CISM International Centre for Mechanical Sciences

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1 CISM International Centre for Mechanical Sciences Courses and Lectures Volume 578 Series editors The Rectors Friedrich Pfeiffer, Munich, Germany Franz G. Rammerstorfer, Vienna, Austria Elisabeth Guazzelli, Marseille, France The Secretary General Bernhard Schrefler, Padua, Italy Executive Editor Paolo Serafini, Udine, Italy

2 The series presents lecture notes, monographs, edited works and proceedings in the field of Mechanics, Engineering, Computer Science and Applied Mathematics. Purpose of the series is to make known in the international scientific and technical community results obtained in some of the activities organized by CISM, the International Centre for Mechanical Sciences. More information about this series at

3 Peter Pivonka Editor Multiscale Mechanobiology of Bone Remodeling and Adaptation 123

4 Editor Peter Pivonka School of Chemistry, Physics and Mechanical Engineering Queensland University of Technology Brisbane, QLD Australia ISSN ISSN (electronic) CISM International Centre for Mechanical Sciences ISBN ISBN (ebook) DOI / Library of Congress Control Number: CISM International Centre for Mechanical Sciences 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

5 To my Mother and Father who have provided a lifetime of encouragement and support and to my wife Carolina in appreciation of her love, spirit and compassion, and who continuously inspires my work and life.

6 Preface Osteoporosis (OP) is a major health problem in society. OP is characterised by low bone mass and deterioration of bone strength, resulting in fragile bones which are more prone to fracture. Osteoporosis is often called the silent disease because bone loss occurs without symptoms. New drugs are continually being developed and trialled in animals, and the most promising ones tested on humans. However, many bone diseases including OP do not have a proven means of prevention or effective treatment. On the one hand, precision medicine is an emerging field for disease treatment and prevention that takes into account the variability in genes, environment, and lifestyle factors for each individual. Any comprehensive approach for understanding bone disease progression and effective drug interventions requires integration of experimental findings and computational modelling. Particularly, over the last few decades, a large number of regulatory factors in bone homeostasis and pathology have been identified together with interactions of bone tissue with other tissues such as muscles, blood vessels, and the nervous system which all have been shown to regulate bone responses. Furthermore, links between bone quality and environmental factors such as nutrition and mechanical loading have been established. On the other hand, material engineering has made significant progress in characterising and modelling of biomaterials such as bone with high accuracy at various scales of observation. In particular, micromechanical approaches have proven to be very powerful in integrating different experimental information from different scales. A long-standing missing link between the mechanical aspects of bone and the biochemical and mechanobiological regulations has recently been established by developing cell-based models of bone remodeling and adaptation. These models allow to integrate subject-specific data and can be used to predict changes in bone mass and the respective mechanical properties. The ultimate goal of any of these models is to predict the fracture risk of a patient in order to start an intervention of either drug or physiological exercise in a timely manner. The present book is a summary of the course notes of the 20th CISM-IUTAM International Summer School on Multiscale Mechanobiology of Bone Remodeling vii

7 viii Preface and Adaptation. This course gathered experts from the fields of applied mechanics and biomedical engineering, complex systems modelling, bone biology, mechanobiology, and materials science, in order to give, in an unprecedented interdisciplinary fashion, the cutting-edge view on bone mechanobiology with emphasis on disease progression analysis in osteoporosis and assessment of changes in material properties. These include disease systems analysis of osteoporosis (P. Pivonka) in order to predict disease progression and drug interventions; musculoskeletal modelling (J. Fernandez) in order to accurately estimate muscle forces acting on bone; bone biology (D. Findlay) including interactions of bone tissue with other tissues such as muscle, cartilage, vascularisation, and central nervous system (CNS); bone mechanobiology (T. Skerry) including Frost s mechanostat theory, animal models of bone mechanical loading, and osteocytes and their role as mechanosensing cells; multiscale bone adaptation algorithms (T. Adachi); and bone quality assessment at different scales using experimental and computational approaches (Ch. Hellmich), including fundamentals of continuum micromechanics with application to bone and merging quantitative computed tomography (qct) with micromechanics as a new clinical tool. The individual chapters of this book were prepared by the respective lecturers and their collaborators with the exception of Prof. Tim Skerry who was not able to contribute due to many other commitments at that time. Fortunately, Prof. Mark Forwood with the assistance of myself was able to summarise the content of the Bone Mechanobiology chapter. It is a pleasure to thank the six lecturers and the 25 attendees who came from 12 different countries and actively participated in the numerous discussions throughout the course. I would like to also extend my thanks and appreciation to the administrative staff of CISM for their help. Last but not least, support by the International Union for Theoretical and Applied Mechanics (IUTAM) is also gratefully acknowledged. Brisbane, Australia March 2017 Peter Pivonka

8 Contents Functional Adaptation of Bone: The Mechanostat and Beyond Peter Pivonka, Aaron Park and Mark R. Forwood Application of Disease System Analysis to Osteoporosis: From Temporal to Spatio-Temporal Assessment of Disease Progression and Intervention Silvia Trichilo and Peter Pivonka Musculoskeletal Modelling and the Physiome Project Justin Fernandez, Ju Zhang, Vickie Shim, Jacob T. Munro, Massimo Sartori, Thor Besier, David G. Lloyd, David P. Nickerson and Peter Hunter Review of Universal Rules Governing Bone Composition, Organization, and Elasticity Across Organizational Hierarchies Viktoria Vass, Claire Morin, Stefan Scheiner and Christian Hellmich Computational Biomechanics of Bone Adaptation by Remodeling Taiji Adachi and Yoshitaka Kameo Biology of Bone and the Interaction of Bone with Other Organ Systems David M. Findlay ix

9 Contributors Taiji Adachi Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan Thor Besier Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand; Department of Engineering Science, University of Auckland, Auckland, New Zealand Justin Fernandez Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand; Department of Engineering Science, University of Auckland, Auckland, New Zealand David M. Findlay Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA, Australia Mark R. Forwood School of Medical Science and Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia Christian Hellmich Institute for Mechanics of Materials and Structures, TU Wien Vienna University of Technology, Vienna, Austria Peter Hunter Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Yoshitaka Kameo Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan David G. Lloyd Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia Claire Morin Ecole Nationale Supérieure des Mines de Saint Etienne, CIS-EMSE-INSERM U1059, SAINBIOSE, Saint-Etienne, France Jacob T. Munro School of Medicine, University of Auckland, Auckland, New Zealand; Auckland City Hospital, University of Auckland, Auckland, New Zealand xi

10 xii Contributors David P. Nickerson Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Aaron Park School of Medical Science and Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia Peter Pivonka St Vincent s Department of Surgery, The University of Melbourne, Melbourne, VIC, Australia; Australian Institute of Musculoskeletal Science, Melbourne, VIC, Australia; School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD, Australia Massimo Sartori Department of Neurorehabilitation Engineering, Göttingen University, Gottingen, Germany Stefan Scheiner Institute for Mechanics of Materials and Structures, TU Wien Vienna University of Technology, Vienna, Austria Vickie Shim Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Silvia Trichilo St Vincent s Department of Surgery, The University of Melbourne, Melbourne, VIC, Australia; Australian Institute of Musculoskeletal Science, Melbourne, VIC, Australia Viktoria Vass Institute for Mechanics of Materials and Structures, TU Wien Vienna University of Technology, Vienna, Austria Ju Zhang Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand

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