**6.1 Prosthesis design**

284 Recent Advances in Arthroplasty

and monocytes (PBMCs) taken from patients with a susceptibility to osteolysis exhibit quantitatively greater inducible cytokine responses to particulate debris in-vitro versus patients without this susceptibility61 . It is suggested that this inter-patient variability may

Fig. 6. Patients exhibit variable osteolytic responses to wear debris. a) radiograph showing marked polyethylene wear, but no osteolytic response, b) radiograph

showing mild wear but pronounced femoral and acetabular osteolysis with prosthesis

Variation within the genes encoding inflammatory cytokines have been associated with osteolysis. Wilkinson *et al* showed an association between variability within the DNA encoding the tumor necrosis factor (TNF) promoter region (dbSNP rs361525) and risk of osteolysis following THA62. Subjects with osteolysis were approximately twice as likely to carry the variant DNA code as those subjects with no osteolysis. This association has been replicated in an independent population by Ambruzova *et al63*. Gordon *et al* have reported genetic variation within the genes encoding Interleukin-1 receptor antagonist (IL-1RN) and IL-6 is also associated with osteolysis64. Similar associations have also been identified in

Variation within genes that regulate bone turnover also associate with osteolysis. Gordon *et al* showed that carriage of the dbSNP rs288326 variant in the FRZB gene encoding secreted frizzled-related protein-3 (Frp3), a regulatory glycoprotein within the osteogenic Wnt signaling pathway that modulates mesenchymal stem cell differentiation of osteoblasts68, associated with susceptibility to osteolysis following THA69. Its carriage also associated with

have a genetic basis.

loosening.

other populations65-67.

Prosthesis design factors, aside from those that modulate wear, contribute to risk of osteolysis. Modularity allows intra-operative adjustment of bearing surfaces, prosthesis length and offset. However, it also creates additional interfaces within the construct at which generation of debris through wear may occur. Such interfaces include the trunion between the femoral head and stem at which corrosive wear may occur, and backside wear between an acetabular liner and its shell at which abrasive wear may occur, and potentially several other prosthetic component junctions in highly modular systems. Hydroxyapatite coating of the prosthesis may prevent osteolysis following injection of intra-articular particles by sealing the implant-bone interface from their ingression though the promotion of osseointegration at this interface75,76, but may also be a source of third-body wear. Selection of bearing diameter is also a factor. The use of larger head sizes reduces the risk of dislocation, but increase volumetric wear77. The need for a thinner liner to accommodate the larger head may also cause increased contact stresses and an increase in wear.

### **6.2 Polyethylene wear**

The metal on polyethylene bearing couple remains the gold standard for THA. However, the manufacturing and sterilization process of polyethylene has changed over time with the aim of improving its wear rate characteristics. The earliest prostheses were made with non-cross-linked ultra-high molecular weight polyethylene (UHWPE) that was irradiated to render it sterile for patient use. The process of sterilization with ionizing radiation leads to cross-linking within the polymer. Cross-linking improves wear resistance of the material, but also causes the formation of free radicals. Free radical species cause the oxidation of UHMWPE over time. Polyethylene oxidation degrades UHMWPE, and decreases its wear resistance.

Several production techniques have been developed to reduce the generation of free radicals, including annealing and melting. Melting reduces free radical concentration more than annealing but adversely affects the yield stress and fatigue resistance of the polymer. Annealing below melting point has a less adverse effect on the mechanical properties, but is less effective than melting at free radical removal. Sterilization in an oxygen-free environment also produces more cross-linking and reduces free radical production78. Irradiation in an inert gas and vacuum packing is also now routinely carried out to reduce pre-implantation oxidation, however this does not prevent oxidation occurring in vivo. Faris

Risk Factors for Aseptic Loosening Following Total Hip Arthroplasty 287

Regardless of prosthesis design and bearing surface, surgical technique is an important factor that affects prosthesis survival. Data from large national joint registries has recently

Type of hospital and the surgeon undertaking the procedure can influence THA survival. Fowles *et al* showed that low operating volume is associated with increased risk of THA revision95. Similarly, Espehaug *et al,* using data from the Norwegian arthroplasty register, found the lowest revision rates amongst surgeons with the highest THA volume96. In the same study, university hospitals had higher revision rates than local and central hospitals. This may be attributed to the lower number of operations per surgeon at these hospitals or possible centralization of high-risk patients and more complex cases. Bordini *et al* found that

Malalignment of prostheses may alter the articulation of prosthesis components with the potential to increase contact stresses and increase wear, this increases the incidence of edge loading and results in stripe wear in hard on hard bearing couples. Despite the advantage of larger femoral head size, soft tissue balancing remains important in the reduction of dislocation of the femoral head. Subluxation of the femoral head during the swing phase of gait, especially in metal on polyethylene couples, causes socket edge contact resulting in wear97. Complete dislocation of the femoral head may damage the head during dislocation-

Prosthesis stability influences the development of aseptic loosening. Motion between the prosthesis and bone contributes to the formation of a fibrous membrane rather than bone98. Bechtold et al found that particulate wear debris prevents bone formation in the presence of prosthesis instability 99. In addition, prosthesis motion alters local joint fluid pressures and

Improvements in prosthesis survival have accompanied advances in cementation technique100. First generation cementing techniques involved finger packing of the cement without bone preparation, pressurization or use of a medullary plug. In the mid-seventies second generation techniques were adopted which involved improved canal preparation by pulsatile lavage that increased cement penetration and interdigitation, retrograde insertion of cement using a gun to reduce blood lamination, and the use of an intramedullary plug to limit the size of the cement column. Studies with 10 year follow up have shown that 2nd generation techniques were associated with a reduced the incidence in femoral loosening with rates of 3 to 7%101,102 compared with rates of approximately 30% at 10 years in first generation reports103,104. Third generation techniques included vacuum mixing of cement to reduce cement porosity and increase fatigue strength105, and cement pressurization to

facilitated examination of these factors in relation to prosthesis survival.

prosthesis survival was negatively associated with lower surgeon skill38.

**7.1 Hospital type and surgeon operating volume** 

**7.2 Prosthesis alignment and soft tissue balancing** 

**7.3 Prosthesis dislocation and interface micromotion** 

can transport particles along the periprosthetic space.

relocation, and can increase wear rates.

**7.4 Cementing techniques** 

**7. Surgical risk factors** 

*et al* compared the wear rates of UHMWPE produced using three combinations of polyethylene production and sterilization techniques79 and found the best wear rates were achieved in sterilization by radiation in an inert gas with molded polyethylene. Irradiation sterilization of ram extruded components in an inert gas and in air had 11% and 16% more wear respectively.

Highly cross-linked polyethylene has exhibited reduced wear rates clinically in short-term studies80,81, and thus their potential role in reducing the incidence of osteolysis is promising. Further developments in polyethylene modification techniques are currently being explored to further reduce oxidization in-vivo and optimize the wear performance of UHMWPE without compromising its other mechanical properties, and include doping with antioxidants such as vitamin E and cycling of annealing and irradiating. However, the macrophage response in osteolysis is influenced by the size, composition and number of wear particles82,83. Particle size and number vary with the extent of cross-linking within the material. Although cross-linking reduces the total amount of wear debris generated versus conventional UHMWPE, the particle size produced is smaller, and the number of particles is increased, which may enhance their osteolytic potential *in-vivo*. Also, whilst increased crosslinking results in enhanced wear resistance there is a reduction in fatigue strength potentially leading to mechanical failure84.

### **6.3 Alternate bearing couples**

Although metal on polyethylene bearings have most commonly been used in THA, there is a long history of use of other bearing couples, including metal on metal, ceramic on ceramic, and ceramic on polyethylene.

Metal on metal bearings have reduced wear rates compared with metal on polyethylene. Jacobbson reported a 77% 20-year survivorship of the metal on metal McKee Farrar THA compared to 73% for the Charnley THA85. Metal on metal prostheses also have the advantages of allowing a larger bearing diameter, improving stability characteristics, and are self-polishing. Although the volumetric wear rate of metal on metal bearings is low, the particles generated are in the nanometer range and the number of particles is far greater86. These particles circulate widely within the body and their systemic effects remain unclear. At a local level metal release can cause an adverse surrounding tissue reaction, termed aseptic lymphocytic vasculitis associated lesions (ALVAL), and inflammatory masses87,88. Metal hypersensitivity may also occur87.

Ceramic on polyethylene and ceramic on ceramic bearing couples have lower wear and osteolysis rates versus metal on polyethylene bearings in some long-term studies89,90. Most ceramic wear particles are also in the nanometer range and wear volume is lower than that of metal on metal bearing couples. A prospective randomized multicenter study of 930 hips comparing alumina-on-alumina with cobalt chromium-on-polyethylene bearing couples reported an alumina-alumina survival rate of 96.8% at 10 years91. However, cases of osteolysis have also been reported in poorly functioning ceramic on ceramic prostheses. Yoon reported osteolysis rates of 22% in a series of patients with ceramic on ceramic prostheses92. Nam reported a case of alumina debris induced pelvic and femoral osteolysis in a well-functioning prosthesis93. Ceramics are also expensive, have a small fracture risk due to their brittleness, and are sensitive to component mal-positioning that may result in impingement damage and stripe wear. There are also some reports of squeaking associated with ceramic on ceramic bearing couples94.
