutic target.

The effect of body weight on progression of knee osteoarthritis is dependent on alignment

Whereas obesity increases overall loading of the knee, limb malalignment concentrates that loading on a focal area, to the level at which cartilage damage may occur. This study evaluated whether the effect of body weight on progression of knee osteoarthritis (OA) differs depending on the degree of limb malalignment. The study population comprised 228 veterans and community recruits with symptomatic knee OA (pain on most days and radiographic disease) who volunteered to participate in a natural history study and from whom baseline radiographs were obtained to assess alignment; 227 (99.6%) completed a 30-month followup. Of 403 knees assessed at baseline, 394 (97.8%) were followed up. Participants' body mass index (BMI) was assessed at each examination. The main outcome measure was progression of knee OA, defined as narrowing of the tibiofemoral joint space by 1 grade (semiquantitative scale 0-3) on radiographs of the fluoroscopically positioned knee. The association between BMI and the risk of knee OA progression was assessed after adjusting for age, sex, and limb alignment, using logistic regression and generalized estimating equations. Of 394 knees, 90 (22.8%) showed disease progression, and limb alignment was strongly associated with progression risk. The risk of progression increased with increasing weight (for each 2-unit increase in BMI, odds ratio [OR] for progression 1.08, 95% confidence interval [95% CI] 1.00-1.16). However, among those knees with neutral alignment (0-2 degrees ), increases in BMI had no effect on risk of progression (OR 1.00), and in those with severe malalignment (> or =7 degrees ), the effect was similarly null (OR 0.93). The effect of BMI on progression was limited to knees in which there was moderate malalignment (OR per 2-unit increase in BMI 1.23, 95% CI 1.05-1.45). Although elevated BMI increases the risk of knee OA progression, the effect of BMI is limited to knees in which moderate malalignment exists, presumably because of the combined focus of load from malalignment and the excess load from increased weight. This has implications for clinical recommendations and for trials testing weight loss in those with knee OA.

The influence of alignment on risk of knee osteoarthritis progression according to baseline stage of disease.

Varus and valgus malalignment increase the risk of medial and lateral osteoarthritis (OA) progression, respectively. The impact of a mechanical factor such as alignment depends not only on the factor itself, but also on the state of the joint. The less-damaged joint of mild OA may be less vulnerable to malalignment effects than the more-damaged joint of moderate OA. Our goal was to explore the impact of alignment on subsequent progression of knee OA according to the baseline stage of disease. Two hundred thirty patients with knee OA (defined by the presence of osteophytes and symptoms) recruited from the community underwent assessment of both lower limbs at baseline and at an 18-month followup. Alignment was measured on a full-limb radiograph as the angle made by the intersection of the femoral and tibial mechanical axes. Compartment-specific progression was defined as an increase between baseline and 18 months in the grade of severity of joint space narrowing on radiographs of semiflexed knees taken after fluoroscopic confirmation of position. Knees were grouped according to their baseline stage of OA as Kellgren/Lawrence (K/L) grades 0-1, 2, or 3. Progression odds ratios were estimated from logistic regression using generalized estimating equations. There were 377 K/L grade 0-3 knees in 230 subjects (173 women and 57 men, mean age 64.0 years, mean body mass index 30.4 kg/m(2)) in this longitudinal study. In knees with mild OA (K/L grade 2), the odds of 18-month progression in the medial compartment were significantly increased 4-fold by varus alignment at baseline. In K/L grade 2 knees, the odds of lateral progression were increased 2-fold by valgus alignment (approaching significance). In knees with moderate OA (K/L grade 3), the risk of progression was comparably increased by varus or valgus alignment (10-fold). While some effect of malalignment was suggested at almost all stages of knee OA examined, the impact of varus or valgus malalignment on the odds of OA progression over the ensuing 18 months was greater in knees with moderate (K/L grade 3) OA at baseline, possibly due to greater joint vulnerability with some contribution from slightly more severe malalignment.