Aseptic Loosening Of Hip Prostheses Research Articles

Effect of Interleukin 1 Receptor Antagonist Gene on Stable Expression Bone Marrow Mesenchymal Stem Cells and Early Aseptic Loosening of Hip Prosthesis of Mouse.

The research aimed to investigate the diagnostic value of Interleukin 1 receptor antagonist (IL-1Ra) in the early aseptic loosening of hip prosthesis and whether IL-1Ra can be expressed in bone marrow mesenchymal stem cells. In this study, the IL-1Ra gene was firstly connected to the lentiviral vector LV5, and the lentiviral vector LV5-home-IL1Ra was obtained by recombination. Then the recombinant LV5-home-IL1Ra was co-transfected with the virus-assisted plasmid into 293T cells and packaged to produce lentivirus. Bone marrow-derived stem cells (BMSCs) were infected with packaged lentiviruses. The relative expression of IL-1Ra mRNA in BMSCs was detected by fluorescence quantitative PCR. The expression of IL-1Ra protein in BMSCs was detected by western blot transfer electrophoresis. Peripheral venous blood samples from 108 patients and healthy subjects underwent total hip replacement were collected to detect the levels of plasma biomarkers procollagen type I carboxy-terminal propeptide (PICP), N-telopeptide cross-links of type I collagen (NTX), osteoprotegerin (OPG), TNGα, receptor activator of NF-kappaB ligand (RANKL), and IL-1β. The recombinant lentivirus vector IL-1Ra was successfully constructed by 2% agarose gel electrophoresis. Lentivirus-mediated IL-1Ra gene could efficiently transfection bone marrow mesenchymal stem cells, and the cell growth density reached about 80% at 72h after infection. The transfection rate was about 90%, and the fluorescence was enhanced. The relative mRNA and protein expression levels of IL-1Ra in the BMSCs-IL-1Ra group were significantly higher than those in the BMSCs group and the BMSCs-con group (P < 0.01). The late loosening group of IL-1β was significantly higher than the stable prosthesis group and the healthy group (P < 0.05). The ROC curve showed that IL-1 background had strong diagnostic sensitivity and specificity, which was similar to the X-ray score of osteolysis and had the most significant diagnostic significance. Lentivirus-transfected exogenous IL-1Ra can be expressed stably in mouse bone marrow mesenchymal stem cells, and IL-1β, an antagonist of IL-1Ra, plays an important role in the early aseptic loosening of hip prosthesis.

Using personalized 3D printed Titanium sleeve-prosthetic composite for reconstruction of severe segmental bone loss of proximal femur in revision total hip arthroplasty

Rationale:Allograft-prosthetic composites (APCs) and proximal femoral replacement have been applied for reconstruction of severe segmental femoral bone loss in revision total hip arthroplasty. The outcomes are encouraging but the complication rate is relatively high. Considering the high complication rates and mixed results of APCs and megaprosthesis, we presented a case using personalized 3D printed Titanium sleeve-prosthetic composite for reconstruction of segmental bone defect.Patient concerns:A 73-year-old woman presented to the emergency department on account of acute severe pain of the left hip without history of trauma. She had undergone a cemented total hip arthroplasty for osteonecrosis of femoral head at the left side in 2000. In 2013 she underwent a cemented revision total hip arthroplasty as a result of aseptic loosening of hip prosthesis. She denied obvious discomfort prior to this episode since the revision surgery in 2013.Diagnosis:According to the clinical history, imaging and physical examination, we confirmed the diagnosis of severe segmental bone loss of proximal femur and fracture of prosthetic stem. The femoral bone defect was evaluated using the Paprosky classification system and rated as Type 3B, and the acetabular bone defect was rated as Type 2C.Interventions:In this study, we present the first case of severe segmental bone loss of proximal femur in revision total hip arthroplasty that was successfully treated using personalized 3D printed Titanium sleeve-prosthetic compositeOutcomes:At the 2-year follow-up, the patient was symptom free with a Harris Hip Score of 91. Radiographs showed excellent osteointegration between the interface of sleeve-prosthetic composite and the host bone, with no signs of implant loosening or subsidence.Lessons:Despite the absence of long term results of 3D printed Titanium sleeve-prosthetic composite reconstruction, the good clinical and radiological outcome at 2 years follow up implied its potential role for reconstruction of segmental femoral bone defect in revision THA.

Mid-Term Outcomes of Primary Hip Replacement in Patients with End-Stage Chronic Renal Disease

Purpose — to evaluate mid-term outcomes of primary hip replacement in patients with end-stage chronic renal disease and to develop an algorithm for selection of surgical tactics and perioperative treatment.Materials and Methods. The authors evaluated outcomes of primary hip replacement in 45 patients receiving renal substitution therapy and 47 patients without chronic renal disease. Patients with end-stage chronic renal disease (CRD) were divided into two groups: group I included 30 (66.6%) patients receiving chronic hemodialysis (CH) and group II included 15 (33.4%) patients after renal transplantation (RT). Group III of 47 (51.1%) patients without any signs of CRD who underwent hip arthroplasty within relevant period of time was established to evaluate the effectiveness of primary hip replacement. Blood serum Ca2+ and P5+ levels as well as levels of parathyroid hormone (PTH) and 1.25-dihydroxyvitamin D were measured to determine the rate of calcium- phosphoric metabolism disturbance. Multi-spiral CT scans of hip joint were performed to identify bone mineral density and the mean Hounsfield (Hu) value was calculated for which the data was obtained from five various points on the proximal femur and acetabulum. Beta-2 microglobulin (B2M) blood test was performed to confirm amyloid bone disease.Results. The authors did not observe statistically significant differences for arthroplasty outcomes in patients of group II and III. Patients receiving long-term hemodialysis demonstrated significantly lower parameters of Harris score and Barthel’s index of social adaptation after hip replacement as compared to groups II and III: patients of group I demonstrated outcomes improvement at 19.55%, in group II — at 13.03%, in group III — at 10.15% as compared to preoperative status. Decrease of 1.25-dihydroxyvitamin D below 20,0 mcg results in resorption of cancellous bone in proximal femur and acetabulum along with myopathy of gluteus muscles. Sharp increase of parathyroid hormone level (over 600 pcg/ml) was accompanied by inhibition of osteoblasts proliferation and differentiation resulting in substantial impairment of mineralization.Conclusion. According to the algorithm suggested by the authors the key parameters that need to be evaluated in preoperative period are parathyroid hormone (PTH) and 1.25-dihydroxyvitamin D. Five-fold increase of PTH (600 pcg/ml) demands parathyroidectomy as the first stage of treatment to decrease risk of early aseptic loosening of hip prosthesis and development of periprosthetic fracture.

Comparative analysis of dual-phase 18F-fluoride PET/CT and three phase bone scintigraphy in the evaluation of septic (or painful) hip prostheses: A prospective study.

The preoperative differentiation of aseptic and septic loosening of hip prostheses remains a diagnostic challenge for clinicians and many molecular imaging techniques have been evaluated. The objective of current study was to establish the clinical utility of dual phase 18F-fluoride PET/CT (DPFP) in diagnosing implant loosening, differentiation between septic and aseptic loosening and to compare the diagnostic accuracy of DPFP and three-phase bone scan (TPBS). In this prospective study, we evaluated 57 hip components in 45 patients (bilateral prostheses in 12 patients, 45 painful and 12 asymptomatic contralateral hip components) with dual phase fluoride PET/CT and TPBS. Findings of skeletal scintigraphy and PET/CT were evaluated by two expert nuclear medicine physicians, blinded with clinical findings and final diagnosis. The patterns of tracer uptake and maximum standardized uptake value (SUVmax) were noted for each joint. The final diagnosis was based on intraoperative findings, histopathological or microbiological examinations. Out of twelve non-painful hips, DPFP correctly identified no loosening in 11 hips while TPBS detected in 10 hips. In the remaining 45 hips with radiological proven loosening to rule out sepsis, DPFP had a sensitivity, specificity, PPV, NPV and accuracy of 75%, 97%, 92%, 88% and 88% respectively while TPBS revealed 81%, 86%, 76%, 89% and 82% respectively. DPFP had shown a higher specificity and PPV as compared to the TPBS in the evaluation of painful hip prostheses. The pattern of tracer uptake may help in the differentiation between the two entities. We also noted a significant difference between SUVmax values of septic and aseptic loosening. The results suggested that DPFP has considerable potential in differentiating septic from aseptic loosening of hip prostheses and more specific to rule out sepsis than TPBS. It may be employed before revision arthroplasty to evaluate implant for loosening and sepsis in loosened implant.

Metadiaphysäre Femurdefektrekonstruktion mit kortikalen Strut-Allografts bei periprothetischen Knochendefekten

Biological augmentation and stabilization of high-grade bone defects with structural allografts from donor femur halfs. Severe bone defects with aseptic loosening of hip prosthesis, periprosthetic femoral fracture or non-union, possibly even in cases of a healed infection. Local or systemic infection. The two modeled strut allografts are temporary fixed epiperiostal anterolateral and -medial with wire cerclages, while protecting the vascular supplying linea aspera of the femur. With the thus stabilized femur, the leg can be placed in the four-position in order to prepare the medullary canal of the revision prosthesis. Finally, the uncemented revision prosthesis is hammered in under successive tightening of the wire cerclages. With this "cracking technique", stem is stabilized and the grafts have repositioning, augmentative, and supportive function. Partial weight-bearing postoperatively for 12weeks. X-ray control during surgery, 10days postoperatively, after 6 and 12weeks and every 1-2years. In four different studies, 123 patients were stabilized from December 1991 to June 2011 due to an extensive periprosthetic femoral bone defect and/or periprosthetic fracture, refracture, or non-union with strut allografts. After an average follow-up of 3.8 years (range 0.3-11years), the average Harris Hip Score was 80.8 (range 44-100). During this time, there was 1refracture, 103stable stems, 20fibrous stable stems, 9patients with low graft resorption, and 122patients with radiographic healing of the strut allografts based on classification according to Emerson et al. (Clin Orthop Relat Res 285:35-44, 1992).

99mTc-labeled ubiquicidin scintigraphy

SummaryAim: Hip prosthesis implantation has witnessed a significant increase in recent years. Despite the advantages of this surgical procedure, it has some complications, the most serious of which is prosthetic infection. This study was conducted to investigate the feasibility of 99mTc-UBI scintigraphy in detection of infectious foci in painful hip prosthesis. UBI (Ubiquicidin 29–41) is an antimicrobial peptide fragment with the ability to target the bacterial colony directly. Patients, methods: 34 patients, aged 20–79 years, with painful hip prosthesis were included. 99mTc-UBI scan and three phase bone scan were performed and two nuclear medicine specialists interpreted the UBI scans with and without bone scan results at hand. Both qualitative and semiquantitative methods were used to interpret the 30 minute post injection images. The patients were actively followed up. According to the surgical findings, microbiological culture and active follow up, final diagnosis was made. Results: 24 negative and 10 positive UBI scans were recorded. The sensitivity, specificity, negative and positive predictive values and accuracy of the study were all 100%. Bone scan did not have any influence on UBI interpretation. We were able to achieve excellent differentiation between infected and non-infected prostheses with a cut off value of 1.8 for target to non target (T/NT) ratio. No adverse effects were noticed following UBI scan. Conclusion: Based on the findings, the authors believe that 99mTc-UBI scintigraphy, with its high sensitivity and specificity, provides the physician with an excellent tool for differentiating infection from aseptic loosening of hip prostheses. Using this radiopharmaceutical, it is possible to obtain highly accurate results only 30 minutes after the beginning of the study.

Prevention of strain‐related osteopenia in aseptic loosening of hip prostheses using perioperative bisphosphonate

The hypothesis tested in this study was that perioperative administration of the bisphosphonate zoledronate will reduce strain protection-related calcar osteopenia and maintain functional integration of the femoral component in an ovine hemiarthroplasty model. Twelve sheep received a unilateral cemented hemiarthroplasty where six animals were given nine intravenous infusions of zoledronate (10 microg/kg) pre-, peri-, and postsurgery over 8 months. Control animals received physiological saline only. Implants remained in vivo for 9 months. Ground reaction force (GRF) was used to assess functional loading of the implanted limb, bone mineral density (BMD) was quantified using dual energy X-ray absorptiometry (DEXA). Cortical bone area, thickness, and viable osteocytes were assessed histologically. No significant differences in GRF data between groups was identified. Results demonstrated a significant drop in BMD values in the control group (9.7%) when compared with the bisphosphonate-treated group (3.2%) (p = 0.0159). Histological results showed that cortical area, thickness, and the percentage of lacunae with viable osteocytes was significantly greater in the bisphosphonate-treated group when compared with control (p = 0.002, p = 0.001, p = 0.003, respectively). The administration of zoledronate reduced cortical osteopenia in the calcar region of the proximal femur and this therapy could be used as a preventive measure to combat strain protection osteopenia and its contribution to associated aseptic loosening in total hip replacement surgery.

Serum Interleukin 8 Levels Correlate With Synovial Fluid Levels in Patients With Aseptic Loosening of Hip Prosthesis

Levels of inflammatory cytokines (tumor necrosis factor α, interleukin [IL] 6, and IL-8) in serum from patients with osteolysis on radiographs after hip arthroplasty [osteolysis(+), n = 28], patients without osteolysis after hip arthroplasty [osteolysis(−), n = 24], and nonoperated healthy subjects [controls, n = 20] were determined. In addition, cytokine levels in synovial fluid from patients undergoing revision total hip arthroplasty (n = 14) for loosening were measured and compared with each other and with the area of osteolysis on radiographs. Serum IL-6 and IL-8 levels were significantly higher in the osteolysis(+) group than in the osteolysis(−) or the control groups. Furthermore, a significant correlation was found between the serum and synovial fluid IL-8 levels and between synovial fluid IL-8 levels and the area of osteolysis in patients undergoing revision total hip arthroplasty. Therefore, serum IL-8 levels could be a useful periprosthetic osteolysis marker.

10.7 The role of muscle spindle afferents and fusimotorneurones in gait control

The role of leg length discrepancy (LLD) both as a biomechanical impediment and a predisposing factor for associated musculoskeletal disorders has been a source of controversy for some time. LLD has been implicated in affecting gait and running mechanics and economy, standing posture, postural sway, as well as increased incidence of scoliosis, low back pain, osteoarthritis of the hip and spine, aseptic loosening of hip prosthesis, and lower extremity stress fractures. Authors disagree on the extent (if any) to which LLD causes these problems, and what magnitude of LLD is necessary to generate these problems. This paper represents an overview of the classification and etiology of LLD, the controversy of several measurement and treatment protocols, and a consolidation of research addressing the role of LLD on standing posture, standing balance, gait, running, and various pathological conditions. Finally, this paper will attempt to generalize findings regarding indications of treatment for specific populations.

An experimental animal model of aseptic loosening of hip prostheses in sheep to study early biochemical changes at the interface membrane.

BackgroundAseptic loosening of hip prosthesis as it occurs in clinical cases in human patients was attributed to wear particles of the implants, the response of the tissue dominated by macrophages and the production of inflammatory mediators and matrix degrading enzymes; however, the cascade of events initiating the process and their interaction regarding the time course is still open and discussed controversially. Therefore, the goal of this study was to establish an experimental animal model in sheep allowing to follow the cascade of early mechanical and biochemical events within the interface membrane and study the sequence of how they contribute to the pathological bone resorption necessary for aseptic loosening of the implant.MethodsA cemented modular system (Biomedtrix) was used as a hip replacement in 24 adult Swiss Alpine sheep, with one group receiving a complete cement mantle as controls (n = 12), and the other group a cement mantle with a standardized, lateral, primary defect in the cement mantle (n = 12). Animals were followed over time for 2 and 8.5 months (n = 6 each). After sacrifice, samples from the interface membranes were harvested from five different regions of the femur and joint capsule. Explant cell cultures were performed and supernatant of cultures were tested and assayed for nitric oxide, prostaglandin E2, caseinolytic and collagenolytic activity. RNA extraction and quantification were performed for inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1, and interleukin 6. Overall differences between groups and time periods and interactions thereof were calculated using a factorial analysis of variance (ANOVA).ResultsThe development of an interface membrane was noticed in both groups at both time points. However, in the controls the interface membrane regressed in thickness and biological activity, while both variables increased in the experimental group with the primary cement mantle defect over time. Nitric oxide (NO) and PGE2 concentrations were higher in the 8.5 months group (P < 0.0001) compared to the 2 months group with a tendency for the unstable group to have higher concentrations. The same was true for collagenolytic activity (P = 0.05), but not for caseinolytic activity that decreased over time (P < 0.0001).ConclusionIn this study, a primary cement mantle defect of the femoral shaft elicited biomechanical instability and biochemical changes over time in an experimental animal study in sheep, that resembled the changes described at the bone cement-interface in aseptic loosening of total hip prosthesis in humans. The early biochemical changes may well explain the pathologic bone resorption and formation of an interface membrane as is observed in clinical cases. This animal model may aid in future studies aiming at prevention of aseptic loosening of hip prosthesis and reflect some aspects of the pathogenesis involved.

Osteoprotegerin and Osteoprotegerin Ligand Expression in the Periprosthetic Tissue of Failed Hip Prosthesis

Purpose: To investigate the pathogenesis of articular prosthesis osteolysis, and to clarify the role of OPG, RANKL and RANK on osteolysis in aseptic loosening of hip prostheses. Materials and Methods: We examined the mRNAs of OPG, RANKL and RANK from cultured peripheral mononuclear cells and the tissue surrounding failed hip prostheses by RT-PCR and gel electrophoresis and performed immunohistochemistry for RANKL and RANK in the periprosthetic tissue of revised hip replacement therapy. Results: RANKL was detected in 32% and RANK was detected in 20% of the periprosthetic tissues of failed hip prostheses. Proliferative responses of cultured PBMCs occurred in cells with the titanium, cobalt and LPS, and highest response was observed in cells with cobalt particles. The mRNAs of RANKL and OPG were expressed in the periprosthetic tissues of loosened hip prostheses, but RANK mRNA was not detected. OPG mRNA was not detected in cultured PBMCs with any particles, RANKL mRNA was detected in cultured PBMCs with titanium and cobalt particles by RT-PCR, and RANK mRNA was detected in PBMCs with cobalt particles, but not with titanium. Conclusion: Osteolysis around the failed hip prosthesis may be related to activation of the OPG-ANKLRANK system. It is suggested that OPG, RANKL and RANK are major mediators of osteolysis in failed hip prosthesis.

Analysis of 18F-FDG uptake patterns in PET for diagnosis of septic and aseptic loosening after total hip arthroplasty

Identification of typical patterns for fluorodeoxy-glucose (FDG) uptake in positron emission tomography (PET) to detect aseptic loosening of hip prosthesis (ace-tabular and/or femoral component) and prosthetic infection. 18 patients with painful hip prosthesis underwent PET using a dedicated full ring scanner after application of 200-300 MBq FDG. The interface between bone and surrounding soft tissue or bone as displayed on coronal slices was divided into 12 segments in accordance with the classifications of Delee and Gruen. FDG uptake in each of the segments was scored (0-3) by two independent observers. Intraoperative findings were regarded as the gold standard. After surgical revision 14 acetabular components and 9 femoral components were found to be loose and prosthetic infection was present in 7 prostheses. Loosening of the acetabular component was correlated to enhanced uptake in the middle of the acetabular interface, while loosening of the femoral component was correlated to enhanced uptake in the proximal and middle segment of the lateral femoral interface and the proximal segment of the medial femoral interface. A similar pattern was found in prosthetic infection with high uptake along the middle portion of the lateral femoral interface. In 6 of 7 infected prostheses loosening of the acetabular and of the femoral component was present. Taking the typical uptake patterns as criteria for loosening and grade 3 uptake as an additional criterion for septic loosening the accuracy of PET imaging in the detection of loosening of the acetabular or the femoral component and of prosthetic infection was 72, 78 and 89%, respectively. This pilot study presents FDG-PET as a promising diagnostic tool for patients with painful hip prostheses. Its clinical value should be evaluated in a larger patient population.

Leg length discrepancy.

The role of leg length discrepancy (LLD) both as a biomechanical impediment and a predisposing factor for associated musculoskeletal disorders has been a source of controversy for some time. LLD has been implicated in affecting gait and running mechanics and economy, standing posture, postural sway, as well as increased incidence of scoliosis, low back pain, osteoarthritis of the hip and spine, aseptic loosening of hip prosthesis, and lower extremity stress fractures. Authors disagree on the extent (if any) to which LLD causes these problems, and what magnitude of LLD is necessary to generate these problems. This paper represents an overview of the classification and etiology of LLD, the controversy of several measurement and treatment protocols, and a consolidation of research addressing the role of LLD on standing posture, standing balance, gait, running, and various pathological conditions. Finally, this paper will attempt to generalize findings regarding indications of treatment for specific populations.

Elevated interleukin-12 in pseudosynovial fluid in patients with aseptic loosening of hip prosthesis

Loosening of a prosthesis is a major problem in total joint arthroplasty. To assess levels of cytokines in patients with such loosening, we measured the pseudosynovial fluid concentration of the following cytokines; tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12, matrix metalloproteinase (MMP)-l, and MMP-3. We examined the pseudosynovial fluid in patients with a loose hip prosthesis (group A; n = 8) and the synovial fluid in patients with osteoarthritis (OA) of the hip (group B; n = 18) using enzyme-linked immunosorbent assays. The mean concentration of IL-12 was significantly higher in group A than in group B (P < 0.01). Also, we found a significant (P < 0.05) correlation between the concentration of IL-12 and the concentration of MMP-1 in the patients with prosthesis loosening. The concentrations of TNF-α, IL-1β, IL-4, IL-6, IL-10, IFN-γ, MMP-1, and MMP-3 appeared to be similar in the two groups, although the small number of samples available precluded us from determining that there was no significant difference. The present study is the first to report elevated IL-12 levels in the pseudosynovial fluid of patients with a loose prosthesis. The immunoregulatory effect of IL-12 against wear particles could play an important role in causing loosening of the prosthesis.

In vitro cytokine production by mononuclear cells exposed to bone cement extracts

The authors evaluated the ability of bone cement to modify the profile of pro-inflammatory cytokines secreted by the immune cells. Peripheral blood mononuclear cells (PBMC) collected from healthy individuals were cultured with cement extracts and tested to assess the release of IL-1 β, TNF α, GM-CSF and IL-6 in both unstimulated and PHA-stimulated PBMC. The cytokine release of unstimulated PBMC was very poor, and in particular the IL-1 β was undetectable: the addition of cement extract increased both TNF α and GM-CSF release and decreased IL-6, sometimes significantly. The most recurrent observation in PHA-stimulated PBMCs exposed to bone cement extract was the increase in both IL-1 β and IL-6 release, while both the mean concentration and the index of release of TNF α and GM-CSF were changeable. In conclusion our results showed that leachable components of some bone cements can induce in vitro the release of pro-inflammatory cytokines which are known to be involved in the bone resorption associated with aseptic loosening of hip prostheses. These findings allowed us to identify materials endowed with the highest inflammatory power.

Autonomic neuropeptides in the interface membrane of aseptic loose hip prostheses

We analyzed the presence of autonomic nerve fibers in the interface membranes ( n = 9) surrounding aseptic loosened hip prostheses by immunohistochemistry. The study focused on the autonomic messengers neuropeptide Y (NPY), tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of noradrenaline (NA), and vasoactive intestinal polypeptide (VIP). Protein gene product (PGP) 9.5, a general marker of peripheral nerve fibers, was also analyzed to establish the neuronal character of the immunoreactive structures. PGP 9.5-positive and NPY-positive nerve fibers were identified in all 9 samples, and VIP-immunoreactive and TH-immunoreactive fibers were found in 7. There was a difference in the distribution of nerve fibers both between and within the samples. Among the neuropeptides analyzed, NPY was most abundant. NPY-positive and TH-positive fibers were predominantly found around the blood vessel walls forming varicose nerve terminals. VIP-positive fibers were mainly observed as thin varicose nerve terminals with no relationship to blood vessels. Autonomic neuropeptides exert not only vasoactive and immunoregulatory effects, but also have been found to have direct effects on bone tissue. Moreover, the autonomic nervous system has been strongly implicated in nociception and inflammation. Neuronal NPY, TH, and VIP in the interface membrane may prove to contribute to the pathologic mechanisms leading to aseptic loosening of hip prostheses.

Bone-resorbing cytokines in serum of patients with aseptic loosening of hip prostheses

Our aim was to determine if the serum levels of bone-resorbing cytokines (IL-1β, TNF-α, IL-6, GM-CSF) are altered in patients with aseptic loosening of a total hip prosthesis, and if such levels are influenced by the type of implant. We determined cytokine levels in sera from 35 patients before revision for failed total hip arthroplasty and compared them with those in 25 healthy donors. We also assessed the soluble receptor of interleukin-2 (sIL-2r) in serum as an indication of a specific immune reaction against the implant. Our findings showed that the sIL-2r and TNF-α serum level did not change. The IL-6 level was not significantly altered, but was higher in patients with TiAlV prostheses than in those with a CrCoMo implant and in patients with cemented prostheses. The IL-1β level was found to be higher in those with a TiAlV cemented prosthesis than in the control group (p = 0.0001) and other groups of patients (p = 0.003 v uncemented TiAlV, p = 0.01 v cemented CrCoMo, p = 0.001 v uncemented CrCoMo). The GM-CSF level significantly increased in patients compared with healthy subjects (p = 0.008), and it was higher in those with cemented than with uncemented implants (p = 0.01). Only patients with cementless CrCoMo prostheses had levels of GM-CSF similar to those of the control group. The highest GM-CSF concentrations were observed in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) in the last months before revision (p = 0.04). In addition, when massive osteolysis was observed, the level of GM-CSF tended to decrease to that of the control group.

Bone-resorbing cytokines in serum of patients with aseptic loosening of hip prostheses.

Our aim was to determine if the serum levels of bone-resorbing cytokines (IL-1beta, TNF-alpha, IL-6, GM-CSF) are altered in patients with aseptic loosening of a total hip prosthesis, and if such levels are influenced by the type of implant. We determined cytokine levels in sera from 35 patients before revision for failed total hip arthroplasty and compared them with those in 25 healthy donors. We also assessed the soluble receptor of interleukin-2 (sIL-2r) in serum as an indication of a specific immune reaction against the implant. Our findings showed that the sIL-2r and TNF-alpha serum level did not change. The IL-6 level was not significantly altered, but was higher in patients with TiAIV prostheses than in those with a CrCoMo implant and in patients with cemented prostheses. The IL-1beta level was found to be higher in those with a TiAIV cemented prosthesis than in the control group (p=0.0001) and other groups of patients (p=0.003 v uncemented TiAIV, p=0.01 v cemented CrCoMo, p=0.001 v uncemented CrCoMo). The GM-CSF level significantly increased in patients compared with healthy subjects (p=0.008), and it was higher in those with cemented than with uncemented implants (p=0.01). Only patients with cementless CrCoMo prostheses had levels of GM-CSF similar to those of the control group. The highest GM-CSF concentrations were observed in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) in the last months before revision (p=0.04). In addition, when massive osteolysis was observed, the level of GM-CSF tended to decrease to that of the control group.

Sensory nerves in the interface membrane of aseptic loose hip prostheses

We studied the presence of sensory nerves by immunohistochemistry in the interface membranes of hip prostheses after aseptic loosening. Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) were analysed as was protein gene product (PGP) 9.5, a general marker for nerve fibres. We identified nerve fibres in all samples but differences in their density were found. SP- and NKA-positive fibres were predominantly non-vascular, forming varicose nerve terminals. CGRP-immunoreactive nerve fibres with varicose terminals were seen mostly close to blood vessels, but also as free nerve endings. Sensory neuropeptides participate not only in nociception but also stimulate immune cells to release cytokines. The presence of sensory nerves in the interface membrane may reflect a pathophysiological response contributing to the aseptic loosening of hip prostheses.

Sensory nerves in the interface membrane of aseptic loose hip prostheses.

We studied the presence of sensory nerves by immunohistochemistry in the interface membranes of hip prostheses after aseptic loosening. Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) were analysed as was protein gene product (PGP) 9.5, a general marker for nerve fibres. We identified nerve fibres in all samples but differences in their density were found. SP- and NKA-positive fibres were predominantly non-vascular, forming varicose nerve terminals. CGRP-immunoreactive nerve fibres with varicose terminals were seen mostly close to blood vessels, but also as free nerve endings. Sensory neuropeptides participate not only in nociception but also stimulate immune cells to release cytokines. The presence of sensory nerves in the interface membrane may reflect a pathophysiological response contributing to the aseptic loosening of hip prostheses.