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      Increased Dickkopf-1 in Recent-onset Rheumatoid Arthritis is a New Biomarker of Structural Severity. Data from the ESPOIR Cohort

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          Abstract

          Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic condition over the world. RA is potentially disabling because chronic inflammation of the joints leads to joint destruction. To date, the best predictor of radiographic progression for patients with early RA is the presence of radiographic erosions at baseline, but a limited number of predictive biomarkers of structural progression are currently used in daily practice. Here, we investigated Dickkopf-1 (DKK-1) and sclerostin (SOST) serum levels in patients with recent inflammatory arthritis from the ESPOIR cohort. This cohort is a prospective, multicenter French cohort of 813 patients with early arthritis. We observed that mean baseline DKK-1 level was higher among RA patients with than without radiological progression within the first 2 years of evolution. DKK-1 level was still associated with radiographic progression in a model including other main predictors of severity (erosions at baseline, and anti-CCP antibody positivity). This study demonstrates that increased DKK-1 level at baseline predicted structural progression after 2-year follow-up and suggests that DKK-1 might be a new structural biomarker for early RA.

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          Most cited references27

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          The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

          The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.
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            Measurement of patient outcome in arthritis.

            A structure for representation of patient outcome is presented, together with a method for outcome measurement and validation of the technique in rheumatoid arthritis. The paradigm represents outcome by five separate dimensions: death, discomfort, disability, drug (therapeutic) toxicity, and dollar cost. Each dimension represents an outcome directly related to patient welfare. Quantitation of these outcome dimensions may be performed at interview or by patient questionnaire. With standardized, validated questions, similar scores are achieved by both methods. The questionnaire technique is preferred since it is inexpensive and does not require interobserver validation. These techniques appear extremely useful for evaluation of long term outcome of patients with rheumatic diseases.
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              Romosozumab in postmenopausal women with low bone mineral density.

              Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                20 January 2016
                2016
                : 6
                : 18421
                Affiliations
                [1 ]Service de Rhumatologie–Hôpitaux Universitaires Paris Sud , Le Kremlin Bicêtre, France
                [2 ]Unité INSERM U1012 - Université Paris Sud , Le Kremlin Bicêtre, France
                [3 ]Groupe Hospitalier Pellegrin , Bordeaux, France
                [4 ]CHU de la Cavale Blanche , Brest Cedex, France
                [5 ]Assistance-Publique- Hôpitaux de Paris, Service d’Endocrinologie et des Maladies de la Reproduction, - Hôpitaux Universitaires Paris Sud , F-94275, Le Kremlin Bicêtre, France
                [6 ]Univ Paris-Sud, UMR S693 , F-94276, Le Kremlin Bicêtre, France
                [7 ]Service de Rhumatologie, Centre National de Référence pour les Maladies Auto-Immunes Systémiques Rares, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg , Strasbourg, France
                Author notes
                Article
                srep18421
                10.1038/srep18421
                4726234
                26785768
                5047bd56-af3c-4721-9375-d922819a6b0c
                Copyright © 2016, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 28 July 2015
                : 18 November 2015
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