Comprehensive overview of the molecular interactions between selected elements and enzymes in hip osteoarthritis

Despite advances in the management of osteoarthritis (OA), clinically validated biomarkers for the early detection and progression assessment of hip OA remain unavailable. This review evaluates evidence concerning selected elements (Zn, Cu, Se, Cr, Fe, Mn, Mg, Cd and Pb), and selected element-dependent enzymes or regulatory factors involved in extracellular-matrix remodeling, oxidative stress, and chondrocyte metabolism. These include MMPs, ADAMs, ADAMTS proteases, lysyl oxidases, transglutaminase 2, HIF-1α, HIF-2α, and SOD2. We distinguish evidence obtained directly from human hip OA from findings derived from knee OA, population studies, animal models, and in vitro systems. The available data support several biologically plausible element-enzyme relationships, but elemental concentrations are inconsistent across studies and cannot currently be considered validated diagnostic biomarkers. Prospective hip-specific studies using standardized sampling, analytical procedures, and simultaneous measurements of elemental status and enzyme activity are required before clinical translation can be considered.