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

Abstract

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.

A Novel Autophagy-Related Marker for Improved Differential Diagnosis of Rheumatoid Arthritis and Osteoarthritis

“…OA which is traditionally classified as non-inflammatory arthritis has predominance as geriatric degenerative disease ( Glyn-Jones et al, 2015 ). In recent years, a deepening understanding of these two diseases, RA and OA, showed similar and overlapping characteristics in their underlying mechanisms ( Frangos and Maret, 2020 ). Therefore, although there are standard differential diagnostic methods for RA and OA, poor differential diagnosis still occurs in some cases ( Toes and van der Woude, 2011 ; Kiltz et al, 2017 ).…”

“…These two are considered the most common rheumatic diseases in the world ( Sangha, 2000 ). A deep understanding of the diseases reveals that although RA and OA have great differences in pathophysiology, similar and overlapping features are presented in their underlying mechanisms ( de Lange-Brokaar et al, 2012 ; Frangos and Maret, 2020 ). Standard differential diagnoses for RA and OA in some cases lead to poor outcomes ( Toes and van der Woude, 2011 ; Kiltz et al, 2017 ).…”

ADAMTS-12: Functions and Challenges for a Complex Metalloprotease

“…Osteoarthritis (OA) and rheumatoid arthritis (RA) are believed to be the most prevalent rheumatic diseases, affecting approximately 11% (10% OA and 1% RA) of the world population (Frangos and Maret, 2020). Both, RA and OA are debilitating degenerative diseases affecting articular joints which are characterized by a deregulation in joint or bone homeostasis.…”

Cadmium Body Burden and Inflammatory Arthritis: A Pilot Study in Patients from Lower Silesia, Poland

“…Cadmium absorption increases under zinc deficiency conditions, as in the case of iron. Cadmium dust inhalation can cause macrophage activation, inflammation, and IA development [ 38 ]. Rentschler et al [ 39 ] conclude that a genetic variation in zinc transporters influences blood cadmium concentrations (Cd-B): individuals with a certain genotype of these transporters have higher Cd-B.…”