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Vitamin D in rheumatoid arthritis—towards clinical application

Key Points

  • Nonclassical effects of vitamin D have been recognized for many years, but were only accepted as an important component of vitamin D physiology in the past decade

  • Prominent among the nonclassical effects of vitamin D are its anti-inflammatory properties

  • Vitamin D deficiency is prevalent worldwide and has been linked to several chronic inflammatory diseases, including rheumatoid arthritis (RA)

  • Randomized controlled trials of vitamin D supplementation in prospective at-risk cohorts and in patients with active RA are needed to assess the effect of vitamin D on disease initiation and progression

Abstract

In addition to its well-documented involvement in mineral homeostasis, vitamin D seems to have broad effects on human health that go beyond the skeletal system. Prominent among these so-called nonclassical effects of vitamin D are its immunomodulatory properties. In vitro studies have shown anti-inflammatory effects of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active form of vitamin D. In addition, epidemiological analysis of patients with established inflammatory disease identified associations between vitamin D deficiency (low serum concentrations of inactive 25-hydroxyvitamin D, abbreviated to 25(OH)D) and inflammatory conditions, including rheumatoid arthritis (RA). The association of vitamin D deficiency with RA severity supports the hypothesis of a role for vitamin D in the initiation or progression of the disease, or possibly both. However, whether 25(OH)D status is a cause or consequence of RA is still incompletely understood and requires further analysis in prospective vitamin D supplementation trials. The characterization of factors that promote the transition from preclinical to clinical phases of RA has become a major focus of research, with the aim to facilitate earlier diagnosis and treatment, and improve therapeutic outcomes. In this Review, we aim to describe the current knowledge of vitamin D and the immune system specifically in RA, and discuss the potential benefits that vitamin D might have on slowing RA progression.

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Figure 1: Renal and extra-renal vitamin D metabolism in RA progression.
Figure 2: Vitamin D status and synovial immune cell function.

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Acknowledgements

This work is supported by the following grants: Arthritis Research UK (Arthritis Research UK Rheumatoid Arthritis Pathogenies Centre of Excellence); EU FP7 HEALTH programme under the grant agreement FP7-HEALTH-F2-2012-305549.

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All authors contributed equally to all aspects of the manuscript (researching data for the article, discussions of its content, writing, review and editing of the manuscript before submission).

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Correspondence to Martin Hewison.

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Jeffery, L., Raza, K. & Hewison, M. Vitamin D in rheumatoid arthritis—towards clinical application. Nat Rev Rheumatol 12, 201–210 (2016). https://doi.org/10.1038/nrrheum.2015.140

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