[Update of the German S3 guideline on atraumatic femoral head necrosis in adults]. / Update S3-Leitlinie Atraumatische Femurkopfnekrose des Erwachsenen.

The update of the German S3 guideline on atraumatic femoral head necrosis in adults aims to provide an overview of diagnosis and treatment. All clinical studies, systematic reviews, and meta-analyses published in German or English between 01.05.2013 and 30.04.2017 were included. Of 427 studies, 28 were suitable for analysis. Risk factors are corticosteroids, chemotherapy, kidney transplants, hemoglobinopathies, and alcoholism. Differential diagnoses are for example bone marrow edema, insufficiency fracture, and destructive arthropathy. Radiography should be performed upon clinical suspicion. In patients with normal radiography findings but persistent complaints, magnetic resonance imaging (ARCO classification) is the method of choice. Computed tomography (CT) can be used to confirm/exclude articular surface collapse. A subchondral sclerosis zone >30% in CT indicates a better prognosis. Left untreated, a subchondral fracture will develop within 2 years. The risk of disease development in the opposite side is high during the first 2 years, but unlikely thereafter. In conservative therapy, iloprost and alendronate can be used in a curative approach, the latter for small, primarily medial necrosis. Conservative therapy alone as well as other drug-based and physical approaches are not suitable for treatment. No particular joint-preserving surgery can currently be recommended. Core decompression should be performed in early stages with <30% necrosis. From ARCO stage IIIc or in stage IV, the indication for total hip arthroplasty should be checked. Results after total hip arthroplasty are comparable with those after coxarthrosis, although the revision rate is higher due to the relatively young age of patients. Statements on the effectiveness of cell-based therapies such as expanded stem cells or bone marrow aspirates cannot currently be made.

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.

Upregulation of LITAF mRNA expression upon exposure to TiAlV and polyethylene wear particles in THP-1 macrophages.

Tumor necrosis factor alpha (TNFalpha) plays a fundamental role in the pathogenesis of wear particle-induced periprosthetic osteolysis. However, particle-induced mechanisms that control TNFalpha gene expression are not yet well characterized. LITAF [lipopolysaccharide (LPS)-induced TNFalpha factor] is a novel transcription factor that regulates expression of the TNFalpha 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 TNFalpha 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 TNFalpha response. These effects were dependent on the particle dose. Low particle concentrations exhibited no significant effect on expression of TNFalpha 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 TNFalpha response. Our findings provide evidence that LITAF is implicated in the pathogenesis of wear particle-induced osteolysis.

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

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.

Activation of NF-kappaB signalling and TNFalpha-expression in THP-1 macrophages by TiAlV- and polyethylene-wear particles.

Wear particles are believed to induce periprosthetic inflammation which contributes to periprosthetic osteolysis. TNFalpha plays a pivotal role in the pathogenesis of this process. The molecular mechanisms leading to the development of periprosthetic inflammation with upregulated TNFalpha expression in monocytic cells in response to different wear particles have yet to be defined. In this study we evaluated the effects of polyethylene- and TiAlV-particles on activation of NF-kappaB signalling pathways and TNFalpha biosynthesis and release in monocytic cells with respect to periprosthetic osteoclastogenesis. THP-1 monocytic cells were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene and prosthesis-derived TiAlV-particles. TNFalpha release was analyzed in culture supernatant by ELISA. NF-kappaB activation was examined by electrophoretic mobility shift assay (EMSA), and NF-kappaB target promoter activities including transactivation of the TNFalpha promoter were determined by luciferase reporter gene assays. Differentiated THP-1 macrophages were exposed to increasing numbers of particles for 0, 60, 180 and 360 min. Both, polyethylene- and TiAlV-particles induced a significant activation of both NF-kappaB and TNFalpha promoters at 180 min. A significant TNFalpha release was detected after 360 min exposure to polyethylene- and TiAlV-particles in a dose dependent manner. In comparison, LPS induced a much greater activation of NF-kappaB and TNFalpha promoters, and TNFalpha secretion into the supernatant was strongly induced. These results provide evidence that induction of the NF-kappaB signal transduction pathway in macrophages plays a major role in initiating and mediating the inflammatory response leading to periprosthetic osteolysis.

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

UNLABELLED: 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. METHOD: Wear particles were obtained intraoperatively from four patients with metallosis resulting from CrCoMo/PE/TiAIV-implants (mode II wear) (3 knee, 1 hip 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-1beta, IL-8, TNF alpha) were determined in an established human macrophage-like cell culture system by ELISA-assays. RESULTS: The metal wear particles consisted of TiAIV with a mean size of 0.1 +/- 0.15 microm, independent of the prosthesis location. CrCoMo particles could not be detected. In the cell culture model 1456 x 10(8) particles per 1 x 10(6) macrophages released maximum amounts of TNFalpha (8-fold) and IL-8 and IL-1beta (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.

[Effects of clinically relevant alumina ceramic, zirconia ceramic and titanium particles of different sizes and concentrations on TNF-alpha release in a human macrophage cell line]. / Auswirkungen von klinisch relevanten Aluminium Keramik-, Zirkonium Keramik- und Titanpartikel unterschiedlicher Grösse und Konzentration auf die TNFalpha-Ausschüttung in einem humanen Makrophagensystem.

INTRODUCTION: Aseptic loosening is considered to be the main problem of modern endoprothesis. Tumor necrosis factor alpha (TNFalpha) seems to be the initiator protein of particle disease. The aim of our study was to investigate the TNFalpha response of macrophage like cells (MLC) after stimulation with periprosthetic particles, typically found during revision surgery. For this purpose alumina ceramic (Al2O3), zirconia ceramic (ZrO2) and titanium (Ti) particles of different sizes and concentrations were used. Important was to study the effects of different sizes due to TNFalpha secretion and the comparison of the biological effects of alumina ceramic and titanium. METHOD: To obtain an TNFalpha profile we used an established macrophage model (Rader et al.) with THP-1 cells (human monocytic cell line). Therefore 106 MLC were incubated with different particle concentrations and sizes for 6 h. The supernatant was then investigated for TNF using ELISA assay. RESULTS: Ti-particles provoked in both sizes (0.2 microm and 2.5 microm) the greatest TNFalpha response, 8 times and 17 times as high in comparison with control. But substantially more 0.2 microm sized Ti-particles were necessary to get the above mentioned results. Al2O3-particles were not as effective as Ti, but they released fourfold more TNFalpha compared to control. There was no difference in TNFalpha-secretion comparing Al2O3-particles of different sizes (0.6 microm and 2 microm), but a 1000 times greater concentration of the 0.6 microm sized particles were needed. Using Al2O3- and Ti-particles of the same size and concentration, Ti provoked a significant higher TNFalpha response. ZrO2 showed no effects on TNFalpha release. CONCLUSION: Because of our results we recommend ceramic articulating surfaces, which are superior to metal on metal matings ion term of biological reactions. Additionally bigger wear particles should be avoided. Revisionoperation should be done early to avoid huge amount of wear particles and to minimize local osteolysis.

Subsidence of titanium straight stems in combination with highly viscous bone cement.

Varying results and a high rate of subsidence have been reported for the straight femoral stem (M.E. Muller) made of titanium alloy. We examined subsidence in 135 titanium-alloy straight stems implanted with high viscosity cement after 68.8+/-11.5 months using a digital high-precision method (EBRA-FCA). One revised implant showed a subsidence of 14.6 mm and another 2.5 mm over 5 years. A third implant without migration was found to be loose. The 122 implants without loosening showed a mean subsidence of 0.1+/-0.1 mm, and focal osteolysis was seen in two. Altogether, we found subsidence of the titanium stems very small. The small subsidence may be related to the use of high viscosity bone cement.

Effects of polyethylene and TiAlV 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-kappaB ligand), RANK (receptor activator of NF-kappaB) and OPG (osteoprotegerin) are three key molecules which regulate differentiation, survival, fusion, and activation of osteoclasts. MATERIAL AND METHODS: We evaluated the effect of TiAIV 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 TiAIV particles. The supernantant was used for measurement of TNFalpha 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 TiAIV particles induced a significant release of TNFalpha after 6 h of exposure and a significant upregulation of RANK mRNA. OPG mRNA expression was transiently upregulated after exposure to polyethylene and TiAIV 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 TiAIV particles induce upregulation of RANK expression in cells of the monocytic lineage, which may be important for periprosthetic osteoclastogenesis.