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Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Metal Metabolism Group, Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London SE1 9NH, UK
Author to whom correspondence should be addressed.
Nutrients 2021, 13(1), 53;
Received: 6 November 2020 / Revised: 18 December 2020 / Accepted: 22 December 2020 / Published: 26 December 2020
(This article belongs to the Special Issue Diet and Rheumatoid Arthritis)
Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory articular conditions with different aetiology, but both result in joint damage. The nutritionally essential metal zinc (Zn2+) and the non-essential metal cadmium (Cd2+) have roles in these arthritic diseases as effectors of the immune system, inflammation, and metabolism. Despite both metal ions being redox-inert in biology, they affect the redox balance. It has been known for decades that zinc decreases in the blood of RA patients. It is largely unknown, however, whether this change is only a manifestation of an acute phase response in inflammation or relates to altered availability of zinc in tissues and consequently requires changes of zinc in the diet. As a cofactor in over 3000 human proteins and as a signaling ion, zinc affects many pathways relevant for arthritic disease. How it affects the diseases is not just a question of zinc status, but also an issue of mutations in the many proteins that maintain cellular zinc homoeostasis, such as zinc transporters of the ZIP (Zrt-/Irt-like protein) and ZnT families and metallothioneins, and the multiple pathways that change the expression of these proteins. Cadmium interferes with zinc’s functions and there is increased uptake under zinc deficiency. Remarkably, cadmium exposure through inhalation is now recognized in the activation of macrophages to a pro-inflammatory state and suggested as a trigger of a specific form of nodular RA. Here, we discuss how these metal ions participate in the genetic, metabolic, and environmental factors that lead to joint destruction. We conclude that both metal ions should be monitored routinely in arthritic disease and that there is untapped potential for prognosis and treatment. View Full-Text
Keywords: osteoarthritis; rheumatoid arthritis; zinc; cadmium osteoarthritis; rheumatoid arthritis; zinc; cadmium
MDPI and ACS Style

Frangos, T.; Maret, W. Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis. Nutrients 2021, 13, 53.

AMA Style

Frangos T, Maret W. Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis. Nutrients. 2021; 13(1):53.

Chicago/Turabian Style

Frangos, Theoharris, and Wolfgang Maret. 2021. "Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis" Nutrients 13, no. 1: 53.

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