In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients.

We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.

The June 2013 Trauma Roundup³⁶⁰ looks at: open foot fractures; the diagnostic accuracy of continuous compartment pressure monitoring; conservative treatment for supracondylar fractures; high complication rates in patellar fractures; vitamin D and fracture; better function with K-wires; and tensionless bands.

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors.

Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Cite this article: Bone Joint J 2014;96-B:1319–24.

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus.

Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells.

In conclusion, it should not be assumed that degenerative changes always precede disc herniation.

Cite this article: Bone Joint J 2013;95-B:1127–33.

Aims

Femoroacetabular Junction Impingement (FAI) describes abnormalities in the shape of the femoral head–neck junction, or abnormalities in the orientation of the acetabulum. In the short term, FAI can give rise to pain and disability, and in the long-term it significantly increases the risk of developing osteoarthritis. The Femoroacetabular Impingement Trial (FAIT) aims to determine whether operative or non-operative intervention is more effective at improving symptoms and preventing the development and progression of osteoarthritis.

Cut-off values with highest sensitivity and specificity for the synovial fluid white cell and differential count will facilitate the accurate diagnosis of infection in total knee (TKR) and total hip replacement (THR). All patients undergoing revision TKR or THR for suspected prosthetic joint infection between 2009 and 2011 at two hospitals were identified. A total of 75 patients were included with a mean age of 70.3 years (38 to 89). Synovial fluid was aspirated pre-operatively and peri-prosthetic tissue samples were taken intra-operatively for histological and microbiological examination.

Receiver operating characteristic (ROC) plots were constructed for white cell and differential counts in aspirated fluid. The optimal cut-off for TKR and THR was 1590 white cells/µl and 65% neutrophilia. The white cell count cut-off value identified for THR was notably lower than previously quoted in the literature. A cut-off value for white cell count in synovial aspirate in suspected prosthetic joint infection of between 1100 and 1700 white cells/µl is likely to be applicable to both THR and TKR.

Cite this article: Bone Joint J 2013;95-B:554–7.

Invasive group A streptococcus (iGAS) is the most common cause of monomicrobial necrotising fasciitis. Necrotising infections of the extremities may present directly to orthopaedic surgeons or by reference from another admitting specialty. Recent epidemiological data from the Health Protection Agency suggest an increasing incidence of iGAS infection in England. Almost 40% of those affected had no predisposing illnesses or risk factors, and the proportion of children presenting with infections has risen. These observations have prompted the Chief Medical Officer for the Central Alerting System in England to write to general practitioners and hospitals, highlighting the need for clinical vigilance, early diagnosis and rapid initiation of treatment in suspected cases.

The purpose of this annotation is to summarise the recent epidemiological trends, describe the presenting features and outline the current investigations and treatment of this rare but life-threatening condition.

Acetabular bone loss is a challenging problem facing the revision total hip replacement surgeon. Reconstruction of the acetabulum depends on the presence of anterosuperior and posteroinferior pelvic column support for component fixation and stability. The Paprosky classification is most commonly used when determining the location and degree of acetabular bone loss. Augments serve the function of either providing primary construct stability or supplementary fixation.

When a pelvic discontinuity is encountered we advocate the use of an acetabular distraction technique with a jumbo cup and modular porous metal acetabular augments for the treatment of severe acetabular bone loss and associated chronic pelvic discontinuity.

Cite this article: Bone Joint J 2014;96-B(11 Suppl A):36–42.

We report the five year outcomes of a two-stage approach for infected total hip replacement. This is a single-surgeon experience at a tertiary centre where the more straightforward cases are treated using single-stage exchange. This study highlights the vital role of the multidisciplinary team in managing these cases.

A total of 125 patients (51 male, 74 female) with a mean age of 68 years (42 to 78) were reviewed prospectively. Functional status was assessed using the Harris hip score (HHS). The mean HHS improved from 38 (6 to 78.5) pre-operatively to 81.2 (33 to 98) post-operatively. Staphylococcus species were isolated in 85 patients (68%).

The rate of control of infection was 96% at five years. In all, 19 patients died during the period of the study. This represented a one year mortality of 0.8% and an overall mortality of 15.2% at five years. No patients were lost to follow-up.

We report excellent control of infection in a series of complex patients and infections using a two-stage revision protocol supported by a multidisciplinary approach. The reason for the high rate of mortality in these patients is not known.

Cite this article: Bone Joint J 2014;96-B:1312–18

The April 2013 Trauma Roundup³⁶⁰ looks at: ankle sprains; paediatric knee haemarthroses; evidence to support a belief; ‘Moonboot’ saves the day; pamphlets and outcomes; poor gait in pilons; lactate and surgical timing; and marginal results with marginal impaction.

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.

Objectives

The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity.

The differential diagnosis of the painful total hip arthroplasty (resurfacing or total hip) includes infection, failure of fixation (loosening), tendinitis, bursitis, synovitis, adverse local tissue reaction (ALTR) to cobalt-chromium alloys, and non-hip issues, such as spinal disorders, hernia, gynecologic, and other pelvic pain. Assuming that the hip is the source of pain, the first level question is prosthetic or non-prosthetic pain generator? The second level prosthetic question is septic or aseptic? The third level question (aseptic hips) is well-fixed or loose? ALTR is best diagnosed by cross-sectional imaging. Successful treatment is dependent on correct identification and elimination of the pain generator. Treatment recommendations for ALTR and taper corrosion are evolving.

The August 2014 Oncology Roundup³⁶⁰ looks at: Anaesthesic modality does not affect outcomes in tumour surgery; infection predictors in orthopaedic oncology; sarcoma depth unimportant in survival; photon/proton radiotherapy surprisingly effective in chondrosarcoma control; total humerus replacement a success!; LDH simple predictor of survival in sarcoma; Denosumab again! and Oops procedures in triplicate.

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing.

The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone.

Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.

We conducted a retrospective study to assess the prevalence of adverse reactions to metal debris (ARMD) in patients operated on at our institution with metal-on-metal (MoM) total hip replacements with 36 mm heads using a Pinnacle acetabular shell. A total of 326 patients (150 males, 175 hips; 176 females, 203 hips) with a mean age of 62.7 years (28 to 85) and mean follow-up of 7.5 years (0.1 to 10.8) participating in our in-depth modern MoM follow-up programme were included in the study, which involved recording whole blood cobalt and chromium ion measurements, Oxford hip scores (OHS) and plain radiographs of the hip and targeted cross-sectional imaging. Elevated blood metal ion levels (> 5 parts per billion) were seen in 32 (16.1%) of the 199 patients who underwent unilateral replacement. At 23 months after the start of our modern MoM follow-up programme, 29 new cases of ARMD had been revealed. Hence, the nine-year survival of this cohort declined from 96% (95% CI 95 to 98) with the old surveillance routine to 86% (95% CI 82 to 90) following the new protocol. Although ARMD may not be as common in 36 mm MoM THRs as in those with larger heads, these results support the Medicines and Healthcare Products Regulatory Agency guidelines on regular reviews and further investigations, and emphasise the need for specific a follow-up programme for patients with MoM THRs.

Cite this article: Bone Joint J 2014; 96-B:1610–17.

The June 2014 Research Roundup³⁶⁰ looks at:Intraoperative irrigation a balance of toxicities; Ibandronate effective in bone marrow oedema; Risk stratification in damage control surgery; Osteoblast like cells potentially safe; Better wear and antibacterial?; Assessing outcomes in hip fracture.

Ketamine has been used in combination with a variety of other agents for intra-articular analgesia, with promising results. However, although it has been shown to be toxic to various types of cell, there is no available information on the effects of ketamine on chondrocytes.

We conducted a prospective randomised controlled study to evaluate the effects of ketamine on cultured chondrocytes isolated from rat articular cartilage. The cultured cells were treated with 0.125 mM, 0.250 mM, 0.5 mM, 1 mM and 2 mM of ketamine respectively for 6 h, 24 hours and 48 hours, and compared with controls. Changes of apoptosis were evaluated using fluorescence microscopy with a 490 nm excitation wavelength. Apoptosis and eventual necrosis were seen at each concentration. The percentage viability of the cells was inversely proportional to both the duration and dose of treatment (p = 0.002 and p = 0.009). Doses of 0.5 mM, 1 mM and 2mM were absolutely toxic.

We concluded that in the absence of solid data to support the efficacy of intra-articular ketamine for the control of pain, and the toxic effects of ketamine on cultured chondrocytes shown by this study, intra-articular ketamine, either alone or in combination with other agents, should not be used to control pain.

Cite this article: Bone Joint J 2014; 96-B:989–94.

Objectives

Effects of insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 2 (BMP2) on the expression of genes involved in the proliferation and differentiation of osteoblasts in culture were analysed. The best sequence of growth factor addition that induces expansion of cells before their differentiation was sought.

Persistent groin pain after seemingly successful total hip replacement (THR) appears to have become more common. Recent studies have indicated a high incidence after metal-on-polyethylene and metal-on-metal conventional THR and it has been documented in up to 18% of patients after metal-on-metal resurfacing. There are many causes, including acetabular loosening, stress fracture, and iliopsoas tendonitis and impingement. The evaluation of this problem requires a careful history and examination, plain radiographs and an algorithmic approach to special diagnostic imaging and tests. Non-operative treatment is not usually successful. Specific operative treatment depending on the cause of the pain usually involves revision of the acetabular component, iliopsoas tenotomy or other procedures, and is usually successful. Here, an appropriate algorithm is described.