Periprosthetic osteolysis: Mechanisms and potential treatment strategies

Periprosthetic osteolysis is a common bone-related disorder that often occurs after total hip arthroplasty. The implants can cause damage to bone and bone-related cells due to mechanical stress and micromotions, resulting in the generation of a large number of wear particles. These wear particles trigger inflammation and oxidative stress in the surrounding tissues, disrupting the delicate balance maintained by osteoblasts and osteoclasts, ultimately leading to bone loss around the implant. Clinical investigations have demonstrated that Epimedium prenylflavonoids, miR-19a-3p, stem cell-derived exosomes, and certain non-PPO category pharmaceuticals have regulatory effects on bone homeostasis through distinct molecular pathways. Notably, this phenomenon reflects inherent biological rationality rather than stochastic occurrence. Extensive research has revealed that multiple natural compounds, non-coding RNAs, exosomes, and non-PPO therapeutics not only exert modulatory influences on critical pathophysiological processes including inflammatory cascades, oxidative stress responses, and tissue regeneration mechanisms, but also effectively regulate bone-related cellular functions to inhibit PPO progression. Therefore, this review comprehensively and systematically summarizes the main pathogenic mechanisms of periprosthetic osteolysis. Furthermore, it delves deeper into the research progress on the applications of currently reported natural products, ncRNAs, exosomes, and non-PPO medications in the treatment of periprosthetic osteolysis. Based on this, we hope that this paper can provide new perspectives and references for the future development of drugs targeting periprosthetic osteolysis.