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      Serum hyaluronic acid concentration predicts the progression of joint space narrowing in normal knees and established knee osteoarthritis – a five-year prospective cohort study

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          Abstract

          Introduction

          Serum hyaluronic acid (sHA) is a serum biomarker for knee osteoarthritis (OA). Although sHA concentration is elevated in patients with knee OA, the relationship between serum concentration and disease progression remains unclear. We examined the relationship between sHA concentration and radiographic progression of knee OA in a cohort of individuals followed for 5 years.

          Methods

          We prospectively enrolled 444 individuals and measured their sHA concentrations at baseline. Anterior-posterior weight bearing knee radiographs were obtained at baseline and the 5-year endpoint. Osteoarthritic knee changes were classified according to Kellgren–Lawrence (KL) grade, and joint space narrowing (JSN) was measured using a Knee Osteoarthritis Computer-Aided Diagnosis (KOACAD) system. Correlations between sHA concentration, progression in KL grade, and JSN were assessed using regression models, taking into account potentially confounding factors.

          Results

          OA progressed from KL grades 0 or 1 in 129 of the 323 knees, and from KL grades 2 or 3 in 61 of the 119 knees. Higher sHA concentrations were correlated with KL grade progression (p = 0.004). The mean JSN, as assessed by KOACAD over 5 years, was 0.23 ± 0.55 mm, and sHA concentration was positively correlated with progression of JSN in KL grades 0 or 1 (p = 0.021) and KL grades 2 or 3 (p = 0.008) knees.

          Conclusion

          Serum HA concentration was positively correlated with progression of KL grade. sHA was also positively correlated with progression of JSN in knees with and without OA, suggesting that sHA concentration may be a useful predictor of knee OA progression.

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          Most cited references38

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          The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

          Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain. The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well. The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis. Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown. Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle. As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression.
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            Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study.

            Musculoskeletal diseases, especially osteoarthritis (OA) and osteoporosis (OP), impair activities of daily life (ADL) and quality of life (QOL) in the elderly. Although preventive strategies for these diseases are urgently required in an aging society, epidemiological data on these diseases are scant. To clarify the prevalence of knee osteoarthritis (KOA), lumbar spondylosis (LS), and osteoporosis (OP) in Japan, and estimate the number of people with these diseases, we started a large-scale population-based cohort study entitled research on osteoarthritis/osteoporosis against disability (ROAD) in 2005. This study involved the collection of clinical information from three cohorts composed of participants located in urban, mountainous, and coastal areas. KOA and LS were radiographically defined as a grade of > or =2 by the Kellgren-Lawrence scale; OP was defined by the criteria of the Japanese Society for Bone and Mineral Research. The 3,040 participants in total were divided into six groups based on their age: or =80 years. The prevalence of KOA in the age groups or =80 years 0, 9.1, 24.3, 35.2, 48.2, and 51.6%, respectively, in men, and the prevalence in women of the same age groups was 3.2, 11.4, 30.3, 57.1, 71.9, and 80.7%, respectively. With respect to the age groups, the prevalence of LS was 14.3, 45.5, 72.9, 74.6, 85.3, and 90.1% in men, and 9.7, 28.6, 41.7, 55.4, 75.1, and 78.2% in women, respectively. Data of the prevalence of OP at the lumbar spine and femoral neck were also obtained. The estimated number of patients with KOA, LS, and L2-L4 and femoral neck OP in Japan was approximately 25, 38, 6.4, and 11 million, respectively. In summary, we estimated the prevalence of OA and OP, and the number of people affected with these diseases in Japan. The ROAD study will elucidate epidemiological evidence concerning determinants of bone and joint disease.
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              Relation of synovitis to knee pain using contrast-enhanced MRIs.

              It has been suggested that synovitis causes joint pain. On non-contrast-enhanced MRIs synovial thickening cannot be assessed and on these images synovitis has been inconsistently associated with pain. To assess synovial thickening in relation to knee pain severity among subjects in the Multicenter Osteoarthritis Study (MOST) using contrast-enhanced (CE) MRI. MOST is a cohort study of people who have, or are at high risk of, knee osteoarthritis (OA). An unselected subset of 535 participants who volunteered underwent CE 1.5 T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. Knee pain severity was assessed using the maximum item score on the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain scale. The association between synovitis and pain severity was examined using a logistic regression model adjusting for age, sex, body mass index (BMI), MRI bone marrow lesions and effusions in the whole sample and in a subgroup without radiographic OA. 454 of the 535 subjects undergoing CE MRI had complete data on synovitis and WOMAC pain. Mean age was 59 years, mean BMI 30 and 48% were women. In knees with moderate pain, 80% had synovitis. For knee pain, synovitis conferred a 9.2-fold increased odds compared with those without synovitis. In knees without radiographic OA (n=329), there was also an association of synovitis with an increased prevalence of pain. Synovitis has a strong relation with knee pain severity, an association detected more clearly with CE MRI than suggested by previous studies using non-CE MRI measures of synovitis.
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                Author and article information

                Contributors
                +81-172-39-5083 , e_sasaki@hirosaki-u.ac.jp
                eiichi@hirosaki-u.ac.jp
                yuji1112@hirosaki-u.ac.jp
                s-maeda@hirosaki-u.ac.jp
                inoueryo@hirosaki-u.ac.jp
                dachiba@hirosaki-u.ac.jp
                hiroshi.fujita@seikagaku.co.jp
                ippei@hirosaki-u.ac.jp
                tume@meijo-u.ac.jp
                nakaji@hirosaki-u.ac.jp
                yasuyuki@hirosaki-u.ac.jp
                Journal
                Arthritis Res Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                10 October 2015
                10 October 2015
                2015
                : 17
                : 283
                Affiliations
                [ ]Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562 Japan
                [ ]Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
                [ ]Glycoconjugate Research Center, Kurihama Plant, Seikagaku Corporation, Yokosuka, Japan
                Article
                793
                10.1186/s13075-015-0793-0
                4600294
                25566937
                188cb0b7-a24f-472a-ac8d-b98c992e7323
                © Sasaki et al. 2015

                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
                : 11 April 2015
                : 22 September 2015
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                © The Author(s) 2015

                Orthopedics
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