The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this. We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks. The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss. Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines

We retrospectively compared the outcome after the treatment of giant cell tumours of bone either with curettage alone or with adjuvant cementation. Between 1975 and 2008, 330 patients with a giant cell tumour were treated primarily by intralesional curettage, with 84 (25%) receiving adjuvant bone cement in the cavity. The local recurrence rate for curettage alone was 29.7% (73 of 246) compared with 14.3% (12 of 84) for curettage and cementation (p = 0.001). On multivariate analysis both the stage of disease and use of cement were independent significant factors associated with local recurrence. The use of cement was associated with a higher risk of the subsequent need for joint replacement. In patients without local recurrence, 18.1% (13 of 72) of those with cement needed a subsequent joint replacement compared to 2.3% (4 of 173) of those without cement (p = 0.001). In patients who developed local recurrence, 75.0% (9 of 12) of those with previous cementation required a joint replacement, compared with 45.2% (33 of 73) of those without cement (p = 0.044).

The augmentation of fixation with bone cement is increasingly being used in the treatment of severe osteoporotic fractures. We investigated the influence of bone quality on the mechanics of augmentation of plate fixation in a distal femoral fracture model (AO 33 A3 type). Eight osteoporotic and eight non-osteoporotic femoral models were randomly assigned to either an augmented or a non-augmented group. Fixation was performed using a locking compression plate. In the augmented group additionally 1 ml of bone cement was injected into the screw hole before insertion of the screw. Biomechanical testing was performed in axial sinusoidal loading. Augmentation significantly reduced the cut-out distance in the osteoporotic models by about 67% (non-augmented mean 0.30 mm (sd 0.08) vs augmented 0.13 mm (sd 0.06); p = 0.017). There was no statistical reduction in this distance following augmentation in the non-osteoporotic models (non-augmented mean 0.15 mm (sd 0.02) vs augmented 0.15 mm (sd 0.07); p = 0.915). In the osteoporotic models, augmentation significantly increased stability (p = 0.017).

Cite this article: Bone Joint J 2013;95-B:1406–9.

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Aims. Tissue responses to debris formed by abrasion of polymethylmethacrylate (PMMA) spacers at two-stage revision arthroplasty for prosthetic joint infection are not well described. We hypothesised that PMMA debris induces immunomodulation in periprosthetic tissues. Patients and Methods. Samples of tissue were taken during 35 two-stage revision arthroplasties (nine total hip and 26 total knee arthroplasties) in patients whose mean age was 67 years (44 to 85). Fourier transform infrared microscopy was used to confirm the presence of PMMA particles. Histomorphometry was performed using Sudan Red and Haematoxylin-Eosin staining. CD-68, CD-20, CD-11(c), CD-3 and IL-17 antibodies were used to immunophenotype the inflammatory cells. All slides were scored semi-quantitatively using the modified Willert scoring system. Results. The mean CD-68 scores did not show any significant change during the six weeks between the stages. Perivascular and diffuse scores showed significant difference in CD-3, CD-20, CD-11(c) and IL-17. At the time of re-implantation, a shift in the pattern of the expression of dendritic cells towards a perivascular arrangement and towards the periphery of PMMA particles was observed. Positive microbiological cultures were found at the time of re-implantation in three patients. Five further revisions were required for other reasons. Conclusion. Our results represent a biological reaction of the synovial tissues to spacers with a less diffuse expression of dendritic cells and an increased expression of perivascular lymphocytes. The use of spacers in two-stage revision for infection probably induces an immunomodulation of synovial tissues. Cite this article: Bone Joint J 2016;98-B:1062–8

We aimed to determine the optimal method of inserting a screw into polymethylmethacrylate (PMMA) cement to enhance fixation. We performed six groups of ten axial pull-out tests with two sizes of screw (3.5 and 4.5 mm AO cortical) and three methods of insertion. Screws were placed into 'fluid' PMMA, into 'solid' PMMA by drilling and tapping, or into 'curing' PMMA with quarter-revolution turns every 30 seconds until the PMMA had hardened. After full hardening, we measured the maximum load to failure for each screw-PMMA construct. We found no significant difference in the pull-out strengths between screw sizes or between screws placed in fluid or solid PMMA. Screws placed in curing PMMA were significantly weaker: the relative strengths of solid, fluid and curing groups were 100%, 97% and 71%, respectively. We recommend the use of either solid or fluid insertion according to the circumstances and the preference of the surgeon

Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However, mechanical loading of cemented implants with the differing elastic moduli of metal stems, polymethylmethacrylate (PMMA) cement and bone can result in relative micromotion, implying the potential for production of metal and PMMA particles from the stem-cement interface by fretting wear. In order to investigate the production and biological reactivity of debris from this interface, PMMA and metal particulate debris was produced by sliding wear of PMMA pins containing barium sulphate and zirconium dioxide against a Vaquasheened stainless steel counterface. This debris was characterised by SEM, energy-dispersive analysis by X-ray (EDAX) and image analysis, then added to cell cultures of a human monocytic cell line, U937, and stimulation of pro-osteolytic cytokines measured by ELISA. Large quantities of PMMA cement debris were generated by the sliding wear of PMMA pins against Vaquasheened stainless steel plates in the method developed for this study. Both cements stimulated the release of pro-osteolytic TNFα from the U937 monocytic cell line, in a dose-dependent fashion. There was a trend towards greater TNFα release with Palacos cement than CMW cement at the same dose. Palacos particles also caused significant release of IL-6, another pro-osteolytic cytokine, while CMW did not. The particulate cement debris produced did not stimulate the release of GM-CSF or IL1β from the U937 cells. These results may explain the cytokine pathway responsible for bone resorption caused by particulate PMMA debris. Radio-opaque additives are of value in surgical practice and clinical studies to quantify the relevance of these in vitro findings are required before the use of cement containing radio-opacifier is constrained

Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

Aims

We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone.

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery. An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified. . Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62). . These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role. Cite this article: Bone Joint J 2015;97-B:1423–7

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1α), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1α expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1α in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1α were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1α inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty

A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO. 4. ) and zirconium dioxide (ZrO. 2. ) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO. 4. or ZrO. 2. , however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO. 4. were associated with 50% more bone resorption than those containing ZrO. 2. . Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing is BaSO. 4. likely to be associated with more osteolysis than that containing ZrO. 2.

Aims

As an increasing number of female surgeons are choosing orthopaedics, it is important to recognize the impact of pregnancy within this cohort. The aim of this review was to examine common themes and data surrounding pregnancy, parenthood, and fertility within orthopaedics.

Aims

In cases of severe periprosthetic joint infection (PJI) of the knee, salvage procedures such as knee arthrodesis (KA) or above-knee amputation (AKA) must be considered. As both treatments result in limitations in quality of life (QoL), we aimed to compare outcomes and factors influencing complication rates, mortality, and mobility.

Giant cell tumours (GCTs) of the small bones of the hands and feet are rare. Small case series have been published but there is no consensus about ideal treatment. We performed a systematic review, initially screening 775 titles, and included 12 papers comprising 91 patients with GCT of the small bones of the hands and feet. The rate of recurrence across these publications was found to be 72% (18 of 25) in those treated with isolated curettage, 13% (2 of 15) in those treated with curettage plus adjuvants, 15% (6 of 41) in those treated by resection and 10% (1 of 10) in those treated by amputation. We then retrospectively analysed 30 patients treated for GCT of the small bones of the hands and feet between 1987 and 2010 in five specialised centres. The primary treatment was curettage in six, curettage with adjuvants (phenol or liquid nitrogen with or without polymethylmethacrylate (PMMA)) in 18 and resection in six. We evaluated the rate of complications and recurrence as well as the factors that influenced their functional outcome. At a mean follow-up of 7.9 years (2 to 26) the rate of recurrence was 50% (n = 3) in those patients treated with isolated curettage, 22% (n = 4) in those treated with curettage plus adjuvants and 17% (n = 1) in those treated with resection (p = 0.404). The only complication was pain in one patient, which resolved after surgical removal of remnants of PMMA. We could not identify any individual factors associated with a higher rate of complications or recurrence. The mean post-operative Musculoskeletal Tumor Society scores were slightly higher after intra-lesional treatment including isolated curettage and curettage plus adjuvants (29 (20 to 30)) compared with resection (25 (15 to 30)) (p = 0.091). Repeated curettage with adjuvants eventually resulted in the cure for all patients and is therefore a reasonable treatment for both primary and recurrent GCT of the small bones of the hands and feet. Cite this article: Bone Joint J 2013;95-B:838–45

We evaluated the impact of pre-coating the tibial component with polymethylmethacrylate (PMMA) on implant survival in a cohort of 16 548 primary NexGen total knee replacements (TKRs) in 14 113 patients. In 13 835 TKRs a pre-coated tray was used while in 2713 TKRs the non-pre-coated version of the same tray was used. All the TKRs were performed between 2001 and 2009 and were cemented. TKRs implanted with a pre-coated tibial component had a lower cumulative survival than those with a non-pre-coated tibial component (p = 0.01). After adjusting for diagnosis, age, gender, body mass index, American Society of Anesthesiologists grade, femoral coupling design, surgeon volume and hospital volume, pre-coating was an independent risk factor for all-cause aseptic revision (hazard ratio 2.75, p = 0.006). Revision for aseptic loosening was uncommon for both pre-coated and non-pre-coated trays (rates of 0.12% and 0%, respectively). Pre-coating with PMMA does not appear to be protective of revision for this tibial tray design at short-term follow-up. Cite this article: Bone Joint J 2013;95-B:367–70

We have developed a bioactive bone cement (BA cement) consisting of Bis-GMA resin and bioactive glass powder. It has high compressive and tensile strengths, a low curing temperature and its bioactivity allows it to bond directly with bone. We operated on the 18 femora of nine mongrel dogs for intercalary replacement of part of the bone by a metal prosthesis using either PMMA cement or BA cement for fixation. Three dogs were killed at each of 4, 12 and 26 weeks after surgery for the evaluation of fixation strength by a push-out test and for histological examination by Giemsa surface staining and SEM. Fixation strengths with PMMA cement at 4, 12 and 26 weeks after surgery were 46.8 ± 18.9, 50.0 ± 24.7, and 58.2 ± 28.9 kgf (mean ±SD), respectively. Those with BA cement were 56.8 ± 26.1, 67.2 ± 19.2, and 72.8 ± 22.2 kgf, respectively. Fibrous tissue intervened between bone and PMMA cement but BA cement had bonded directly to bone at 12 and 26 weeks. This suggests that BA cement will be useful in providing long-lasting fixation of implants to bone under weight-bearing conditions

Aims

Refobacin Bone Cement R and Palacos R + G bone cement were introduced to replace the original cement Refobacin Palacos R in 2005. Both cements were assumed to behave in a biomechanically similar fashion to the original cement. The primary aim of this study was to compare the migration of a polished triple-tapered femoral stem fixed with either Refobacin Bone Cement R or Palacos R + G bone cement. Repeated radiostereometric analysis was used to measure migration of the femoral head centre. The secondary aims were evaluation of cement mantle, stem positioning, and patient-reported outcome measures.

Recent publications have drawn attention to the fact that some brands of joint replacement may contain variants which perform significantly worse (or better) than their ‘siblings’. As a result, the National Joint Registry has performed much more detailed analysis on the larger families of knee arthroplasties in order to identify exactly where these differences may be present and may hitherto have remained hidden. The analysis of the Nexgen knee arthroplasty brand identified that some posterior-stabilized combinations have particularly high revision rates for aseptic loosening of the tibia, and consequently a medical device recall has been issued for the Nexgen ‘option’ tibial component which was implicated. More elaborate signal detection is required in order to identify such variation in results in a routine fashion if patients are to be protected from such variation in outcomes between closely related implant types.

Cite this article: Bone Joint J 2023;105-B(3):221–226.

Aims

Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants – modular fluted tapered (MFT) femoral components – in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components.