**1. Introduction** *(Gallo)*

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> Total hip arthoplasty (THA) is the most effective and safest method for treating severe degenerative, post-traumatic and other diseases of the hip joint. It is estimated that more than 1,000,000 THAs are performed each year globally. The incidence of primary THA increased in the period 1990 to 2002 in the USA from 47/100,000 to 69/100,000 (Kurtz et al. 2007). A similar study in Denmark reported an increased rate of THAs from 101/100,000 to 131/100,000 during the period 1996 to 2002 (Pedersen et al. 2005). More importantly, modelled future projections expect further increase in the need for THAs.

> It is believed that THA can reliably relieve pain and improve function in the majority of patients for a period of 15 to 20 years or more postoperatively. On this basis, with the extension of THAs to a younger and generally more active population, the expected time of service of THAs would be insufficient and the number of revision surgeries would therefore increase during this time. The Kaplan-Meier ten-year revision-free survival estimates for younger patients range from 72% (95%CI: 67-76) in Finland to 86% (95%CI: 84,5-88,2) in Sweden (Corbett et al. 2010). Hence, 14% to 28% of such patients on average did not achieve a 10-year THA functioning without revision.

> The main reason for late failure of THA is *aseptic loosening accompanied by osteolysis* followed by infection and instability of the THA that compromise more the early postoperative

Rihard Trebse9, Andrei Coer10 and Michiaki Takagi5

<sup>\*</sup> Yrjö T. Konttinen1, Stuart B. Goodman2, Jacob P. Thyssen3, Emmanuel Gibon4, Jukka Pajarinen1, Yuya Takakubo5, Peter Schalock6, Zygmunt Mackiewicz7, Eemeli Jämsen1, Martin Petrek8,

*<sup>1</sup>Department of Medicine and Department of Anatomy, Helsinki University Central Hospital, ORTON* 

*Orthopaedic Hospital of the Invalid Foundation, COXA Hospital for Joint Replacement, Finland 2Department of Orthopaedic Surgery, Stanford University, USA 3Department of Dermato-Allergology Copenhagen University Hospital Gentofte, Denmark 4Department of Orthopaedic Surgery, Bichat Teaching Hospital, Paris School of Medicine, France 5Department of Orthopaedics, Yamagata University, Japan* 

*<sup>6</sup>Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston, USA 7Department of Histology and Embryology, Medical University in Bialystok, Poland* 

*<sup>8</sup>Department of Immunology, Palacky University Olomouc, Czech Republic 9Valdoltra Orthopaedic Hospital, Ankaran, Slovenia 10College of Health Care, University of Primorska, Izola, Slovenia* 

Aseptic Loosening of Total Hip Arthroplasty as a Result of Local Failure of Tissue Homeostasis 321

osteolysis significantly influence the rate of aseptic loosening as it is believed that severe bone loss can facilitate the process of destabilisation of the implant regardless of its original

Proponents of mechanical theories explain aseptic loosening and periprosthetic osteolysis *to be the result of predominantly mechanical events* with stress and strain being the major drivers of the disease. These refer to the stresses and strains affecting the implant-bone interface during each step until they overwhelm the firmness of the interface. On this basis, Mjöberg stressed the importance of the quality of the initial fixation because he and others had revealed the close association between early migration of implant and risk of premature failure of THA due to aseptic loosening (Mjoberg 1994). Unfortunately, there is no agreed threshold of migration above which loosening can be predicted. Further it is not possible to compare directly the migration data of different studies (Derbyshire et al. 2009). In addition, it seems that the majority of cemented cups migrate during the first postoperative year and thus the revision rate is poorly predictable one year postoperatively even in cases with significant migration (Aspenberg et al. 2008). For this reason, the "mechanical theory" should be revised to include at least the distinction between stable, osseointegrated prostheses and those in which osseointegration has not developed after the first postoperative year and exhibit radiolucency around the implant, and continuous migration

According to biological theory, aseptic loosening is the *result of a series of predominantly biological processes*. Of these, the most important is the complex adverse host response to prosthetic particles and by-products which produce particle disease. Willert and Semlitsch were the first to introduce the concept of aseptic loosening as a result of periprosthetic tissue reaction to massive amounts of prosthetic microparticles (Willert and Semlitsch 1977). The key concept in particle disease is that *very small prosthetic particles* (the size of micrometers and less) *stimulate periprosthetic cells to express proinflammatory/ pro-osteoclastic cytokines and other substances that orchestrate increased accumulation/activity/survival of osteoclasts, and inhibit the osteogenic activity of osteoblasts*. As a result, osteoresorption predominates over osteogenesis at each bone multicellular unit on the bone surface around the implant leading eventually to macroscopically observed bone defects. The degree of bone loss according to this concept is a function of number and depth of deregulated

The expansion of particle disease across the joint is facilitated by joint fluid that is abundantly synthesized by synovial-like macrophages and fibroblasts. Joint fluid contributes to conversion of M0 on M1 macrophages (*Part 4.4*). In addition, it washes the prosthetic microparticles from the articulating surfaces, mediates signal molecules and enzymes and delivers them to the bone. For this reason, particle disease can recur at new

A question remains as to what other biological factors underlie the destabilization of the implant associated with severity of bone defects. Of these, aging of the bone bed (senescence), stress-shielding, and cumulative fatigue changes at the bone-implant interface may contribute to weakening of the implant-bone fixation. Eventually, these separately or

sites, contributing in this way to overall weakening of the bone-implant interface.

sound placement (Gallo et al. 2010).

resulting in loosening.

resorption sites.

**2.1 Mechanical theories on aseptic loosening** 

**2.2 Biological theories on aseptic loosening** 

period than the later one (Ulrich, Seyler et al. 2008). For this reason the above mentioned increase in rate of primary THAs is closely associated with increase in demand for revision THAs. The incidence of revision THAs in the USA increased from 9.5/100,000 to 15.2/100,000 between 1990 and 2002 and the projections by 2030 are even more impressive (Kurtz et al. 2007). With this in mind, research on the pathophysiology of aseptic loosening and osteolysis is of paramount importance and well justified.

This chapter provides a background on the current theory of aseptic loosening and osteolysis together with a brief overview of preventive measures.
