The tissues surrounding 65 cemented and 36 cementless total joint replacements undergoing revision were characterised for cell types by immunohistochemistry and for cytokine expression by in situ hybridisation. We identified three distinct groups of revised implants: loose implants with ballooning radiological osteolysis, loose implants without osteolysis, and well-fixed implants. In the cemented series, osteolysis was associated with increased numbers of macrophages (p = 0.0006), T-lymphocyte subgroups (p = 0.03) and IL-1 (p = 0.02) and IL-6 (p = 0.0001) expression, and in the cementless series with increased numbers of T-lymphocyte subgroups (p = 0.005) and increased TNFα expression (p = 0.04). For cemented implants, the histological, histochemical and cytokine profiles of the interface correlated with the clinical and radiological grade of loosening and osteolysis. Our findings suggest that there are different biological mechanisms of loosening and osteolysis for cemented and cementless implants. T-lymphocyte modulation of macrophage function may be an important interaction at prosthetic interfaces

We evaluated the effects of a serum protein coating on prosthetic infection in 29 adult male rabbits divided into three groups: control, albumin-coated and uncoated. We used 34 grit-blasted, commercially pure titanium implants. Eleven were coated with cross-linked albumin. All the implants were exposed to a suspension of Staphylococcus epidermidis before implantation. Our findings showed that albumin-coated implants had a much lower infection rate (27%) than the uncoated implants (62%). This may be a useful method of reducing the infection of prostheses

The complications of impaction bone grafting in revision hip replacement includes fracture of the femur and subsidence of the prosthesis. In this in vitro study we aimed to investigate whether the use of vibration, combined with a perforated tamp during the compaction of morsellised allograft would reduce peak loads and hoop strains in the femur as a surrogate marker of the risk of fracture and whether it would also improve graft compaction and prosthetic stability. We found that the peak loads and hoop strains transmitted to the femoral cortex during graft compaction and subsidence of the stem in subsequent mechanical testing were reduced. This innovative technique has the potential to reduce the risk of intra-operative fracture and to improve graft compaction and therefore prosthetic stability

Extensive osteolysis adjacent to implants is often associated with wear particles of prosthetic material. We have investigated if RANKL, also known as osteoprotegerin ligand, osteoclast differentiation factor or TRANCE, and its natural inhibitor, osteoprotegerin (OPG), may be important in controlling this bone loss. Cells isolated from periprosthetic tissues containing wear particles expressed mRNA encoding for the pro-osteoclastogenic molecules, RANKL, its receptor RANK, monocyte colony-stimulating factor (M-CSF), interleukin (IL)-1β, tumour necrosis factor (TNF)α, IL-6, and soluble IL-6 receptor, as well as OPG. Osteoclasts formed from cells isolated from periprosthetic tissues in the presence and absence of human osteoblastic cells. When osteoclasts formed in the absence of osteoblastic cells, markedly higher levels of RANKL mRNA relative to OPG mRNA were expressed. Particles of prosthetic materials also stimulated human monocytes to express osteoclastogenic molecules in vitro. Our results suggest that ingestion of prosthetic wear particles by macrophages results in expression of osteoclast-differentiating molecules and the stimulation of macrophage differentiation into osteoclasts

A three-dimensional computer model of a total hip replacement was used to examine the relationship between the position of the components, the range of motion and the prosthetic joint contact area. Horizontal acetabular positions with small amounts of acetabular and femoral anteversion provide the largest contact areas, but result in limited joint movement. These data will allow surgeons to select implant positions that will provide the largest possible joint contact area for a given joint range of motion although these are conflicting goals. In some component positions a truncated spherical prosthetic head resulted in smaller contact areas than a completely spherical head

Inadequate bone stock is often found in revision surgery of femoral components of total knee replacements. Our aim was to test the hypothesis that these remodelling patterns can be explained by stress shielding, and that prosthetic bonding characteristics affect maintenance of bone mass. We made a three-dimensional finite-element model of an average male femur with a cemented femoral knee component. This model was integrated with iterative remodelling procedures. Two extreme prosthetic bonding conditions were analysed and gradual changes in bone density were calculated. The long-term bone loss under the femoral knee component resembled clinical findings which confirms the hypothesis that stress shielding can cause distal femoral bone loss. Our study predicts, contrary to clinical findings, that an equilibrium situation is not reached after two years, but that bone resorption may continue. This hidden bone loss may be so drastic that large reconstructions are needed at the time of revision

Bone loss around replacement prostheses may be related to the activation of mononuclear phagocytes (MNP) by prosthetic wear particles. We investigated how osteoblast-like cells were regulated by human MNP stimulated by particles of prosthetic material. Particles of titanium-6-aluminium-4-vanadium (TiAlV) stimulated MNP to release interleukin (IL)-1β, tumour necrosis factor (TNF)α, IL-6 and prostaglandin E. 2. (PGE. 2. ). All these mediators are implicated in regulating bone metabolism. Particle-activated MNP inhibited bone cell proliferation and stimulated release of IL-6 and PGE. 2. The number of cells expressing alkaline phosphatase, a marker associated with mature osteo-blastic cells, was reduced. Experiments with blocking antibodies showed that TNFα was responsible for the reduction in proliferation and the numbers of cells expressing alkaline phosphatase. By contrast, IL-1β stimulated cell proliferation and differentiation. Both IL-1β and TNFα stimulated IL-6 and PGE. 2. release from the osteoblast-like cells. Our results suggest that particle-activated mono-nuclear phagocytes can induce a change in the balance between bone formation and resorption by a number of mechanisms

One of the most controversial issues in total knee replacement is whether or not to resurface the patella. In order to determine the effects of different designs of femoral component on the conformity of the patellofemoral joint, five different knee prostheses were investigated. These were Low Contact Stress, the Miller-Galante II, the NexGen, the Porous-Coated Anatomic, and the Total Condylar prostheses. Three-dimensional models of the prostheses and a native patella were developed and assessed by computer. The conformity of the curvature of the five different prosthetic femoral components to their corresponding patellar implants and to the native patella at different angles of flexion was assessed by measuring the angles of intersection of tangential lines. The Total Condylar prosthesis had the lowest conformity with the native patella (mean 8.58°; 0.14° to 29.9°) and with its own patellar component (mean 11.36°; 0.55° to 39.19°). In the other four prostheses, the conformity was better (mean 2.25°; 0.02° to 10.52°) when articulated with the corresponding patellar component. The Porous-Coated Anatomic femoral component showed better conformity (mean 6.51°; 0.07° to 9.89°) than the Miller-Galante II prosthesis (mean 11.20°; 5.80° to 16.72°) when tested with the native patella. Although the Nexgen prosthesis had less conformity with the native patella at a low angle of flexion, this improved at mid (mean 3.57°; 1.40° to 4.56°) or high angles of flexion (mean 4.54°; 0.91° to 9.39°), respectively. The Low Contact Stress femoral component had the best conformity with the native patella (mean 2.39°; 0.04° to 4.56°). There was no significant difference (p > 0.208) between the conformity when tested with the native patella or its own patellar component at any angle of flexion. The geometry of the anterior flange of a femoral component affects the conformity of the patellofemoral joint when articulating with the native patella. A more anatomical design of femoral component is preferable if the surgeon decides not to resurface the patella at the time of operation

The biomechanics of the patellofemoral joint can become disturbed during total knee replacement by alterations induced by the position and shape of the different prosthetic components. The role of the patella and femoral trochlea has been well studied. We have examined the effect of anterior or posterior positioning of the tibial component on the mechanisms of patellofemoral contact in total knee replacement. The hypothesis was that placing the tibial component more posteriorly would reduce patellofemoral contact stress while providing a more efficient lever arm during extension of the knee. We studied five different positions of the tibial component using a six degrees of freedom dynamic knee simulator system based on the Oxford rig, while simulating an active knee squat under physiological loading conditions. The patellofemoral contact force decreased at a mean of 2.2% for every millimetre of posterior translation of the tibial component. Anterior positions of the tibial component were associated with elevation of the patellofemoral joint pressure, which was particularly marked in flexion > 90°. From our results we believe that more posterior positioning of the tibial component in total knee replacement would be beneficial to the patellofemoral joint

We implanted titanium and carbon fibre-reinforced plastic (CFRP) femoral prostheses of the same dimensions into five prosthetic femora. An abductor jig was attached and a 1 kN load applied. This was repeated with five control femora. Digital image correlation was used to give a detailed two-dimensional strain map of the medial cortex of the proximal femur. Both implants caused stress shielding around the calcar. Distally, the titanium implant showed stress shielding, whereas the CFRP prosthesis did not produce a strain pattern which was statistically different from the controls. There was a reduction in strain beyond the tip of both the implants. This investigation indicates that use of the CFRP stem should avoid stress shielding in total hip replacement

Using a rat model, we created a bone-to-titanium interface and applied phagocytosable high-density polyethylene pArticles between the bone and implant, either initially or when the interface had matured. No fibrous membrane developed and no bone resorption was found. If sliding movements were initiated at the interface after two weeks, there was formation of a fibrous membrane. The additional application of pArticles did not change the thickness of the membrane, and there were only minor qualitative changes. Creation of a membrane by movement followed by cessation of movement and the application of pArticles caused the membrane to persist, whereas in a pArticle-free control group bone-to-metal contact was re-established. Our findings suggest that mechanical stimuli are of primary importance for prosthetic loosening, and that pArticles may modulate the later stages of the loosening process

Aseptic loosening and osteolysis around prosthetic joints are the principal causes of failure and consequent revision. During this process activated macrophages produce cytokines which are thought to promote osteolysis by osteoclasts. Changes in pressure within the space around implants have been proposed as a cause of loosening and osteolysis. We therefore studied the effect of two different regimes of cyclic pressure on the production of interleukin-1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α) by cultured human monocyte-derived (M-D) macrophages. There was a wide variation in the expression of cytokines in non-stimulated M-D macrophages from different donors and therefore cells from the same donor were compared under control and pressurised conditions. Both regimes of cyclic pressure were found to increase expression of IL-6 and TNF-α. Expression of IL-1β was increased by a higher-frequency regime only. Our findings suggest that M-D macrophages are activated by cyclic pressure. Further work will be required to understand the relative roles of frequency, amplitude and duration of applied pressure in the cellular effects of cyclic pressure in this system

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 have studied the three-dimensional geometry of the proximal humerus on human cadaver specimens using a digitised measuring device linked to a computer. Our findings demonstrated the variable shape of the proximal humerus as well as its variable dimensions. The articular surface, which is part of a sphere varies individually in its orientation as regards inclination and retroversion, and it has variable medial and posterior offsets. These variations cannot be accommodated by the designs of most contemporary humeral components. Although good clinical results can be achieved with current modular and non-modular components their relatively fixed geometry prevents truly anatomical restoration in many cases. To try to restore the original three-dimensional geometry of the proximal humerus, we have developed a new type of humeral component which is modular and adaptable to the individual anatomy. Such adaptability allows correct positioning of the prosthetic head in relation to an individual anatomical neck, after removal of the marginal osteophytes. The design of this third-generation prosthesis respects the four geometrical variations which have been demonstrated in the present study. These are inclination, retroversion, medial offset and posterior offset

It has been suggested that the endurance of cemented femoral reconstructions in total hip arthroplasty is affected by the creep of acrylic cement, but it is not known to what extent cement creeps under loading conditions in vivo, or how this affects load transfer. We have simulated the long-term creep properties of acrylic cement in finite-element models of femoral stem constructs and analysed their effects. We investigated whether subsidence rates measured in vivo could be explained by creep of acrylic cement, and if polished, unbonded, stems accommodated creep better than bonded stems. Our findings showed that polished prostheses subsided only about 50 μm as a result of cement creep. The long-term prosthetic subsidence rates caused by creep of acrylic cement are therefore very small and do not explain the excessive migration rates which have sometimes been reported. Cement creep did, however, relax cement stresses and create a more favourable stress distribution at the interfaces. These trends were found around both the bonded and unbonded stems. Our results did not confirm that polished, unbonded, stems accommodated creep better than bonded stems in terms of cement and interface stress patterns

We have tested the axial and torsional stability of femoral components after revision arthroplasty in a cadaver model, using impacted morsellised cancellous graft and cement. Each one of six matched pairs of fresh frozen human femora had either a primary or a revision prosthesis cemented in place. For the ‘revision’ experiments, all cancellous bone was removed from the proximal femur which was then over-reamed to create a smooth-walled cortical shell. An MTS servohydraulic test frame was used to apply axial and torsional loads to each specimen through the prosthetic femoral heads with the femur submerged in isotonic saline solution at 37°C. The mean subsidence was 0.27 ± 0.17 mm for the primary and 0.52 ± 0.30 mm for the revision groups. The difference was statistically significant (p < 0.025), but the mean subsidence was < 1 mm in both groups. The mean maximum torque before failure was 42.9 ± 26.9 N-m for the primary and 34.8± 20.7 N-m for the revision groups. This difference was not statistically significant (p > 0.015). Based on our results we suggest that revision of the femoral component using morsellised cancellous graft followed by cementing with a collarless prosthesis with a polished tapered stem restores the integrity of the proximal femur and provides immediate stability of the implant

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-β1 (rhTGF-β1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-β1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation. We inserted cylindrical grit-blasted titanium alloy implants bilaterally into the weight-bearing part of the medial femoral condyles of ten skeletally mature dogs. The implants were mounted on special devices which ensured stable weight-loading during each gait cycle. All implants were initially surrounded by a 0.75 mm gap and were coated with TCP ceramic. Each animal received two implants, one with 0.3 μg rhTGF-β1 adsorbed on the ceramic surface and the other without growth factor. Histological analysis showed that bone ongrowth was significantly increased from 22 ± 5.6% bone-implant contact in the control group to 36 ± 2.9% in the rhTGF-β stimulated group, an increase of 59%. The volume of bone in the gap was increased by 16% in rhTGF-β1-stimulated TCP-coated implants, but this difference was not significant. Mechanical push-out tests showed no difference in fixation of the implant between the two groups. Our study suggests that rhTGF-β1 adsorbed on TCP-ceramic-coated implants can enhance bone ongrowth

We used dual-energy x-ray absorptiometry (DEXA) to evaluate the extent of periprosthetic bone remodelling around a prosthesis for distal femoral reconstruction, the Kotz modular femoral tibial replacement (KMFTR; Howmedica, Rutherford, New Jersey). A total of 23 patients was entered into the study which had four parts: 1) 17 patients were scanned three times on both the implant and contralateral legs to determine whether the precision of DEXA measurements was adequate to estimate bone loss surrounding the anchorage piece of the KMFTR; 2) in 23 patients the bone mineral density (BMD) in different regions of interest surrounding the diaphyseal anchorage was compared with that of the contralateral femur at the same location to test whether there was consistent evidence of loss of BMD adjacent to the prosthetic stem; 3) in 12 patients sequential studies were performed about one year apart to compare bone loss; and 4) bone loss was compared in ten patients with implants fixed by three screws and in 13 without screws. The mean coefficients of variation (SD/mean) for the 17 sets of repeated scans ranged from 2.9% to 7.8% at different regions of interest in the KMFTR leg and from 1.4% to 2.5% in the contralateral leg. BMD was decreased in the KMFTR leg relative to the contralateral limb and the percentage of BMD loss in general increased as the region of interest moved distally in the femur. Studies done after one year showed no consistent pattern of progressive bone loss between the two measurements. The ten patients with implants fixed by screws were found to have a mean loss of BMD of 42% in the most distal part of the femur, while the 13 without screw fixation had a mean loss of 11%. DEXA was shown to have adequate precision to evaluate loss of BMD around the KMFTR. This was evident relative to the contralateral leg in all patients and generally increased in the most distal part of the femur. In general, it stabilised between two measurements taken one year apart and was greater surrounding implants fixed by cross-locking screws

Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E. 2. (PGE. 2. ), as an indicator of COX-2 activity, was measured using an enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68. +. macrophages. The presence of calcium-independent iNOS activity and PGE. 2. production was confirmed in the homogenized interface membrane. Immunocytochemistry showed that periprosthetic CD68. +. wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68. +. macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68. +. macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and have been implicated in the induction and PGE. 2. maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening

High-intensity narrow-spectrum (HINS) light is a novel violet-blue light inactivation technology which kills bacteria through a photodynamic process, and has been shown to have bactericidal activity against a wide range of species. Specimens from patients with infected hip and knee arthroplasties were collected over a one-year period (1 May 2009 to 30 April 2010). A range of these microbial isolates were tested for sensitivity to HINS-light. During testing, suspensions of the pathogens were exposed to increasing doses of HINS-light (of 123mW/cm² irradiance). Non-light exposed control samples were also used. The samples were then plated onto agar plates and incubated at 37°C for 24 hours before enumeration. Complete inactivation (greater than 4-log₁₀ reduction) was achieved for all of the isolates. The typical inactivation curve showed a slow initial reaction followed by a rapid period of inactivation. The doses of HINS-light required ranged between 118 and 2214 J/cm². Gram-positive bacteria were generally found to be more susceptible than Gram-negative.

As HINS-light uses visible wavelengths, it can be safely used in the presence of patients and staff. This unique feature could lead to its possible use in the prevention of infection during surgery and post-operative dressing changes.

Cite this article: Bone Joint J 2015;97-B:283–8.