Aims. Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA. Methods. A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score. Results. Change in OHS was associated with blood concentrations of tumour necrosis factor (TNF), interleukin-8 (IL-8), interleukin-6 receptor (IL-6R), glycoprotein 130 (gp130), and IL-1β (R. 2. = 0.28, p = 0.006), but not with CSF biomarkers. Baseline pain was associated with blood concentrations of lymphotoxin alpha (LTα), TNFR1, TNFR2, and IL-6R (R. 2. = 0.37, p < 0.001) and CSF concentrations of TNFR1, TNFR2, IL-6, IL-6R, and IL-1Ra (R. 2. = 0.40, p = 0.001). Baseline disability was associated with blood concentrations of TNF, LTα, IL-8, IL-6, and IL-1α (R. 2. = 0.53, p < 0.001) and CSF concentrations of gp130, TNF, and IL-1β (R. 2. = 0.26, p = 0.002). Thus, preoperative systemic low-grade inflammation predicted 12-month postoperative outcome after THA, and was associated with preoperative pain and disability. Conclusion. This study highlights the importance of systemic inflammation in osteoarthritis, and presents a possible path for better patient selection for THA in the future. Preoperative central neuroinflammation was associated with preoperative pain and disability, but not change in OHS after THA. Cite this article: Bone Joint Res 2024;13(12):741–749

Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results. Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion. Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513

Aims

Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs.

Aims. Intravenous dexamethasone has been shown to reduce immediate postoperative pain after total hip arthroplasty (THA), though the effects are short-lived. We aimed to assess whether two equivalent perioperative split doses were more effective than a single preoperative dose. Methods. A total of 165 patients were randomly assigned into three groups: two perioperative saline injections (Group A, placebo), a single preoperative dose of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative doses of 10 mg dexamethasone (Group C). Patients, surgeons, and staff collecting outcome data were blinded to allocation. The primary outcome was postoperative pain level reported on a ten-point Numerical Rating Scale (NRS) at rest and during activity. The use of analgesic and antiemetic rescue, incidence of postoperative nausea and vomiting (PONV), CRP and interleukin-6 (IL-6) levels, range of motion (ROM), length of stay (LOS), patient satisfaction, and the incidence of surgical site infection (SSI) and gastrointestinal bleeding (GIB) in the three months postoperatively, were also compared. Results. The pain scores at rest were significantly lower in Groups B and C than in Group A on postoperative days 1 and 2. The dynamic pain scores and CRP and IL-6 levels were significantly lower for Groups B and C compared to Group A on postoperative days 1, 2, and 3. Patients in Groups B and C had a lower incidence of PONV, reduced use of analgesic and antiemetic rescue, improved ROM, shorter LOS, and reported higher satisfaction than in Group A. Patients in Group C had significantly lower dynamic pain scores and IL-6 and CRP levels on postoperative days 2 and 3, and higher ROM and satisfaction on postoperative day 3 than in Group B. No SSI or GIB occurred in any group. Conclusion. Perioperative dexamethasone provides short-term advantages in reducing pain, PONV, and inflammation, and increasing range of motion in the early postoperative period after THA. A split-dose regimen was superior to a single high dose in reducing pain and inflammation, and increasing ROM, with better patient satisfaction. Level of evidence: I. Cite this article: Bone Joint J 2020;102-B(11):1497–1504

Aims. The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA. Methods. This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo). Results. Mean total blood loss (TBL) in groups A (605.0 ml (SD 235.9)), B (790.9 ml (SD 280.7)), and C (844.8 ml (SD 248.1)) were lower than in group D (1,064.9 ml (SD 318.3), p < 0.001). We also found that compared with group D, biomarker level of inflammation, transfusion rate, pain score, and hip range of motion at discharge in groups A, B, and C were significantly improved. There were no differences among the four groups in terms of intraoperative blood loss (IBL), intramuscular venous thrombosis (IMVT), and length of hospital stay (LOS). Conclusion. The combined application of CSS and TXA is more effective than TXA alone in reducing perioperative blood loss and transfusion rates, inflammatory response, and postoperative hip pain, results in better early hip flexion following THA, and did not increase the associated venous thromboembolism (VTE) events. Intravenous combined with topical injection of CSS was superior to intravenous or topical injection of CSS alone in reducing perioperative blood loss. Cite this article: Bone Joint Res 2021;10(6):354–362

Aims. The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous (IV) tranexamic acid (TXA) on the hidden blood loss (HBL) and inflammatory response following primary total hip arthroplasty (THA). Patients and Methods. A total of 150 patients were allocated randomly to receive a single bolus of 20 mg/kg IV TXA before the incision (group A), a single bolus followed by a second bolus of 1 g IV-TXA three hours later (group B) or a single bolus followed by two boluses of 1 g IV-TXA three and six hours later (group C). All patients were treated using a standard peri-operative enhanced recovery protocol. Primary outcomes were HBL and the level of haemoglobin (Hb) as well as the levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers of inflammation. Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism (VTE). Results. The mean HBL was significantly lower in group C (402.13 ml standard deviation (. sd). 225.97) than group A (679.28 ml. sd. 277.16, p < 0.001) or B (560.62 ml . sd. 295.22, p = 0.010). The decrease in the level of Hb between the pre-operative baseline and the level on the third post-operative day was 30.82 g/L (. sd. 6.31 g/L) in group A, 27.16 g/L (. sd. 6.83) in group B and 21.98 g/L (. sd. 3.72) in group C. This decrease differed significantly among the three groups (p < 0.01). The mean level of CRP was significantly lower in group C than in the other two groups on the second (p ≤ 0.034) and third post-operative days (p ≤ 0.014). The levels of IL-6 were significantly lower in group C than group A on the first three post-operative days (p = 0.023). The mean length of stay was significantly lower in group C than group A (p = 0.023). No VTE or other adverse events occurred. Conclusion. Multiple boluses of IV-TXA can effectively reduce HBL following primary THA. A regime of three boluses leads to a smaller decrease in the level of Hb, less post-operative inflammation and a shorter length of stay in hospital than a single bolus. Cite this article: Bone Joint J 2017;99-B:1442–9

Introduction. In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits. Methods. Thirty-six male skeletally mature NZW rabbits received methylprednisolone acetate (20mg/kg) IM once 4 weeks before surgery. There were 6 groups:. CD alone – a 3 mm drill hole. + injection into the CD of:. hydrogel (HG) - 200 μl of hydrogel carrier. MSCs–1 million rabbit MSCs. pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs. IL4-MSCs – rabbit IL-4 over-expressing MSCs. IL4-pMSCs – preconditioned IL-4 over-expressing MSCs. Eight weeks after surgery, femurs were harvested, and evaluated by microCT, biomechanical, and histological analyses. Results. Bone mineral density (BMD) and bone volume fraction (BVF) increased in the pMSC group compared to the CD and MSC groups . outside. of the CD area (p < 0.05, Fig.1). Similarly, the IL4-pMSC group was increased compared to the CD group (p < 0.05). The percentage of empty lacunae in the IL4-MSC group was significantly less than other groups . outside. the CD area (p < 0.05, Fig.2); however, IL4-MSC group had less trabecular bone formation . inside. the CD. The mechanical tests demonstrated no differences. Discussion. This rabbit steroid-associated ONFH model demonstrated that pMSC increased new bone formation after CD; IL4-MSCs that continuously secreted IL-4 decreased the number of empty lacunae . Immunomodulation of bone healing has the potential to improve bone healing after CD for early stage ONFH; these interventions must be applied in a temporally sensitive fashion. For any figures, tables, or references, please contact the authors directly

Wear induces osteolysis leading to periprosthetic bone loss and TJA loosening. Inflammatory immune cells can form an aggressive interface membrane activating osteoclasts. The current study shows the effect of metal particles and ions triggering cellular responses. Blood samples from primary and revision TJA were analysed for systemic inflammation. PBMCs were cultured on different implant materials. Cellular response was monitored by qRT-PCR. Furthermore, cells were exposed to increasing concentrations of metal particles (10-7 and 10–8 particles/ml) and CoCl2 (50 µM and 100 µM). Cellular response was measured using WST-1 reduction, MitoSox-fluorescence and TUNEL-staining. Cobalt ion influx into osteoblasts was measured using FURA2-staining, cellular effects for HIF-1alpha and qRT-PCR. No inflammatory parameters were detected in patients' blood from primary and revision TJA. Short inflammatory reaction of their PBMCs was observed in in vitro culture on ceramic implants, whereas there was no such reaction to other tested implant martials. In MM6 and Jurkat cells only metal ions induced oxidative stress but did not significantly reduce cell viability. An increase in HIF1-alpha was observed in tissue containing large amounts of metal wear in comparison to plastic wear containing tissues and OA synovial tissue without wear particles. Cobalt ions were stored by osteoblasts via a calcium channel inducing hypoxia. This effect could be blocked using a TRPM blocking agent. Ceramic induces a short inflammatory response that may induce periprosthetic inflammation. Ionic Cobalt induces oxidative stress and hypoxia. Ionic metal exerts a more intense reaction on cells than particles

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

Introduction. There are several potential biological mechanisms that may influence aseptic implant failure including excessive innate and adaptive immune responses to implant debris. We investigated the hypothesis that patients with painful total joint replacements will exhibit elevated levels of metal reactivity and inflammatory markers compared to patients with well-performing TJA. We evaluated this hypothesis by testing for metal hypersensitivity using in vitro LTT assay and analyzing serum levels of selected inflammatory markers. Methods. Subject Groups: Blinded de-identified data from patients with TJR referred for metal hypersensitivity testing using a lymphocyte transformation test (LTT) and serum markers of inflammation using Luminex Multi-Analyte Assay was approved by Rush University IRB and retrospectively reviewed. None of the patients had radiographically identifiable osteolysis. Two groups of TJA patients were tested: Group 1: Well-functioning implant (<3 yrs. post-op), with no self-reported pain, i.e. <1 on 0–10 VAS scale (n=8) and Group 2: Painful TJR (<3 yrs. post-op), with self-determined pain of >8 on a 0–10 VAS scale at the time of blood draw (n=25). Metal-LTT: Peripheral blood mononuclear cells (PBMCs) were collected from 30mL of peripheral blood by Ficoll gradient separation. PBMCs were cultured with NiCl2. 3H Thymidine was added at day 5 of culture and 3H thymidine incorporation was analyzed using a beta scintillation counter at day 6. A stimulation index (SI) of reactivity was calculated by dividing scintillation counts per minute (cpms) of Ni challenged cells by those of untreated controls. A SI of <2 was considered nonreactive, 2 to <4 was mildly reactive and 4 to <8 was reactive. Luminex Assay: Serum samples were collected from whole blood and were analyzed according to manufacturer's protocols. Statistical analysis: Statistical differences were determined using unpaired t-test with Welch's correction with statistical significance at p≤0.1 (90% confidence interval). Results. To test if differences in metal sensitization exist among individuals with joint pain following TJR vs. well-functioning TJR (no pain), we analyzed each person-specific PBMC SI of reactivity to NiCl2. Painful TJR group exhibited greater sensitivity as demonstrated by significantly higher in vitro metal SI level. In general, inflammatory markers measured in serum among patients with pain following TJR were significantly increased compared to patients with no pain following TJR. Specifically, inflammatory markers that are classified as prototypical markers of a M1 inflammatory macrophage i.e. GMCSF, IL-12, IL-18, IL-1β and TNFα were significantly greater in TJR patients with pain compared to TJR patients with no pain. Due to this increase in inflammatory markers, IL-4, an anti-inflammatory marker was also significantly greater in TJR patients with pain in order to combat/mitigate the inflammatory microenvironment. While VEGF was the only marker that was significantly greater in TJR patients with no pain and is characteristic of M2 anti-inflammatory macrophage phenotype. Discussion. Metal sensitivity reactivity and serum markers of inflammation demonstrated significant differences between groups of patients with painful TJRs vs. well-functioning TJR. Classical markers of M1 phenotype were significantly greater in painful TJR group. Our data suggests that patients with self-reported pain following a TJR demonstrate active innate and adaptive immune responses that are significantly higher than patients with a well-performing TJR and that these differences are associated with detectable serum inflammatory markers. An important limitation of this study however, is that group subject numbers were low and that statistical differences found in these groups suggests these inflammatory markers may be more marked than was anticipated

Aims

Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH.

Aims

A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach.

Aims. The objective of this study was to investigate bone healing after internal fixation of displaced femoral neck fractures (FNFs) with the Dynamic Locking Blade Plate (DLBP) in a young patient population treated by various orthopaedic (trauma) surgeons. Patients and Methods. We present a multicentre prospective case series with a follow-up of one year. All patients aged ≤ 60 years with a displaced FNF treated with the DLBP between 1st August 2010 and December 2014 were included. Patients with pathological fractures, concomitant fractures of the lower limb, symptomatic arthritis, local infection or inflammation, inadequate local tissue coverage, or any mental or neuromuscular disorder were excluded. Primary outcome measure was failure in fracture healing due to nonunion, avascular necrosis, or implant failure requiring revision surgery. Results. In total, 106 consecutive patients (mean age 52 years, range 23 to 60; 46% (49/106) female) were included. The failure rate was 14 of 106 patients (13.2%, 95% confidence interval (CI) 7.1 to 19.9). Avascular necrosis occurred in 11 patients (10.4%), nonunion in six (5.6%), and loss of fixation in two (1.9%). Conclusion. The rate of fracture healing after DLBP fixation of displaced femoral neck fracture in young patients is promising and warrants further investigation by a randomized trial to compare the performance against other contemporary methods of fixation. Cite this article: Bone Joint J 2018;100-B:443–9

Aims

Obesity is associated with an increased risk of hip osteoarthritis, resulting in an increased number of total hip arthroplasties (THAs) performed annually. This study examines the peri- and postoperative outcomes of morbidly obese (MO) patients (BMI ≥ 40 kg/m²) compared to healthy weight (HW) patients (BMI 18.5 to < 25 kg/m²) who underwent a THA using the anterior-based muscle-sparing (ABMS) approach.

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Iliopsoas impingement occurs in 4% to 30% of patients after undergoing total hip arthroplasty (THA). Despite a relatively high incidence, there are few attempts at modelling impingement between the iliopsoas and acetabular component, and no attempts at modelling this in a representative cohort of subjects. The purpose of this study was to develop a novel computational model for quantifying the impingement between the iliopsoas and acetabular component and validate its utility in a case-controlled investigation.

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

Aims

Avascular femoral head necrosis in the context of gymnastics is a rare but serious complication, appearing similar to Perthes’ disease but occurring later during adolescence. Based on 3D CT animations, we propose repetitive impact between the main supplying vessels on the posterolateral femoral neck and the posterior acetabular wall in hyperextension and external rotation as a possible cause of direct vascular damage, and subsequent femoral head necrosis in three adolescent female gymnasts we are reporting on.

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

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The aim of this study was to estimate time to arthroplasty among patients with hip and knee osteoarthritis (OA), and to identify factors at enrolment to first-line intervention that are prognostic for progression to surgery.

Introduction. In 2010, a widely used metal-on-metal hip implant was voluntarily recalled from the market by the manufacturer. Our lab performed detailed retrieval analysis of 548 of the explanted devices and 165 periprosthetic tissue specimens. We reported a high degree of variability in the multiple measurements that we performed on the components, including volumetric wear. Other studies using semi-quantitative tissue grading methods to describe the histology of the periprosthetic tissues from metal-on-metal hips have looked for relationships between component wear and histological features. Grammatopoulos et al found higher ALVAL scores in 45 hip resurfacing patients with pseudotumors compared to 11 without pseudotumors and a moderately positive correlation between wear and the histological rankings for tissue necrosis and lymphocytic response. We examined correlations between the component wear measurements from retrieval analysis and the tissue features in this large group of one metal-on-metal hip design. Materials and Methods. Tissues were processed routinely into paraffin sections, stained with H&E and characterized with light microscopic semi-quantitative scores for ALVAL features and for the number of macrophages and lymphocytes, extent of metal debris and the estimated percentage of necrosis per slide. Spearman correlation analysis was conducted to evaluate any correlations between retrieval wear measurements and histological findings. Results. The median combined cup and ball wear volume was 17.5mm3 in these 165 cases. The median tissue ALVAL score was 5.5 out of 10. Component total wear volume was not predictive of the ALVAL score (P = 0.09, R = −0.007) or the number of lymphocytes (P= 0.170, R= −0.077) but there was a positive correlation between wear volume and the ranking for macrophages in the tissues (P< 0.001, R=0.215). No other correlations were found for component wear. The median time to revision was 4.84 years. There was a negative correlation between tissue inflammation ranking (P=0.002, R=−0.183) and for lymphocyte ranking and time to revision (P=0.003, R=−0.173). There was a positive correlation between time to revision and the macrophage ranking (P=0.005, R=0.166). Conclusion. From this large-scale retrieval analysis of one design of metal-on-metal total hip, a high degree of variability was observed over the multiple analyses performed, including volumetric wear and tissue features. This likely reflects our previous observation that no single particular failure mechanism was predominant in this large cohort. Funded by DePuy Synthes Companies of Johnson & Johnson