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Metabolic syndrome and knee osteoarthritis Obesity is a well-known risk factor for OA (8, 25). Abdominal obesity might affect knee OA development by the combined metabolic effects of adipose tissue and mechanical stress of body weight. In our study, hypertension, in addition to abdominal obesity, was significantly associated with an increased risk of knee OA. The association was valid even after adjusting for abdominal obesity. Moreover, this relationship was also present in men. Zhang et al. reported that multiple genes or the proinflammatory cytokine interleukin-6 plays an important role in the association between hypertension and knee OA (26). Yoshimura et al. also clarified that hypertension was significantly associated with the occurrence of knee OA and vice versa (23, 27). Other metabolic syndrome components, apart from abdominal obesity and hypertension, showed a significant association with the development of knee OA in several analysis models. However, after adjusting for all compounding factors in model 2, the effects were insignificant. Nevertheless, caution is needed in determining the individual effect of each component based solely on the results of the current study, because every metabolic component interacts with, and usually coexists with, other components. Considering the dose-response relationship for meta- bolic syndrome components, each factor has an effect on the development of knee OA with some interactions and accumulative effects. Strengths and limitations The present study has several strengths. First, not only did it investigate the association between the presence of metabolic syndrome and development of knee OA, but it also evaluated the dose-response relationship by considering the number of metabolic syndrome com- ponents. Moreover, this study assessed the individual effect of each metabolic syndrome component. These analyses revealed that some components may be more associated with the development of knee OA than other components. Secondly, the current study evaluated knee OA in an objective manner, using radiographic images. In addition, it divided the disease into knee OA and severe knee OA, based on the KL grading system. Therefore, it was possible to make a more detailed ana- lysis. Thirdly, participants were divided and analysed by sex, and substantial differences were confirmed between the 2 groups. Fourthly, the current study was based on a nationwide representative large-sample survey. Thus it was possible to reduce selection bias and the results are applicable to the general population. The current study also has some limitations. First, it was a cross-sectional study, and thus could not establish a causal relationship between metabolic syndrome and knee OA. Secondly, various risk factors 469 that may affect the development of knee OA were ad- justed for, but there could be more factors affecting the development of OA that need to be adjusted. Thirdly, there were many fewer men with OA than women with OA, which will have reduced the statistical power to investigate associations in men. Conclusion Overall, the results of this study showed that the presence of metabolic syndrome was associated with increased risk of knee OA and severe knee OA in women. The risk of knee OA in women increased as the number of metabolic syndrome components increased. However, these findings were not definite in men. Hypertension and abdominal obesity were significantly associated with the development of knee OA and severe knee OA in women. In men, abdominal obesity and hypertension significantly increased the risk of knee OA, but only abdominal obesity increased the risk of severe knee OA. Further studies are needed to determine the exact mechanism by which metabolic syndrome affects the development of knee OA. ACKNOWLEDGEMENTS This study was supported by a grant (2017–661) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The authors have no conflicts of interests to declare. REFERENCES 1. Osgood E, Trudeau JJ, Eaton TA, Jensen MP, Gammaitoni A, Simon LS, et al. Development of a bedside pain as- sessment kit for the classification of patients with osteo- arthritis. Rheumatol Int 2015; 35: 1005–1013. 2. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ez- zati M, et al. 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