Connecting Mechanics and Bone Cell Activities in the Bone Remodeling Process: An Integrated Finite Element Modeling

Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain–damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.’s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone adaptation. The proposed FEM model gives insight into how bone cells adapt their architecture to the mechanical and biological environment.

[1]  Patrick J Prendergast,et al.  Bone remodelling algorithms incorporating both strain and microdamage stimuli. , 2007, Journal of biomechanics.

[2]  V. Nicolin,et al.  Receptor Activator for Nuclear Factor kappa B Ligand (RANKL) as an osteoimmune key regulator in bone physiology and pathology. , 2011, Acta histochemica.

[3]  G. Beaupré,et al.  An approach for time‐dependent bone modeling and remodeling—application: A preliminary remodeling simulation , 1990, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[4]  T. Martin,et al.  Role of osteoblasts in hormonal control of bone resorption - a hypothesis. , 1982, Calcified tissue international.

[5]  K. Ito,et al.  Analysis of bone architecture sensitivity for changes in mechanical loading, cellular activity, mechanotransduction, and tissue properties , 2011, Biomechanics and modeling in mechanobiology.

[6]  B. Martin,et al.  Mathematical model for repair of fatigue damage and stress fracture in osteonal bone , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[7]  Tomonori Yamada,et al.  Computer simulation of trabecular remodeling in human proximal femur using large-scale voxel FE models: Approach to understanding Wolff's law. , 2009, Journal of biomechanics.

[8]  H. Grootenboer,et al.  Adaptive bone-remodeling theory applied to prosthetic-design analysis. , 1987, Journal of biomechanics.

[9]  A. Parfitt Osteonal and hemi‐osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone , 1994, Journal of cellular biochemistry.

[10]  B. Riggs,et al.  The Type I/Type II Model for Involutional Osteoporosis: Update and Modification Based on New Observations , 2001 .

[11]  J. C. Simo,et al.  Numerical instabilities in bone remodeling simulations: the advantages of a node-based finite element approach. , 1995, Journal of biomechanics.

[12]  Stuart J Warden,et al.  Cellular accommodation and the response of bone to mechanical loading. , 2005, Journal of biomechanics.

[13]  S. Manolagas,et al.  Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. , 2000, Endocrine reviews.

[14]  M. Rashid,et al.  A mechanistic model for internal bone remodeling exhibits different dynamic responses in disuse and overload. , 2001, Journal of biomechanics.

[15]  H. Rodrigues,et al.  A Model of Bone Adaptation Using a Global Optimisation Criterion Based on the Trajectorial Theory of Wolff. , 1999, Computer methods in biomechanics and biomedical engineering.

[16]  G. Rodan,et al.  Role of osteoblasts in hormonal control of bone resorption—A hypothesis , 2006, Calcified Tissue International.

[17]  M Zidi,et al.  A theoretical model of the effect of continuum damage on a bone adaptation model. , 2001, Journal of biomechanics.

[18]  P. Lipinski,et al.  Modeling of bone adaptative behavior based on cells activities , 2011, Biomechanics and modeling in mechanobiology.

[19]  Primer on the metabolic bone diseases and disorders of mineral metabolism. , 2013 .

[20]  Ridha Hambli,et al.  Numerical procedure for multiscale bone adaptation prediction based on neural networks and finite element simulation , 2011 .

[21]  Ridha Hambli,et al.  Strain–damage coupled algorithm for cancellous bone mechano-regulation with spatial function influence , 2009 .

[22]  Peter Pivonka,et al.  Model structure and control of bone remodeling: a theoretical study. , 2008, Bone.

[23]  R. Hambli Micro-CT finite element model and experimental validation of trabecular bone damage and fracture. , 2013, Bone.

[24]  A. Parfitt,et al.  Bone remodeling. , 1988, Henry Ford Hospital medical journal.

[25]  A. Amis,et al.  The effect of muscle loading on the simulation of bone remodelling in the proximal femur. , 2005, Journal of biomechanics.

[26]  David B. Burr,et al.  Skeletal Tissue Mechanics , 1998, Springer New York.

[27]  F. Allgöwer,et al.  Mathematical Modeling and Analysis of Force Induced Bone Growth , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[28]  Geoff Smith,et al.  Phenomenological model of bone remodeling cycle containing osteocyte regulation loop. , 2006, Bio Systems.

[29]  T. Adachi,et al.  Trabecular bone remodelling simulation considering osteocytic response to fluid-induced shear stress , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[30]  R. Huiskes,et al.  Proposal for the regulatory mechanism of Wolff's law , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[31]  R Huiskes,et al.  A theoretical framework for strain-related trabecular bone maintenance and adaptation. , 2005, Journal of biomechanics.

[32]  Ridha Hambli,et al.  Physiologically based mathematical model of transduction of mechanobiological signals by osteocytes , 2011, Biomechanics and Modeling in Mechanobiology.

[33]  Yoshitaka Wada,et al.  Computer-simulated bone architecture in a simple bone-remodeling model based on a reaction-diffusion system , 2004, Journal of Bone and Mineral Metabolism.

[34]  N. Kikuchi,et al.  A homogenization sampling procedure for calculating trabecular bone effective stiffness and tissue level stress. , 1994, Journal of biomechanics.

[35]  Svetlana V Komarova,et al.  Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling. , 2003, Bone.

[36]  Vincent Lemaire,et al.  Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. , 2004, Journal of theoretical biology.

[37]  Chontita Rattanakul,et al.  Modeling of bone formation and resorption mediated by parathyroid hormone: response to estrogen/PTH therapy. , 2003, Bio Systems.

[38]  R. T. Hart,et al.  Introduction to Finite Element Based Simulation of Functional Adaptation of Cancellous Bone , 1998 .

[39]  John E. Renaud,et al.  Topology Optimization Using a Hybrid Cellular Automaton Method With Local Control Rules , 2006 .

[40]  Akio Tamura,et al.  Mathematical approaches to bone reformation phenomena and numerical simulations , 2003 .

[41]  D P Fyhrie,et al.  Trabecular bone density and loading history: regulation of connective tissue biology by mechanical energy. , 1987, Journal of biomechanics.

[42]  David Taylor,et al.  Predicting stress fractures using a probabilistic model of damage, repair and adaptation , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[43]  H. Frost,et al.  Toward a Mathematical Description of Bone Biology: The Principle of Cellular Accommodation , 2014, Calcified Tissue International.

[44]  P Zioupos,et al.  Mechanical properties and the hierarchical structure of bone. , 1998, Medical engineering & physics.

[45]  P. Thurner,et al.  Finite element prediction with experimental validation of damage distribution in single trabeculae during three-point bending tests. , 2013, Journal of the mechanical behavior of biomedical materials.

[46]  W. J. Whitehouse,et al.  Scanning electron microscope studies of trabecular bone in the proximal end of the human femur. , 1974, Journal of anatomy.

[47]  In Gwun Jang,et al.  Application of design space optimization to bone remodeling simulation of trabecular architecture in human proximal femur for higher computational efficiency , 2010 .

[48]  Ridha Hambli,et al.  Application of neural networks and finite element computation for multiscale simulation of bone remodeling. , 2010, Journal of biomechanical engineering.

[49]  J. C. Simo,et al.  Adaptive bone remodeling incorporating simultaneous density and anisotropy considerations. , 1997, Journal of biomechanics.

[50]  M Bagge,et al.  A model of bone adaptation as an optimization process. , 2000, Journal of biomechanics.

[51]  In Gwun Jang,et al.  Computational study of Wolff's law with trabecular architecture in the human proximal femur using topology optimization. , 2008, Journal of biomechanics.

[52]  John A. Kanis Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism , 2000 .

[53]  Rik Huiskes,et al.  Effects of mechanical forces on maintenance and adaptation of form in trabecular bone , 2000, Nature.

[54]  Ridha Hambli,et al.  Multiscale methodology for bone remodelling simulation using coupled finite element and neural network computation , 2011, Biomechanics and modeling in mechanobiology.

[55]  Jean-Louis Chaboche,et al.  Continuous damage mechanics — A tool to describe phenomena before crack initiation☆ , 1981 .

[56]  J. M. García-Aznar,et al.  A bone remodelling model coupling microdamage growth and repair by 3D BMU-activity , 2005, Biomechanics and modeling in mechanobiology.

[57]  D. Taylor.,et al.  Microdamage and mechanical behaviour: predicting failure and remodelling in compact bone , 2003, Journal of anatomy.

[58]  Harold M. Frost,et al.  The Utah paradigm of skeletal physiology: an overview of its insights for bone, cartilage and collagenous tissue organs , 2000, Journal of Bone and Mineral Metabolism.

[59]  P J Prendergast,et al.  Prediction of bone adaptation using damage accumulation. , 1994, Journal of biomechanics.

[60]  Yoshitaka Wada,et al.  iBone: A Reaction Diffusion Based Shape Optimization Method , 2003 .

[61]  G S Beaupré,et al.  A model of mechanobiologic and metabolic influences on bone adaptation. , 2000, Journal of rehabilitation research and development.

[62]  Nilima Nigam,et al.  Mathematical Modeling of Spatio‐Temporal Dynamics of a Single Bone Multicellular Unit , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[63]  G. Beaupré,et al.  The influence of bone volume fraction and ash fraction on bone strength and modulus. , 2001, Bone.

[64]  C. H. Turner,et al.  Toward a Mathematical Description of Bone Biology: The Principle of Cellular Accommodation , 1999, Calcified Tissue International.

[65]  D. Carter,et al.  Relationships between loading history and femoral cancellous bone architecture. , 1989, Journal of biomechanics.