**2. Pathophysiology of osteolysis**

The term aseptic loosening describes mechanical failure of the prosthesis-host interface, and arises primarily as the end result of focal periprosthetic inflammatory bone loss occurring at this interface. This pro-inflammatory microenvironment is driven by particulate wear debris, which is generated primarily at the articular bearing surface and at other non-articular prosthesis or cement surfaces9. Willert first proposed the involvement of prosthetic debris in the development of oesteolysis. He identified a resultant foreign body reaction and granuloma formation which included macrophages and multinucleated giant cells10. This foreign body reaction has subsequently been reproduced in animal models11. Once particulate wear debris has been dispersed into the joint fluid it may initiate a foreign body reaction at contact surfaces with the host tissues. Schmalzried coined the term "effective joint space" to describe all areas where open communication with the joint pseudo-capsule may allow circulation of the joint fluid and particulate debris12. The effective joint space is thus dynamic and may advance along a tissue plane as osteolysis progresses. Variations in hydrostatic pressure within the joint space during activity may contribute to this circulation12.

As well as its role in the migration of wear particles, hydrostatic fluid pressure changes within the joint have been implicated as an osteolytic stimulus. Aspenberg showed in an animal model that fluid pressure alone can lead to osteolysis13*.* Skoglund also showed that the osteolytic effect of fluid pressure on the bone was greater than that of particles14. However, it remains unclear what contribution this potential mechanism makes to the development of osteolysis clinically. Early migration of the femoral component may predict early and mid-term prosthesis failure. It has been suggested that this migration may lead to instability resulting in locally high fluid pressures which may, in turn, lead to osteolysis15. However, it is also likely that the predictive value of early migration measurements is due to the identification of failures of initial prosthesis fixation, resulting in loosening due to technical failure.
