Aseptic loosening (AL) represents the leading cause of long-term failure in total joint arthroplasty, often necessitating revision surgery. This review explores the complex mechanisms underlying AL, which involve a multifaceted interaction between the implanted biomaterials and the host immune response. We outline the key inflammatory mechanisms triggered by wear debris from polyethylene, polymethylmethacrylate, metal, and ceramic materials. We also examine emerging biomarkers for early detection and differentiation between stable and loosened implants, including proinflammatory cytokines, bone metabolism markers, extracellular matrix degradation products, microRNAs, and genetic polymorphisms. Lastly, we discuss current and future strategies for prevention and treatment, ranging from surgical optimization and biomaterial selection to pharmacological interventions. A comprehensive understanding of these mechanisms may help reduce the incidence of AL and improve long-term outcomes in arthroplasty patients.

Aseptic loosening (AL) represents the leading cause of long-term failure in total joint arthroplasty, often necessitating revision surgery. This review explores the complex mechanisms underlying AL, which involve a multifaceted interaction between the implanted biomaterials and the host immune response. We outline the key inflammatory mechanisms triggered by wear debris from polyethylene, polymethylmethacrylate, metal, and ceramic materials. We also examine emerging biomarkers for early detection and differentiation between stable and loosened implants, including pro-inflammatory cytokines, bone metabolism markers, extracellular matrix degradation products, microRNAs, and genetic polymorphisms. Lastly, we discuss current and future strategies for prevention and treatment, ranging from surgical optimization and biomaterial selection to pharmacological interventions. A comprehensive understanding of these mechanisms may help reduce the incidence of AL and improve long-term outcomes in arthroplasty patients.