Metal-on-metal hip implants: Revisiting degradation product chemistry and molecular mechanisms of ARMD.

Over the past decade, publications, legal cases, and regulatory panels have intensified scrutiny of implant degradation products-particularly nanoparticles and chemically reacted corrosion products-in the failure of total hip prostheses. While orthopedics has long linked wear to loosening, the mechanisms and exposure conditions that drive adverse local tissue reactions remain incompletely defined. Historically, microscale polymer particles were considered the primary drivers of inflammation; however, reductions in polyethylene wear have made nanoscale species and metal degradation products more prominent around some implants. Advances in analytical techniques now show that "metal debris" often consists of oxidized chromium(III) oxides/phosphates with cobalt largely present as soluble or complexed species, and that modular taper junctions can contribute mixed degradation products that differ from bearing-surface debris. Clinically, these issues remain relevant because many patients implanted during the peak adoption period of metal-on-metal (MoM) systems still live with these devices and may present across diverse health systems, where prior implant records and standardized surveillance may be incomplete. Unfortunately, in vitro studies have not always been as informative as expected because static, bolus exposures and idealized particles fail to capture in vivo speciation, dose rate (flux), protein corona formation, and physiologic transport. This review summarizes current knowledge on particle size distributions and degradation product chemistry in hip arthroplasty and discusses how these variables shape molecular and cellular pathways implicated in ARMD, while outlining experimental strategies that better reproduce physiological exposure conditions.