المؤلفون: Byers Kraus, Virginia, Collins, Jamie E., Hargrove, David, Losina, Elena, Nevitt, Michael, Katz, Jeffrey N., Wang, Susanne X., Sandell, Linda J., Hoffmann, Steven C., Hunter, David J., Kraus, Virginia Byers, OA Biomarkers Consortium

المصدر: Annals of the Rheumatic Diseases; Jan2017, Vol. 76 Issue 1, p186-195, 10p, 5 Charts, 1 Graph

مصطلحات موضوعية: OSTEOARTHRITIS diagnosis, COMPARATIVE studies, KNEE diseases, RESEARCH methodology, MEDICAL cooperation, OSTEOARTHRITIS, PROGNOSIS, RADIOGRAPHY, RESEARCH, RESEARCH funding, EVALUATION research, PAIN measurement, PREDICTIVE tests, SEVERITY of illness index, CASE-control method, RECEIVER operating characteristic curves, DISEASE progression, DIAGNOSIS

مستخلص: Objective: To investigate a targeted set of biochemical biomarkers as predictors of clinically relevant osteoarthritis (OA) progression.Methods: Eighteen biomarkers were measured at baseline, 12 months (M) and 24 M in serum (s) and/or urine (u) of cases (n=194) from the OA initiative cohort with knee OA and radiographic and persistent pain worsening from 24 to 48 M and controls (n=406) not meeting both end point criteria. Primary analyses used multivariable regression models to evaluate the association between biomarkers (baseline and time-integrated concentrations (TICs) over 12 and 24 M, transposed to z values) and case status, adjusted for age, sex, body mass index, race, baseline radiographic joint space width, Kellgren-Lawrence grade, pain and pain medication use. For biomarkers with adjusted p<0.1, the c-statistic (area under the curve (AUC)), net reclassification index and the integrated discrimination improvement index were used to further select for hierarchical multivariable discriminative analysis and to determine the most predictive and parsimonious model.Results: The 24 M TIC of eight biomarkers significantly predicted case status (ORs per 1 SD change in biomarker): sCTXI 1.28, sHA 1.22, sNTXI 1.25, uC2C-HUSA 1.27, uCTXII, 1.37, uNTXI 1.29, uCTXIα 1.32, uCTXIβ 1.27. 24 M TIC of uCTXII (1.47-1.72) and uC2C-Human Urine Sandwich Assay (HUSA) (1.36-1.50) both predicted individual group status (pain worsening, joint space loss and their combination). The most predictive and parsimonious combinatorial model for case status consisted of 24 M TIC uCTXII, sHA and sNTXI (AUC 0.667 adjusted). Baseline uCTXII and uCTXIα both significantly predicted case status (OR 1.29 and 1.20, respectively).Conclusions: Several systemic candidate biomarkers hold promise as predictors of pain and structural worsening of OA. [ABSTRACT FROM AUTHOR]

: Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Hunter, David, Nevitt, Michael, Lynch, John, Kraus, Virginia Byers, Katz, Jeffrey N., Collins, Jamie E., Bowes, Mike, Guermazi, Ali, Roemer, Frank W., Losina, Elena, FNIH OA Biomarkers Consortium

المصدر: Annals of the Rheumatic Diseases; Sep2016, Vol. 75 Issue 9, p1607-1614, 8p, 1 Black and White Photograph, 1 Diagram, 4 Charts

مصطلحات موضوعية: COMPARATIVE studies, FEMUR, KNEE diseases, LONGITUDINAL method, MAGNETIC resonance imaging, RESEARCH methodology, MEDICAL cooperation, OSTEOARTHRITIS, PATELLA, RESEARCH, TIBIA, TIME, LOGISTIC regression analysis, EVALUATION research, CASE-control method, DISEASE progression, JOINT pain, DISEASE complications

مستخلص: Objective: To perform a longitudinal validation study of imaging bone biomarkers of knee osteoarthritis (OA) progression.Methods: We undertook a nested case-control study within the Osteoarthritis Initiative in knees (one knee per subject) with a Kellgren and Lawrence grade of 1-3. Cases were defined as knees having the combination of medial tibiofemoral radiographic progression and pain progression at the 24-month, 36-month or 48-month follow-up compared with baseline. Controls (n=406) were eligible knees that did not meet both endpoint criteria and included 200 with neither radiographic nor pain progression, 103 with radiographic progression only and 103 with pain progression only. Bone surfaces in medial and lateral femur, tibia and patella compartments were segmented from MR images using active appearance models. Independent variables of primary interest included change from baseline to 24 months in (1) total area of bone and (2) position on three-dimensional (3D) bone shape vectors that discriminate OA versus non-OA shapes. We assessed the association of bone markers changes over 24 months with progression using logistic regression.Results: 24-month changes in bone area and shape in all compartments were greater in cases than controls, with ORs of being a case per 1 SD increase in bone area ranging from 1.28 to 1.71 across compartments, and per 1 SD greater change in 3D shape vectors ranging from 1.22 to 1.64. Bone markers were associated most strongly with radiographic progression and only weakly with pain progression.Conclusions: In knees with mild-to-moderate radiographic OA, changes in bone area and shape over 24 months are associated with the combination of radiographic and pain progression over 48 months. This finding of association with longer term clinical outcome underscores their potential for being an efficacy of intervention biomarker in clinical trials. [ABSTRACT FROM AUTHOR]

: Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Hanchate, Amresh D., Kapoor, Alok, Katz, Jeffrey N., McCormick, Danny, Lasser, Karen E., Chen Feng, Manze, Meredith G., Kressin, Nancy R.

المصدر: BMJ: British Medical Journal (Online content); 2/16/2015, p1-10, 10p