TY - JOUR A1 - Wimmer, Matthias D. A1 - Randau, Thomas M. A1 - Deml, Moritz C. A1 - Ascherl, Rudolf A1 - Forst, Raimund A1 - Gravius, Nadine A1 - Wirtz, Dieter A1 - Gravius, Sascha T1 - Impaction grafting in the femur in cementless modular revision total hip arthroplasty: a descriptive outcome analysis of 243 cases with the MRP-TITAN revision implant JF - BMC Musculoskeletal Disorders N2 - Background: We present a descriptive and retrospective analysis of revision total hip arthroplasties (THA) using the MRP-TITAN stem (Peter Brehm, Weisendorf, GER) with distal diaphyseal fixation and metaphyseal defect augmentation. Our hypothesis was that the metaphyseal defect augmentation (Impaction Bone Grafting) improves the stem survival. Methods: We retrospectively analyzed the aggregated and anonymized data of 243 femoral stem revisions. 68 patients with 70 implants (28.8%) received an allograft augmentation for metaphyseal defects; 165 patients with 173 implants (71.2%) did not, and served as controls. The mean follow-up was 4.4 +/- 1.8 years (range, 2.1-9.6 years). There were no significant differences (p > 0.05) between the study and control group regarding age, body mass index (BMI), femoral defects (types I-III as described by Paprosky), and preoperative Harris Hip Score (HHS). Postoperative clinical function was evaluated using the HHS. Postoperative radiologic examination evaluated implant stability, axial implant migration, signs of implant loosening, periprosthetic radiolucencies, as well as bone regeneration and resorption. Results: There were comparable rates of intraoperative and postoperative complications in the study and control groups (p > 0.05). Clinical function, expressed as the increase in the postoperative HHS over the preoperative score, showed significantly greater improvement in the group with Impaction Bone Grafting (35.6 +/- 14.3 vs. 30.8 +/- 15.8; p <= 0.05). The study group showed better outcome especially for larger defects (types II C and III as described by Paprosky) and stem diameters >= 17 mm. The two groups did not show significant differences in the rate of aseptic loosening (1.4% vs. 2.9%) and the rate of revisions (8.6% vs. 11%). The Kaplan-Meier survival for the MRP-TITAN stem in both groups together was 93.8% after 8.8 years. [Study group 95.7% after 8.54 years; control group 93.1% after 8.7 years]. Radiologic evaluation showed no significant change in axial implant migration (4.3% vs. 9.3%; p = 0.19) but a significant reduction in proximal stress shielding (5.7% vs. 17.9%; p < 0.05) in the study group. Periprosthetic radiolucencies were detected in 5.7% of the study group and in 9.8% of the control group (p = 0.30). Radiolucencies in the proximal zones 1 and 7 according to Gruen occurred significantly more often in the control group without allograft augmentation (p = 0.05). Conclusion: We present the largest analysis of the impaction grafting technique in combination with cementless distal diaphyseal stem fixation published so far. Our data provides initial evidence of improved bone regeneration after graft augmentation of metaphyseal bone defects. The data suggests that proximal metaphyseal graft augmentation is beneficial for large metaphyseal bone defects (Paprosky types IIC and III) and stem diameters of 17 mm and above. Due to the limitations of a retrospective and descriptive study the level of evidence remains low and prospective trials should be conducted. KW - prosthesis KW - replacement KW - collarless KW - surgery KW - allografts KW - porous-coated stems KW - femoral revision KW - roentgenographic assessment KW - tapered stem KW - follow-up KW - modular KW - revision KW - hip KW - arthroplasty KW - impaction bone grafting Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122061 SN - 1471-2474 VL - 14 IS - 19 ER - TY - JOUR A1 - Ljunggren, Osten A1 - Barrett, Annabel A1 - Stoykov, Ivaylo A1 - Langdahl, Bente L. A1 - Lems, Willem F. A1 - Walsh, J. Bernard A1 - Fahrleitner-Pammer, Astrid A1 - Rajzbaum, Gerald A1 - Jakob, Franz A1 - Karras, Dimitrios A1 - Marin, Fernando T1 - Effective osteoporosis treatment with teriparatide is associated with enhanced quality of life in postmenopausal women with osteoporosis: the European Forsteo Observational Study JF - BMC Musculoskeletal Disorders N2 - Background: To describe changes in health-related quality of life (HRQoL) of postmenopausal women with osteoporosis treated with teriparatide for up to 18 months and followed-up for a further 18 months, and to assess the influence of recent prior and incident fractures. Methods: The European Forsteo Observational Study (EFOS) is an observational, prospective, multinational study measuring HRQoL using the EQ-5D. The primary objective was to assess changes in HRQoL during 36 months in the whole study population. A secondary post-hoc analysis examined fracture impact on HRQoL in four subgroups classified based on recent prior fracture 12 months before baseline and incident clinical fractures during the study. Changes from baseline were analysed using a repeated measures model. Results: Of the 1581 patients, 48.4% had a recent prior fracture and 15.6% of these patients had an incident fracture during follow-up. 10.9% of the 816 patients with no recent prior fracture had an incident fracture. Baseline mean EQ-VAS scores were similar across the subgroups. In the total study cohort (n = 1581), HRQoL (EQ-VAS and EQ-5D index scores) improved significantly from baseline to 18 months and this improvement was maintained over the 18-month post-teriparatide period. Improvements were seen across all five EQ-5D domains during teriparatide treatment that were maintained after teriparatide was discontinued. Subjects with incident clinical fractures had significantly less improvement in EQ-VAS than those without incident fractures. Recent prior fracture did not influence the change in EQ-VAS during treatment. Conclusions: EFOS is the first longitudinal study in women with severe postmenopausal osteoporosis in the real world setting to show a substantial improvement in HRQoL during teriparatide treatment that was sustained during subsequent treatment with other medications. The increase in HRQoL was lower in the subgroups with incident fracture but was not influenced by recent prior fracture. The results should be interpreted in the context of the design of an observational study. KW - fracture KW - osteoporosis KW - quality of life KW - teriparatide KW - EQ-5D KW - database KW - alendronate KW - persistence KW - metaanalysis KW - prevalent fractures KW - bone-mineral density KW - vertebral fractures KW - back pain KW - impact KW - responsiveness Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122057 SN - 1471-2474 VL - 14 IS - 251 ER - TY - JOUR A1 - Wehrle, Esther A1 - Liedert, Astrid A1 - Heilmann, Aline A1 - Wehner, Tim A1 - Bindl, Ronny A1 - Fischer, Lena A1 - Haffner-Luntzer, Melanie A1 - Jakob, Franz A1 - Schinke, Thorsten A1 - Amling, Michael A1 - Ignatius, Anita T1 - The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice JF - Disease Models & Mechanisms N2 - Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81%) and bone formation (-80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations. KW - fracture healing KW - LMHFV KW - oestrogen receptor signalling KW - whole-body vibration KW - Wnt-signalling Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121109 VL - 8 ER - TY - JOUR A1 - Boelch, Sebastian Philipp A1 - Barthel, Thomas A1 - Goebel, Sascha A1 - Rudert, Maximilian A1 - Plumhoff, Piet T1 - Calcinosis universalis - a rare case with classical presentation JF - Case Reports in Orthopedics N2 - Juvenile Dermatomyositis (JDM) is a rare autoimmune disease in children and adolescents. In these patients calcinosis might be the most characteristic symptom. However there are only few reported cases of intramuscular calcinosis in Dermatomyositis. We report a case of calcinosis universalis (CU) of the elbow in JDM successfully treated with broaching. The patient, a 24-year-old woman, suffered from a long history of JDM. On examination she presented with a fistula lateral to the olecranon and pain of the right elbow joint. Plain X-rays displayed a diffuse pattern of multiple periarticular, subcutaneous, and intramuscular calcifications. The patient underwent surgery for histological and microbiological sampling as well as broaching. Intraoperatively sinus formation and subfascial hard calcium deposition were found. Due to the risk of collateral tissue damage, incomplete broaching was performed. A local infection with Staphylococcus was diagnosed and treated with antibiotics. On six-week and 30-month follow-up the patient was free of pain and had very good function. Calcifications on standard radiographs had almost resolved entirely. This case report gives a summary on calcinosis in Dermatomyositis and adds a new case of recalcitrant CU to the literature. Broaching surgery proved to be a reliable treatment option in symptomatic calcinosis. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126300 VL - 2015 ER - TY - JOUR A1 - Boelch, S. P. A1 - Jansen, H. A1 - Meffert, R. H. A1 - Frey, S. P. T1 - Six Sesamoid Bones on Both Feet: Report of a Rare Case JF - Journal of Clinical and Diagnostic Research N2 - There is a variation of the total number of distinct bones in the human in the literature. This difference is mainly caused by the variable existence of sesamoid bones. Sesamoid bones at the first MTP are seen regularly. In contrast additional sesamoid bones at the divond to fifth MTP are rare. We report a case of additional sesamoid bones at every metatarsophalangeal joint (MTP) of both feet. A 22-year-old female Caucasian presented with weight-dependent pain of the divond MTP of the left foot. In the radiographs of both feet additional sesamoid bones at every MTP could be seen. This case reports a very rare variation in human anatomy. A similar case has not been displayed to the academic society and therefore should be acknowledged. KW - anatomy KW - genetics KW - variation Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126073 VL - 9 IS - 8 ER - TY - THES A1 - Lüker, Anna-Lena T1 - Funktionelle Ergebnisse der zweizeitigen Hüftendoprothesenrevision bei periprothetischer Infektion T1 - Two-stage Cementless Revision of Infected Hip Endoprotheses N2 - Diese retrospektive Studie analysierte die Ergebnisse der zweizeitigen, unzementierten Revision bei periprothetischer Infektion der Hüftendoprothese. Dabei wurde besonders auf die Eradikationsrate, die Rate septischer und aseptischer Rezidive, die Standzeit des Spacers, die Art der lokalen Antibiotikatherapie und die postoperativen funktionellen Ergebnisse eingegangen. Die Studie umfasst die klinische Nachuntersuchung der Patienten unter Verwendung des Harris Hip Scores, sowie die radiologische Kontrolle des Sitzes der Hüftendoprothese und die laborchemische Überprüfung der Entzündungsparameter. Insgesamt wurden 52 Patienten von 2000 bis 2007 in der Orthopädischen Klinik König Ludwig Haus in Würzburg mit einer zweizeitigen Revision der Hüftendoprothese bei periprothetischer Infektion versorgt. 36 dieser 52 Patiente konnten 2008 im Rahmen dieser Studie nachuntersucht werden. Dabei betrug die mittlere Nachuntersuchungszeit 42 Monate. Das mittlere Patientenalter war 66,3 Jahre. 81% der Patienten hatten zum Zeitpunkt der Infektion internistische oder orthopädische Grunderkrankungen, oftmals auch multiple, welche das Risiko für die Entstehung einer periprothetischen Infektion erhöhten. 47% der Patienten waren zum Zeitpunkt der zweizeitigen Revision bereits mehr als einmal an der Hüfte voroperiert, die Hälfte davon mussten aufgrund von septischen Komplikationen bereits revidiert werden. 10% der Patienten hatten eine akute Frühinfektion, 90% ein chronisches Geschehen (51% low-grade Infekt, 39% Spätinfekt). Die häufigsten bakteriellen Erreger waren Staphylococcus epidermidis (39%), Staphylococcus aureus (14%), Streptococcus agalactiae (14%) und weitere koagulase negative Staphylokokken (11%). Bei zwei Patienten konnten Methicillin-resistente Keime isoliert werden. Insgesamt waren 25% der Infektionen Mischinfektionen. Bei drei Patienten konnte kein Keim nachgewiesen werden. Diese Patienten wurden anhand ihrer eindeutigen klinischen Symptome bei gleichzeitiger Erhöhung der Entzündungsparameter behandelt. Zur besseren Eradikation der chronischen, persistierenden und komplizierten Infektionen wurden die Patienten mit einer zweizeitigen Revision der Hüftendoprothese behandelt. Hierbei wurde nach Explantation der infizierten Prothese mit ausführlichem chirurgischen Debridement ein - soweit möglich - patientenspezifischer antibiotikaimprägnierter Spacer vor Implantation der Zweitprothese eingesetzt. Diese Methode dient einerseits der Vermeidung einer Girdlestone-Situation und der damit verbundenen Komplikationen, andererseits ermöglicht der Spacer eine kalkulierte und hoch dosierte lokale, weitreichende und patientenspezifische Antibiotikatherapie (Kombinationstherapie) zur sicheren Eradikation der Infektion. Die Standzeit (zwischen vier und neunzehn Wochen, Mittelwert von 9 Wochen) des Spacers wurde individuell anhand des klinischen Bildes und dem Rückgang der laborchemischen Entzündungsparameter entschieden. Die Eradiaktionsrate durch die zweizeitige Revision lag in dieser Studie bei 94%. Lediglich zwei Patienten zeigten eine persistierende bzw. wiederkehrende Infektion im Verlauf und mussten erneut revidiert werden. Es konnten keine aseptische Komplikationen, insbesondere keine Prothesenlockerung oder –sinterung nachgewiesen werden. Sechs Patienten mussten aufgrund anderer, nicht Infekt-assoziierter Komplikationen im Verlauf erneut operiert werden. Die funktionellen Ergebnisse wurden anhand des Harris Hip Scores untersucht. Der Median lag bei 74 Punkten. Somit lässt sich auch funktionell ein insgesamt zufriedenstellendes Ergebnis präsentieren. Schlussfolgernd ist die Aussage möglich, dass die zweizeitige, unzementierte Revision unter Verwendung eines antibiotikabeladenen Spacers eine zuverlässige Methode zur Behandlung auch chronischer und komplizierter periprothetischer Infektionen der Hüftendoprothese ist. Insgesamt konnten mit einer Eradikationsrate von 94% und keinen aseptischen Rezidiven gute Ergebnisse erzielt werden. Bezüglich der Antibiotikatherapie lässt sich eine kalkulierte, lokale Kombinationstherapie zur optimalen Eradikation der Infektion empfehlen. Des Weiteren empfiehlt es sich, die Standzeit des Spacers ebenfalls individuell bis zum klinischen und laborchemischen Nachweis der Infektfreiheit festzulegen. Dadurch wird eine ausreichende Dauer der lokalen Antibiotikatherapie gewährleistet, und gleichzeitig die Standzeit des Spacers auf eine möglichst kurze Zeit beschränkt um eine frühe Mobilisation und gute Funktionalität und Zufriedenheit des Patienten zu erreichen. N2 - Background: Periprosthetic infections remain a rare but potentially severe complication of hip arthroplasty. Based on the type and duration of the infection, numerous management options have been described. Although the two-stage revision has emerged as the mainstay treatment choice for chronic infections, there remains no clear consensus on the optimal management of periprosthetic infections. Methods: 36 patients were retrospectively analyzed following a two-stage cementless exchange with the use of an antibiotic-impregnated spacer following periprosthetic infection. 90% of these patients presented with a chronic infection. The treatment consisted of the use of a patient-specific combined local and systemic antibiotic therapy, with a mean spacer duration of 9 weeks (range 4 - 19 weeks) based on clinical and laboratory parameters. Clinical, laboratory, and radiologic outcomes were evaluated with an average follow up of 42 months (range 12 months - 8 years). 81% of patients had underlying orthopedic or medical conditions increasing their risk for periprosthetic infections. 47% had undergone previous revision surgery, of which 47% had undergone previous septic revision surgery. The most common pathogens isolated included various strains of staphylococcal species (64%). MRSA was isolated in two of these patients and 25% of isolates grew out multiple pathogens. Results: Successful eradication was achieved in 94% of patients. Two patients required additional revisions. One patient had a recurring infection that was successfully eradicated following repeat exchange revision. Another patient proceeded to have a complicated course requiring several revision surgeries and continued to exhibit signs of persistent infection at time of follow up. None of the patients showed signs of aseptic loosening. Postoperatively, the median Harris Hip Score was 74 points. Conclusion: The two-stage cementless revision of septic hip arthroplasty using an antibiotic-impregnated spacer is a reliable method for the treatment of chronic and complicated periprosthetic infections, with successful eradication seen in 94% of our patients and no aseptic loosening documented. We recommend patient-specific local and systemic antibiotic management until clinical and laboratory eradication is confirmed in order to achieve optimal duration of antibiotic therapy while simultaneously minimizing the duration of the spacer to improve patient mobility and satisfaction. KW - periprothetische Infektion KW - Hüftendoprothese KW - Spacer KW - zementfrei KW - Revision KW - zweizeitig KW - unzementiert KW - hip arthroplasty KW - two-stage revision KW - spacer KW - cementless KW - infected hip endoprothesis Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123829 ER - TY - JOUR A1 - Steinert, Andre F. A1 - Kunz, Manuela A1 - Prager, Patrick A1 - Göbel, Sascha A1 - Klein-Hitpass, Ludger A1 - Ebert, Regina A1 - Nöth, Ulrich A1 - Jakob, Franz A1 - Gohlke, Frank T1 - Characterization of bursa subacromialis-derived mesenchymal stem cells JF - Stem Cell Research & Therapy N2 - Introduction The bursa subacromialis (BS) provides the gliding mechanism of the shoulder and regenerates itself after surgical removal. Therefore, we explored the presence of mesenchymal stem cells (MSCs) within the human adult BS tissue and characterized the BS cells compared to MSCs from bone marrow (BMSCs) on a molecular level. Methods BS cells were isolated by collagenase digest from BS tissues derived from patients with degenerative rotator cuff tears, and BMSCs were recovered by adherent culture from bone-marrow of patients with osteoarthritis of the hip. BS cells and BMSCs were compared upon their potential to proliferate and differentiate along chondrogenic, osteogenic and adipogenic lineages under specific culture conditions. Expression profiles of markers associated with mesenchymal phenotypes were comparatively evaluated by flow cytometry, immunohistochemistry, and whole genome array analyses. Results BS cells and BMSCs appeared mainly fibroblastic and revealed almost similar surface antigen expression profiles, which was \(CD44^+, CD73^+, CD90^+, CD105^+, CD106^+\),\(STRO-1^+, CD14^−, CD31^−, CD34^− , CD45^−, CD144^−\). Array analyses revealed 1969 genes upregulated and 1184 genes downregulated in BS cells vs. BMSCs, indicating a high level of transcriptome similarity. After 3 weeks of differentiation culture, BS cells and BMSCs showed a similar strong chondrogenic, adipogenic and osteogenic potential, as shown by histological, immunohistochemical and RT-PCR analyses in contrast to the respective negative controls. Conclusions Our in vitro characterizations show that BS cells fulfill all characteristics of mesenchymal stem cells, and therefore merit further attention for the development of improved therapies for various shoulder pathologies. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126446 VL - 6 IS - 114 ER - TY - THES A1 - Leiblein, Maximilian T1 - MPFL-Rekonstruktion mit autologer Gracilissehne bei Patellaluxation T1 - MPFL-reconstruction with autologous gracilis tendon graft for patella dislocation N2 - Die patellofemorale Instabilität bzw. die Patellaluxation hat eine Inzidenz von 7 - 49 pro 100.000 Einwohner und verursacht 2-3% aller Knieverletzungen. Über 10% der muskuloskelettalen Symptome werden durch die patellofemorale Instabilität verursacht. Die Ätiologie der Patellaluxation ist stets multifaktoriell, als Risikofaktoren gelten jedoch die Trochleadysplasie, ein erhöhter Patellatilt, die Patella alta, ein erhöhter TTTG- Abstand und die Beschaffenheit des Ligamentum patellofemorale mediale. Zur Therapie eignen sich je nach individueller Symptomatik und Risikofaktoren sowohl konservative als auch operative Maßnahmen. In den letzten Jahren wurden zahlreiche Operationsmethoden und -techniken mit unterschiedlichem Ansatz und Erfolg beschrieben. Bei der hier untersuchten Technik wird das Ligamentum patellofemorale mediale mit Hilfe einer autologen Sehnenplastik (Sehne des M. gracilis) und einer Weichteilfixation an der patellaren Insertion ohne Einbringung weiteren Fremdmaterials anatomisch rekonstruiert. Das Ziel dieser prospektiven Verlaufsbeobachtung war es, die postoperative Entwicklung von Funktion, Stabilität und Schmerzen, sowie die Beurteilung der Einschränkung des Gesamtgesundheitszustandes der Patienten nach MPFL-Rekonstruktion zu untersuchen. Dazu wurden 27 Patienten im Alter zwischen zwölf und 45 Jahren, die zwischen Januar 2011 und November 2012 wegen habitueller bzw. habituell rezidivierender und in einem Fall traumatischer Patellaluxation operiert wurden, nach festgesetzten Kriterien in die Studie eingeschlossen und über den Zeitraum von zwölf Monaten postoperativ nachuntersucht. Die Ergebnisse wurden anhand des „Kujala Anterior Knee Pain Score“ und des „Validierten Fragebogen über Kniebeschwerden nach F. Flandry“ erhoben. Außerdem wurde eine standardisierte körperliche Untersuchung durchgeführt. Von den 27 eingeschlossenen Patienten konnten 24 über die volle Dauer nachuntersucht werden, drei Patienten nur über sechs Monate postoperativ. Die Ergebnisse im Kujala- Score verbesserten sich von durchschnittlich 72 Punkten (IQR = 35) präoperativ auf 95 Punkte (IQR = 9,25) nach zwölf Monaten. Nach bereits sechs Monaten war die Verbesserung hochsignifikant. Die Ergebnisse des Flandry-Score zeigten eine Verbesserung von 65,7 Punkten (IQR = 29,5) präoperativ auf 89,9 Punkte (IQR = 7,75) nach zwölf Monaten. Auch hier war die Verbesserung bereits nach einem halben Jahr hochsignifikant. Postoperativ gaben die Patienten am häufigsten Schwierigkeiten bei der Hocke und beim Knien an. Weitere Einschränkungen der Alltagsaktivitäten traten sechs Monate postoperativ nicht mehr auf. Auch die Häufigkeit und Intensität der Schmerzen aufgrund des Kniegelenkes entwickelten sich nach Ablauf eines halben Jahres sehr gut. Probleme bei sportlichen Aktivitäten wurden nach sechs Monaten nicht mehr angegeben, allerdings war bei 51,9% der Patienten noch nach einem Jahr eine Atrophie der Quadrizepsmuskulatur festzustellen. Bereits nach drei Monaten wurde kein „Giving Way“ mehr berichtet. Bei den 27 untersuchten Patienten trat insgesamt eine traumatische Reluxation auf. Weitere Komplikationen wurden nicht bekannt. Die subjektive Beurteilung des Gesamtgesundheitszustandes verbesserte sich bereits ein halbes Jahr nach der Operation hochsignifikant im Vergleich zum präoperativen Status. Die MPFL-Rekonstruktion mit autologer Gracilissehne und Weichteilfixation zeigte bezüglich Reluxationen und Stabilität nach einem Jahr sehr gute Ergebnisse. Die Rehabilitation und Wiederaufnahme von sportlichen Aktivitäten verlief zügig. Die Resultate dieser Untersuchung sind vielversprechend, es wird jedoch noch Studien mit größeren Patientenzahlen und längerem Nachuntersuchungszeitraum geben müssen. N2 - Patellofemoral instability, respectively dislocation of the patella is reported with an incidence of 7-49/100000 and causes 2-3 per cent of all knee injuries. More than 10 per cent of all musculoskeletal symptoms are caused by patellofemoral instability. The etiology of patella dislocation is multifactorial, common risk factors are a dysplastic trochlea, patella alta, increased patella tilt and TTTG-distance as well as the condition of the medial patellofemoral ligament. Depending on individual symptoms and risk factors therapy can be held conservatively or operatively. Multiple techniques with different approaches and outcomes have been described. With the evaluated technique the medial patellofemoral ligament is reconstructed with an autologous graft (Gracilis-tendon) and anatomically inserted at the patellar site by a soft tissue fixation without further implants. This prospective follow-up aims to examine postoperative development of function, stability and pain of the injured knee as well as the patient’s subjective evaluation of their condition. Between January 2011 and November 2012 27 patients between 12 and 45 years of age who underwent surgical reconstruction due to recurrent dislocation of the patella were included in the study following the before stated inclusion criteria. The follow up was 12 months. Besides the “Kujala Anterior Knee Pain Score” and “Flandry-Score” a standardized clinical examination was performed. Of the 27 included patients we were able to follow up 24 patients over 12 months, 3 patients dropped out after 6 months postoperatively. Results of “Kujala Anterior Knee Pain Score” improved from 72 points (IQR=35) to 95 points (IQR=9.25) after 12 months with a highly significant improvement after 6 months already. Results of “Flandry-Score” improved from 65.7 points (IQR=29.5) to 89.9 points (IQR=7.75) after 12 months with again a highly significant improvement after 6 months already. Postoperatively the most often stated problems were squatting and kneeling. No further limitations of ADL were reported after 6 months. Intensity and frequency of pain caused by the operated knee was decreasing after 6 months. No problems with sporting activities were reported after 6 months, the quadriceps muscle showed atrophy in 51.9 per cent after 12 months though. Already after 3 months no giving way was reported. Within the 27 examined patients one traumatic re-dislocation occurred. No further complications could be found. Subjective evaluation of the patient’s health condition improved highly significant after 6 months compared to the preoperatively reported state. Reconstruction of the medial patellofemoral ligament with autologous gracilis graft and soft tissue fixation showed very good results concerning re-dislocations and stability after one year. Rehabilitation and resumption of sporting activities proceeded quickly. The reported results are promising, still further studies with higher numbers of patients and longer follow up are will be needed. KW - Patellaluxation KW - MPFL-Rekonstruktion Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124273 ER - TY - JOUR A1 - Walsh, J. Bernard A1 - Lems, Willem F. A1 - Karras, Dimitrios A1 - Langdahl, Bente L. A1 - Ljunggren, Osten A1 - Fahrleitner-Pammer, Astrid A1 - Barrett, Annabel A1 - Rajzbaum, Gerald A1 - Jakob, Franz A1 - Marin, Fernando T1 - Effectiveness of Teriparatide in Women Over 75 Years of Age with Severe Osteoporosis: 36-Month Results from the European Forsteo Observational Study (EFOS) JF - Calcified Tissue International N2 - This predefined analysis of the European Forsteo Observational Study (EFOS) aimed to describe clinical fracture incidence, back pain, and health-related quality of life (HRQoL) during 18 months of teriparatide treatment and 18 months post-teriparatide in the subgroup of 589 postmenopausal women with osteoporosis aged ≥75 years. Data on clinical fractures, back pain (visual analogue scale, VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. A repeated-measures model analyzed changes from baseline in back pain VAS and EQ-VAS. During the 36-month observation period, 87 (14.8 %) women aged ≥75 years sustained a total of 111 new fractures: 37 (33.3 %) vertebral fractures and 74 (66.7 %) nonvertebral fractures. Adjusted odds of fracture was decreased by 80 % in the 30 to <36–month interval compared with the first 6-month interval (P < 0.009). Although the older subgroup had higher back pain scores and poorer HRQoL at baseline than the younger subgroup, both age groups showed significant reductions in back pain and improvements in HRQoL postbaseline. In conclusion, women aged ≥75 years with severe postmenopausal osteoporosis treated with teriparatide in normal clinical practice showed a reduced clinical fracture incidence by 30 months compared with baseline. An improvement in HRQoL and, possibly, an early and significant reduction in back pain were also observed, which lasted for at least 18 months after teriparatide discontinuation when patients were taking other osteoporosis medication. The results should be interpreted in the context of an uncontrolled observational study. KW - teriparatide KW - osteoporosis KW - health-related quality of life KW - fracture KW - back pain KW - age Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124746 VL - 90 IS - 5 ER - TY - JOUR A1 - Jakob, Franz A1 - Ebert, Regina A1 - Rudert, Maximilian A1 - Nöth, Ulrich A1 - Walles, Heike A1 - Docheva, Denitsa A1 - Schieker, Matthias A1 - Meinel, Lorenz A1 - Groll, Jürgen T1 - In situ guided tissue regeneration in musculoskeletal diseases and aging JF - Cell and Tissue Research N2 - In situ guided tissue regeneration, also addressed as in situ tissue engineering or endogenous regeneration, has a great potential for population-wide “minimal invasive” applications. During the last two decades, tissue engineering has been developed with remarkable in vitro and preclinical success but still the number of applications in clinical routine is extremely small. Moreover, the vision of population-wide applications of ex vivo tissue engineered constructs based on cells, growth and differentiation factors and scaffolds, must probably be deemed unrealistic for economic and regulation-related issues. Hence, the progress made in this respect will be mostly applicable to a fraction of post-traumatic or post-surgery situations such as big tissue defects due to tumor manifestation. Minimally invasive procedures would probably qualify for a broader application and ideally would only require off the shelf standardized products without cells. Such products should mimic the microenvironment of regenerating tissues and make use of the endogenous tissue regeneration capacities. Functionally, the chemotaxis of regenerative cells, their amplification as a transient amplifying pool and their concerted differentiation and remodeling should be addressed. This is especially important because the main target populations for such applications are the elderly and diseased. The quality of regenerative cells is impaired in such organisms and high levels of inhibitors also interfere with regeneration and healing. In metabolic bone diseases like osteoporosis, it is already known that antagonists for inhibitors such as activin and sclerostin enhance bone formation. Implementing such strategies into applications for in situ guided tissue regeneration should greatly enhance the efficacy of tailored procedures in the future. KW - in situ guided tissue regeneration KW - stem cells KW - scaffolds KW - regenerative medicine KW - mesenchymal tissues Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124738 VL - 347 IS - 3 ER - TY - THES A1 - von Rottkay, Eberhard T1 - Aktivität und Funktionalität nach Hüfttotalendoprothese über einen direkten anterioren Zugang verglichen mit einem gesunden Bevölkerungskollektiv T1 - Activity and functionality after total hip arthroplasty via direct anterior approach compared to a healthy population N2 - Die Möglichkeiten der operativen Rekonstruktion degenerativ veränderter Hüftgelenke sind komplex und vielfältig. Bei den derzeit zur Verfügung stehenden operativen Behandlungsmassnahmen führen die Vor- und Nachteile immer wieder zur Diskussionen und Abwägung der Operationsverfahren. Hierbei stehen sich die rasche postoperative Mobilisierung sowie eine verminderte Rekonvaleszenzzeit mit den diskutierten Nachteilen einer schlechteren Übersichtlichkeit und damit verbundenen Fehlimplantationen gegenüber. Dies und die damit verbundene volkswirtschaftliche Bedeutung sind ein ständiger Ausgangspunkt für das Bemühen den optimalen Zugangsweg zu etablieren. Daher stellte das von Smith-Peterson 1949 publizierte Verfahren einen Meilenstein in der operativen Therapie dar. Hierdurch konnten zum einen die operationstechnischen Vorteile wie auch das volkswirtschaftliche Begehren nach kürzeren postoperativen Verweildauern vereint werden. Die Modifizierung dieses Zugangsweges hat sich bereits in einer großen Anzahl prospektiver Studien als zuverlässiges Rekonstruktionsverfahren etabliert und erfüllt zudem auch die Anforderungen der heutigen Medizin nach ästhetisch schönen Ergebnissen. In der vorliegenden Arbeit wurde eine prospektive Fallstudie des direkten anterioren Zugangs mit einem gesunden Vergleichskollektiv durchgeführt. Mit dem Ziel, die Aktivität ein Jahr postoperativ nach Implantation einer HTEP mit gesunden Probanden zu vergleichen. Von Januar 2009 bis Mai 2011 wurden insgesamt 77 Patienten und 59 Probanden in die Studie aufgenommen. Als Vergleichswerte wurde zum einen die klinische wie auch die radiologische Untersuchung herangezogen. In der klinischen Untersuchung zeigte sich insgesamt ein signifikanter Anstieg der untersuchten Scores im Vergleich mit den präoperativen Ergebnissen bei den Operierten. Im Vergleich zu den Probanden erzielen die Patienten ein Jahr nach HTEP teilweise noch schlechtere Werte in dem Bewegungsumfang und den Aktivitätsniveaus welche mittels der Auswertung des Stepwatches, des TWB und des Arzt-Patienten-Fragebogens erhoben wurden. Die radiologische Bewertung diente zur Feststellung der Positionierung der HTEP. Mit guten Positionierungen durch den direkten anterioren Zugang. Die Bewertung der Funktionalität zwischen den beiden Gruppen erfolgte durch den HHS, XSFMA- D und den Arzt-Patientenfragenbogen. Hierbei konnten ähnliche Ergebnisse, wie bereits oben beschrieben, verzeichnet werden mit guten Werten in der Gruppe der untersuchten Patienten, jedoch einer geringeren Funktionalität im Vergleich zu den Probanden. Die vorliegende Arbeit zeigt, dass der direkte anteriore Zugang die Wiederherstellung eines guten postoperativen Gesundheitszustandes mit erreichen eines hohen postoperativen Aktivitätslevels der Patienten ermöglicht. Ebenso erfüllt dieser Zugangsweg die Anforderungen der heutigen Medizin im Sinne einer schnellen postoperativen Mobilisation. Im Vergleich zu anderen minimal-invasiven Verfahren zeigen sich eine gute Implantierbarkeit, eine gute Positionierung und ein niedriges Komplikationsniveau. Prinzipiell hat der minimal-invasive anteriore Zugang das Potenzial sich als ein Standardverfahren in der operativen Rekonstruktion bei Hüftgelenksersatz zu etablieren, jedoch wäre ein direkter Vergleich mit dem lateralen Zugang erstrebenswert und sollte in weiteren Studien verglichen werden. N2 - Background: The aim of this prospectve study was to evaluate the clinical results one year after total hip arthroplasty performed through a minimally invasive direct anterior approach versus a healthy volunteer group. Methods: 77 patients and 59 probands have been evaltuated applying the Stepwatch activity monitor (SAM), the Harris hip score (HHS), the SF 36, a daliy activity questionnaire (DAQ) and the XSFMA. Results: The average SAM showed significant differences of 5658 steps (patients) compared to 6417 steps (proband) (p=0,011). The same routcome can be seen in the DAQ with 4226 (patients) and 4686 (proband) cycles (p=0,327) respectively. No significant difference occured by using the average HHS reflecting an equal outcome of 90,7 points in the patient group compared to 90.8 points in the proband group (p=0,022). In contrast tot he afore-mentioned HHS, was a significant increase of the XSFMA reported with 10,9 (patients) and 5.0 (proband) (p=0,001). The SF -36 physical component scores were 45.8 (patients) and 50.6 (proband) while the psychometric properties added up to 56.6 (patients) and 55.9 (proband). While the physical component scores (p=0,001) showed a significant difference this couldnt be observed for the psychometric properties (p=0,511). Conclusion: In our study, good results have been obtained after the first year of the total hip arthroplasty, however these are not as beneficial as the outcomes in the healthy volunteer group. KW - AMIS, Direct anterior approach, hip arthroplasty, stepwatch, comparison KW - AMIS, Direct anterior approach, hip arthroplasty, stepwatch, comparison Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123448 N1 - Aus urheberrechtlichen Gründen wurde der Zugriff auf den Volltext zu diesem Dokument gesperrt. Eine neue Version ist erhältlich unter: urn:nbn:de:bvb:20-opus-178206 ER - TY - JOUR A1 - Thibaudeau, Laure A1 - Taubenberger, Anna V. A1 - Holzapfel, Boris M. A1 - Quent, Verena M. A1 - Fuehrmann, Tobias A1 - Hesami, Parisa A1 - Brown, Toby D. A1 - Dalton, Paul D. A1 - Power, Carl A. A1 - Hollier, Brett G. A1 - Hutmacher, Dietmar W. T1 - A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone JF - Disease Models & Mechanisms N2 - The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact 'organ' bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo. KW - breast cancer KW - bone metastasis KW - humanized xenograft model KW - melt electrospinning KW - tissue engineering KW - osteotropism KW - in vivo KW - stem-cell niche KW - human prostate-cancer KW - morphogenetic protein KW - osteoprogenitor cells KW - endochondral ossification KW - mouse model KW - trabecular bone KW - calcium phosphate KW - skeletal metastases Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117466 VL - 7 IS - 2 ER - TY - JOUR A1 - Staab, Wieland A1 - Hottowitz, Ralf A1 - Sohns, Christian A1 - Sohns, Jan Martin A1 - Gilbert, Fabian A1 - Menke, Jan A1 - Niklas, Andree A1 - Lotz, Joachim T1 - Accelerometer and Gyroscope Based Gait Analysis Using Spectral Analysis of Patients with Osteoarthritis of the Knee JF - Journal of Physical Therapy Science N2 - [Purpose] A wide variety of accelerometer tools are used to estimate human movement, but there are no adequate data relating to gait symmetry parameters in the context of knee osteoarthritis. This study's purpose was to evaluate a 3D-kinematic system using body-mounted sensors (gyroscopes and accelerometers) on the trunk and limbs. This is the first study to use spectral analysis for data post processing. [Subjects] Twelve patients with unilateral knee osteoarthritis (OA) (10 male) and seven age-matched controls (6 male) were studied. [Methods] Measurements with 3-D accelerometers and gyroscopes were compared to video analysis with marker positions tracked by a six-camera optoelectronic system (VICON 460, Oxford Metrics). Data were recorded using the 3D-kinematic system. [Results] The results of both gait analysis systems were significantly correlated. Five parameters were significantly different between the knee OA and control groups. To overcome time spent in expensive post-processing routines, spectral analysis was performed for fast differentiation between normal gait and pathological gait signals using the 3D-kinematic system. [Conclusions] The 3D-kinematic system is objective, inexpensive, accurate and portable, and allows long-term recordings in clinical, sport as well as ergonomic or functional capacity evaluation (FCE) settings. For fast post-processing, spectral analysis of the recorded data is recommended. KW - gait KW - accelerometer KW - gyroscope KW - HIP osteoarthritis KW - kinematic analysis KW - human movement KW - in-vivo KW - artifact KW - systems KW - people Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115907 VL - 26 IS - 7 ER - TY - JOUR A1 - Liedert, Astrid A1 - Röntgen, Viktoria A1 - Schinke, Thorsten A1 - Benisch, Peggy A1 - Ebert, Regina A1 - Jakob, Franz A1 - Klein-Hitpass, Ludger A1 - Lennerz, Jochen K. A1 - Amling, Michael A1 - Ignatius, Anita T1 - Osteoblast-Specific Krm2 Overexpression and Lrp5 Deficiency Have Different Effects on Fracture Healing in Mice JF - PLOS ONE N2 - The canonical Wnt/beta-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5(-/-)) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5(-/-) mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5(-/-) mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active beta-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis. KW - autosomal-dominant osteopetrosis KW - receptor related protein KW - high-bone-mass KW - WNT pathway KW - in-vitro KW - cells KW - gene KW - proliferation KW - osteoclasts KW - mutations Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115782 SN - 1932-6203 VL - 9 IS - 7 ER - TY - JOUR A1 - Wirtz, Dieter C. A1 - Gravius, Sascha A1 - Ascherl, Rudolf A1 - Thorweihe, Miguel A1 - Forst, Raimund A1 - Noeth, Ulrich A1 - Maus, Uwe M. A1 - Wimmer, Matthias D. A1 - Zeiler, Guenther A1 - Deml, Moritz C. T1 - Uncemented femoral revision arthroplasty using a modular tapered, fluted titanium stem 5-to 16-year results of 163 cases JF - Acta Orthopaedica N2 - Background and purpose - Due to the relative lack of reports on the medium- to long-term clinical and radiographic results of modular femoral cementless revision, we conducted this study to evaluate the medium- to long-term results of uncemented femoral stem revisions using the modular MRP-TITAN stem with distal diaphyseal fixation in a consecutive patient series. Patients and methods - We retrospectively analyzed 163 femoral stem revisions performed between 1993 and 2001 with a mean follow-up of 10 (5-16) years. Clinical assessment included the Harris hip score (HHS) with reference to comorbidities and femoral defect sizes classified by Charnley and Paprosky. Intraoperative and postoperative complications were analyzed and the failure rate of the MRP stem for any reason was examined. Results - Mean HHS improved up to the last follow-up (37 (SD 24) vs. 79 (SD 19); p < 0.001). 99 cases (61%) had extensive bone defects (Paprosky IIB-III). Radiographic evaluation showed stable stem anchorage in 151 cases (93%) at the last follow-up. 10 implants (6%) failed for various reasons. Neither a breakage of a stem nor loosening of the morse taper junction was recorded. Kaplan-Meier survival analysis revealed a 10-year survival probability of 97% (95% CI: 95-100). Interpretation - This is one of the largest medium- to longterm analyses of cementless modular revision stems with distal diaphyseal anchorage. The modular MRP-TITAN was reliable, with a Kaplan-Meier survival probability of 97% at 10 years. KW - follow-up KW - distal fixation KW - bone loss KW - replacement KW - register KW - junction KW - cement KW - prosthesis KW - roentgenographic assessment KW - total HIP-arthroplasty Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114555 SN - 1745-3674 VL - 85 IS - 6 ER - TY - THES A1 - Hewera, Judith Maria Johanna T1 - Genpolymorphismen bei Patienten mit Omarthrose T1 - Gene polymorphisms in patients with osteoarthrosis of the shoulder joint N2 - Ziel dieser Studie war einen molekulargenetischen Beitrag zur Entschlüsselung der Arthroseentstehung am Schultergelenk zu leisten. Hierzu erfolgte die Rekrutierung von Patienten mit fortgeschrittener Omarthrose Grad 3 nach Samilson & Prieto aus der Orthopädischen Klinik der Universität Würzburg im Zeitraum von 2004 bis 2005. Die erste Gruppe setzte sich aus Patienten mit primärer Omarthrose, die zweite aus Patienten mit Defektarthropathie und die dritte aus Patienten mit zumeist posttraumatischer Omarthrose als Vergleichsgruppe zusammen. Um mechanische Faktoren näher zu evaluieren, wurde die Einteilung der Gruppe der primären Omarthrose nach dem Glenoidabrieb in der Walch-Klassifikation vorgenommen. Bei 303 dieser Patienten konnten molekulargenetische Analysen hinsichtlich der arthroseassoziierten Polymorphismen MMP-3, TNF α, IL-1 α und β sowie die statistische Auswertung erfolgen. Die Ergebnisse der vorliegenden Studie zeigten hinsichtlich des Vergleichs der drei untersuchten Studiengruppen in der Allelverteilung der untersuchten Polymorphismen keinen signifikanten Unterschied. Diese Polymorphismen scheinen nach den vorliegenden Ergebnissen im Zusammenhang mit der Entstehung der primären und sekundären Omarthrose keine Rolle zu spielen. Beim Vergleich der Walch-Typen mit der Allelverteilung für TNF α konnten zwischen Walch-Typ C (Dysplasie) und A2 bzw. B2 ein signifikanter Unterschied (p=0,049) bei der Allelverteilung von Zustand A und C ermittelt werden. Bei der Gesamtallelverteilung konnten für die Polymorphismen TNF α (p=0,092), IL-1 α (p=0,080) und β (p=0,071) ein Trend zwischen den Walch- Typen A2 und C aufgezeigt werden. Gleiches gilt für IL-1 β (p=0,068) und die Walch-Typen B2 und C. In diesen Fällen ist eine Beteiligung der untersuchten Genpolymorphismen an der Glenoidentstehung denkbar. Eine altersabhängige Entwicklung der Walch-Typen ist in den Untergruppen A sowie B denkbar (p=0,047). N2 - Gene polymorphisms in patients with osteoarthrosis of the shoulder joint KW - Omarthrose KW - Polymorphismen MMP-3 KW - TNF α KW - IL-1 α und β Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113837 ER - TY - THES A1 - Schellenberger, Michael T1 - Mineralisation im proximalen Humerus - Messungen im Q-CT mit dreidimensionaler Rekonstruktion T1 - Mineralization in the proximal humerus - measurements in the Q-CT with three-dimensional reconstruction N2 - Ziel der vorliegenden Arbeit war es, die Verteilung der Knochenmineraldichte im proximalen Humerus bezogen auf mögliche Regionen, die als Verankerungsfläche für Implantate dienen, zu untersuchen. Diese Erkenntnisse sollten dazu beitragen, das Design der Implantate (z. B. Fadenanker, Schraube) zu optimieren. Außerdem sollen die Untersuchungsergebnisse als Grundlage für weitere Finite Elemente Berechnungen dienen, indem die gewonnenen Daten in digitalisierter Form in weitere biomechanische Studien einfließen können. Für die Untersuchung wurden vom anatomischen Institut der Universität Würzburg insgesamt 23 Humerusköpfe, von denen acht keine Markierungsplakette besaßen, zur Verfügung gestellt. Somit konnte nur bei 15 Präparaten das Geschlecht und das Sterbealter der dazugehörigen Leichen zurückverfolgt werden. Es handelte sich um 11 weibliche und vier männliche Verstorbene mit einem mittleren Sterbealter von 81,5 Jahren ± 10,2 (55 - 93 Jahre). Die Präparate wurden in einer Alkohol-Formalin-Lösung konserviert. Eine etwaige Schulteranamnese konnte post mortem nicht eruiert werden. Die Humerusköpfe wurden mit einem pQCT-Scanner (Stratec 2000), welcher eine selektive, volumenbezogene Bestimmung der Bereiche des Knochens erlaubt, untersucht. 30 definierte Schnittbilder pro Humerus wurden anschließend auf einem UNIX-System der Firma HERMES in digitale 3D-Modelle umgewandelt. Die Auswertung der Daten sowie die Berechnung der Knochendichte erfolgte mit Hilfe des Programms AVS-Express der Firma Advanced Visual Systems. Für die Knochendichtemessung wurde das Caput humeri in drei transversale Schnittebenen gedrittelt. Hier wurde jeweils die Dichte im Bereich der dorsalen, medialen sowie ventralen Gelenkflächenregion, im Bereich des Tuberculum minus, des Sulcus intertubercularis und des Tuberculum majus gemessen. Weiter distal wurde eine vierte Ebene im Schaftbereich festgelegt, auf deren Höhe die Knochendichte der dorsalen, ventralen, medialen und lateralen Kortikalis bestimmt wurde. Abgesehen von drei ROI`s fand sich beim männlichen Kollektiv die gemessene Knochendichte signifikant höher als bei den Frauen, was mit der Zunahme osteoporotischer Frakturen bei älteren Frauen korreliert. Die regionale Verteilung der Knochendichte korreliert gut bis auf den Sulcus intertubercularis mit den klinischen Frakturtypen nach Neer, wobei dieses Areal in Bezug auf den Verlauf der Frakturlinien eher den gemessenen Werten als dieser häufig verwendeten Klassifikation folgt. Mit zunehmender Tiefe vermindert sich insbesondere in den Tuberkula die Mineralisationsdichte, so dass die meisten Anker oberflächennah im Kortex die beste Substanz für eine Fixierung finden. N2 - The aim of the present study was to analyse the distribution of bone mineral density in the proximal humerus in relation to potential regions serving as anchoring surface for implants. These results should help to optimize the design of implants (for example suture anchors, screws). In addition the results should serve as a basis for other finite element calculations by the data collected may be taken into other biomechanical studies in digitalized form. KW - Proximaler Humerus KW - Alterstraumatologie KW - Knochendichte KW - Q-CT KW - dreidimensionale Rekonstruktion KW - Osteoporose KW - Finite Elemente Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112255 ER - TY - THES A1 - Bischofberger, Simon T1 - Entwicklung und biomechanische Untersuchungen eines Kreuzbandkonstrukts aus biomaterialbasiertem Kollagen I T1 - Development and biomechanical studies of biomaterial based collagen I anteriorcruciate ligament construct N2 - Das ACL ist eine der am häufigsten verletzten Strukturen des menschlichen Körpers bei Sportunfällen und die Anzahl der Rekonstruktionen wird weiterhin zunehmen. In den letzten Jahren wurden große Fortschritte in der Charakterisierung der biomechanischen Eigenschaften von Sehnen und Bändern erzielt und neue Ansätze auf dem Gebiet des Tissue Engineering eröffnen neue Möglichkeiten. In dieser Arbeit wurde ein ACL-Konstrukt aus biomaterialbasiertem Kollagen I entwickelt und getestet. Die gewonnenen Ergebnisse können als Grundlage für die Herstellung eines Kreuzbandkonstruktes verwendet werden. N2 - The ACL is one of the most common injured structures of the human body in sports accidents and the number of reconstructions will continue to grow. In recent years, major advances in the characterization of the biomechanical properties of tendons and ligaments have been achieved and new approaches in the field of tissue engineering offer new opportunities. In this work an ACL construct of biomaterial based collagen I was developed and tested. The results can be used as a basis for the production of a ligament constructs. KW - Kreuzband KW - Kollagen KW - Konstrukt KW - ACL KW - Collagen KW - Scaffold Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85648 ER - TY - JOUR A1 - Ebert, Regina A1 - Jakob, Franz A1 - Meissner-Weigl, Jutta A1 - Zeck, Sabine A1 - Määttä, Jorma A1 - Auriola, Seppo A1 - de Sousa, Sofia Coimbra A1 - Mentrup, Birgit A1 - Graser, Stephanie A1 - Rachner, Tilman D. A1 - Hofbauer, Lorenz C. T1 - Probenecid as a sensitizer of bisphosphonate-mediated effects in breast cancer cells N2 - Background: Anti-resorptive bisphosphonates (BP) are used for the treatment of osteoporosis and bone metastases. Clinical studies indicated a benefit in survival and tumor relapse in subpopulations of breast cancer patients receiving zoledronic acid, thus stimulating the debate about its anti-tumor activity. Amino-bisphosphonates in nM concentrations inhibit farnesyl pyrophosphate synthase leading to accumulation of isopentenyl pyrophosphate (IPP) and the ATP/ pyrophosphate adduct ApppI, which induces apoptosis in osteoclasts. For anti-tumor effects μM concentrations are needed and a sensitizer for bisphosphonate effects would be beneficial in clinical anti-tumor applications. We hypothesized that enhancing intracellular pyrophosphate accumulation via inhibition of probenecid-sensitive channels and transporters would sensitize tumor cells for bisphosphonates anti-tumor efficacy. Methods: MDA-MB-231, T47D and MCF-7 breast cancer cells were treated with BP (zoledronic acid, risedronate, ibandronate, alendronate) and the pyrophosphate channel inhibitors probenecid and novobiocin. We determined cell viability and caspase 3/7 activity (apoptosis), accumulation of IPP and ApppI, expression of ANKH, PANX1, ABCC1, SLC22A11, and the zoledronic acid target gene and tumor-suppressor KLF2. Results: Treatment of MDA-MB-231 with BP induced caspase 3/7 activity, with zoledronic acid being the most effective. In MCF-7 and T47D either BP markedly suppressed cell viability with only minor effects on apoptosis. Co-treatment with probenecid enhanced BP effects on cell viability, IPP/ApppI accumulation as measurable in MCF-7 and T47D cells, caspase 3/7 activity and target gene expression. Novobiocin co-treatment of MDA-MB-231 yielded identical results on viability and apoptosis compared to probenecid, rendering SLC22A family members as candidate modulators of BP effects, whereas no such evidence was found for ANKH, ABCC1 and PANX1. Conclusions: In summary, we demonstrate effects of various bisphosphonates on caspase 3/7 activity, cell viability and expression of tumor suppressor genes in breast cancer cells. Blocking probenecid- and novobiocin-sensitive channels and transporters enhances BP anti-tumor effects and renders SLC22A family members good candidates as BP modulators. Further studies will have to unravel if treatment with such BP-sensitizers translates into preclinical and clinical efficacy. KW - Bisphosphonates KW - Caspase 3/7 activity KW - Cell viability, KW - Probenecid KW - Novobiocin KW - Breast cancer cells Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111174 ER - TY - JOUR A1 - Ebert, Regina A1 - Dotterweich, Julia A1 - Kraus, Sabrina A1 - Tower, Robert J. A1 - Jakob, Franz A1 - Schütze, Norbert T1 - Mesenchymal stem cell contact promotes CCN1 splicing and transcription in myeloma cells N2 - CCN family member 1 (CCN1), also known as cysteine-rich angiogenic inducer 61 (CYR61), belongs to the extracellular matrix-associated CCN protein family. The diverse functions of these proteins include regulation of cell migration, adhesion, proliferation, differentiation and survival/apoptosis, induction of angiogenesis and cellular senescence. Their functions are partly overlapping, largely non-redundant, cell-type specific, and depend on the local microenvironment. To elucidate the role of CCN1 in the crosstalk between stromal cells and myeloma cells, we performed co-culture experiments with primary mesenchymal stem cells (MSC) and the interleukin-6 (IL-6)-dependent myeloma cell line INA-6. Here we show that INA-6 cells display increased transcription and induction of splicing of intron-retaining CCN1 pre-mRNA when cultured in contact with MSC. Protein analyses confirmed that INA-6 cells co-cultured with MSC show increased levels of CCN1 protein consistent with the existence of a pre-mature stop codon in intron 1 that abolishes translation of unspliced mRNA. Addition of recombinant CCN1-Fc protein to INA-6 cells was also found to induce splicing of CCN1 pre-mRNA in a concentration-dependent manner. Only full length CCN1-Fc was able to induce mRNA splicing of all introns, whereas truncated recombinant isoforms lacking domain 4 failed to induce intron splicing. Blocking RGD-dependent integrins on INA-6 cells resulted in an inhibition of these splicing events. These findings expand knowledge on splicing of the proangiogenic, matricellular factor CCN1 in the tumor microenvironment. We propose that contact with MSC-derived CCN1 leads to splicing and enhanced transcription of CCN1 which further contributes to the translation of angiogenic factor CCN1 in myeloma cells, supporting tumor viability and myeloma bone disease. KW - CCN1 KW - Multiple myeloma KW - Mesenchymal stem cells KW - Splicing Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110497 ER -