TY - JOUR A1 - Johanssen, Sarah A1 - Hahner, Stefanie A1 - Saeger, Wolfgang A1 - Quinkler, Marcus A1 - Beuschlein, Felix A1 - Dralle, Henning A1 - Haaf, Michaela A1 - Kroiss, Matthias A1 - Jurowich, Christian A1 - Langer, Peter A1 - Oelkers, Wolfgang A1 - Spahn, Martin A1 - Willenberg, Holger S. A1 - Maeder, Uwe A1 - Allolio, Bruno A1 - Fassnacht, Martin T1 - Deficits in the Management of Patients With Adrenocortical Carcinoma in Germany N2 - Background: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Often, the physicians who first treat patients with ACC have no prior experience with the disease. The aim of our study was to evaluate the quality of medical care for patients with ACC in Germany. Methods: Data from the German ACC registry were analyzed with regard to the patients’ preoperative diagnostic evaluation, histopathological reporting, and clinical followup. The findings were compared with the recommendations of the European Network for the Study of Adrenal Tumors (ENSAT). Results: Data were analyzed from 387 patients who had been given an initial diagnosis of ACC in the years 1998 to 2009. 21% of them underwent no hormonal evaluation before surgery, and 59% underwent an inadequate hormonal evaluation. This exposed the patients to unnecessary perioperative risks and impaired their follow-up. 48% did not undergo CT scanning of the chest, even though the lungs are the most frequent site of metastases of ACC. For 13% of the patients, the diagnosis of ACC was later revised by a reference pathologist. For 11% of the patients, the histopathology report contained no information about resection status, even though this is an important determinant of further treatment and prognosis. Optimal management requires re-staging at three-month intervals, yet some patients underwent re-staging only after a longer delay, or not at all. Conclusion: We have identified significant deficits in the care of patients with ACC in Germany. We suspect that the situation is similar for other rare diseases. The prerequisite to better care is close and early cooperation of the treating physicians with specialized centers. Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85897 ER - TY - THES A1 - Wiemer, Laura Elisa T1 - In-vitro-Untersuchungen zur molekularen Wirkung von Mitotane beim Nebennierenrindenkarzinom T1 - In-vitro studies to elucidate the moclecuar actions of Mitotane in adrenocortical carcinoma N2 - Das Nebennierenrindenkarzinom ist eine hochmaligne Erkrankung und hat eine schlechte Prognose. Mitotane ist bis heute die einzige hierfür zugelassene Therapie. Um die molekularen Mechanismen der Mitotanetherapie besser zu verstehen, wurde die Nebennierenkarzinom-Zelllinie NCI-H295 mit unterschiedlichen Konzentrationen von Mitotane inkubiert und die Wirkung auf mehreren Ebenen untersucht. Dabei kam der Untersuchung der Steroidogenese und apoptotischer Vorgänge ein besonderer Fokus zu. In den Hormonanalysen via Immunoassay zeigte sich eine zeit- und konzentrationsabhängige Hemmung der adrenalen Steroidsekretion. So kam es unter 24-stündiger Inkubation mit 100µM Mitotane zu einer Reduktion der Cortisolsekretion um 89%. Diese Hormonsuppression geht einher mit einer Herabregulation von steroidogenen Enzymen in den durchgeführten Microarray-basierten Genexpressionsanalysen. So konnte gezeigt werden, dass vor allem Steroidbiosynthese-Enzyme der Zona fasciculata und reticularis betroffen sind. Als weitere wichtige Gene im Zusammenhang mit der Beeinflussung des Steroidhaushalts unter Mitotanetherapie konnten SQLE, LDLR, SCD, SREBF1 und ABCG1 identifiziert werden. Gleichzeitig konnte durch Durchflusszytometrie und Zelltod-ELISA die proapoptotische Wirkung von Mitotane gezeigt werden (FACS: 100µM Mitotane, 24 Stunden; Zunahme der Apoptose um den Faktor 2,13). Dies bestätigte sich beispielsweise auch in der Überexpression des Apoptosegens BAX in der Real-Time-PCR. Weiterhin zeigte der RNA-Microarray eine starke Expressionszunahme bei Genen, die mit dem programmierten Zelltod zusammenhängen wie GDF15, DUSP4, TRIB3 und CHOP. Ausgehend von den klinischen Effekten und bestätigt durch die oben genannten in vitro Ergebnisse bewirkt Mitotane auch molekular folgende Änderungen in Nebennierenrindenzellen: Hemmung der Steroidogenese und Induktion von Apotose. Es stellt sich damit die Frage, ob diese Mechanismen parallel und separat voneinander ablaufen oder ob es einen gemeinsamen Nenner gibt. Interessanterweise ergab die Analyse der Genexpressionsdaten, dass viele der proapoptotischen Gene mit dem sogenannten ER-Stress zusammenhängen. Einerseits könnte Mitotane durch direkte Inhibition der Hormonsekretion wirken, andererseits könnte ER-Stress durch Mitotane-induzierte-Bildung toxischer Lipide, wie Cholesterol, ausgelöst werden. Um den genauen Wirkmechanismus endgültig zu klären, werden weitere Experimente benötigt. Mitotane-induzierter ER-Stress liefert einen vollständig neuen Blickwinkel auf die molekulare Wirkweise von Mitotane auf Nebennierenrindenkarzinomzellen. Gerade da die Mediatoren des ER-Stresses gut definiert und ER-Stress spezifisch sind, könnten sie sinnvolle Ziele in der Therapie darstellen. Die Beobachtung, dass Mitotane ER-Stress hervorruft, könnte in Zukunft somit zur Entwicklung wirksamerer und spezifischerer Therapien des Nebennierenrindenkarzinoms führen und so die infauste Prognose dieser malignen Krankheit verbessern. N2 - In-vitro studies to elucidate the moclecuar actions of Mitotane in adrenocortical carcinoma KW - Nebenniere KW - Mitotane Nebennierenkarzinom KW - Genexpression KW - Mikroarray KW - Zellkultur Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-94526 ER - TY - JOUR A1 - Chopra, Martin A1 - Lang, Isabell A1 - Salzmann, Steffen A1 - Pachel, Christina A1 - Kraus, Sabrina A1 - Bäuerlein, Carina A. A1 - Brede, Christian A1 - Jordán Garrote, Ana-Laura A1 - Mattenheimer, Katharina A1 - Ritz, Miriam A1 - Schwinn, Stefanie A1 - Graf, Carolin A1 - Schäfer, Viktoria A1 - Frantz, Stefan A1 - Einsele, Hermann A1 - Wajant, Harald A1 - Beilhack, Andreas T1 - Tumor Necrosis Factor Induces Tumor Promoting and Anti-Tumoral Effects on Pancreatic Cancer via TNFR1 JF - PLoS ONE N2 - Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors and furthermore displayed enhanced tumor progression. In contrast, a fraction of wild type (37.5%), TNF deficient (12.5%), and TNFR2 deficient mice (22.2%) were able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1 deficient mice displayed increased vascular density, enhanced infiltration of CD4+ T cells and CD4+ forkhead box P3 (FoxP3)+ regulatory T cells (Treg) but reduced numbers of CD8+ T cells. These alterations were further accompanied by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in pancreatic ductal carcinoma to ensure optimal CD8+ T cell-mediated immunosurveillance and tumor rejection. Exogenous systemic administration of human TNF, however, which only interacts with murine TNFR1, accelerated tumor progression. This suggests that TNFR1 has basically the capability in the Panc02 model to trigger pro-and anti-tumoral effects but the spatiotemporal availability of TNF seems to determine finally the overall outcome. KW - Bioluminescence KW - cancer treatment KW - cell staining KW - cytokines KW - immune cells KW - metastasis KW - regulatory T cells KW - T cells Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97246 ER - TY - JOUR A1 - Sbiera, Silviu A1 - Ronchi, Cristina L. A1 - Leich, Ellen A1 - Henzel, Katharina A1 - Rosenwald, Andreas A1 - Allolio, Bruno A1 - Fassnacht, Martin T1 - Single Nucleotide Polymorphism Array Profiling of Adrenocortical Tumors - Evidence for an Adenoma Carcinoma Sequence? JF - PLoS ONE N2 - Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs >100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91% vs 29%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr 1, 2, 13, 17, and 22) was associated with a better prognosis (overall survival: 72.2 vs 35.4 months, P=0.063). Interestingly, >70% of gains frequent in beningn were also present in malignant tumors. Notch signaling was the most frequently involved pathway in both tumor entities. Finally, a CN gain at imprinted “IGF2” locus chr 11p15.5 appeared to be an early alteration in a multi-step tumor progression, followed by the loss of one or two alleles, associated with increased IGF2 expression, only in carcinomas. Our study serves as database for the identification of genes and pathways, such as Notch signaling, which could be involved in the pathogenesis of adrenocortical tumors. Using these data, we postulate an adenoma-carcinoma sequence for these tumors. KW - adenomas KW - cancer diagnosis KW - cancer detection KW - carcinogenesis KW - carcinomas KW - chromosomes KW - genetic loci KW - malignant tumors KW - notch signaling Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97218 ER - TY - THES A1 - Schönfeld, Stephan T1 - Aldosteron und Cortisol bei Dialysepatienten – Effekt auf kardiale und vaskuläre Ereignisse T1 - Aldosterone and cortisol in haemodialysis patients – effect on cardiac and vascular events N2 - Dialysepatienten weisen eine hohe Anzahl kardiovaskulärer Ereignisse auf. Betrachtet man die häufigsten Todesursachen von Dialysepatienten, so fällt ein großer Teil in den kardiovaskulären Bereich. In dieser Arbeit wurde der Einfluss von Aldosteron und Cortisol auf kardiale und vaskuläre Ereignisse bei Dialysepatienten mit Diabetes mellitus untersucht. Dazu wurden Daten von 1255 Dialysepatienten mit Diabetes mellitus aus der Deutschen Diabetes Dialyse Studie analysiert. In der vorliegenden Arbeit konnte gezeigt werden, dass mit erhöhten Aldosteronkonzentrationen ein signifikanter Anstieg des Risikos für plötzlichen Herztod (HR: 1.69; 95% CI: 1.06–2.69) einhergeht. Das Risiko an plötzlichem Herztod zu versterben war bei hohen Konzentrationen von Aldosteron und gleichzeitig vorliegenden hohen Konzentrationen von Cortisol noch deutlicher erhöht (HR: 2.86, 95% CI: 1.32–6.21). Ebenso war die Gesamtsterblichkeit signifikant erhöht bei Patienten, die hohe Aldosteron- und Cortisolkonzentrationen aufwiesen im Vergleich zu Patienten mit niedrigen Spiegeln beider Hormone (HR: 1.62, 95% CI: 1.01–2.62). In dieser Arbeit konnte somit ein deutlicher Zusammenhang hoher Aldosteron- und Cortisolkonzentrationen mit plötzlichem Herztod und Gesamtsterblichkeit gezeigt werden. N2 - Dialysis patients demonstrate a high number of cardio-vascular events. Investigating the most common causes of death of dialysis patients reveals a large share of causes lying in the cardio-vascular area. This paper examines the influence of aldosterone and cortisol on cardiac and vascular events of dialysis patients with diabetes mellitus. In doing so, data from 1255 dialysis patients with diabetes mellitus from the German Diabetes Dialysis Study was analyzed. The findings of this study show that a heightened concentration of aldosterone significantly increases the risk of sudden cardiac death (HR: 1.69; 95% CI: 1.06–2.69). The combined presence of high aldosterone and cortisol levels raises this risk even more (HR: 2.86, 95% CI: 1.32–6.21). Furthermore, the mortality rate is substantially increased for patients that demonstrate high concentrations of Aldosterone and Cortisol as compared to patients with low levels of both hormones (HR: 1.62, 95% CI: 1.01–2.62). In conclusion, the thesis demonstrates a significant association between high concentrations of aldosterone, cortisol and sudden cardiac death as well as overall mortality. KW - Aldosteron KW - Dialyse KW - Aldosteron KW - Cortisol KW - Plötzlicher Herztod Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96156 ER - TY - JOUR A1 - Winter, Patrick A1 - Kampf, Thomas A1 - Helluy, Xavier A1 - Gutjahr, Fabian T. A1 - Meyer, Cord B. A1 - Rommel, Eberhard A1 - Bauer, Wolfgang R. A1 - Jakob, Peter M. A1 - Herold, Volker T1 - Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory JF - Journal of Cardiovascular Magnetic Resonance N2 - Background The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed. Methods The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence. Results In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method. Conclusion With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware. KW - pulse-wave velocity KW - mouse KW - self-gating KW - phase-contrast CMR KW - non-triggered KW - retrospective KW - radial KW - aorta Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96602 UR - http://jcmr-online.com/content/15/1/88 ER - TY - JOUR A1 - Gassenmaier, Tobias A1 - Gorski, Armin A1 - Aleksic, Ivan A1 - Deubner, Nikolas A1 - Weidemann, Frank A1 - Beer, Meinrad T1 - Impact of cardiac magnet resonance imaging on management of ventricular septal rupture after acute myocardial infarction JF - World Journal of Cardiology N2 - A 74-year-old man was admitted to the cardiac catheterization laboratory with acute myocardial infarction. After successful angioplasty and stent implantation into the right coronary artery, he developed cardiogenic shock the following day. Echocardiography showed ventricular septal rupture. Cardiac magnet resonance imaging (MRI) was performed on the critically ill patient and provided detailed information on size and localization of the ruptured septum by the use of fast MRI sequences. Moreover, the MRI revealed that the ventricular septal rupture was within the myocardial infarction area, which was substantially larger than the rupture. As the patient’s condition worsened, he was intubated and had intra-aortic balloon pump implanted, and extracorporeal membrane oxygenation was initiated. During the following days, the patient’s situation improved, and surgical correction of the ventricular septal defect could successfully be performed. To the best of our knowledge, this case report is the first description of postinfarction ventricular septal rupture by the use of cardiac MRI in an intensive care patient with cardiogenic shock and subsequent successful surgical repair. KW - Cardiac magnetic resonance imaging KW - Ventricular septal rupture KW - Myocardial infarction KW - surgical repair KW - Extracorporeal membrane oxygenation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96562 ER - TY - JOUR A1 - Üçeyler, Nurcan A1 - Kahn, Ann-Kathrin A1 - Kramer, Daniela A1 - Zeller, Daniel A1 - Casanova-Molla, Jordi A1 - Wanner, Christoph A1 - Weidemann, Frank A1 - Katsarava, Zaza A1 - Sommer, Claudia T1 - Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study JF - BMC Neurology N2 - Background Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP). Methods In this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function. Results All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients. Conclusion Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction. KW - Fabry disease KW - Pain-related evoked potentials KW - Small fiber neuropathy KW - A-delta fibers Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96527 UR - http://www.biomedcentral.com/1471-2377/13/47 ER - TY - JOUR A1 - Elias, Johannes A1 - Heuschmann, Peter U. A1 - Schmitt, Corinna A1 - Eckhardt, Frithjof A1 - Boehm, Hartmut A1 - Maier, Sebastian A1 - Kolb-Mäurer, Annette A1 - Riedmiller, Hubertus A1 - Müllges, Wolfgang A1 - Weisser, Christoph A1 - Wunder, Christian A1 - Frosch, Matthias A1 - Vogel, Ulrich T1 - Prevalence dependent calibration of a predictive model for nasal carriage of methicillin-resistant Staphylococcus aureus JF - BMC Infectious Diseases N2 - Background Published models predicting nasal colonization with Methicillin-resistant Staphylococcus aureus among hospital admissions predominantly focus on separation of carriers from non-carriers and are frequently evaluated using measures of discrimination. In contrast, accurate estimation of carriage probability, which may inform decisions regarding treatment and infection control, is rarely assessed. Furthermore, no published models adjust for MRSA prevalence. Methods Using logistic regression, a scoring system (values from 0 to 200) predicting nasal carriage of MRSA was created using a derivation cohort of 3091 individuals admitted to a European tertiary referral center between July 2007 and March 2008. The expected positive predictive value of a rapid diagnostic test (GeneOhm, Becton & Dickinson Co.) was modeled using non-linear regression according to score. Models were validated on a second cohort from the same hospital consisting of 2043 patients admitted between August 2008 and January 2012. Our suggested correction score for prevalence was proportional to the log-transformed odds ratio between cohorts. Calibration before and after correction, i.e. accurate classification into arbitrary strata, was assessed with the Hosmer-Lemeshow-Test. Results Treating culture as reference, the rapid diagnostic test had positive predictive values of 64.8% and 54.0% in derivation and internal validation corhorts with prevalences of 2.3% and 1.7%, respectively. In addition to low prevalence, low positive predictive values were due to high proportion (> 66%) of mecA-negative Staphylococcus aureus among false positive results. Age, nursing home residence, admission through the medical emergency department, and ICD-10-GM admission diagnoses starting with “A” or “J” were associated with MRSA carriage and were thus included in the scoring system, which showed good calibration in predicting probability of carriage and the rapid diagnostic test’s expected positive predictive value. Calibration for both probability of carriage and expected positive predictive value in the internal validation cohort was improved by applying the correction score. Conclusions Given a set of patient parameters, the presented models accurately predict a) probability of nasal carriage of MRSA and b) a rapid diagnostic test’s expected positive predictive value. While the former can inform decisions regarding empiric antibiotic treatment and infection control, the latter can influence choice of screening method. KW - Methicillin-resistant staphylococcus aureus KW - Infection control KW - Clinical prediction rule KW - Predictive value of tests KW - False positive reactions KW - Calibration Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96091 UR - http://www.biomedcentral.com/1471-2334/13/111 ER - TY - JOUR A1 - Haring, Bernhard A1 - Pettinger, Mary A1 - Bea, Jennifer W. A1 - Wactawski-Wende, Jean A1 - Carnahan, Ryan M. A1 - Ockene, Judith K. A1 - Wyler von Ballmoos, Moritz A1 - Wallace, Robert B. A1 - Wassertheil-Smoller, Sylvia T1 - Laxative use and incident falls, fractures and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative JF - BMC Geriatrics N2 - Background Laxatives are among the most widely used over-the-counter medications in the United States but studies examining their potential hazardous side effects are sparse. Associations between laxative use and risk for fractures and change in bone mineral density [BMD] have not previously been investigated. Methods This prospective analysis included 161,808 postmenopausal women (8907 users and 151,497 nonusers of laxatives) enrolled in the WHI Observational Study and Clinical Trials. Women were recruited from October 1, 1993, to December 31, 1998, at 40 clinical centers in the United States and were eligible if they were 50 to 79 years old and were postmenopausal at the time of enrollment. Medication inventories were obtained during in-person interviews at baseline and at the 3-year follow-up visit on everyone. Data on self-reported falls (≥2), fractures (hip and total fractures) were used. BMD was determined at baseline and year 3 at 3 of the 40 clinical centers of the WHI. Results Age-adjusted rates of hip fractures and total fractures, but not for falls were similar between laxative users and non-users regardless of duration of laxative use. The multivariate-adjusted hazard ratios for any laxative use were 1.06 (95% confidence interval [CI], 1.03-1.10) for falls, 1.02 (95% CI, 0.85-1.22) for hip fractures and 1.01 (95% CI, 0.96-1.07) for total fractures. The BMD levels did not statistically differ between laxative users and nonusers at any skeletal site after 3-years intake. Conclusion These findings support a modest association between laxative use and increase in the risk of falls but not for fractures. Its use did not decrease bone mineral density levels in postmenopausal women. Maintaining physical functioning, and providing adequate treatment of comorbidities that predispose individuals for falls should be considered as first measures to avoid potential negative consequences associated with laxative use. KW - laxative KW - use KW - fall KW - fracture KW - bone mineral density KW - aging Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95960 UR - http://www.biomedcentral.com/1471-2318/13/38 ER -