Bernd Baumann

Effects of polyethylene and TiAIV wear particles on expression of RANK, RANKL and OPG mRNA

Background Wear debris has been associated with periprosthetic osteolysis and loosening of total joint arthroplasties. RANKL (receptor activator of NF-κB ligand), RANK (receptor activator of NF-κB) and OPG (osteoprotegerin) are three key molecules which regulate differentiation, survival, fusion, and activation of osteoclasts.Material and methods We evaluated the effect of TiAlV and polyethylene particles on expression of RANK, RANKL and OPG mRNA. We used a human monocytic leukemic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated into macrophage-like cells and exposed to polyethylene particles and prosthesis-derived TiAlV particles. The supernantant was used for measurement of TNFα protein and total RNA was extracted from the cells. Expression of the genes coding for OPG, RANKL and RANK was analysed at the mRNA level using a semiquantitative RT-PCR method.Results Both polyethylene and TiAlV particles induced a significant release of TNFα after 6 h of exposure and a significant upregulation of RANK mRNA. OPG mRNA expression was transiently upregulated after exposure to polyethylene and TiAlV particles. These effects were dependent on particle dose. RANKL mRNA was not detectable in our THP-1 model. In contrast, LPS exhibited a different pattern of RANK/RANKL/OPG mRNA expression.Interpretation Our findings provide evidence that both polyethylene and TiAlV particles induce upregulation of RANK expression in cells of the monocytic lineage, which may be important for periprosthetic osteoclastogenesis.

Prophylaxis of heterotopic ossification after total hip arthroplasty: a prospective randomized study comparing indomethacin and meloxicam.

: We performed a randomized, prospective study on the prophylaxis of heterotopic ossification (HO) after total hip arthroplasty (THR), comparing indomethacin and the selective COX-2 inhibitor meloxicam. From the day after surgery, 272 patients were treated with 7.5 mg meloxicam, 15 mg meloxicam, or 2 x 50 mg indomethacin a day, for 14 days. After 6 months, radiographs of patients treated with 7.5 mg meloxicam showed that HO had occurred in one third. This treatment was therefore stopped after 26 patients have been assigned to this group. According to the intention-to-treat principle, patients given 15 mg meloxicam developed HO in 25% (20% Brooker grade I, 4% grade II and 1% grade III) and those given indomethacin in 10% (7% Brooker grade I, 1% grade II and 2% grade III), a statistically significant difference.

9- to 11-Year Results of Cemented Titanium Mueller Straight Stem in Total Hip Arthroplasty

This retrospective study reviewed 9- to 11-year results after total hip arthroplasty (THA) with cemented titanium stems (Mueller-Straight-Stem). Ninety-one patients (110 hips) were examined clinically and radiologically at an average 9.5-year follow-up. Revisions for aseptic loosening were performed in 4 (4%) patients. Subsidence or varus position could only be observed in one of these patients. Radiolucent lines were found in 37 patients, mainly located around the proximal zones of the stem (zone 1, 7, 8, and 14). Harris scores were good or excellent in 78% and satisfactory in 20% of patients. The 9.5-year survival rate of the cemented titanium stem with regard to aseptic loosening was 96.4%. Body weight was significantly higher (88 +/- 5.4 kg) in the 4 patients with aseptic loosening, compared to patients without radiolucent lines (75 +/- 15 kg). The body weight to stem surface ratio showed a significant difference (1.5 kg/cm2 versus 1 kg/cm2; P < .05). No significant differences were found in other factors, including sex, size or type of stem, Harris score, heterotopic ossification, or body mass index. Good long-term results can be achieved with cemented titanium stem implants. This titanium implant is recommended for patients with hypersensitivity to chrome, cobalt, and nickel. mplanting the biggest possible stem seems to be most beneficial.

Synergistic effects of mixed TiAlV and polyethylene wear particles on TNFalpha response in THP-1 macrophages.

Abstract TNFα is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particle-induced osteolysis. Wear particles of one composition and their biological effects are well characterised. In contrast, little is known about the effects of mixed particles with respect to mix ratio and particle concentration. We evaluated the effects of different mix ratios of polyethylene and TiAlV particles on TNFα response. We used a human monocytic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to different mixtures of lipopolysaccharide-detoxified polyethylene and TiAlV particles. TNFα was analysed in culture supernatants using ELISAs. Both polyethylene and TiAlV particles induced a dose- and time-related release of TNFα, with maximum levels after 6 h. A PE/TiAlV mix ratio of 36:1 at 108 particles/ml induced significantly higher TNFα concentrations compared to equal particle concentrations of isolated TiAlV (p=0.047) or PE (p=0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAlV and polyethylene particles have significant synergistic effects, depending on the mix ratio and particle concentrations. This supra-additive effect can contribute substantially to the pathogenesis of implant particle-induced osteolysis.TNFalpha is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particle-induced osteolysis. Wear particles of one composition and their biological effects are well characterised. In contrast, little is known about the effects of mixed particles with respect to mix ratio and particle concentration. We evaluated the effects of different mix ratios of polyethylene and TiAlV particles on TNFalpha response. We used a human monocytic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to different mixtures of lipopolysaccharide-detoxified polyethylene and TiAlV particles. TNFalpha was analysed in culture supernatants using ELISAs. Both polyethylene and TiAlV particles induced a dose- and time-related release of TNFalpha, with maximum levels after 6 h. A PE/TiAlV mix ratio of 36:1 at 10(8) particles/ml induced significantly higher TNFalpha concentrations compared to equal particle concentrations of isolated TiAlV (p=0.047) or PE (p=0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAlV and polyethylene particles have significant synergistic effects, depending on the mix ratio and particle concentrations. This supra-additive effect can contribute substantially to the pathogenesis of implant particle-induced osteolysis.

Prophylaxis of heterotopic ossification after total hip arthroplasty

We performed a randomized, prospective study on the prophylaxis of heterotopic ossification (HO) after total hip arthroplasty (THR), comparing indomethacin and the selective COX-2 inhibitor meloxicam. From the day after surgery, 272 patients were treated with 7.5 mg meloxicam, 15 mg meloxicam, or 2 × 50 mg indomethacin a day, for 14 days. After 6 months, radiographs of patients treated with 7.5 mg meloxicam showed that HO had occurred in one third. This treatment was therefore stopped after 26 patients have been assigned to this group. According to the intention-to-treat principle, patients given 15 mg meloxicam developed HO in 25% (20% Brooker grade I,4% grade II and 1 % grade III) and those given indomethacin in 10% (7% Brooker grade I,1% grade II and 2% grade III), a statistically significant difference.

Characterization of mode II-wear particles and cytokine response in a human macrophage-like cell culture.

Abstract Informations about wear particles in metallosis (mode II wear) and their effects in vitro and in vivo are limited. The aim of this study was to characterize wear particles obtained intraoperatively and to analyse their effects on cytokine response in an established human macrophage-like cell culture model [15]. Method: Wear particles were obtained intraoperatively from four patients with metallosis resulting from CrCoMo/PE/TiAlV-implants (mode II wear) (3 knee, 1hip prosthesis). After purification, particles were characterized regarding to their composition and size (particle size analyser, electron microscopy, edx-analysis, histological slices). The effects of particles on the release of cytokines (PDGF, IL-1β, IL-8, TNF α) were determined in an established human macrophage-like cell culture system by ELISA-assays. Results: The metal wear particles consisted of TiAlV with a mean size of 0,1± 0,15 μm, independent of the prosthesis location. CrCoMo particles could not be detected. In the cell culture model 1456 × 108 particles per 1 × 106 macrophages released maximum amounts of TNFα (8-fold) and IL-8 and IL-1ß (5-fold) while the survival rate of the cells was more than 90 percent. A particle-dependent increase of PDGF-levels could not be detected. Conclusion: As already shown for mode I wear particles (contact between primary bearing surfaces), also mode II wear particles cause release of bone resorbing cytokines in a macrophage-like cell culture model. Because their local and systemic effects in vivo are still not completely understood, we recommend a complete removal of wear particles in cases of metallosis to avoid possible immunological reactions of the body as well as periprosthetic osteolysis. Informationen über Abriebpartikel in Fällen von Metallose (Mode IIAbrieb) und über deren Effekte in vitro und in vivo sind limitiert. Ziel dieser Studie war die Charakterisierung von intraoperativ gewonnenen Abriebpartikeln und die Analyse ihrer Effekte auf die Zytokinausschüttung in einem etablierten, humanen Makrophagen-ähnlichen Zellkulturmodell [15]. Methode: Bei vier Patienten resultierte eine Metallose aufgrund pathologischen Abriebs von CrCoMo/PE/TiAlV – Implantaten (Mode IIAbrieb, 3 Knie, 1 Hüftprothese). Die intraoperativ gewonnenen Abriebpartikel wurden aufgereinigt und bezüglich ihrer Zusammensetzung und Größe charakterisiert (particle size analyser, Elektronenmikroskopie, Edx-Analyse, Histologie). Die Effekte der Partikel auf die Freisetzung von Zytokinen (PDGF, IL-1β, IL-8, TNF α) wurden mittels ELISA in einem etablierten, humanen Makrophagen-ähnlichen Zellkulturmodell untersucht. Ergebnisse: Unabhängig von der Lokalisation der Prothese bestanden die metallernen Abriebpartikel aus TiAlV einer durchschnittlichen Größe von 0,1± 0,15 μm. CrCoMo-Partikel konnten nicht nachgewiesen werden. Im Zellkulturmodell verursachten 1456 × 108 Partikel pro 1 × 106 Makrophagen maximale Zytokinausschüttungen (8-fache TNFα -, 5-fache IL-8 und IL-1ß Ausschüttung) bei einer Überlebensrate der Zellen von mehr als 90 Prozent. Ein Partikel-abhängiger PDGF-Anstieg konnte nicht beobachtet werden. Schlussfolgerung: Wie bereits für Mode I- Abriebpartikel gezeigt (Kontakt zwischen primär belasteten Oberflächen), verursachen auch Mode II- Abriebpartikel die Freisetzung von Knochenresorption auslösenden Zytokinen in einem Makrophagen-ähnlichen Zellkulturmodell. Weil ihre lokalen und systemischen Effekte in vivo nicht komplett verstanden sind, empfehlen wir die vollständige Entfernung von Abriebpartikeln bei Patienten mit Metallose, um mögliche immunologische Reaktionen des Körpers sowie periprothetische Osteolysen zu vermeiden.

Elevated postoperative pain levels following orthopedic surgery. Depression as a strong predictor

The aim of this study was to examine whether depression is a strong predictor of elevated postoperative pain levels following orthopedic surgery and whether the implementation of standardized pain management is more beneficial for patients with depression. We performed a non-randomized, prospective study with two different groups of patients who underwent orthopedic surgery. Group 1 (n=249) received non-standardized pain therapy whereas group 2 (n = 243) was treated with a standardized pain management concept. Effects of the treatment were monitored with a VAS-based pain assessment protocol. Depression was measured preoperatively with the self-reported Patient Health Questionnaire (PHQ-9). Patients with the probable diagnosis of a current episode of major depression showed significantly higher postoperative pain than patients without a depressive episode. On the other hand, patients with depression benefited from the implementation of standardized pain management. Our data suggest a predictive value of depression for severe postoperative pain. Patients with depression benefited from standardized postoperative pain therapy, but were still suffering from significantly higher postoperative pain.

Upregulation of LITAF mRNA expression upon exposure to TiAlV and polyethylene wear particles in THP-1 macrophages / Hochregulation der LITAF-mRNA Expression nach Exposition gegenüber TiAlV- und Polyethylen-Abriebpartikeln in THP-1 Makrophagen

Abstract Tumor necrosis factor α (TNFα) plays a fundamental role in the pathogenesis of wear particle-induced periprosthetic osteolysis. However, particle-induced mechanisms that control TNFα gene expression are not yet well characterized. LITAF [lipopolysaccharide (LPS)-induced TNFα factor] is a novel transcription factor that regulates expression of the TNFα gene, but nothing is known about its role in wear particle-induced osteolysis. We evaluated the effect of titanium aluminum vanadium (TiAlV) and polyethylene particles on mRNA expression of LITAF. A human monocytic leukemia cell line (THP-1) was used in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene particles and prosthesis-derived TiAlV particles. Supernatant was used for TNFα protein measurement and total RNA was extracted from cells. LITAF was analyzed at the mRNA level using semiquantitative RT-PCR. Both polyethylene and TiAlV particles induced significant upregulation of LITAF mRNA that was followed by a significant TNFα response. These effects were dependent on the particle dose. Low particle concentrations exhibited no significant effect on expression of TNFα and LITAF mRNA. In comparison to exposure to polyethylene and TiAlV particles, LPS stimulation exhibited similar upregulation of LITAF mRNA, but led to an overwhelming TNFα response. Our findings provide evidence that LITAF is implicated in the pathogenesis of wear particle-induced osteolysis. Zusammenfassung Tumor necrosis factor α (TNFα) spielt eine fundamentale Rolle in der Pathogenese der abriebpartikelinduzierten Osteolyse. Indes sind die partikelinduzierten Mechanismen, die die Genexpression von TNFα kontrollieren, bisher nicht gut charakterisiert. LITAF [lipopolysaccharide (LPS)-induced TNFα] ist ein kürzlich identifizierter Transkriptionsfaktor, der die TNFα-Genexpression reguliert, wobei aber nichts bekannt ist über dessen Rolle bei der partikelinduzierten Osteolyse. Unser Ziel war es, die Effekte von Titan-Aluminium-Vanadium- (TiAlV) und Polyethylen-Partikeln auf die mRNA-Expression von LITAF zu untersuchen. In dieser in vitro-Studie verwendeten wir eine humane, monozytäre Zelllinie (THP-1). Die Zellen wurden zu makrophagenähnlichen Zellen differenziert und LPS-detoxifizierten Polyethylen- und TiAlV-Partikeln ausgesetzt. Im Überstand wurde TNFα gemessen, zudem wurde die gesamte RNA aus den Zellen extrahiert. LITAF wurde auf mRNA-Ebene mittels semiquantitativer RT-PCR analysiert. Sowohl Polyethylen- als auch TiAlV-Partikel induzierten eine signifikante Hochregulation von LITAF-mRNA, die von einer signifikanten TNFα-Antwort zeitlich gefolgt war. Die Effekte waren abhängig von der Partikelkonzentration. Niedrige Partikelkonzentrationen zeigten keine signifikanten Effekte auf die Expression von TNFα und LITAF-mRNA. Im Vergleich zur Stimulation mit Polyethylen- und TiAlV-Partikeln bewirkte LPS eine ähnliche Hochregulation von LITAF-mRNA, aber eine überschießende TNFα-Antwort. Die Ergebnisse liefern Beweiskraft, dass LITAF substanziell bei der Pathogenese der abriebpartikelinduzierten Osteolyse beteiligt ist.

Total Knee Arthroplasty in a Patient with Erdheim-Chester Disease with Massive Joint Destruction

Erdheim-Chester disease was named after William Chester, who described the disease in 1930, and the Viennese pathologist Jakob Erdheim. Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis that causes a systemic disease with involvement of the tubular long bones, sparing the axial skeleton, as well as the hands and feet1. The prognosis depends in large part on the extent and distribution of extraosseous manifestations, which most commonly includes diabetes insipidus; these manifestations can also include involvement of the retroperitoneum, skin, lung, and heart and include painless bilateral exophthalmus in >50% of cases2-4. Together with bone pain that arises from bone destruction affecting nociceptors within periosteum and bone marrow, mainly of the lower limbs, these clinical symptoms lead to the diagnosis of Erdheim-Chester disease. The diagnosis is usually based on typical radiographic findings, with symmetric bilateral osteosclerosis involving metaphyseal and diaphyseal regions of the long bones with sparing of the epiphyses. Bone scintigraphy reveals increased tracer uptake in Erdheim-Chester disease lesions, while magnetic resonance imaging shows replacement of the normal fatty bone marrow as well as periostitis2-6. Our report highlights a case of severe bilateral knee joint destruction and varus deformity in a fifty-eight-year-old man with Erdheim-Chester disease and describes the clinical details, technical aspects of surgery, and short-term outcome one year after surgery. To our knowledge, this is the first report of a joint arthroplasty (specifically, bilateral total knee replacement) in a patient with Erdheim-Chester disease. The patient was informed that data concerning the case would be submitted for publication, and he consented. This fifty-eight-year-old male winegrower with a body-mass index of 39.5 kg/m2 and a five-year history of Erdheim-Chester disease developed progressive motion-dependent pain and varus deformity in both knees two years prior to presentation. There was no …

Versagensursachen primärer Implantationen

Eine Analyse aller Endoprothesenregister und groser Huftendoprothetik-Studien [19, 26] zeigt, dass die Pfannenkomponente das Hauptproblem im Rahmen eines Implantatversagens darstellt. Die Pfanne fuhrt doppelt so haufig zu Problemen wie der Schaft.