Quality of life and radiographic severity of knee osteoarthritis predict total knee arthroplasty: data from the osteoarthritis initiative

s / Osteoarthritis and Cartilage 21 (2013) S9–S62 S11 influenced by the highly anisotropic organization of the collagenmatrix and regional variation in cartilage water content. We hypothesize that loss of the normal spatial distribution of cartilage MRI T2 values, as quantified by texture features, will identify distinctive signatures of OA prior to symptomatic or radiographic evidence of OA. This change in T2 signal homogeneity could be used to predict symptomatic disease progression. Methods: Patients were selected from the Osteoarthritis Initiative (OAI) databasebasedon the change in totalWOMACscore frombaseline to three year follow-up (79 non-OA progression and 103 OA progression patients). The incidence cohort was used to identify a rapid progression population of OA defined as asymptomaticwith no radiographic changes at the initial time point (WOMAC<3; KL<2) that had a large increase inWOMAC score (greater than 10) at the three year time point. For each patient, at baseline, 725 image texture features were measured from each knee T2 map. A linear discriminant function and feature reduction method was then trained to quantify a texturemetric, the T2 texture index of cartilage (TIC), based on 20 image features, to identify early OA changes on MRI. Results: Statistically significant differences were seen in the T2 TIC between the OA non-progression and progression populations at the initial baseline measurement. This image biomarker differentiates subjects that develop OA prior to clinically significant OA symptoms or radiographic findings with an accuracy of 80.3% 4.3%, a sensitivity of 83.4% 5.2% and a specificity of 77.4 4.8%. These image features used to quantify signal homogeneity through a texture metric can be considered “image biomarkers”. These features included run length, cooccurrence matrix, entropy, and local energy measures. When the knee is separated into the patella, medial, and lateral compartments, in more than 80% of knees, the texture metric that identified a knee with early signs of OA were primarily located in only one of these compartments. These signal changes were observed in a dominant knee compartment that correlated with the mechanical axis of the knee. Conclusion: We demonstrate that the T2 TIC, derived from local variation in cartilage T2 values, is able to differentiate and predict individuals that will develop symptomatic knee OA from those that remain asymptomatic. The observation that these image features are localized to knee compartments associated with deviation of the mechanical axis suggests this index reflects early structural cartilage change related to biomechanical properties of the knee. The ability to differentiate patients at risk for OA progression prior to symptomatic or radiographic presentation based on qMRI signal changeswould be valuable in clinical and epidemiological studies for disease-modifying OA drugs (DMOADs), joint preservation surgical interventions, and the development of posttraumatic arthritis in ACL and meniscal injuries. 5 QUALITY OF LIFE AND RADIOGRAPHIC SEVERITY OF KNEE OSTEOARTHRITIS PREDICT TOTAL KNEE ARTHROPLASTY: DATA FROM THE OSTEOARTHRITIS INITIATIVE M.C. Hochberg y,z, K. Favors y,z, J.D. Sorkin y,z. yUniv. of Maryland, Baltimore, MD, USA; zVA Maryland Hlth. Care System, Baltimore, MD, USA Purpose: Total knee arthroplasty (TKA) is a clinically important outcome in persons with symptomatic osteoarthritis (OA) of the knee. Few studies, however, have examined predictors of TKA in communitybased cohorts. We analyzed data from the Osteoarthritis Initiative (OAI) to determine the most parsimonious group of baseline variables that robustly predicted undergoing a TKA during 5 years of follow-up. Methods: Data for this analysis were obtained from the OAI public access database (http://www.oai.ucsf.edu). At each annual visit through 48 months, subjects completed an extensive battery of questionnaires, weight was measured with a balance beam scale, and fixed flexion, weight-bearing PA radiographs of both knees were obtained using a standard protocol and the Synaflexer platform; the 60-month follow-up visit only involved completion of questionnaires. Subjects reported TKAs at the time of their annual follow-up visits; these were confirmed by the Coordinating Center after review of medical records obtained by the Clinical Centers. We examined selected variables measured at the baseline visit for their role as predictors of TKA using knee-specific multiple variable logistic regression models. The best models were selected for each knee based on Chi-square values and area under the receiver operating characteristic curve (AUC). Results: Data from 4674 subjects enrolled in the OAI who either had symptomatic radiographic knee OA or were at risk for this condition were included in this analysis. At entry, subjects had a mean (SD) age of 61.32 (9.17) years and body mass index (BMI) of 28.74 (4.82) kg/m2; 2729 (58.4%) were women and 3677 (78.75%) were white. Baseline knee-specificWOMAC pain (0-20 scale) and function (0-68 scale) scores were 2.56 (3.26) and 8.26 (10.63) for the right knee and 2.39 (3.43) and 8.39 (11.44) for the left knee, respectively. Baseline KOOS pain and symptoms scores (0-100 scale) were 83.56 (17.37) and 85.95 (14.60) for the right knee and 84.80 (18.26) and 86.49 (15.87) for the left knee, respectively; KOOS quality of life (QoL, 0-100 scale) was 66.10 (22.43). Distribution of Kellgren-Lawrence (KL) grades of severity of radiographic knee OA at baseline was similar for both knees: 37,18, 27,14 and 4 percent had Grade 0, 1, 2, 3, 4 changes, respectively. During 60months of follow-up, there were 91 right and 102 left TKAs. In models containing clinical variables and adjusted for age, gender, BMI and race, the best models includedWOMAC pain and KOOS QoL (AUC1⁄4 0.80 and 0.82 for right and left knees, respectively). When KL grade was added to these models, the AUC improved to 0.89 and 0.90 for the right and left knees, respectively; race, BMI and WOMAC pain were no longer significantly associated with TKA outcome. The best parsimonious model included age, gender, KOOS QoL score and KL grade with an AUC 1⁄4 0.89 and 0.90 for the right and left knee, respectively. Subjects with highest odds for a TKA were those in the lowest quartile of QoL scores and with KL grade 3 or 4 radiographic severity. Conclusions: These data suggest that knowledge of only a patient's age, gender, KOOSQoL score and KL grade of severity of radiographic knee OA can predict with high accuracy the odds of undergoing a TKA over the ensuing5years. Thesefindingsextendourprior report (ShurupoffK, et al: Osteoarthritis Cart 2011;19S1:S134 [abstract #284]) that KOOS QoL and radiographic severity can be used tomodel the outcome of "Virtual TKA". 6 THE CANONICAL WNT PATHWAY IS PREDOMINANTLY ACTIVATED IN BONE IN OSTEOARTHRITIS T. Funck-Brentano y,z, W. Bouaziz y, V. Geoffroy y, D. Hannouche k,x, C. Marty y, E. Hay y, M.E. Cohen-Solal y,z. y INSERM U606 Paris Diderot Univ., Paris, France; zDept. of Rheumatology, Lariboisiere Hosp., Paris, France; xCNRS UMR 7052 Paris Diderot Univ., Paris, France; kDept. of Orthopedics, Lariboisiere Hosp., Paris, France Purpose: Wnt/b-catenin pathway is a main regulator of cartilage in osteoarthritis (OA). However, previous studies targeting this pathway in the cartilage have brought conflicting results, and the kinetic of activation of this pathway in the joint is poorly known during the development of OA. Moreover, the activation of the pathway in the tissues surrounding the cartilage should also be characterized as they might impact cartilage loss. Here, we aimed to investigate Wnt activation in cartilage, bone and synovium and the expression of Wnt antagonists over time. Methods: Topgal mice, that express b-galactosidasewhenWnt/b-catenin is activated, were used to assess Wnt activation in the joints in vivo. To promote a mechanical model of OA, mice underwent joint instability by partial meniscectomy of the medial meniscus until baseline (n1⁄43), 4 (n1⁄414), 6 (n1⁄413), and9 (n1⁄49)weeks.Dissectedkneeswere scannedusing an ex vivo microCT, then prepared for cryosectioning to quantify variations of Wnt activity in the 3 joint tissues by X-gal staining and the expression ofWnt antagonists such asDickkopf-relatedprotein 1 (Dkk-1), sclerostin and secreted frizzled-related protein 3 (sFRP-3) in the cartilage overtime.Wnt activity was assessed by the number of X-gal positive cells per tissue volume, and was expressed as a ratio of operated to shamoperated knees for each animal and at each time point. Non parametric testswere used: theWilcoxon's rank test for paired variables or theMann Withney's test for independent variables. A p value< 0.05was considered as statistically significant. Results: At baseline, X-gal staining was mainly located in osteocytes of the subchondral bone and mostly absent in the articular cartilage. Wnt activity decreased in osteocytes at week 4 (mean expression in operated relative to sham-operated knees 0.50 0.08, p1⁄40.034), and then increased at weeks 6 and 9 (1.63 0.43, p1⁄40.004 and 2.33 0.82, p1⁄40.009, respectively). This activity paralleled the changes of subchondral bone volume. Wnt activity was found in the endocortical surface of growing osteophytes, and in the perichondrial groove of Ranvier. They were lowWnt activation in articular chondrocytes during the course of OA that were however more frequently observed in focal cartilage lesions. At week 9, Wnt activation was predominant in subchondral bone, osteophytes and synovium of operated knees.