W Rüther

University Medical Center Hamburg - Eppendorf, Hamburg, Hamburg, Germany

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Publications (260)447.33 Total impact

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    ABSTRACT: Background and objectives: Surgical interventions can alter the balance between pro- and anti-angiogenic growth factors and thereby modulate tumor growth. Since the microcirculatory properties of tumors underlie organ-specific differences, the microhemodynamic characteristics of bone metastasis have not yet been fully described. Angiogenesis inhibitors are increasingly being used to treat advanced stages of cancer. We hypothesized that the anti-angiogenic drug sunitinib abrogates alterations in microvascular properties following a minor surgical intervention in an in vivo model of secondary breast cancer growth in the bone. Methods: Intravital microscopy was performed over 25 days using a xenograft model of breast cancer tumor growth in the bone to determine changes in microvascular properties during sunitinib treatment. Mastectomy was performed on day 5 to evaluate the effect of a minor surgical trauma on tumor growth and microvascular properties. Results: Anti-angiogenic therapy resulted in reduced tumor growth, decreased vascular density, and increased vascular diameters. Blood flow velocity remained constant while microvascular permeability temporarily increased after the surgical intervention. Conclusions: Administration of sunitinib reduced tumor growth and altered microcirculatory properties in a time-dependent manner. The observed dramatic increase in microvascular permeability after the surgical intervention may have implications for local tumor growth, and metastatic dissemination. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
    No preview · Article · Jan 2016 · Journal of Surgical Oncology
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    ABSTRACT: Objectives Health risks due to chronic exposure to highly fluoridated groundwater could be underestimated because fluoride might not only influence the teeth in an aesthetic manner but also seems to led to dentoalveolar structure changes. Therefore, we studied the tooth and alveolar bone structures of Dorper sheep chronically exposed to very highly fluoridated and low calcium groundwater in the Kalahari Desert in comparison to controls consuming groundwater with low fluoride and normal calcium levels within the World Health Organization (WHO) recommended range. Materials and methods Two flocks of Dorper ewes in Namibia were studied. Chemical analyses of water, blood and urine were performed. Mineralized tissue investigations included radiography, HR-pQCT analyses, histomorphometry, energy-dispersive X-ray spectroscopy and X-ray diffraction-analyses. Results Fluoride levels were significantly elevated in water, blood and urine samples in the Kalahari group compared to the low fluoride control samples. In addition to high fluoride, low calcium levels were detected in the Kalahari water. Tooth height and mandibular bone quality were significantly decreased in sheep, exposed to very high levels of fluoride and low levels of calcium in drinking water. Particularly, bone volume and cortical thickness of the mandibular bone were significantly reduced in these sheep. Conclusions The current study suggests that chronic environmental fluoride exposure with levels above the recommended limits in combination with low calcium uptake can cause significant attrition of teeth and a significant impaired mandibular bone quality. Clinical relevance In the presence of high fluoride and low calcium-associated dental changes, deterioration of the mandibular bone and a potential alveolar bone loss needs to be considered regardless whether other signs of systemic skeletal fluorosis are observed or not.
    Full-text · Article · Jan 2016 · Clinical Oral Investigations
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    ABSTRACT: Objective: To determine the lifetime QALYs gained by total joint arthroplasty (TJA) and assess the QALYs attributed to specific postoperative rehabilitation interventions. Design: Secondary analysis of two multicenter randomized controlled trials with 3-, 6-, 12-, and 24-month follow-up. Setting: Two university hospitals, two municipal hospitals, and one rural hospital. Participants: 837 patients who underwent THA or TKA INTERVENTIONS: RCT A: 465 patients were randomly assigned to receive aquatic therapy (pool exercises aimed at training of proprioception, coordination, and strengthening) after 6 versus 14 days after THA or TKA. Rct b: 362 patients were randomly assigned to either perform or not perform ergometer-cycling beginning two weeks after THA or TKA. Main outcome measure: QALYs, based on the SF-6D (Short-Form, 6 Dimension) utility, measured at baseline and 3, 6, 12 and 24-months follow-up. Results: After hip (knee) arthroplasty, the lifetime QALYs increased by 2.35 (1.81) years in the non-ergometer group, and by 2.30 (1.60) years in the late aquatic-therapy group. By ergometer-cycling, 0.55 additional QALYs could be gained after hip and 0.10 after knee arthroplasty, while the additional QALYs attributed to early aquatic-therapy were 0.12 years after hip and 0.01 years after knee arthroplasty. Conclusions: This analysis provides a sound estimate for the determination of the lifetime QALYs gained by THA and TKA. In addition, this analysis demonstrates that specific postoperative rehabilitation can result in an additional mean QALY gain of 0.55 years, which represents one fourth of the effect of surgery. Even if this was interpreted as a small effect at an individual level, it is important when extrapolated to all patients undergoing TJA. At a national level, these improvements appear to have a similar magnitude of QALY gain when compared to published data regarding medications to lower blood pressure in all persons with arterial hypertension.
    No preview · Article · Jan 2016 · Archives of physical medicine and rehabilitation
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    ABSTRACT: Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4). In the present study we analyzed Thbs4 expression in mice, thereby confirming its predominant expression in articular cartilage, but also identifying expression in other tissues, including bone. To study the role of Thbs4 in skeletal development and integrity we took advantage of a Thbs4-deficient mouse model that was analyzed by undecalcified bone histology. We found that Thbs4-deficient mice do not display phenotypic differences towards wildtype littermates in terms of skeletal growth or bone mass acquisition. Since Thbs4 has previously been found over-expressed in bones of Phex-deficient Hyp mice, we additionally generated Thbs4-deficient Hyp mice, but failed to detect phenotypic differences towards Hyp littermates. With respect to articular cartilage we found that Thbs4-deficient mice display transient thinning of articular cartilage, suggesting a protective role of Thbs4 for joint integrity. Gene expression analysis using porcine primary cells revealed that Thbs4 is not expressed by synovial fibroblasts and that it represents the only member of the Thbs gene family with specific expression in articular, but not in growth plate chondrocytes. In an attempt to identify specific molecular effects of Thbs4 we treated porcine articular chondrocytes with human THBS4 in the absence or presence of conditioned medium from porcine synovial fibroblasts. Here we did not observe a significant influence of THBS4 on proliferation, metabolic activity, apoptosis or gene expression, suggesting that it does not act as a signaling molecule. Taken together, our data demonstrate that Thbs4 is highly expressed in articular chondrocytes, where its presence in the extracellular matrix is required for articular cartilage integrity.
    Preview · Article · Dec 2015 · PLoS ONE
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    F.T. Beil · W. Rüther
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    ABSTRACT: Background Radiosynoviorthesis (RSO) provides a simple method for the treatment of patients with chronic synovitis and has only few side effects. Objectives Evidence-based indications and contraindications for performing RSO based on the current literature are presented. Material and methods Published information on the indications and contraindications for performing RSO in chronic synovitis were analyzed and summarized. Results According to the guideline recommendations of the German Society of Rheumatology indications for RSO are given in patients with rheumatoid arthritis, seronegative spondyloarthropathy, crystal arthropathy, villonodular synovitis and hemophilia with recurrent joint bleeding. Osteoarthritis with documented reactive synovitis is also regarded as an indication in the guidelines of the nuclear medicine societies. The European League Against Rheumatism (EULAR) and the German Society of Rheumatology (DGRh) have given no recommendations for using RSO in osteoarthritis. Given the correct indications RSO shows high success rates. Conclusion The effects of RSO with the named secondary side effects last on average for 5 years. Crucial for the success of RSO are the correct indications, the correct timing and combination with other therapeutic procedures, such as surgical synovectomy.
    Full-text · Article · Nov 2015 · Zeitschrift für Rheumatologie

  • No preview · Article · Apr 2015 · Osteoarthritis and Cartilage
  • J. Bertrand · T. Gronau · I. Leifert · T. Pap · W. Rüther

    No preview · Article · Apr 2015 · Osteoarthritis and Cartilage
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    ABSTRACT: The purpose of our study was to analyze the distribution of the major extracellular matrix glycosaminoglycan hyaluronan (HA), its receptor CD44 and cells which influence (re)modeling of the extracellular matrix (T- and B-cells, macrophages, endothelial cells) in menisci obtained from patients suffering from rheumatoid arthritis or osteoarthritis in order to analyze whether these markers could be useful to differentiate between both arthropathies. Human menisci were sampled from patients undergoing total knee arthroplasty. Histological staining (H&E, PAS/Alcian Blue for neutral and charged carbohydrate residues) and (immuno)histochemistry were performed for detection of HA, CD44, sphingosine-1-phosphate receptor 1 (EDG-1) as a marker for endothelial cells, CD3 as a marker for T-cells, CD20 as a marker for B-cells and CD68 as a marker for macrophages. The extracellular matrix in the vascularized zone showed higher amounts of HA as well as acid carbohydrate residues in comparison to the poorly vascularized zones of the meniscus in both disease entities. EDG-1 positive endothelial cells were present in all zones, with fewer cells being detected in the inner zones of the rheumatoid menisci than in the osteoarthritic ones. Macrophages, T- and B-cells as well as CD44-positive cells were more prominent in the vascularized zone of the meniscus than in the poorly vascularized central zone. The distribution patterns of the extracellular matrix components as well as the CD44-positive cells and the inflammation markers in the peripheral zone resembled the distribution in synovial tissue, indicating that both synovia and meniscus were involved in pathological changes in osteoarthritis and rheumatoid arthritis. the distribution of extracellular glycoconjugates and of cells modulating their synthesis showed similar results in both arthropathies, not enabling a differentiation between rheumatoid arthritis and osteoarthritis but underlining the role of these markers in inflammation and degradation in human meniscus. Copyright © 2015 Elsevier GmbH. All rights reserved.
    No preview · Article · Mar 2015 · Acta histochemica
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    ABSTRACT: Enhanced wear resistance of ceramics in general and improved mechanical characteristics of composite ceramics in terms of strength and resistance meet the demands for application in TKA. The aim of this prospective international multi-centre study was to evaluate the 5-year clinical and radiological outcomes of an unconstrained TKA with a composite ceramic femoral component. A total of 107 patients (109 knees) underwent TKA with the MULTIGEN-PLUS Ceramic Knee at seven centres in three European countries. Clinical and radiological assessments were performed preoperatively and postoperatively at 3, 12, 24 and 60months, using HSS, WOMAC, SF-36 and standardised radiographs. Mean HSS and WOMAC increased significantly from 55.1±11.5 (21-83) and 48.1±16.6 (3-90) preoperatively to 85.6±9.6 (49-98) and 73.3±20.4 (17-100) at 60months. Mean SF-36 showed significant improvements in patients' quality of life (49.1±17.6 (12-96) preoperatively versus 67.7±23.1 (12-100) at 60months). Non-progressive radiolucent lines (<1mm) were observed around the femoral component in four cases. Neither implant migration nor loosening were registered. Kaplan-Meier survivorship was 96.0% at 60months (92.1-100%, CI 95%). Five-year implant survival rate of the ceramic knee is comparable to other metallic and ceramic unconstrained TKA systems. Although the assessment of long-term implant survivorship is still pending, the ceramic implants represent a promising solution for patients with allergies against metallic components and furthermore for the general osteoarthritis population due to enhanced wear resistance. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Mar 2015 · The Knee
  • M Seller · S Kahl · S Seitz · W Rüther

    No preview · Article · Dec 2014 · Zeitschrift für Rheumatologie
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    ABSTRACT: This extended classification of joint implant related pathology is a practical histopathologic classification based on defined morphological criteria covering the complete spectrum of pathohistologic changes in periprosthetic tissues. These changes may occur as a consequence of endoprosthetic replacement of large joints and may lead to a reduction in the prosthesis survival rate. We describe the established consensus classification of the periprosthetic membrane, in which aseptic and septic prosthetic loosening can be subdivided into four histological types, as well as histopathological criteria for additional significant pathologies including endoprosthetic-associated arthrofibrosis, particle-induced immunological, inflammatory and toxic mechanisms (adverse reactions), and bone tissue pathologies. These characteristic tissue alterations and their relationships are summarized in the extended classification. Since particle heterogeneity in periprosthetic tissue is high and particle identification is a necessary part of diagnosis, the identification of different types of particles is described in the histopathological particle algorithm. The morphological qualities of prosthetic material particles and the demarcation between abrasion and non-abrasion endogenous particles are also summarized. This feasible classification which is based on low cost standard tissue processing and examination and on well-defined diagnostic criteria is a solid platform for the histological diagnosis of implant associated pathologies providing a stable and reproducible tool for the surgical pathologist. Since this classification is suitable for standardized histopathological diagnostics, it might also provide a useful data set for joint arthroplasty registers, particularly for registers based on so-called routine data.
    Full-text · Article · Dec 2014 · Pathology - Research and Practice
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    ABSTRACT: The term rapid destructive hip disease (RDHD) designates a rare coxarthropathy characterized by a rapid destruction of the femoral head within a few weeks to several months. The etiology and pathogenesis of RDHD are not understood. The goal of this study was to define the histological and histomorphometric hallmarks of RDHD to provide a basis for a deeper understanding of the underlying mechanisms. Fifteen consecutive RDHD patients (mean age 78.9 ± 6.4 years, 14 females) demonstrated the characteristic radiographic appearance of vanishing femoral head bone stock without signs of reactive anabolic changes. Histologic and histomorphometric analyses revealed severe bone resorption with significantly increased numbers of morphologically altered giant osteoclasts, the formation of giant cell granulomas both in bone marrow and the synovium and significantly increased osteoblast numbers and osteoid as compared to controls with primary osteoarthritis (OA). These results suggest that in RDHD, an unknown stimulus leads to a massive activation of osteoclasts and this in turn provokes a reactive increase in osteoblast activity that is too weak to counteract the rapid destruction of the hip, thus providing a rationale for a prospective systematic search for the stimuli upstream of the massively increased osteoclast activation in RDHD. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
    No preview · Article · May 2014 · Journal of Orthopaedic Research
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    ABSTRACT: Chronic environmental fluoride exposure under calcium stress causes fragility fractures due to osteoporosis and bone quality deterioration, at least in sheep. Proof of skeletal fluorosis, presenting without increased bone density, calls for a review of fracture incidence in areas with fluoridated groundwater, including an analysis of patients with low bone mass. Understanding the skeletal effects of environmental fluoride exposure especially under calcium stress remains an unmet need of critical importance. Therefore, we studied the skeletal phenotype of sheep chronically exposed to highly fluoridated water in the Kalahari Desert, where livestock is known to present with fragility fractures. Dorper ewes from two flocks in Namibia were studied. Chemical analyses of water, blood and urine were executed for both cohorts. Skeletal phenotyping comprised micro-computer tomography (μCT), histological, histomorphometric, biomechanical, quantitative backscattered electron imaging (qBEI) and energy-dispersive X-ray (EDX) analysis. Analysis was performed in direct comparison with undecalcified human iliac crest bone biopsies of patients with fluoride-induced osteopathy. The fluoride content of water, blood and urine was significantly elevated in the Kalahari group compared to the control. Surprisingly, a significant decrease in both cortical and trabecular bones was found in sheep chronically exposed to fluoride. Furthermore, osteoid parameters and the degree and heterogeneity of mineralization were increased. The latter findings are reminiscent of those found in osteoporotic patients with treatment-induced fluorosis. Mechanical testing revealed a significant decrease in the bending strength, concurrent with the clinical observation of fragility fractures in sheep within an area of environmental fluoride exposure. Our data suggest that fluoride exposure with concomitant calcium deficit (i) may aggravate bone loss via reductions in mineralized trabecular and cortical bone mass and (ii) can cause fragility fractures and (iii) that the prevalence of skeletal fluorosis especially due to groundwater exposure should be reviewed in many areas of the world as low bone mass alone does not exclude fluorosis.
    Full-text · Article · Apr 2014 · Osteoporosis International
  • S. Seitz · W. Rüther

    No preview · Article · Apr 2014 · Aktuelle Rheumatologie
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    ABSTRACT: A number of unexpected molecules were recently identified as products of osteoblasts, linking bone homeostasis to systemic energy metabolism. Here we identify the lipolytic enzyme hepatic lipase (HL, encoded by Lipc) as a novel cell-autonomous regulator of osteoblast function. In an unbiased genome-wide expression analysis, we find Lipc to be highly induced upon osteoblast differentiation, verified by quantitative Taqman analyses of primary osteoblasts in vitro and of bone samples in vivo. Functionally, loss of HL in vitro leads to increased expression and secretion of osteoprotegerin (OPG), while expression of some osteoblast differentiation makers is impaired. When challenging energy metabolism in a diet-induced obesity (DIO) study, lack of HL leads to a significant increase in bone formation markers and a decrease in bone resorption markers. Accordingly, in the DIO setting, we observe in Lipc(-/-) animals but not in wild-type controls a significant increase in lumbar vertebral trabecular bone mass and formation rate as well as in femoral trabecular bone mass and cortical thickness. Taken together, we demonstrate that HL expressed by osteoblasts has an impact on osteoblast OPG expression and that lack of HL leads to increased bone mass in DIO. These data provide a novel and completely unexpected molecular link in the complex interplay of osteoblasts and systemic energy metabolism.
    Full-text · Article · Jan 2014 · Bone
  • T R Liebs · L Nasser · W Herzberg · W Rüther · J Hassenpflug
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    ABSTRACT: Several factors have been implicated in unsatisfactory results after total hip replacement (THR). We examined whether femoral offset, as measured on digitised post-operative radiographs, was associated with pain after THR. The routine post-operative radiographs of 362 patients (230 women and 132 men, mean age 70.0 years (35.2 to 90.5)) who received primary unilateral THRs of varying designs were measured after calibration. The femoral offset was calculated using the known dimensions of the implants to control for femoral rotation. Femoral offset was categorised into three groups: normal offset (within 5 mm of the height-adjusted femoral offset), low offset and high offset. We determined the associations to the absolute final score and the improvement in the mean Western Ontario and McMaster Universities osteoarthritis index (WOMAC) pain subscale scores at three, six, 12 and 24 months, adjusting for confounding variables. The amount of femoral offset was associated with the mean WOMAC pain subscale score at all points of follow-up, with the low-offset group reporting less WOMAC pain than the normal or high-offset groups (six months: 7.01 (sd 11.69) vs 12.26 (sd 15.10) vs 13.10 (sd 16.20), p = 0.006; 12 months: 6.55 (sd 11.09) vs 9.73 (sd 13.76) vs 13.46 (sd 18.39), p = 0.010; 24 months: 5.84 (sd 10.23) vs 9.60 (sd 14.43) vs 13.12 (sd 17.43), p = 0.004). When adjusting for confounding variables, including age and gender, the greatest improvement was seen in the low-offset group, with the normal-offset group demonstrating more improvement than the high-offset group. Cite this article: Bone Joint J 2014;96-B:36-42.
    No preview · Article · Jan 2014 · Bone and Joint Journal
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    ABSTRACT: When it comes to endoprosthesis pathologies, for example implant-allergic/toxic problems, as a cause of implant failure, particle identification has an important role to play in the histopathological diagnostics of the neosynovial/periprosthetic membrane (synovial-like interface membrane, SLIM). The variability of materials in endoprosthetics and differences in particle pathogenesis explain the particle heterogeneity that hampers the diagnostic identification of particles. For this reason, a histopathological particle algorithm has been developed that, with minimal methodical complexity, offers a guide to particle identification. Light microscopic-morphological as well as enzyme-histochemical characteristics and polarization-optical proporties have been defined. Particles are characterized in accordance with a dichotomous principle. Based on these criteria, identification and validation of the particles was carried out in 105 joint endoprosthesis pathological cases. A particle score is proposed that summarizes the most important information for the orthopedist.
    No preview · Article · Jan 2014 · Seminars in Arthroplasty

  • No preview · Article · Dec 2013
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    ABSTRACT: Ceramic components in total knee arthroplasty (TKA) are evolving. We analyze the first case of BIOLOX delta ceramic femoral component fracture. A longitudinal midline fracture in the patellar groove was present, with an intact cement mantle and no bony defects. Fractographic analysis with laser scanning microscopy and white light interferometry showed no evidence of arrest lines, hackles, wake hackles, material flaws, fatigue or crack propagation. Analysis of periprosthetic tissues with Fourier-transform infrared (FT-IR) microscopy, contact radiography, histology, and subsequent digestion and high-speed centrifugation did not show ceramic debris. A macrophage-dominated response was present around polyethylene debris. We conclude that ceramic femoral component failure in this case was related to a traumatic event. Further research is needed to determine the suitability of ceramic components in TKA.
    Full-text · Article · Nov 2013 · The Journal of arthroplasty
  • Andreas Niemeier · Björn Behrmann · Bernd Fink · Wolfgang Rüther
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    ABSTRACT: Background Little is known about the long-term results of shoulder arthroplasty in patients with rheumatoid arthritis (RA). The goal of the present study was the clinical and radiological evaluation of a cemented resurfacing of the humeral head in patients with RA after a minimum follow-up of 10 years. Patients and methods From 1997–2000 a total of 42 cemented humeral head resurfacing hemi-arthroplasties were performed in 35 patients with RA (average age 61 years) and included in a prospective long-term observational study with follow-up evaluations at 3, 12, > 60 and > 120 months postoperatively. At an average of 131 ± 21 months 16 shoulders (14 patients, average age 70.9 years) could be evaluated by the Constant Murley score (CMS) and standard radiographs. For seven patients who were unable to attend hospital a CMS self-evaluation form was used and X-rays were made elsewhere and sent for analysis. Results The average total CMS was 62.6 ± 10.6 points (pre-operative 20.8 ± 8.3 points) and 88 % of the patients were satisfied or very satisfied with the results. Radiographically, a progressive proximal migration of the center of rotation and a continuous increase of the glenoid depth were observed between 3 and 130 months post-operatively. However, the radiographic progression did not correlate with either CMS values or with patient satisfaction. Conclusions The cemented humeral head resurfacing as a hemi-arthroplasty represents a valuable option for the treatment of advanced shoulder RA in elderly patients.
    No preview · Article · Sep 2013 · Obere Extremität

Publication Stats

3k Citations
447.33 Total Impact Points


  • 1997-2015
    • University Medical Center Hamburg - Eppendorf
      • Department of Orthopaedics
      Hamburg, Hamburg, Germany
  • 2013-2014
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
    • Orthopädische Klinik Markgröningen
      Ludwigsburg, Baden-Württemberg, Germany
  • 2011-2013
    • University Hospital Magdeburg
      Magdeburg, Saxony-Anhalt, Germany
    • Asklepios Klinikum Bad Abbach
      Abach, Bavaria, Germany
  • 1996-2013
    • University of Hamburg
      • Department of Orthopaedics
      Hamburg, Hamburg, Germany
  • 2003-2011
    • Schön Klinik Bad Bramstedt
      Chiemsee, Bavaria, Germany
    • Orthopädische Universitätsklinik Friedrichsheim
      Frankfurt, Hesse, Germany
  • 2010
    • University of Rostock
      • Orthopädische Klinik und Poliklinik
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2006
    • Evangelisches Waldkrankenhaus Spandau
      Berlin, Germany
  • 2004
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
    • Charité Universitätsmedizin Berlin
      • Institute of Pathology
      Berlin, Land Berlin, Germany
  • 1993-2003
    • Heinrich-Heine-Universität Düsseldorf
      • Orthopädische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2002
    • Christian-Albrechts-Universität zu Kiel
      Kiel, Schleswig-Holstein, Germany
    • Medical School Hamburg
      Hamburg, Hamburg, Germany