The most frequent cause of failure after total hip replacement in all reported arthroplasty registries is peri-prosthetic osteolysis. Osteolysis is an active biological process initiated in response to wear debris. The eventual response to this process is the activation of macrophages and loss of bone.

Activation of macrophages initiates a complex biological cascade resulting in the final common pathway of an increase in osteolytic activity. The biological initiators, mechanisms for and regulation of this process are beginning to be understood. This article explores current concepts in the causes of, and underlying biological mechanism resulting in peri-prosthetic osteolysis, reviewing the current basic science and clinical literature surrounding the topic.

We investigated 219 revisions of total hip replacement (THR) in 211 patients using a collarless double-taper cemented femoral component. The mean age of the patients was 72 years (30 to 90). The 137 long and 82 standard length stems were analysed separately. The mean follow-up was six years (2 to 18), and no patient was lost to follow-up.

Survival of the long stems to re-revision for aseptic loosening at nine years was 98% (95% confidence interval (CI) 94 to 100), and for the standard stems was 93% (95% CI 85 to 100). At five years, one long stem was definitely loose radiologically and one standard stem was probably loose. Pre-operative femoral bone deficiency did not influence the results for the long stems, and corrective femoral osteotomy was avoided, as were significant subsidence, major stress shielding and persistent thigh pain.

Because of these reliable results, cemented long collarless double-taper femoral components are recommended for routine revision THR in older patients.

In 20 patients undergoing hybrid total hip arthroplasty, the reproducibility and accuracy of templating using digital radiographs were assessed. Digital images were manipulated using either a ten-pence coin as a marker to scale for magnification, or two digital-line methods using computer software. On-screen images were templated with standard acetate templates and compared with templating performed on hard-copy digital prints.

The digital-line methods were the least reliable and accuracy of sizing compared with the inserted prostheses varied between −1.6% and +10.2%. The hard-copy radiographs showed better reproducibility than the ten-pence coin method, but were less accurate with 3.7% undersizing. The ten-pence coin method was the most accurate, with no significant differences for offset or acetabulum, and undersizing of only 0.9%.

On-screen templating of digital radiographs with standard acetate templates is accurate and reproducible if a radiopaque marker such as a ten-pence coin is included when the original radiograph is taken.

Particulate prosthetic materials are often studied by adding them to monocytic cells in vitro and measuring the release of cytokines as an indicator of their inflammatory potential. Endotoxin is known to be a contaminant of particle preparations and also stimulates the release of cytokines. It is usual to use a proprietary endotoxin test to avoid erroneous results.

Four different formulations of cement were found to be free from endotoxin using standard, gelclot tests but stimulated different levels of release of cytokines from macrophages. These differences were explained when a more sensitive, kinetic endotoxin assay showed that release correlated with minor contamination with endotoxin. In a repeat experiment using cement particles with low or undetectable levels of endotoxin by kinetic assay, differences in the ability of the formulations to stimulate the release of cytokines were not seen.

Endotoxin is adsorbed on to the surface of particles and it is this combination which stimulates increased release of cytokines. In both the above methods for determination of endotoxin, the water in which the particles had been soaked was examined rather than the particles directly. Further investigations showed that a kinetic assay directly on a particle suspension is the most sensitive method to measure contamination with endotoxin.

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO₂) and with barium sulphate (BaSO₄). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 10⁹ particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis.

All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO₄-containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO₄ is used as the radiopaque agent.

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO₄, Palacos R with ZrO₂ and from CMW3 which contains BaSO₄. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis.

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10⁴, 10⁶ or 10⁸ high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined.

Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05).

Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10⁸ particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process.