We analysed synovial fluid from 88 hips, 38 with osteoarthritis and 12 with well-functioning and 38 with loose hip prostheses. The levels of TNF-α, IL-1ß (71 hips) and IL-6 (45 hips) were measured using the ELISA technique. Joints with well-functioning or loose prostheses had significantly increased levels of TNF-α compared with those with osteoarthritis. Hips with aseptic loosening also had higher levels of IL-1ß but not of IL-6 compared with those without an implant. The levels of TNF-α and IL-1ß did not differ between hips with stable and loose prostheses. Higher levels of TNF-α were found in hips with bone resorption of type II and type III (Gustilo-Pasternak) compared with those with type-I loosening. The level of cytokines in joint fluid was not influenced by the time in situ of the implants or the age, gender or area of the osteolysis as measured on conventional radiographs. Our findings support the theory that macrophages in the joint capsule increase the production of TNF-α at an early phase probably because of particle load and in the absence of clinical loosening. Since TNF-α has an important role in the osteolytic process, the interfaces should be protected from penetration of joint fluid

Metal-on-metal (MOM) bearings for hip arthroplasty are increasing in popularity. Concern remains, however, regarding the potential toxicological effects of the metal ions which these bearings release. The serum levels of cobalt and chromium in 22 patients who had undergone MOM resurfacing arthroplasty were compared with a matched group of 22 patients who had undergone 28 mm MOM total hip arthroplasty (THA). At a median of 16 months (7 to 56) after resurfacing arthroplasty, we found the median serum levels of cobalt and chromium to be 38 nmol/l (14 to 44) and 53 nmol/l (23 to 165) respectively. These were significantly greater than the levels after 28 mm MOM THA which were 22 nmol/l (15 to 87, p = 0.021) and 19 nmol/l (2 to 58, p < 0.001) respectively. Since the upper limit for normal patients without implants is typically 5 nmol/l, both groups had significantly raised levels of metal ions. MOM bearings of large diameter, however, result in a greater systemic exposure of cobalt and chromium ions than bearings of small diameter. This may be of relevance for potential long-term side-effects. It is not known to what extent this difference is due to corrosion of the surfaces of the component or of the wear particles produced

1. Experiments using radio-isotope techniques show that whenever an orthopaedic appliance is inserted into the body tiny fragments of the instruments used to handle it become detached and welded on to the surface of the buried metal. 2. There is evidence that these particles of non-passive tool-metal may cause a small but continuing dissolution of the stainless metal to which they are attached, and that this dissolution, although too small to be detected as visible corrosion, may produce an adverse tissue reaction. 3. In samples of human tissue taken from sites adjacent to buried metal the greatest level of tissue reaction and the highest concentration of iron were found near those parts of the appliances that had been handled with the tools and received the greatest amount of transferred metal. 4. Spectroscopic analyses of similar samples confirmed that the concentration of metal in the tissues surrounding a buried appliance correlates closely with the distribution on its surface of transferred tool metal. Particularly high concentrations of chromium, nickel, and cobalt were found near regions where the transfer had been heavy. The dissolution was not limited to the non-passive foreign metal; the stainless appliance was also dissolved in those regions. 5. The influence of the manner of handling the tools on the amount and distribution of transfer has been studied, and suggestions are made whereby the transfer might be reduced

A foreign-body-type host response can contribute to the induction and release of collagenolytic tissue-destructive enzymes of pathogenetic significance. Our aim was to analyse collagenase-3 in two conditions with putative involvement of foreign-body reactions. Synovial membrane-like tissue samples were obtained from cases of aseptic loosening of a total hip replacement (THR) and osteoarthritis (OA). The reverse transcription polymerase chain reaction (RT-PCR) disclosed that all the samples from patients contained collagenase-3 mRNA compared with only three out of ten control samples. The identity of the RT-PCR amplification product was confirmed by nucleotide sequencing. Immunohistochemical staining showed that collagenase-3 was present in endothelial cells, macrophages and fibroblasts, including those found in the synovial lining. This finding was confirmed by avidin-biotin-peroxidase complex-alkaline phosphatase-anti-alkaline phosphatase double staining and the specificity of the staining by antigen preabsorption using recombinant human collagenase-3. Collagenase-3 was released into the extracellular space and thus found in the synovial fluid in all patient samples as shown by Western blotting. The similar extent of collagenase-3 expression in aseptic loosening and OA compared with the low expression in control synovial membrane suggests involvement of a similar, foreign-body-based pathogenetic component in both. Comparative analysis of collagenase-3 and of foreign particles indicates that paracrine factors rather than phagocytosis per se are responsible for the induction of collagenase-3. We suggest that due to its localisation and substrate specificity, collagenase-3 may play a significant pathogenetic role in accelerating tissue destruction in OA and in aseptic loosening of a THR

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1β, IL-6 and PGE. 2. in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant

Aims

The diversity of femoral morphology renders femoral component sizing in total hip arthroplasty (THA) challenging. We aimed to determine whether femoral morphology and femoral component filling influence early clinical and radiological outcomes following THA using fully hydroxyapatite (HA)-coated femoral components.

Objectives

Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb.

Cytological analysis of material aspirated from the effusion which occasionally develops around a polyglycolic acid (PGA) osteosynthesis implant showed a predominance of inflammatory monocytes and in particular lymphocytes. In order to discover whether PGA implants are immunologically inert, density gradient-isolated peripheral blood mononuclear cells were cultured in 0.2 ml of 10% delta FCS-RPMI 1640 culture medium supplemented with 10 mg PGA. Phytohaemagglutinin (PHA) lectin, a purified protein derivate of tuberculin (PPD) antigen and culture medium alone were used as positive and negative controls. We studied lymphocyte activation kinetics on days 0, 1, 3 and 5. Major histocompatibility complex locus II antigen (MHC locus II antigen) and interleukin-2 receptor (IL-2R) expression were analysed using the avidin-biotin-peroxidase complex (ABC) method and lymphocyte DNA synthesis by using 3H-thymidine incorporation and beta-scintillation counting. Especially on culture days 0 and 1, lymphocytes and monocytes were seen by light microscopy to be attached to PGA particles. However, our results show no PGA-induced lymphocyte DNA synthesis, but PGA-induced MHC locus II antigen and IL-2R activation marker expression was seen, greater than in negative controls, but less than that seen in PPD antigen driven lymphocyte response. This suggests that PGA is an immunologically inert implant material, but it does seem to induce inflammatory mononuclear cell migration and adhesion, leading to a slight non-specific lymphocyte activation. This activation is lower than that seen in mitogen and antigen-driven lymphocyte responses

We investigated the implant-bone interface around one design of femoral stem, proximally coated with either a plasma-sprayed porous coating (plain porous) or a hydroxyapatite porous coating (porous HA), or which had been grit-blasted (Interlok). Of 165 patients implanted with a Bimetric hip hemiarthroplasty (Biomet, Bridgend, UK) specimens were retrieved from 58 at post-mortem. We estimated ingrowth and attachment of bone to the surface of the implant in 21 of these, eight plain porous, seven porous HA and six Interlok, using image analysis and light morphometric techniques. The amount of HA coating was also quantified. There was significantly more ingrowth (p = 0.012) and attachment of bone (p > 0.05) to the porous HA surface (mean bone ingrowth 29.093 ± 2.019%; mean bone attachment 37.287 ± 2.489%) than to the plain porous surface (mean bone ingrowth 21.762 ± 2.068%; mean bone attachment 18.9411 ± 1.971%). There was no significant difference in attachment between the plain porous and Interlok surfaces. Bone grew more evenly over the surface of the HA coating whereas on the porous surface, bone ingrowth and attachment occurred more on the distal and medial parts of the coated surface. No significant differences in the volume of HA were found with the passage of time. This study shows that HA coating increases the amount of ingrowth and attachment of bone and leads to a more even distribution of bone over the surface of the implant. This may have implications in reducing stress shielding and limiting osteolysis induced by wear particles

Since wear and loosening of the ultra-high-molecular-weight polyethylene cup are factors which limit the life of an arthroplasty we have attempted to identify factors associated with either low wear (0.02 mm/year or less) or high wear (0.2 mm/year or more). In a series of 1434 Charnley low-friction arthroplasties (1092 patients) 190 (13.2%) showed low wear while 149 (10.4%) showed high wear. We used chi-squared test to assess the significance of various factors. The significant factors of the low-wear group were female gender (p = 0.042), rheumatoid arthritis (p = 0.014), Charnley grade C (p = 0.03) and varus position of the stem (p = 0.003). The use of acetabular cement pressurisation (p = 0.07) and medialisation of the cup (p = 0.07) approached significance. In the high-wear group there was a predominance of men (p = 0.042) with osteoarthritis (p = 0.006) as the underlying hip pathology, and the stem in a valgus position (p = 0.023). Support of the cup by the rim of the acetabulum approached significance (p = 0.07). There was no statistical significance between the two groups for revision for aseptic loosening of the stem or fracture of the stem (p = 0.49). There was a highly significant difference (p < 0.0001) between the two groups for revision for wear and aseptic loosening of the cup, 5.3% compared with 39%. Changes in the cup geometry are probably sufficient to explain the increasing incidence of loosening and revisions with the increasing depth of penetration of the cup. There is much to be gained from the use of a low-wearing ceramic-ultra-high-molecular-weight combination. Tissue reaction to the polyethylene particles cannot be the cause of aseptic loosening of the stem

Aims

This aim of this study was to assess the feasibility of designing and introducing generic 3D-printed instrumentation for routine use in total knee arthroplasty.

Objectives

We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL).

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

Objectives

Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty with isolated medial or lateral compartment osteoarthritis. However, polyethylene wear can significantly reduce the lifespan of UKA. Different bearing designs and materials for UKA have been developed to change the rate of polyethylene wear. Therefore, the objective of this study is to investigate the effect of insert conformity and material on the predicted wear in mobile-bearing UKA using a previously developed computational wear method.

Aims

Cardiac magnetic resonance (CMR) was used to assess whether cardiac function or tissue composition was affected in patients with well-functioning metal-on-metal hip resurfacing arthroplasties (MoMHRA) when compared with a group of controls, and to assess if metal ion levels correlated with any of the functional or structural parameters studied.

Aims

The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components.

Aims

There is insufficient evidence to recommend the use of alternative polyethylene bearings in modular, fixed-bearing total knee arthroplasty (TKA). The purpose of this study was to compare standard polyethylene (SP) and highly crosslinked polyethylene (XLP) tibial liners in posterior-stabilized TKA, with osteolysis as the primary outcome and clinical results and the rate of re-operation as the secondary outcomes.

Objectives

Previous studies have evidenced cement-in-cement techniques as reliable in revision arthroplasty. Commonly, the original cement mantle is reshaped, aiding accurate placement of the new stem. Ultrasonic devices selectively remove cement, preserve host bone, and have lower cortical perforation rates than other techniques. As far as the authors are aware, the impact of ultrasonic devices on final cement-in-cement bonds has not been investigated. This study assessed the impact of cement removal using the Orthosonics System for Cemented Arthroplasty Revision (OSCAR; Orthosonics) on final cement-in-cement bonds.