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      Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative

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          Abstract

          Background

          Greater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features. We examined if serum concentrations of glucose homeostasis (glucose, glycated serum protein [GSP]) or inflammation (C-reactive protein [CRP]) were associated with prevalent knee bone marrow lesions (BMLs) or effusion among adults without knee OA.

          Methods

          We conducted a cross-sectional study using baseline data from the Osteoarthritis Initiative. We selected participants who had no radiographic knee OA but were at high risk for knee OA. Blinded staff conducted assays for CRP, GSP, and glucose. Readers segmented BML volume and effusion using semi-automated programs. Our outcomes were prevalent BML (knee with a BML volume > 1 cm 3) and effusion (knee with an effusion volume > 7.5 cm 3). We used logistic regression models with CRP, GSP, or glucose concentrations as the predictors. We adjusted for age, sex, body mass index (BMI), and Physical Activity Scale for the Elderly (PASE) scores.

          Results

          We included 343 participants: mean age = 59 ± 9 years, BMI = 27.9 ± 4.5 kg/m 2, PASE score = 171 ± 82, and 64% female. Only CRP was associated with BML prevalence (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09 to 1.87). For effusion, we found an interaction between BMI and CRP: only among adults with a BMI <25 kg/m 2 was there a significant trend towards a positive association between CRP and effusion (OR = 1.40, 95% CI = 1.00 to 1.97). We detected a U-shaped relationship between GSP and effusion prevalence. Fasting glucose levels were not significantly associated with the presence of baseline effusion or BML.

          Conclusions

          Among individuals without knee OA, CRP may be related to the presence of BMLs and effusion among normal weight individuals. Abnormal GSP may be associated with effusion. Future studies should explore whether inflammation and glucose homeostasis are predictive of symptomatic knee OA.

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          Most cited references37

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          Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization.

          To quantify the incidence of symptomatic hand, hip, and knee osteoarthritis (OA) among members of the Fallon Community Health Plan, a health maintenance organization located in central Massachusetts. Incident OA was defined as the first evidence of OA by radiography (grade > or = 2 on the Kellgren-Lawrence scale of 0-4) plus joint symptoms at the time the radiograph was obtained or up to 1 year before the radiograph was obtained. The age- and sex-standardized incidence rate for hand OA was 100/100,000 person-years (95% confidence interval [95% CI] 86, 115), for hip OA 88/100,000 person-years (95% CI 75, 101), and for knee OA 240/100,000 person-years (95% CI 218, 262). The incidence of hand, hip, and knee OA increased with age, and women had higher rates than men, especially after age 50. A leveling off or decline occurred for both groups around the age of 80. In a large study of symptomatic OA we observed incidence rates that increased with age. In women ages 70-89, the incidence of knee OA approached 1% per year.
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            The osteoarthritis initiative: report on the design rationale for the magnetic resonance imaging protocol for the knee.

            To report on the process and criteria for selecting acquisition protocols to include in the osteoarthritis initiative (OAI) magnetic resonance imaging (MRI) study protocol for the knee. Candidate knee MR acquisition protocols identified from the literature were first optimized at 3Tesla (T). Twelve knees from 10 subjects were scanned one time with each of 16 acquisitions considered most likely to achieve the study goals and having the best optimization results. The resultant images and multi-planar reformats were evaluated for artifacts and structural discrimination of articular cartilage at the cartilage-fluid, cartilage-fat, cartilage-capsule, cartilage-meniscus and cartilage-cartilage interfaces. The five acquisitions comprising the final OAI MRI protocol were assembled based on the study goals for the imaging protocol, the image evaluation results and the need to image both knees within a 75 min time slot, including positioning. For quantitative cartilage morphometry, fat-suppressed, 3D dual-echo in steady state (DESS) acquisitions appear to provide the best universal cartilage discrimination. The OAI knee MRI protocol provides imaging data on multiple articular structures and features relevant to knee OA that will support a broad range of existing and anticipated measurement methods while balancing requirements for high image quality and consistency against the practical considerations of a large multi-center cohort study. Strengths of the final knee MRI protocol include cartilage quantification capabilities in three planes due to multi-planar reconstruction of a thin slice, high spatial resolution 3D DESS acquisition and the multiple, non-fat-suppressed image contrasts measured during the T2 relaxation time mapping acquisition.
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              Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial.

              To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs). Adults aged 50-80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale. At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm(2). VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (-14.5 mm, 95% CI -28.1 to -0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (-175.7 mm(2), 95% CI -327.2 to -24.3) with a trend after 12 months (-146.5 mm(2), 95% CI -307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms. ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach. ACTRN 12609000399291.
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                Author and article information

                Contributors
                stout.a@husky.neu.edu
                mary.barbe@temple.edu
                CEaton@carene.org
                mamta@temple.edu
                fatimahbader@yahoo.com
                LPrice1@tuftsmedicalcenter.org
                blu1@rics.bwh.harvard.edu
                ghlo@bcm.edu
                MZhang@tuftsmedicalcenter.org
                jinchengpang@gmail.com
                tmcalindon@tuftsmedicalcenter.org
                jeffrey.driban@tufts.edu
                Journal
                BMC Musculoskelet Disord
                BMC Musculoskelet Disord
                BMC Musculoskeletal Disorders
                BioMed Central (London )
                1471-2474
                5 January 2018
                5 January 2018
                2018
                : 19
                : 1
                Affiliations
                [1 ]ISNI 0000 0000 8934 4045, GRID grid.67033.31, Division of Rheumatology, , Tufts Medical Center, ; 800 Washington Street, Box #406, Boston, MA 02111 USA
                [2 ]ISNI 0000 0001 2248 3398, GRID grid.264727.2, Department of Anatomy and Cell Biology, , Temple University School of Medicine, ; 3500 North Broad Street, Philadelphia, PA 19140 USA
                [3 ]ISNI 0000 0004 1936 9094, GRID grid.40263.33, Center for Primary Care and Prevention, , Alpert Medical School of Brown University, ; 111 Brewster Street, Pawtucket, RI 02860 USA
                [4 ]ISNI 0000 0000 8934 4045, GRID grid.67033.31, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, ; 800 Washington Street, Box #63, Boston, MA 02111 USA
                [5 ]ISNI 0000 0004 1936 7531, GRID grid.429997.8, Tufts Clinical and Translational Science Institute, Tufts University, ; 800 Washington Street, Box #63, Boston, MA 02111 USA
                [6 ]ISNI 0000 0004 0378 8294, GRID grid.62560.37, Brigham & Women’s Hospital and Harvard Medical School, ; 75 Francis Street PBB-B3, Boston, MA 02115 USA
                [7 ]ISNI 0000 0004 0420 5521, GRID grid.413890.7, Medical Care Line and Research Care Line, Houston Health Services Research and Development (HSR&D) Center of Excellence Michael E. DeBakey VAMC, ; 2002 Holcombe Blvd, Houston, TX 77030 USA
                [8 ]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
                [9 ]ISNI 0000 0004 1936 7531, GRID grid.429997.8, Department of Electrical Engineering, , Tufts University, ; 161 College Avenue, Medford, MA 02155 USA
                Article
                1921
                10.1186/s12891-017-1921-6
                5755424
                29304778
                4e790135-17af-4b7a-8413-2c32aa166bfa
                © The Author(s) 2018

                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
                : 19 September 2017
                : 22 December 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000069, National Institute of Arthritis and Musculoskeletal and Skin Diseases;
                Award ID: R01 AR065977
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Orthopedics
                bone marrow lesions,effusion,magnetic resonance imaging,osteoarthritis
                Orthopedics
                bone marrow lesions, effusion, magnetic resonance imaging, osteoarthritis

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