Involvement of Immunogenetic Factors in the Development of Periprosthetic Osteolysis

Aseptic loosening and osteolysis are the most frequent causes of total hip or total knee arthroplasty failure. Osteolysis is induced predominantly by polyethylene particles that are produced by adhesive wear of the prosthesis. The particles trigger a complex host's reaction varying in intensity even in response to the same number of particles. These differences indicate that individual predisposition may have an important role in the pathogenesis of osteolysis. The major key mediators of wear-induced osteolysis include the cytokines RANKL, TNF-a, IL-1, IL-6 and IL-8. The inter-individual differences in the extent of bone destruction may therefore be related to variation in the amount and/or activity of these cytokines based on their gene polymorphism. Our pilot study suggests an association of some variants of the cytokine genes (e.g., IL1A-889) with a predisposition to development of severe osteolysis. If this assumption is confirmed by future investigations, this approach can facilitate the pre-operative identification of patients at risk of the development of severe periprosthetic osteolysis and premature failure of the implant.