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

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

Aims

To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements.

Aims

Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.

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

The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis.

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.

Objectives

This study investigated the biomechanical performance of decellularized porcine superflexor tendon (pSFT) grafts of varying diameters when utilized in conjunction with contemporary ACL graft fixation systems. This aimed to produce a range of ‘off-the-shelf’ products with predictable mechanical performance, depending on the individual requirements of the patient.

Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles.

Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure. Bone Joint Res 2016;5:162–168. DOI: 10.1302/2046-3758.55.BJR-2016-0086.

Objectives

This study aimed to characterise and qualitatively grade the severity of the corrosion particles released into the hip joint following taper corrosion.

We explored the literature surrounding whether allergy and hypersensitivity has a clinical basis for implant selection in total knee arthroplasty (TKA). In error, the terms hypersensitivity and allergy are often used synonymously. Although a relationship is present, we could not find any evidence of implant failure due to allergy. There is however increasing basic science that suggests a link between loosening and metal ion production. This is not an allergic response but is a potential problem. With a lack of evidence logically there can be no justification to use ‘hypoallergenic’ implants in patients who have pre-existing skin sensitivity to the metals used in TKA.

Cite this article: Bone Joint J 2016;98-B:437–41.

Objectives

We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days.

Atypical cartilaginous tumours are usually treated by curettage. The purpose of this study was to show that radiofrequency ablation was an effective alternative treatment.

We enrolled 20 patients (two male, 18 female, mean age 56 years (36 to 72) in a proof-of-principle study. After inclusion, biopsy and radiofrequency ablation were performed, followed three months later by curettage and adjuvant phenolisation. The primary endpoint was the proportional necrosis in the retrieved material. Secondary endpoints were correlation with the findings on gadolinium enhanced MRI, functional outcome and complications.

Our results show that 95% to 100% necrosis was obtained in 14 of the 20 patients. MRI had a 91% sensitivity and 67% specificity for detecting residual tumour after curettage. The mean functional outcome (MSTS) score six weeks after radiofrequency ablation was 27.1 (23 to 30) compared with 18.1 (12 to 25) after curettage (p < 0.001). No complications occurred after ablation, while two patients developed a pathological fracture after curettage.

We have shown that radiofrequency ablation is capable of completely eradicating cartilaginous tumour cells in selective cases. MRI has a 91% sensitivity for detecting any residual tumour. Radiofrequency ablation can be performed on an outpatient basis allowing a rapid return to normal activities. If it can be made more effective, it has the potential to provide better local control, while improving functional outcome.

Cite this article: Bone Joint J 2014;96-B:1540–5.

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression.

These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement.

Cite this article: Bone Joint J 2014; 96-B:1172–7.

We undertook a retrospective cohort study to determine clinical outcomes following the revision of metal-on-metal (MoM) hip replacements for adverse reaction to metal debris (ARMD), and to identify predictors of time to revision and outcomes following revision. Between 1998 and 2012 a total of 64 MoM hips (mean age at revision of 57.8 years; 46 (72%) female; 46 (72%) hip resurfacings and 18 (28%) total hip replacements) were revised for ARMD at one specialist centre. At a mean follow-up of 4.5 years (1.0 to 14.6) from revision for ARMD there were 13 hips (20.3%) with post-operative complications and eight (12.5%) requiring re-revision.

The Kaplan–Meier five-year survival rate for ARMD revision was 87.9% (95% confidence interval 78.9 to 98.0; 19 hips at risk). Excluding re-revisions, the median absolute Oxford hip score (OHS) following ARMD revision using the percentage method (0% best outcome and 100% worst outcome) was 18.8% (interquartile range (IQR) 7.8% to 48.3%), which is equivalent to 39/48 (IQR 24.8/48 to 44.3/48) when using the modified OHS. Histopathological response did not affect time to revision for ARMD (p = 0.334) or the subsequent risk of re-revision (p = 0.879). Similarly, the presence or absence of a contralateral MoM hip bearing did not affect time to revision for ARMD (p = 0.066) or the subsequent risk of re-revision (p = 0.178).

Patients revised to MoM bearings had higher rates of re-revision (five of 16 MoM hips re-revised; p = 0.046), but those not requiring re-revision had good functional results (median absolute OHS 14.6% or 41.0/48). Short-term morbidity following revision for ARMD was comparable with previous reports. Caution should be exercised when choosing bearing surfaces for ARMD revisions.

Cite this article: Bone Joint J 2014;96-B:1600–9.

Our aim was to compare polylevolactic acid screws with titanium screws when used for fixation of the distal tibiofibular syndesmosis at mid-term follow-up. A total of 168 patients, with a mean age of 38.5 years (18 to 72) who were randomly allocated to receive either polylevolactic acid (n = 86) or metallic (n = 82) screws were included. The Baird scoring system was used to assess the overall satisfaction and functional recovery post-operatively. The demographic details and characteristics of the injury were similar in the two groups. The mean follow-up was 55.8 months (48 to 66). The Baird scores were similar in the two groups at the final follow-up. Patients in the polylevolactic acid group had a greater mean dorsiflexion (p = 0.011) and plantar-flexion of the injured ankles (p < 0.001). In the same group, 18 patients had a mild and eight patients had a moderate foreign body reaction. In the metallic groups eight had mild and none had a moderate foreign body reaction (p <  0.001). In total, three patients in the polylevolactic acid group and none in the metallic group had heterotopic ossification (p = 0.246).

We conclude that both screws provide adequate fixation and functional recovery, but polylevolactic acid screws are associated with a higher incidence of foreign body reactions.

Cite this article: Bone Joint J 2014;96-B:548–54.

Our understanding of the origin of hip pain in degenerative disorders of the hip, including primary osteoarthritis, avascular necrosis and femoroacetabular impingement (FAI), is limited. We undertook a histological investigation of the nociceptive innervation of the acetabular labrum, ligamentum teres and capsule of the hip, in order to prove pain- and proprioceptive-associated marker expression. These structures were isolated from 57 patients who had undergone elective hip surgery (44 labral samples, 33 ligamentum teres specimens, 34 capsular samples; in 19 patients all three structures were harvested). A total of 15 000 histological sections were prepared that were investigated immunohistochemically for the presence of protein S-100, 68 kDa neurofilament, neuropeptide Y, nociceptin and substance P. The tissues were evaluated in six representative areas.

Within the labrum, pain-associated free nerve ending expression was located predominantly at its base, decreasing in the periphery. In contrast, the distribution within the ligamentum teres showed a high local concentration in the centre. The hip capsule had an almost homogeneous marker expression in all investigated areas.

This study showed characteristic distribution profiles of nociceptive and pain-related nerve fibres, which may help in understanding the origin of hip pain.

Cite this article: Bone Joint J 2013;95-B:770–6.

Hip implant retrieval analysis is the most important source of insight into the performance of new materials and designs of hip arthroplasties. Even the most rigorous in vitro testing will not accurately simulate the behavior of implant materials and new designs of prosthetic arthroplasties. Retrieval analysis has revealed such factors as the effects of gamma-in-air sterilisation of polyethylene, fatigue failure mechanisms of polymethylmethacrylate bone cement, fretting corrosion of Morse taper junctions, third body wear effects of both hard-on-hard and hard-on-soft bearing couples, and the effects of impingement of components on the full spectrum of bearing surfaces, none of which was predicted by pre-implantation in vitro testing of these materials and combinations. The temporal sequence of the retrieval process is approximately six years from first implantation through retrieval analysis, laboratory investigation, and publication of results, and thus, in addition to rigorous clinical evaluation, represents the true development and insight cycle for new designs and materials.

Femoroacetabular impingement (FAI) is commonly associated with early hip arthritis. We reviewed our series of 1300 hip resurfacing procedures. More than 90% of our male patients, with an average age of 53 years, had cam impingement lesions. In this condition, there are anterior femoral neck osteophytes, and a retroverted femoral head on a normally anteverted neck. It is postulated that FAI results in collision of the anterior neck of the femur against the rim of the acetabulum, causing damage to the acetabular labrum and articular cartilage, resulting in osteoarthritis. Early treatment of FAI involves arthroscopic or open removal of bone from the anterior femoral neck, as well as repair or removal of labral tears. However, once osteoarthritis has developed, hip replacement or hip resurfacing is indicated. Hip resurfacing can re-orient the head and re-shape the neck. This helps to restore normal biomechanics to the hip, eliminate FAI, and improve range of motion. Since many younger men with hip arthritis have FAI, and are also considered the best candidates for hip resurfacing, it is evident that resurfacing has a role in these patients.

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls.

Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively.