**2. Overview of the current theories on aseptic loosening and periprosthetic osteolysis** *(Gallo, Goodman)*

The term "aseptic loosening" is closely related to the finding of *gross mechanical instability at the interface between the implant and bone bed* (Fig. 1). It is generally associated with pain and loss of function although it may also occur asymptomatically. Regarding the prevention the key question is what is the mechanism that first erodes the firm bond between implant and the bone bed.

Fig. 1. Severe medial migration of the cemented cup at the right site in 86 year old female (17 yrs. postoperatively)

Aseptic loosening of total hip arthroplasty is hypothesised to be the *result of a harmful combination of mechanical and biological events destroying the bond between the implant and bone bed*. To date, a variety of host-, implant- and surgery-related factors have been delineated to explain the development of aseptic loosening and osteolysis. Some of these are accepted by the scientific community, others are the subject of intensive research, while yet others are only speculative having little or no clinical or research evidence.

There are specific factors that directly increase the risk of aseptic loosening while others induce conditions that increase the probability of developing aseptic loosening. A well acknowledged factor in preventing aseptic loosening is surgical experience and technique resulting in firm fixation and correct implant placement. Failure to achieve sound and longterm fixation of the implant to the bone bed is closely associated with premature aseptic loosening (Mjoberg 1994). Factors associated with the development of severe periprosthetic 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 sound placement (Gallo et al. 2010).

### **2.1 Mechanical theories on aseptic loosening**

320 Recent Advances in Arthroplasty

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

This chapter provides a background on the current theory of aseptic loosening and

**2. Overview of the current theories on aseptic loosening and periprosthetic** 

The term "aseptic loosening" is closely related to the finding of *gross mechanical instability at the interface between the implant and bone bed* (Fig. 1). It is generally associated with pain and loss of function although it may also occur asymptomatically. Regarding the prevention the key question is what is the mechanism that first erodes the firm bond between implant and

Fig. 1. Severe medial migration of the cemented cup at the right site in 86 year old female (17

Aseptic loosening of total hip arthroplasty is hypothesised to be the *result of a harmful combination of mechanical and biological events destroying the bond between the implant and bone bed*. To date, a variety of host-, implant- and surgery-related factors have been delineated to explain the development of aseptic loosening and osteolysis. Some of these are accepted by the scientific community, others are the subject of intensive research, while yet others are

There are specific factors that directly increase the risk of aseptic loosening while others induce conditions that increase the probability of developing aseptic loosening. A well acknowledged factor in preventing aseptic loosening is surgical experience and technique resulting in firm fixation and correct implant placement. Failure to achieve sound and longterm fixation of the implant to the bone bed is closely associated with premature aseptic loosening (Mjoberg 1994). Factors associated with the development of severe periprosthetic

only speculative having little or no clinical or research evidence.

and osteolysis is of paramount importance and well justified.

**osteolysis** *(Gallo, Goodman)* 

the bone bed.

yrs. postoperatively)

osteolysis together with a brief overview of preventive measures.

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 resulting in loosening.

### **2.2 Biological theories on aseptic loosening**

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 resorption sites.

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

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

Aseptic Loosening of Total Hip Arthroplasty as a Result of Local Failure of Tissue Homeostasis 323

of intraarticular pressure depends in part on the volume of joint fluid, changes in position of the joint, and volume/draining capacity of the joint space assuming that high-volume and effectively drained joint space are associated with lower intraarticular pressures and vice versa. Other factors that may be important, but are not readily analysed include at least interactions between implant and its surroundings in terms of local tissue homeostasis maintenance/distortion, favourable composition of joint fluid, type of lubrication,

individual motion/stress pattern, and genetic predisposition to aseptic loosening.

**3.1 What we know about the physiological reactions of the local tissues on the** 

**prosthesis and its waste products** *(Konttinen, Pajarinen, Mackiewicz, Takagi, Jämsen,* 

A lot of research has been done on aseptic implant loosening, but there are few studies about the physiological, adaptive host responses to joint implants with a long and painless life-in-service. Loosened implants are surrounded by a fibrous implant capsule (Fig. 2). Contrary, well (physiologically) fixed implants are not characterized by fibrous implant capsule, synovial-membrane-like interface membrane (SLIM) or aggressive granulomatosis.

Cemented implants are fixed to bone with bone cement, polymethylmethacrylate (PMMA). Hip implant surgery damages descending metaphyseal arteries during the resection of the femoral head and the intramedullary nutritional artery during the implant bed preparation, which contribute to ischemia, lowering of pH and bone infarctions (Willert et al. 1974;

Willert and co-workers made a cadaver study of well-fixed implants to describe the physiological three-phase response of host bone to cement fixed implants. Toxic and lipolytic PMMA monomers and the exothermic polymerisation cause a marginal rim of necrosis of bone trabeculae at the cement-bone interface. After three weeks and up to two years postoperatively signs of repair of the implant bed are seen. This is perhaps in part stimulated by a local release of bone growth factors from the bone matrix and activated osteoclasts. Necrotic bone and bone fragments are resorbed by osteoclasts and macrophages. Newly produced or extended, irregularly orientated bone trabeculae grow as a laceworklike structure into the relatively smooth necrotic-fibrin clot-fatty-fibrotic bone-cement interface, which contains cement plugs, some of which protrude to reach direct contact with peri-implant bone. After two years bone repair is followed by remodelling of bone trabeculae, which are separated from the cement surface by a 0.1-1.5 mm thick fibrous membrane. This membrane grows into the empty spaces between the rough or cracked cement surface and contains some polyacrylamide pearls (from non-polymerized PMMA powder) close to the cement surface surrounded (isolated) by foreign-body giant cells and granulomas. Trabeculae of the already remodelled peri-implant bone were in the

longitudinal sections orientated in parallel to the cement surface (Willert et al. 1974).

This work was nicely extended by Jasty and co-workers, who studied serial horizontal sections of the proximal femoral bone that enclosed the cemented femoral component still in place in the implant bed. They confirm that the bone is remodelled and disclose a curious pattern for this remodelling. The cement mantles of the well-fixed implants are surrounded

**3. Local bone-soft tissue adaptations on an implant** 

They are characterized by some other features described below.

**3.1.1 Physiological fixation of cemented implants** 

*Takakubo, Gallo)* 

Konttinen et al. 2001).

together lead to degradation of the fixation interface and increase the probability of aseptic loosening. The ultimate pathway of aseptic loosening is undoubtedly of mechanical origin. For this reason, a comprehensive theory of aseptic loosening has been proposed involving both biological and mechanical factors.
