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103. Tumor cell lysis and synergistically enhanced antibody-dependent cell-mediated cytotoxicity by NKG2D engagement with a bispecific immunoligand targeting the HER2 antigen.

Author

Kellner, Christian, Lutz, Sebastian, Oberg, Hans-Heinrich, Wesch, Daniela, Otte, Anna, Diemer, Katarina J., Wilcken, Hauke, Bauerschlag, Dirk, Glüer, Claus-Christian, Wichmann, Christian, Kabelitz, Dieter, Leusen, Jeanette H. W., Klausz, Katja, Humpe, Andreas, Gramatzki, Martin, and Peipp, Matthias

Subjects
ANTIBODY-dependent cell cytotoxicity, LYSIS, BISPECIFIC antibodies, IRINOTECAN, KILLER cells, ANTIGENS, CELL receptors
Abstract

ULBP2:HER2-scFv simultaneously bound to HER2 and NKG2D and triggered NK cells to kill HER2-expressing tumor cells in the nanomolar concentration range. Keywords: ADCC; antibody therapy; EGFR; NK cells; NKG2D EN ADCC antibody therapy EGFR NK cells NKG2D 545 556 12 04/12/22 20220401 NES 220401 Introduction Exploiting natural killer (NK) cells is a promising approach in cancer immunotherapy. ULBP2:HER2-scFv induces NK cell cytotoxicity To analyze whether ULBP2:HER2-scFv was able to trigger NK cell cytotoxicity SP 51 sp Cr release experiments were performed (Figure 3A). [Extracted from the article]

Published
2022
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105. Abschätzung kortikaler Eigenschaften des Tibiaschafts mit Quantitativem Ultraschall

Author

Fischer, Florian, Glüer, Claus-Christian, Gräsel, Melanie, and Barkmann, Reinhard

Subjects
ddc: 610, axiale Transmission, 610 Medical sciences, Medicine, Osteoporose, Quantitativer Ultraschall
Abstract

Fragestellung: Quantitatives Standardverfahren in der Osteoporosediagnostik ist die DXA zur Messung der Knochendichte an Wirbelsäule und proximalem Femur. Nachteilig ist, dass dabei nicht zwischen trabekuklärer und kortikaler Dichte unterschieden werden kann, und auch Feinstrukturen wie kortikale[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019)

Published
2019

112. Preclinical evaluation of Sunitinib as a single agent in the prophylactic setting in a mouse model of bone metastases

Author

Schem Christian, Bauerschlag Dirk, Bender Sascha, Lorenzen Ann-Christin, Loermann Daniel, Hamann Sigrid, Rösel Frank, Kalthoff Holger, Glüer Claus C, Jonat Walter, and Tiwari Sanjay

Subjects
Sunitinib, Bone metastases, Breast cancer, Imaging, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background A substantial number of breast cancer patients are identified as being at high risk of developing metastatic disease. With increasing number of targeted therapeutics entering clinical trials, chronic administration of these agents may be a feasible approach for the prevention of metastases within this subgroup of patients. In this preclinical study we examined whether Sunitinib, a multi-tyrosine kinase inhibitor which has anti-angiogenic and anti-resorptive activity, is effective in the prevention of bone metastases. Method Sunitinib was administered daily with the first dose commencing prior to tumor cell inoculation. Intracardiac injection was performed with MDA-MB23 bone-seeking cells, which were stably transfected with DsRed2. In vivo plain radiography and fluorescent imaging (Berthold NightOwl) was used in the analysis of bone metastases. Histomorphometry was used for the quantification of TRAP+ cells from bone sections and immunohistochemistry was performed using an antibody reactive to CD34 for quantification of microvessel density. Results Preventive dosing administration of Sunitinib does not inhibit colonization of tumor cells to bone or reduce the size of osteolytic lesions. There was a decrease in the number of TRAP+ cells with Sunitinib treatment but this did not reach significance. Sunitinib inhibited tumor growth as determined by imaging of fluorescent tumor area. Immunohistochemical analyses of microvessel density revealed a concomitant decrease in the number of tumor blood vessels. Conclusions The findings suggest that Sunitinib can be used as a therapeutic agent for the treatment of bone metastases but as a single agent it is not effective in terms of prevention. Therefore a combination approach with other cytostatic drugs should be pursued.

Published
2013
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113. Reduction of Vertebral Fracture Risk in Postmenopausal Women With Osteoporosis Treated With Raloxifene: Results From a 3-Year Randomized Clinical Trial

Author

Ettinger, Bruce, Black, Dennis M., Mitlak, Bruce H., Knickerbocker, Ronald K., Nickelsen, Thomas, Genant, Harry K., Christiansen, Claus, Delmas, Pierre D., Zanchetta, Jose R., Stakkestad, Jacob, Glüer, Claus C., Krueger, Kathryn, Cohen, Fredric J., Eckert, Stephen, Ensrud, Kristine E., Avioli, Louis V., Lips, Paul, and Cummings, Steven R.

Published
1999

114. Correction: Large cortical bone pores in the tibia are associated with proximal femur strength

Author

Iori, Gianluca, primary, Schneider, Johannes, additional, Reisinger, Andreas, additional, Heyer, Frans, additional, Peralta, Laura, additional, Wyers, Caroline, additional, Gräsel, Melanie, additional, Barkmann, Reinhard, additional, Glüer, Claus C., additional, van den Bergh, J. P., additional, Pahr, Dieter, additional, and Raum, Kay, additional

Published
2019
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117. Assessment of anti-inflammatory tumor treatment efficacy by longitudinal monitoring employing sonographic micro morphology in a preclinical mouse model

Author

Trauzold Anna, Köhler Linda, Korniienko Olena, Egberts Jan H, Tiwari Sanjay, Glüer Claus C, and Kalthoff Holger

Subjects
Medical technology, R855-855.5
Abstract

Abstract Background With the development of increasingly sophisticated three-dimensional volumetric imaging methods, tumor volume can serve as a robust and reproducible measurement of drug efficacy. Since the use of molecularly targeted agents in the clinic will almost certainly involve combinations with other therapeutic modalities, the use of volumetric determination can help to identify a dosing schedule of sequential combinations of cytostatic drugs resulting in long term control of tumor growth with minimal toxicity. The aim of this study is to assess high resolution sonography imaging for the in vivo monitoring of efficacy of Infliximab in pancreatic tumor. Methods In the first experiment, primary orthotopic pancreatic tumor growth was measured with Infliximab treatment. In the second experiment, orthotopic tumors were resected ten days after inoculation of tumor cells and tumor recurrence was measured following Infliximab treatment. Tumor progression was evaluated using 3D high resolution sonography. Results Sonography measurement of tumor volume in vivo showed inhibitory effect of Infliximab on primary tumor growth in both non-resected and resected models. Measurement of the dynamics of tumor growth by sonography revealed that in the primary tumor Infliximab is effective against established tumors while in the resection model, Infliximab is more effective at an early stage following tumor resection. Infliximab treatment is also effective in inhibiting tumor growth growth as a result of tumor cell contamination of the surgical field. Conclusions Clinical application of Infliximab is feasible in both the neoadjuvant and adjuvant setting. Infliximab is also effective in slowing the growth of tumor growth under the peritoneum and may have application in treating peritoneal carcinomatosis. Finally the study demonstrates that high resolution sonography is a sensitive imaging modality for the measurement of pancreatic tumor growth.

Published
2011
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119. Dynamic in vivomonitoring of fracture healing process in response to magnesium implant with multimodal imaging: pilot longitudinal study in a rat external fixation modelElectronic supplementary information (ESI) available. See DOI: 10.1039/d2bm00051b

Author

Sun, Yu, Helmholz, Heike, Will, Olga, Damm, Timo, Wiese, Björn, Luczak, Monika, Peschke, Eva, Luthringer-Feyerabend, Bérengère, Ebel, Thomas, Hövener, Jan-Bernd, Glüer, Claus-Christian, and Willumeit-Römer, Regine

Abstract

Rodent models are commonly used in pre-clinical research of magnesium (Mg)-based and other types of biomaterials for fracture treatment. Most studies selected unstable fixation methods, and there is a lack of multimodal longitudinal in vivomonitoring of bone healing. The purpose of this study is to develop a rat femoral fracture model stabilized by external fixation with intra-medullary Mg implant, and to investigate the dynamic bone union process with several imaging techniques offering complementing insights into the process. Pure Mg pins were prepared, followed by an in vitrodegradation test. Male Sprague-Dawley rats in the experimental group underwent femoral osteotomy stabilized by external fixators with intra-medullary implantation of Mg pins, and the control group underwent external fixation without intra-medullary implants. Post-operative radiograph, micro-CT and B-mode ultrasonography were acquired directly after surgery, and re-examined at week 4, 8 and 12. Bone tissue volume, in vivoimplant degradation, histological staining and MRI images were analyzed using ex vivosamples. Both groups achieved fracture union at week 12, and the dynamic healing process was illustrated by in vivoradiograph, micro-CT and ultrasonography. Bilateral whole femur ex vivoanalysis further demonstrated increased ratio of bone tissue volume in the surgical femur with Mg implants, and in vivodegradation of Mg pins was slower than in vitroresults. Titanium screws rather than intra-medullary Mg pins were the source of artifact in MRI. This pilot study showed the rat fracture model with external fixation and intra-medullary Mg implantation to be an effective method for dynamic in vivomonitoring of the bone healing process. Future application of the animal model may facilitate pre-clinical translational research of biodegradable orthopaedic implant materials for fracture treatment.

Published
2022
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122. The effect of in situ/in vitro three-dimensional quantitative computed tomography image voxel size on the finite element model of human vertebral cancellous bone

Author

Lu, Yongtao, Engelke, Klaus, Glüer, Claus Christian, Morlock, Michael, Huber, Gerd, Lu, Yongtao, Engelke, Klaus, Glüer, Claus Christian, Morlock, Michael, and Huber, Gerd

Abstract

Quantitative computed tomography-based finite element modeling technique is a promising clinical tool for the prediction of bone strength. However, quantitative computed tomography-based finite element models were created from image datasets with different image voxel sizes. The aim of this study was to investigate whether there is an influence of image voxel size on the finite element models. In all 12 thoracolumbar vertebrae were scanned prior to autopsy (in situ) using two different quantitative computed tomography scan protocols, which resulted in image datasets with two different voxel sizes (0.29 × 0.29 × 1.3 mm(3) vs 0.18 × 0.18 × 0.6 mm(3)). Eight of them were scanned after autopsy (in vitro) and the datasets were reconstructed with two voxel sizes (0.32 × 0.32 × 0.6 mm(3) vs. 0.18 × 0.18 × 0.3 mm(3)). Finite element models with cuboid volume of interest extracted from the vertebral cancellous part were created and inhomogeneous bilinear bone properties were defined. Axial compression was simulated. No effect of voxel size was detected on the apparent bone mineral density for both the in situ and in vitro cases. However, the apparent modulus and yield strength showed significant differences in the two voxel size group pairs (in situ and in vitro). In conclusion, the image voxel size may have to be considered when the finite element voxel modeling technique is used in clinical applications.

Published
2018

124. Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT-Based Finite Element Modeling

Author

Campbell, Graeme M, Peña, Jaime A, Giravent, Sarah, Thomsen, Felix Sebastian Leo, Damm, Timo, Glüer, Claus C., and Borggrefe, Jan

Subjects
Medicina Básica, CIENCIAS MÉDICAS Y DE LA SALUD, PRIMARY TUMORS OF BONE AND CARTILAGE, RADIOLOGY, Inmunología, purl.org/becyt/ford/3 [https], purl.org/becyt/ford/3.1 [https], BIOMECHANICS, BONE QCT
Abstract

Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)-based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T12 (T11 if T12 was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low-dose scan protocol (1.5 mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (–15.2%; p = 0.010; sOR = 1.73; 95% CI, 1.11 to 2.70), yield force (–21.5%; p = 0.002; sOR = 2.09; 95% CI, 1.27 to 3.43), and work to yield (–27.4%; p = 0.001; sOR = 2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R2 = 0.57, yield force: R2 = 0.59, work to yield: R2 = 0.50, p < 0.001), BV/TV (stiffness: R2 = 0.56, yield force: R2 = 0.58, work to yield: R2 = 0.49, p < 0.001), and Tb.Sp (stiffness: R2 = 0.51, yield force: R2 = 0.53, work to yield: R2 = 0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. Fil: Campbell, Graeme M. University Hospital Schleswig‐HolsteinKiel; Alemania. Universitat Hamburg; Alemania Fil: Peña, Jaime A. University Hospital Schleswig‐HolsteinKiel; Alemania Fil: Giravent, Sarah. University Hospital Schleswig‐HolsteinKiel; Alemania Fil: Thomsen, Felix Sebastian Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones en Ingeniería Eléctrica ; Argentina Fil: Damm, Timo. University Hospital Schleswig‐HolsteinKiel; Alemania Fil: Glüer, Claus C.. University Hospital Schleswig‐HolsteinKiel; Alemania Fil: Borggrefe, Jan. University Hospital Schleswig‐HolsteinKiel; Alemania. Universitat zu Köln; Alemania

Published
2017
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125. A new algorithm for estimating the rod volume fraction and the trabecular thickness from in vivo computed tomography

Author

Thomsen, Felix Sebastian Leo, Peña, Jaime Andrés, Lu, Yongtao, Huber, Gerd, Morlock, Michael, Glüer, Claus Christian, and Delrieux, Claudio Augusto

Subjects
Ingeniería de Sistemas y Comunicaciones, FAILURE LOAD, LOCAL FRACTAL DIMENSION, TRABECULAR THICKNESS, INGENIERÍAS Y TECNOLOGÍAS, ROD VOLUME RATIO, QCT, Ingeniería Eléctrica, Ingeniería Electrónica e Ingeniería de la Información, Ingeniería Médica
Abstract

Purpose: Existing microstructure parameters are able to predict vertebral in vitro failure load, but for noisy in vivo data more complex algorithms are needed for a robust assessment. Methods: A new algorithm is proposed for the microstructural analysis of trabecular bone under in vivo quantitative computed tomography (QCT). Five fractal parameters are computed: (1) the average local fractal dimension FD, (2) its standard deviation FD.SD, (3) the fractal rod volume ratio fRV/BV, (4) the average fractal trabecular thickness fTb.Th, and (5) its coefcient of variation fTb.Th.CV. The algorithm requires neither an explicit skeletonization of the trabecular bone, nor a well-defned transition between bone and marrow phases. Two experiments were conducted to compare the fractal with established microstructural parameters. In the frst, 20 volumes-of-interest of embedded vertebrae phantoms were scanned fve times under QCT and high-resolution (HR-)QCT and once under peripheral HRQCT (HRpQCT), to derive accuracy and precision. In the second experiment, correlations between in vitro HRQCT structural parameters were obtained from 76 human T11, T12, or L1 vertebrae. In vitro fracture data were available for a subset of 17 human T12 vertebrae so that linear regression models between failure load and microstructural HRQCT parameters could be analyzed. Results: The results showed correlations of fTb.Th and fRV/BV with their nonfractal pendants trabecular thickness (Tb.Th) and respective structure model index (SMI) while higher precision and accuracy was observed on the fractal measures. Linear models of bone mineral density with two and three fractal microstructural HRQCT parameters explained 86% and 90% (adjusted R2) of the failure load and signifcantly improved the linear models based only on BMD and established standard microstructural parameters (68%-77% adjusted R2). Conclusions: The application of fractal methods may grant further insight into the study of bone quality in vivo when image resolution and quality are less than optimal for current standard methods. Fil: Thomsen, Felix Sebastian Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras; Argentina Fil: Peña, Jaime Andrés. University Hospital Schleswig‐Holstein; Alemania Fil: Lu, Yongtao. Universitat Hamburg; Alemania Fil: Huber, Gerd. Universitat Hamburg; Alemania Fil: Morlock, Michael. University Hospital Schleswig‐Holstein; Alemania Fil: Glüer, Claus Christian. University Hospital Schleswig‐Holstein; Alemania Fil: Delrieux, Claudio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras; Argentina

Published
2016
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126. Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

Author

Peña, Jaime A., Thomsen, Felix Sebastian Leo, Damm, Timo, Campbell, Graeme M., Bastgen, Jan, Barkmann, Reinhard, and Glüer, Claus C.

Subjects
CIENCIAS MÉDICAS Y DE LA SALUD, MARROW FAT, BONE MARROW, BONE DENSITOMETRY, Medicina Critica y de Emergencia, Medicina Clínica, COMPUTED TOMOGRAPHY, IMAGE ANALYSIS
Abstract

Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat‐induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow‐fat density in the axial skeleton. Methods: The authors developed and tested two high resolution‐QCT (HR‐QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone‐void space. To determine their performance, data were compared ex vivo to high‐resolution peripheral CT (HR‐pQCT) images as the gold‐standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR‐pQCT images were correctly identified on HR‐QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm3 corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR‐QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods. Fil: Peña, Jaime A.. Christian‐Albrechts‐Universität zu Kiel; Alemania Fil: Thomsen, Felix Sebastian Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur; Argentina Fil: Damm, Timo. Christian‐Albrechts‐Universität zu Kiel; Alemania Fil: Campbell, Graeme M.. Christian‐Albrechts‐Universität zu Kiel; Alemania. Technische Universität Hamburg‐Harburg; Alemania Fil: Bastgen, Jan. Christian‐Albrechts‐Universität zu Kiel; Alemania Fil: Barkmann, Reinhard. Christian‐Albrechts‐Universität zu Kiel; Alemania Fil: Glüer, Claus C.. Christian‐Albrechts‐Universität zu Kiel; Alemania

Published
2016
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130. An extract from the Atlantic brown algae Saccorhiza polyschides counteracts diet-induced obesity in mice via a gut related multi-factorial mechanisms

Author

Huebbe, Patricia, primary, Nikolai, Sibylle, additional, Schloesser, Anke, additional, Herebian, Diran, additional, Campbell, Graeme, additional, Glüer, Claus-Christian, additional, Zeyner, Annette, additional, Demetrowitsch, Tobias, additional, Schwarz, Karin, additional, Metges, Cornelia C., additional, Roeder, Thomas, additional, Schultheiss, Gerhard, additional, Ipharraguerre, Ignacio R., additional, and Rimbach, Gerald, additional

Published
2017
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132. Association of QCT Bone Mineral Density and Bone Structure With Vertebral Fractures in Patients With Multiple Myeloma

Author

Borggrefe, Jan, Giravent, Sarah, Thomsen, Felix Sebastian Leo, Peña, Jaime, Campbell, Graeme, Wulff, A., Günther, A., Heller, Martin, and Glüer, Claus C.

Subjects
CIENCIAS MÉDICAS Y DE LA SALUD, Fracture risk, BMD, Osteoporosis, Trabecular separation, Vertebral fracture, Medicina Clínica, Radiología, Medicina Nuclear y Diagnóstico por Imágenes, Multiple Myeloma, QCT
Abstract

Purpose: Computed tomography (CT) is used for staging osteolytic lesions and detecting fractures in patients with multiple myeloma (MM). In the OsteoLysis of Metastases and Plasmacell-infiltration Computed Tomography (OLyMP-CT) study we investigated whether patients with and without vertebral fractures show differences in bone mineral density (BMD) or microstructure that could be used to identify patients at risk for fracture. Methods and Materials: We evaluated whole-body CT scans in a group of 104 MM patients without visible osteolytic lesions using an underlying lightweight calibration phantom (Image Analysis Inc., Columbia, KY, USA). QCT software (StructuralInsight) was used for the assessment of BMD and bone structure of the T11 or T12 vertebral body. Age-adjusted standardized odds ratios (sORs) per SD change were derived from logistic regression analyses, and areas under the receiver operating characteristics (ROC) curve (AUCs) analyses were calculated. Results: Forty-six of the 104 patients had prevalent vertebral fractures (24/60 men, 22/44 women). Patients with fractures were not significantly older than patients without fractures (mean ± SD, 64 ± 9.2 versus 62 ± 12.3 years; p = 0.4). Trabecular BMD in patients with fractures versus without fractures was 169 ± 41 versus 192 ± 51 mg/cc (AUC = 0.62 ± 0.06, sOR = 1.6 [1.1 to 2.5], p = 0.02). Microstructural variables achieved optimal discriminatory power at bone thresholds of 150 mg/cc. Best fracture discrimination for single microstructural variables was observed for trabecular separation (Tb.Sp) (AUC = 0.72 ± 0.05, sOR = 2.4 (1.5 to 3.9), p

Published
2015
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134. Utilizing ICG Spectroscopical Properties for Real-Time Nanoparticle Release Quantification In vitroand In vivoin Imaging Setups

Author

Peñate-Medina, Tuula, Kraas, Eike, Luo, Kunliang, Humbert, Jana, Zhu, Hanwen, Mertens, Fabian, Gerle, Mirko, Rohwedder, Arndt, Damoah, Christabel, Will, Olga, Acil, Yahya, Kairemo, Kalevi, Wiltfang, Jörg, Glüer, Claus-C., Scherließ, Regina, Sebens, Susanne, and Peñate-Medina, Oula

Abstract

Background: Nanoparticle imaging and tracking the release of the loaded material from the nanoparticle system have attracted significant attention in recent years. If the release of the loaded molecules could be monitored reliably in vivo, it would speed up the development of drug delivery systems remarkably. Methods: Here, we test a system that uses indocyanine green (ICG) as a fluorescent agent for studying release kinetics in vitro and in vivo from the lipid iron nanoparticle delivery system. The ICG spectral properties like its concentration dependence, sensitivity and the fluctuation of the absorption and emission wavelengths can be utilized for gathering information about the change of the ICG surrounding. Results: We have found that the absorption, fluorescence, and photoacoustic spectra of ICG in lipid iron nanoparticles differ from the spectra of ICG in pure water and plasma. We followed the ICG containing liposomal nanoparticle uptake into squamous carcinoma cells (SCC) by fluorescence microscopy and the in vivo uptake into SCC tumors in an orthotopic xenograft nude mouse model under a surgical microscope. Conclusion: Absorption and emission properties of ICG in the different solvent environment, like in plasma and human serum albumin, differ from those in aqueous solution. Photoacoustic spectral imaging confirmed a peak shift towards longer wavelengths and an intensity increase of ICG when bound to the lipids. The SCC cells showed that the ICG containing liposomes bind to the cell surface but are not internalized in the SCC-9 cells after 60 minutes of incubation. We also showed here that ICG containing liposomal nanoparticles can be traced under a surgical camera in vivo in orthotopic SCC xenografts in mice.

Published
2020
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135. Letter

Author

Genant, Harry K, Glüer, Claus C., Faulkner, Kenneth G, Majumdar, Sharmila, Harris, Steve T., Engelke, Klaus, Hagiwara, Satoshi, and van Kuijk, Cornelis

Published
1992
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136. A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

Author

McCloskey, Eugene V, Odén, Anders, Harvey, Nicholas C, Leslie, William D, Hans, Didier, Johansson, Helena, Barkmann, Reinhard, Boutroy, Stephanie, Brown, Jacques, Chapurlat, Roland, Elders, Petra Jm, Fujita, Yuki, Glüer, Claus-C, Goltzman, David, Iki, Masayuki, Karlsson, Magnus, Kindmark, Andreas, Kotowicz, Mark, Kurumatani, Norio, Kwok, Timothy, Lamy, Oliver, Leung, Jason, Lippuner, Kurt, Ljunggren, Östen, Lorentzon, Mattias, Mellström, Dan, Merlijn, Thomas, Oei, Ling, Ohlsson, Claes, Pasco, Julie A., Rivadeneira, Fernando, Rosengren, Björn, Sornay-Rendu, Elisabeth, Szulc, Pawel, Tamaki, Junko, Kanis, John A, McCloskey, Eugene V, Odén, Anders, Harvey, Nicholas C, Leslie, William D, Hans, Didier, Johansson, Helena, Barkmann, Reinhard, Boutroy, Stephanie, Brown, Jacques, Chapurlat, Roland, Elders, Petra Jm, Fujita, Yuki, Glüer, Claus-C, Goltzman, David, Iki, Masayuki, Karlsson, Magnus, Kindmark, Andreas, Kotowicz, Mark, Kurumatani, Norio, Kwok, Timothy, Lamy, Oliver, Leung, Jason, Lippuner, Kurt, Ljunggren, Östen, Lorentzon, Mattias, Mellström, Dan, Merlijn, Thomas, Oei, Ling, Ohlsson, Claes, Pasco, Julie A., Rivadeneira, Fernando, Rosengren, Björn, Sornay-Rendu, Elisabeth, Szulc, Pawel, Tamaki, Junko, and Kanis, John A

Abstract

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

Published
2016
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137. A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

Author

McCloskey, Eugene V., Odén, Anders, Harvey, Nicholas C., Leslie, William D., Hans, Didier, Johansson, Helena, Barkmann, Reinhard, Boutroy, Stephanie, Brown, Jacques, Chapurlat, Roland, Elders, Petra J. M., Fujita, Yuki, Glüer, Claus-C., Goltzman, David, Iki, Masayuki, Karlsson, Magnus, Kindmark, Andrea, Kotowicz, Mark, Kurumatani, Norio, Kwok, Timothy, Lamy, Oliver, Leung, Jason, Lippuner, Kurt, Ljunggren, Östen, Lorentzon, Mattias, Mellström, Dan, Merlijn, Thomas, Oei, Ling, Ohlsson, Claes, Pasco, Julie A., Rivadeneira, Fernando, Rosengren, Björn, Sornay-Rendu, Elisabeth, Szulc, Pawel, Tamaki, Junko, Kanis, John A., McCloskey, Eugene V., Odén, Anders, Harvey, Nicholas C., Leslie, William D., Hans, Didier, Johansson, Helena, Barkmann, Reinhard, Boutroy, Stephanie, Brown, Jacques, Chapurlat, Roland, Elders, Petra J. M., Fujita, Yuki, Glüer, Claus-C., Goltzman, David, Iki, Masayuki, Karlsson, Magnus, Kindmark, Andrea, Kotowicz, Mark, Kurumatani, Norio, Kwok, Timothy, Lamy, Oliver, Leung, Jason, Lippuner, Kurt, Ljunggren, Östen, Lorentzon, Mattias, Mellström, Dan, Merlijn, Thomas, Oei, Ling, Ohlsson, Claes, Pasco, Julie A., Rivadeneira, Fernando, Rosengren, Björn, Sornay-Rendu, Elisabeth, Szulc, Pawel, Tamaki, Junko, and Kanis, John A.

Abstract

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

Published
2016

140. Pharmacologically Inactive Bisphosphonates as an Alternative Strategy for Targeting Osteoclasts: In Vivo Assessment of 5-Fluorodeoxyuridine-Alendronate in a Preclinical Model of Breast Cancer Bone Metastases

Author

Schem, Christian, primary, Tower, Robert J, additional, Kneissl, Philipp, additional, Rambow, Anna-Christina, additional, Campbell, Graeme M, additional, Desel, Christine, additional, Damm, Timo, additional, Heilmann, Thorsten, additional, Fuchs, Sabine, additional, Zuhayra, Maaz, additional, Trauzold, Anna, additional, Glüer, Claus C, additional, Schott, Sarah, additional, and Tiwari, Sanjay, additional

Published
2016
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141. Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma

Author

Will, Olga Maria, primary, Purcz, N, additional, Chalaris, Athena, additional, Heneweer, Carola, additional, Boretius, Susann, additional, Purcz, Larissa, additional, Nikkola, Lila, additional, Ashammakhi, Nureddin, additional, Kalthoff, Holger, additional, Glüer, Claus-Christian, additional, Wiltfang, Jörg, additional, Açil, Yahya, additional, and Tiwari, Sanjay, additional

Published
2016
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146. Acronyms in bone densitometry

Author

Genant, Harry K., Glüer, Claus C., Faulkner, Kenneth G., Majumdar, Sharmila, Haffis, Steve T., Engelke, Klaus, Hagiwaea, Satoshi, and van Kuijk, Cornelis

Published
1992
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147. Einfluss von Langzeit-Bisphosphonat-Therapie auf Knochenfestigkeit

Author

Krause, Matthias, Hahn, Michael, Soltau, Marcus, Wulff, Birgit, Püschel, Klaus, Glüer, Claus-C., Amling, Michael, and Busse, Björn

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Fragestellung: Vertebrale Frakturen sind die häufigsten atraumatischen Frakturen im Rahmen einer manifesten Osteoporose. Bisphosphonate (BP) sind diesbezüglich die am häufigsten angewendete Medikamentengruppe, da sie das Frakturrisiko von zukünftigen vertebralen Frakturen um bis [for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2013)

Published
2013
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148. Neue Horizonte für die in vivo Bestimmung wesentlicher Aspekte der Knochenqualität: Mikrostruktur und Materialeigenschaften, bestimmt mit Quantitativer Computertomographie und Quantitativen Ultrasound Methoden, entwickelt durch das BioAsset Konsortium

Author

Glüer, Claus C., Krausse, Matthias, Museyko, Oleg, Wulff, Birgit, Campbell, Graeme, Damm, Timo, Daugschies, Melanie, Huber, Gerd, Lu, Yongtao, Peña, Jaime, Waldhausen, Sonja, Bastgen, Jan, Rodhe, Kerstin, Steinebach, Inga, Thomsen, Felix Sebastian Leo, Amling, Michael, Barkmann, Reinhard, Engelke, Klaus, Morlock, Michael M., Pfeilschifter, Johannes, and Püschel, Klaus

Subjects
Medicina Básica, CIENCIAS MÉDICAS Y DE LA SALUD, Mineralization, Quantitative Ultrasound, Finite Element Analysis, Osteoporosis, purl.org/becyt/ford/3 [https], Bone Quality, purl.org/becyt/ford/3.1 [https], Anatomía y Morfología, High Resolution Quantitative Computed Tomography
Abstract

The Biomechanically founded individualised osteoporosis Assessment and treatment (BioAsset) consortium pursues experimental and clinical studies in the context of skeletal effects of bisphosphonate treatment. Here, first results using newly developed diagnostic methods in a set of vertebral bone specimen obtained from donors with documented bisphosphonate history ranging from 0 to more than 5 years of treatment are presented. A new thoracolumbar quantitative computed tomography (QCT) protocol covering T6 to L4 plus high-resolution QCT (HRQCT) assessment of T12 were compared with high-resolution peripheral QCT (HRpQCT) and micro-CT scans of excised specimens serving as gold standard techniques. Finite element (FE) modelling was performed. Material, ultrastructural, and micromechanical properties were tested on a set of single trabeculae obtained from the donor specimens. A newly developed quantitative ultrasound (QUS) device for measuring the anisotropy of cortical material properties was designed and built. The thoracolumbar QCT protocol permitted in situ imaging with good image quality and automated segmentation of vertebral bodies in the whole range from T6 to L4. The duration of bisphosphonate treatment was significantly associated with increased levels of mineralization and this effect could be measured with HRQCT performed on excised specimens. Microstructural parameters contributed to vertebral bone strength modelled by FE analysis independently of bone mineral density. The new QUS scanner permitted measuring the acoustical anisotropy of reference materials. Taken together, these results document that new methods developed in BioAsset permit a more comprehensive assessment of bone fragility. The set of donor specimens with a documented history of bisphosphonate treatment allows for the assessment of the effects of long-term treatment from the organ down to the tissue and material level. These results will ultimately be linked to the parallel clinical study to provide guidance for determining the optimum duration of bisphosphonate treatment to reduce the incidence of osteoporotic fractures. Das Biomechanically founded individualised osteoporosis Assessment and treatment (BioAsset) Konsortium führt experimentelle und klinische Studien zu skelettalen Effekten von Bisphosphonaten durch. Neue diagnostische Verfahren zur Analyse von Wirbelkörperproben von Spendern mit dokumentierter Bisphosphonateinnahme über 0 bis >5 Jahre wurden entwickelt. Mittels thorakolumbaler Quantitativer Computertomographie (QCT) und hochauflösender QCT (HRQCT) wurden Knochenmineraldichte (BMD), Mikrostrukturvariablen und Materialeigenschaften, insbesondere Mineralisierung, untersucht. Finite Element (FE) Modellierung dient der Bestimmung der Wirbelkörperbruchlast. Ein neues Quantitatives Ultraschall (QUS) Gerät zur Messung anisotroper kortikaler Materialeigenschaften wurde konstruiert. Ein signifikanter Zusammenhang von Mineralisierung und (Dauer der) Bisphosphonattherapie konnte mit Mikro-CT und HRQCT nachgewiesen werden. Das thorakolumbale QCT Protokoll ermöglichte eine Dosisreduktion von 60% gegenüber Standardprotokollen. Eine Finite Elemente Analyse zeigte BMD und Trabekelanzahl als unabhängige Determinanten der Bruchlast. Mit dem neuen QUS Gerät konnte die akustische Anisotropie von Referenzmaterialien bestimmt werden. Die Daten dokumentieren erweitere Diagnosemöglichkeiten zur Abschätzung von Knochenfragilität durch die neuen Verfahren. Parallel durchgeführte klinische Studien sollen die Frage der optimalen Dauer von Bisphosphonattherapie klären. Fil: Glüer, Claus C.. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Krausse, Matthias. Universitätsklinikum Hamburg-Eppendorf. Institut für Osteologie und Biomechanik; Alemania. Universitat Hamburg; Alemania Fil: Museyko, Oleg. Universität Erlangen. Institut für Medizinische Physik; Alemania Fil: Wulff, Birgit. Universitätsklinikum Hamburg-Eppendorf. Institut für Rechtsmedizin; Alemania Fil: Campbell, Graeme. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Damm, Timo. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Daugschies, Melanie. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Huber, Gerd. Technische Universität Hamburg-Harburg. Institut für Biomechanik; Alemania Fil: Lu, Yongtao. Technische Universität Hamburg-Harburg. Institut für Biomechanik; Alemania Fil: Peña, Jaime. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Waldhausen, Sonja. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Bastgen, Jan. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Rodhe, Kerstin. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Steinebach, Inga. Alfried Krupp Krankenhaus Steele. Osteologisches Forschungszentrum Essen; Alemania Fil: Thomsen, Felix Sebastian Leo. Universitätsklinikum Schleswig-Holstein; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca; Argentina Fil: Amling, Michael. Universitätsklinikum Hamburg-Eppendorf. Institut für Osteologie und Biomechanik; Alemania Fil: Barkmann, Reinhard. Universitätsklinikum Schleswig-Holstein; Alemania Fil: Engelke, Klaus. Universität Erlangen. Institut für Medizinische Physik; Alemania Fil: Morlock, Michael M.. Technische Universität Hamburg-Harburg. Institut für Biomechanik; Alemania Fil: Pfeilschifter, Johannes. Alfried Krupp Krankenhaus Steele. Osteologisches Forschungszentrum Essen; Alemania Fil: Püschel, Klaus. Universitätsklinikum Hamburg-Eppendorf. Institut für Rechtsmedizin; Alemania

Published
2013

149. Tracking the Progression of Osteolytic and Osteosclerotic Lesions in Mice Using Serial In Vivo μCT: Applications to the Assessment of Bisphosphonate Treatment Efficacy.

Author

Damm, Timo, Tiwari, Sanjay, Glüer, Claus C., Campbell, Graeme M., Tower, Robert J., Kneissl, Philipp, Rambow, Anna C., and Schem, Christian

Abstract

ABSTRACT: The metastasis of tumor cells to bone can lead to osteolytic and osteosclerotic lesions, which cause severe, highly‐localized bone destruction and abnormal bone apposition, respectively. Accurate quantification of lesion progression is critical to understand underlying mechanisms and assess treatment efficacy; however, standard structural parameters may be insensitive to local changes. We developed methods to quantify osteolytic and osteosclerotic lesions using micro–computed tomography (μCT) within in vivo mouse datasets. Two Balb/c nude datasets were used: (i) bone‐homing MDA‐MB‐231 (osteolytic) cells injected into the left ventricle, treatment with alendronate or vehicle, and weekly μCT (proximal tibia) for 4 weeks, and (ii) MCF7 (osteosclerotic) cells injected into the right tibia and weekly μCT over 12 weeks. After registering images to baseline, osteolytic lesion volume was determined by summing all baseline bone voxels at distances greater than a threshold (150 μm) from the nearest follow‐up. Osteosclerotic lesions were determined by measuring the distance from each follow‐up surface voxel to the nearest baseline surface and calculating the standard deviation of distance values (SDDT) of the surrounding voxels. Bone mineral density (BMD), bone volume density (BV/TV), and separation (Sp) were determined for comparison. Osteolytic lesions were observed 1 week after tumor cell injection; however, no corresponding BV/TV losses or Sp increases were observed, indicating that standard parameters were unable to detect early metastatic changes. Lesion volume was smaller in the alendronate versus control group (15.0%, p = 0.004 and 18.6%, p = 0.002 of control lesion volume at weeks 3 and 4, respectively). In the osteosclerotic dataset, increased SDDT was observed following injection, providing a potential new measure of osteosclerotic bone apposition. These data show that quantification of local structural change with serial μCT may overcome the limitations of standard mineral and microstructural parameters, and successfully separates metastatic and normal bone turnover. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Published
2018
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150. Veränderte Knochenheilung nach hämorrhagischem Schock?

Author

Lichte, Philipp, Kobbe, Philipp, Campbell, Graeme, Pfeifer, Roman, Glüer, Claus-C., Pape, Hans-Christoph, and Pufe, Thomas

Subjects
hämorrhagischer Schock, ddc: 610, Frakturheilung, 610 Medical sciences, Medicine
Abstract

Fragestellung: Verschiedene Faktoren, z.B. Schädel-Hirn-Traumata und Langzeitbeatmung, können die Frakturheilung bei Schwerverletzen beeinflussen. Die Auswirkungen einer isolierten Hämorrhagie und der damit verbundenen systemischen Inflammation sind derzeit jedoch noch unzureichend bekannt.[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2012)

Published
2012

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