A mechano‐regulation model of fracture repair in vertebral bodies

In this study a multi‐scale mechano‐regulation model was developed in order to investigate the mechanobiology of trabecular fracture healing in vertebral bodies. A macro‐scale finite element model of the spinal segment L3–L4–L5, including a mild wedge fracture in the body of the L4 vertebra, was used to determine the boundary conditions acting on a micro‐scale finite element model simulating a portion of fractured trabecular bone. The micro‐scale model, in turn, was utilized to predict the local patterns of tissue differentiation within the fracture gap and then how the equivalent mechanical properties of the macro‐scale model change with time. The patterns of tissue differentiation predicted by the model appeared consistent with those observed in vivo. Bone formation occurred primarily through endochondral ossification. New woven bone was predicted to occupy the majority of the space within the fracture site approximately 7–8 weeks after the fracture event. Remodeling of cancellous bone architecture was then predicted, with complete new trabeculae forming due to bridging of the microcallus between the remnant trabeculae. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:433–443, 2011

[1]  Rik Huiskes,et al.  Corroboration of mechanoregulatory algorithms for tissue differentiation during fracture healing: comparison with in vivo results , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  M J Gómez-Benito,et al.  Influence of fracture gap size on the pattern of long bone healing: a computational study. , 2005, Journal of theoretical biology.

[3]  P J Prendergast,et al.  Three-dimensional Simulation of Fracture Repair in the Human Tibia , 2002, Computer methods in biomechanics and biomedical engineering.

[4]  Rik Huiskes,et al.  A mechano-regulatory bone-healing model incorporating cell-phenotype specific activity. , 2008, Journal of theoretical biology.

[5]  R. Haut,et al.  A finite element model predicts the mechanotransduction response of tendon cells to cyclic tensile loading , 2008, Biomechanics and modeling in mechanobiology.

[6]  Rüdiger Weiner,et al.  Angiogenesis in bone fracture healing: a bioregulatory model. , 2008, Journal of theoretical biology.

[7]  D Lacroix,et al.  A finite element study of mechanical stimuli in scaffolds for bone tissue engineering. , 2008, Journal of biomechanics.

[8]  Rüdiger Weiner,et al.  Mathematical modeling of fracture healing in mice: comparison between experimental data and numerical simulation results , 2006, Medical and Biological Engineering and Computing.

[9]  R. Eastell,et al.  Classification of vertebral fractures , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

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

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

[12]  Friedrich Pauwels,et al.  A New Theory Concerning the Influence of Mechanical Stimuli on the Differentiation of the Supporting Tissues , 1980 .

[13]  T. Hansson,et al.  Microcalluses of the Trabeculae in Lumbar Vertebrae and Their Relation to the Bone Mineral Content , 1981, Spine.

[14]  R. Huiskes,et al.  Biophysical stimuli on cells during tissue differentiation at implant interfaces , 1997 .

[15]  G S Beaupré,et al.  Correlations between mechanical stress history and tissue differentiation in initial fracture healing , 1988, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[16]  A. Leblanc,et al.  Regional Variation in Vertebral Bone Density and Trabecular Architecture Are Influenced by Osteoarthritic Change and Osteoporosis , 1997, Spine.

[17]  T. Einhorn The Science of Fracture Healing , 2005, Journal of orthopaedic trauma.

[18]  Pedro Moreo,et al.  On the effect of substrate curvature on cell mechanics. , 2009, Biomaterials.

[19]  M. Nevitt,et al.  Vertebral fracture assessment using a semiquantitative technique , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  Sandra J Shefelbine,et al.  Trabecular bone fracture healing simulation with finite element analysis and fuzzy logic. , 2005, Journal of biomechanics.

[21]  Michael Hahn,et al.  Architecture and distribution of cancellous bone yield vertebral fracture clues , 1996, Archives of Orthopaedic and Trauma Surgery.

[22]  L. Claes,et al.  Magnitudes of local stress and strain along bony surfaces predict the course and type of fracture healing. , 1998, Journal of biomechanics.

[23]  J. Lewis,et al.  Mechanical properties of the fibrous tissue found at the bone-cement interface following total joint replacement. , 1982, Journal of biomedical materials research.

[24]  T. Diamond,et al.  Histomorphometric analysis of fracture healing cascade in acute osteoporotic vertebral body fractures. , 2007, Bone.

[25]  Patrick J. Prendergast,et al.  A Mechanobiological Model for Tissue Differentiation that Includes Angiogenesis: A Lattice-Based Modeling Approach , 2008, Annals of Biomedical Engineering.

[26]  G. Bergmann,et al.  Spinal loads after osteoporotic vertebral fractures treated by vertebroplasty or kyphoplasty , 2006, European Spine Journal.

[27]  M. V. D. van der Meulen,et al.  A mathematical framework to study the effects of growth factor influences on fracture healing. , 2001, Journal of theoretical biology.

[28]  P J Prendergast,et al.  Random-walk models of cell dispersal included in mechanobiological simulations of tissue differentiation. , 2007, Journal of biomechanics.

[29]  D T Davy,et al.  The biomechanical behavior of healing canine radii and ribs. , 1982, Journal of biomechanics.

[30]  C. Jungreuthmayer,et al.  Deformation simulation of cells seeded on a collagen-GAG scaffold in a flow perfusion bioreactor using a sequential 3D CFD-elastostatics model. , 2009, Medical engineering & physics.

[31]  P. J. Prendergast,et al.  Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells , 2008, Biomechanics and modeling in mechanobiology.

[32]  V C Mow,et al.  Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. , 1982, The Journal of bone and joint surgery. American volume.

[33]  M. Heggeness,et al.  A Histologic Study of Fractured Human Vertebral Bodies , 2002, Journal of spinal disorders & techniques.

[34]  R. Huiskes,et al.  A biomechanical regulatory model for periprosthetic fibrous-tissue differentiation , 1997, Journal of materials science. Materials in medicine.

[35]  D P Fyhrie,et al.  Human vertebral body apparent and hard tissue stiffness. , 1998, Journal of biomechanics.

[36]  D Kaspar,et al.  Effects of Mechanical Factors on the Fracture Healing Process , 1998, Clinical orthopaedics and related research.

[37]  F. Pauwels,et al.  Eine neue Theorie über den Einfluß mechanischer Reize auf die Differenzierung der Stützgewebe , 2004, Zeitschrift für Anatomie und Entwicklungsgeschichte.

[38]  P J Prendergast,et al.  Bone ingrowth simulation for a concept glenoid component design. , 2005, Journal of biomechanics.

[39]  Patrick J. Prendergast,et al.  Tissue differentiation and bone regeneration in an osteotomized mandible: a computational analysis of the latency period , 2008, Medical & Biological Engineering & Computing.

[40]  Thomas A Einhorn,et al.  Fracture healing as a post‐natal developmental process: Molecular, spatial, and temporal aspects of its regulation , 2003, Journal of cellular biochemistry.

[41]  V. Mow,et al.  The mechanical environment of the chondrocyte: a biphasic finite element model of cell-matrix interactions in articular cartilage. , 2000, Journal of biomechanics.

[42]  P. Prendergast,et al.  A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. , 2002, Journal of biomechanics.

[43]  D. Lacroix,et al.  Biomechanical model to simulate tissue differentiation and bone regeneration: Application to fracture healing , 2006, Medical and Biological Engineering and Computing.

[44]  S. Cummings,et al.  Epidemiology and outcomes of osteoporotic fractures , 2002, The Lancet.

[45]  I. Lieberman,et al.  Histological Evaluation of Biopsies Obtained From Vertebral Compression Fractures: Unsuspected Myeloma and Osteomalacia , 2005, Spine.

[46]  R. Gilbert,et al.  Application of the multiscale FEM to the modeling of cancellous bone , 2010, Biomechanics and modeling in mechanobiology.

[47]  Friedrich Pauwels Eine neue Theorie über den Einfluß mechanischer Reize auf die Differenzierung der Stützgewebe , 1965 .

[48]  C. Pappalettere,et al.  The Influence of Expansion Rates on Mandibular Distraction Osteogenesis: A Computational Analysis , 2007, Annals of Biomedical Engineering.

[49]  R Pietrabissa,et al.  Finite element analysis of cancellous bone failure in the vertebral body of healthy and osteoporotic subjects , 2008, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[50]  P J Prendergast,et al.  Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects. , 2005, Journal of biomechanics.

[51]  P. Prendergast,et al.  Loss of trabeculae by mechano-biological means may explain rapid bone loss in osteoporosis , 2008, Journal of The Royal Society Interface.

[52]  Numerical Simulation of the Influence of Rough Bone-Callus Interface on the Healing of Fractured Bone , 2000 .

[53]  J. A. Sanz-Herrera,et al.  A mathematical model for bone tissue regeneration inside a specific type of scaffold , 2008, Biomechanics and modeling in mechanobiology.

[54]  PhD M. H. Heggeness MD Spine fracture with neurological deficit in osteoporosis , 2005, Osteoporosis International.