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      Development of a clinical prediction algorithm for knee osteoarthritis structural progression in a cohort study: value of adding measurement of subchondral bone density

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          Abstract

          Background

          Risk prediction algorithms increase understanding of which patients are at greatest risk of a harmful outcome. Our goal was to create a clinically useful prediction algorithm for structural progression of knee osteoarthritis (OA), using medial joint space loss as a proxy; and to quantify the benefit of including periarticular bone mineral density (BMD) in the algorithm.

          Methods

          Participants were from the Osteoarthritis Initiative (OAI) Progression Cohort, with X-ray readings of medial joint space at 36- and 48-month visits, and a 30- or 36-month medial-to-lateral tibial BMD ratio (M:L BMD ratio) value. Loss of medial joint space was the outcome and clinically available factors associated with OA progression were employed in the base prediction algorithm, with M:L BMD ratio added to an enhanced prediction algorithm. The benefit of adding M:L BMD ratio was evaluated by change in area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

          Results

          Five hundred thirty-three participants were included; 51 (14%) had medial joint space loss; 47% were female; the mean (SD) age was 64.6 (9.2) years and BMI was 29.6 (4.8) kg/m 2. The base algorithm model included age, BMI, gender, recent injury, knee pain, and hand OA as predictors and had an AUC value of 0.65. The algorithm adding M:L BMD ratio had an AUC value of 0.73, and the AUC, NRI and IDI were all significantly improved ( p ≤ 0.002).

          Conclusions

          This clinical prediction algorithm predicts structural progression in individuals with OA using only clinically available predictors supplemented by the M:L BMD ratio, a biomarker that could be made available at clinical sites.

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          Most cited references29

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          Applied Logistic Regression

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            Atlas of individual radiographic features in osteoarthritis, revised.

            Develop a radiographic atlas of osteoarthritis (OA) to be used as a template and guide for grading radiographs of osteoarthritic lesions of the hand, hip and knee. The 1995 atlas was reviewed for the images most useful for clinical trials. Replacement images were selected from the Stanford University Radiology Department Picture Archive and Communications System by reviewing consecutive radiographs obtained from patients. Selected images were downloaded without patient identification information. Images were organized by hand, hip and knee. They were reviewed for findings of OA and images grouped into image files by individual findings and degree of change. Both investigators individually selected the most promising images. Final images were selected by consensus. Original electronic images were then cropped and placed in sequence. Individual radiographic features (e.g., osteophytes, joint space narrowing) were recorded for hand (distal interphalangeal joint, proximal interphalangeal joint, trapeziometacarpal joint), hip (acetabular, femoral) and knee (medial compartment, lateral compartment, tibial, femoral); they were also sequenced for normal, 1+, 2+, and 3+ change. Images were made available in print and electronic formats. An updated atlas of radiographic images was produced to assist in grading individual radiographic features of the hand, hip and knee for clinicians and for use in clinical trials.
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              The association of bone marrow lesions with pain in knee osteoarthritis.

              The cause of pain in osteoarthritis is unknown. Bone has pain fibers, and marrow lesions, which are thought to represent edema, have been noted in osteoarthritis. To determine whether bone marrow lesions on magnetic resonance imaging (MRI) are associated with pain in knee osteoarthritis. Cross-sectional observational study. Veterans Affairs Medical Center. 401 persons (mean age, 66.8 years) with knee osteoarthritis on radiography who were drawn from clinics in the Veterans Administration health care system and from the community. Of these persons, 351 had knee pain and 50 had no knee pain. Knee radiography and MRI of one knee were performed in all participants. Those with knee pain quantified the severity of their pain. On MRI, coronal T(2)-weighted fat-saturated images were used to score the size of bone marrow lesions, and each knee was characterized as having any lesion or any large lesion. The prevalence of lesions and large lesions in persons with and without knee pain was compared; in participants with knee pain, the presence of lesions was correlated with severity of pain. Bone marrow lesions were found in 272 of 351 (77.5%) persons with painful knees compared with 15 of 50 (30%) persons with no knee pain (P < 0.001). Large lesions were present almost exclusively in persons with knee pain (35.9% vs. 2%; P < 0.001). After adjustment for severity of radiographic disease, effusion, age, and sex, lesions and large lesions remained associated with the occurrence of knee pain. Among persons with knee pain, bone marrow lesions were not associated with pain severity. Bone marrow lesions on MRI are strongly associated with the presence of pain in knee osteoarthritis.
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                Author and article information

                Contributors
                mlava@bu.edu
                ghlo@bcm.edu
                lprice1@tuftsmedicalcenter.org
                Jeffrey.driban@tufts.edu
                cbeaton51@gmail.com
                tmcalindon@tuftsmedicalcenter.org
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                16 May 2017
                16 May 2017
                2017
                : 19
                : 95
                Affiliations
                [1 ]ISNI 0000 0004 1936 7558, GRID grid.189504.1, Department of Biostatistics, , Boston University School of Public Health, ; 801 Massachusetts Avenue 3rd Floor, Boston, MA 02118 USA
                [2 ]Medical Care Line and Research Care Line, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Medical Center, Houston, TX 77030 USA
                [3 ]ISNI 0000 0001 2160 926X, GRID grid.39382.33, , Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, ; 1 Baylor Plaza, BCM-285, Houston, TX 77030 USA
                [4 ]ISNI 0000 0004 1936 7531, GRID grid.429997.8, Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, Tufts Clinical and Translational Science Institute, , Tufts University, ; 800 Washington Street, Box #63, Boston, MA 02111 USA
                [5 ]ISNI 0000 0000 8934 4045, GRID grid.67033.31, , Division of Rheumatology Tufts Medical Center, ; Box #406, 800 Washington Street, Boston, MA 02111 USA
                [6 ]ISNI 0000 0004 1936 9094, GRID grid.40263.33, Department of Family Medicine, , Alpert Medical School of Brown University, ; 111 Brewster Street, Pawtucket, RI 02860 USA
                Article
                1291
                10.1186/s13075-017-1291-3
                5433155
                28511690
                bf7ebd6f-3b38-4aa8-8794-d7811b39e2e1
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 20 September 2016
                : 7 April 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 AR 060718
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Orthopedics
                arthritis,calibration,discrimination,joint space loss,logistic regression,roc curve,x-ray
                Orthopedics
                arthritis, calibration, discrimination, joint space loss, logistic regression, roc curve, x-ray

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