Aseptic loosening induced by UHMWPE wear particles is considered the main cause of longterm implant failure in orthopaedic surgery. The current therapy consists of surgical revision
and implant replacement, carrying severe consequences for public health. Over the past 20
years, preclinical approaches including mouse models have been essential in the advances
made in the understanding of the pathophysiology of periprosthetic osteolysis involved in the
loosening process. However, while encouraging results have been obtained in vivo, there is
still no valid clinical alternative to revision surgery. This review provides an overview of the
current approaches used to study the biology of periprosthetic osteolysis and discusses the
contributions, limitations and future challenges of mouse models for a successful translation
of the preclinical advances into clinical applications.