Review Article | Published:

Metabolic syndrome meets osteoarthritis

Nature Reviews Rheumatology volume 8, pages 729737 (2012) | Download Citation

Abstract

Metabolic osteoarthritis (OA) has now been characterized as a subtype of OA, and links have been discovered between this phenotype and metabolic syndrome (MetS)—both with individual MetS components and with MetS as a whole. Hypertension associates with OA through subchondral ischaemia, which can compromise nutrient exchange into articular cartilage and trigger bone remodelling. Ectopic lipid deposition in chondrocytes induced by dyslipidemia might initiate OA development, exacerbated by deregulated cellular lipid metabolism in joint tissues. Hyperglycaemia and OA interact at both local and systemic levels; local effects of oxidative stress and advanced glycation end-products are implicated in cartilage damage, whereas low-grade systemic inflammation results from glucose accumulation and contributes to a toxic internal environment that can exacerbate OA. Obesity-related metabolic factors, particularly altered levels of adipokines, contribute to OA development by inducing the expression of proinflammatory factors as well as degradative enzymes, leading to the inhibition of cartilage matrix synthesis and stimulation of subchondral bone remodelling. In this Review, we summarize the shared mechanisms of inflammation, oxidative stress, common metabolites and endothelial dysfunction that characterize the aetiologies of OA and MetS, and nominate metabolic OA as the fifth component of MetS. We also describe therapeutic opportunities that might arise from uniting these concepts.

Key points

  • Osteoarthritis (OA) is a heterogeneous disease; the metabolic subtype is distinguishable by the presence of its major causative features, adipokines, hyperglycaemia and hormonal imbalance, and its prevalence in middle-aged people

  • The link between hypertension and OA centres on subchondral ischaemia, which can compromise nutrient exchange into the articular cartilage and trigger bone remodelling

  • Dyslipidemia-induced deregulation of cellular lipid metabolism in joint tissues might initiate OA development

  • Hyperglycaemia leads to local accumulation of advanced glycation end-products, which contribute to a toxic internal environment that facilitates OA pathogenesis

  • Obesity-altered adipokine levels induce the expression of proinflammatory factors and degradative enzymes, leading to the inhibition of cartilage matrix synthesis and stimulation of subchondral bone remodelling

  • Metabolic OA and MetS share mechanisms of inflammation, oxidative stress, common metabolites and endothelial dysfunction in their aetiologies

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Acknowledgements

The authors wish to thank Dr Wei Chai and Dr Guoqiang Zhang for helpful discussions during the revision of this manuscript.

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  1. Department of Orthopaedics, Chinese PLA General Hospital, Fuxing Road 28#, Haidian District, Beijing 100853, People's Republic of China

    • Qi Zhuo
    • , Jiying Chen
    •  & Yan Wang
  2.  Department of Endocrinology, Chinese PLA General Hospital, Fuxing Road 28#, Haidian District, Beijing 100853, People's Republic of China

    • Wei Yang

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Q. Zhuo, W. Yang and Y. Wang contributed equally to researching data for the article, discussions of content, writing the article and review/editing of the manuscript before submission. J. Chen made substantial contributions to researching data for the article, discussions of content and review/editing of the manuscript before submission.

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The authors declare no competing financial interests.

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Correspondence to Yan Wang.

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https://doi.org/10.1038/nrrheum.2012.135

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