Unwrapping microcomputed tomographic images for measuring cortical osteolytic lesions in the 5T2 murine model of myeloma treated by bisphosphonate |
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| Institution: | 1. GEROM Groupe Etudes Remodelage Osseux et bioMatériaux, LUNAM Université, IRIS-IBS Institut de Biologie en Santé, CHU d‘Angers, 49933 Angers Cedex, France;2. UPSP “Biologie et Biomatériaux du Tissus Osseux – Chirurgie Expérimentale”, ONIRIS – National Veterinary School of Nantes, LUNAM Université, Route de Gâchet, BP 44706, F44307 Nantes cedex 03, France;3. Service de Rhumatologie, CHU d‘Angers, 49933 Angers Cedex, France;1. Wroc?aw University of Technology, Faculty of Microsystem Electronics and Photonics, ul. Z. Janiszewskiego 11/17, PL-50372 Wroc?aw, Poland;2. Institute of Electronic Materials Technology, ul. Wolczynska 133, PL-01919 Warsaw, Poland;1. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China;2. Key Laboratory of Optoelectronic Devices and Systems of Ministry of Guangdong Province, and Shenzhen Key Laboratory of Micro-Nano Biomedical Optical Detection and Imaging, Shenzhen University, Shenzhen 518060, China;1. National Tsing-Hua University Hsin Chu, Taiwan;2. National Center for Electron Microscopy and Joint Center for Artificial Photosynthesis, Lawrence Berkeley National Laboratory, One Cyclotron Road,, Berkeley, CA 94720, USA;3. University of Antwerp, EMAT, Department of Physics, Belgium;1. University of Silesia, Department of Animal Histology and Embryology, Bankowa 9, 40-007 Katowice, Poland;2. Charles University, Faculty of Science, Department of Zoology, Vinicna 7, 128 44 Prague 2, Czech Republic;3. Institute of Soil Biology, Biology Centre AS CR, Na Sadkach 7, CZ-370 05 Ceske Budejovice, Czech Republic;1. Shanghai Key Laboratory of Advanced High Temperature Materials and Precision Forming, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China;2. Canadian Centre of Electron Microscopy and Department of Materials Science and Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada |
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| Abstract: | Multiple myeloma is due to the proliferation of malignant plasma cells which increase the number of osteoclasts leading to trabecular and cortical bone osteolysis. The 5T2MM murine model reproduces the human disease and microcomputed tomography is a precise tool to investigate bone loss. Bisphosphonates (zoledronic acid or pamidronate) are used in preventing osteolysis. However, loss of cortical bone in not possible to quantify by histomorphometry on histological sections or microCT images.Osteolysis was studied in mice grafted with the 5THL subline to see if one drug was more active after 10 weeks. Mice were distributed into 4 groups: control, untreated, treated with pamidronate or with zoledronic acid. The left femurs were embedded undecalcified and sectioned at 7 μm. The right tibias and femurs were analyzed by microCT and trabecular morphometric parameters were obtained. Cortical bone osteolysis was analyzed by developing a new algorithm to unwrap microCT sections of the cortices, allowing measurement of the number of perforations, porosity and mean perforation area.The bisphosphonates had no significant effect on the tumor growth as evidence by the absence of effect on the M-protein level. Cortical perforations were evidenced on histological sections and their number seemed to be reduced by both bisphosphonates. MicroCT was used to quantify the trabecular bone: a bone loss was evidenced in the untreated myeloma group and both bisphosphonates appeared equal to preserve trabecular mass. However, the number and size of cortical perforations cannot be determined on 3D models. Unwrapping microCT images provided flat images allowing a precise determination of cortical perforations. Pamidronate did not reduce the number and size of cortical perforations but significantly reduced porosity. Zoledronic acid appeared significantly superior and considerably reduced all parameters.Unwrapping microCT image is a new method allowing the measurement of cortical perforations in bone malignancies, a parameter that cannot be measured correctly on 2D histological sections. |
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| Keywords: | Myeloma Bisphosphonate Cortical bone Osteolysis MicroCT |
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