Elemental Influence: The Emerging Role of Zinc, Copper, and Selenium in Osteoarthritis.

Osteoarthritis (OA) is a prevalent and disabling joint disorder characterized by progressive cartilage degradation, subchondral bone changes, synovial inflammation, and chronic pain. While traditionally attributed to mechanical and age-related factors, increasing attention has been directed toward the role of nutritional components in disease modulation. This article critically examines the emerging role of three essential trace elements, zinc, copper, and selenium, in the pathophysiology of OA. These micronutrients are fundamental to antioxidant defense, immune modulation, and extracellular matrix (ECM) integrity. Altered systemic or local levels of zinc, copper, and selenium have been associated with oxidative stress, inflammation, and dysregulated cartilage metabolism in OA. Drawing on clinical studies, in vivo and in vitro experimental models, and population-based data, we synthesize evidence on trace element status in OA patients, mechanistic pathways, and therapeutic potential, including emerging nanomedicine strategies that enhance the targeted delivery and therapeutic efficacy of trace elements in joint tissues. This review highlights the need for integrated trace element profiling in OA research and clinical care and supports the exploration of targeted nutritional interventions in OA prevention and management.