Skip to main content
SpringerLink
Log in

In Vivo Validation of Predictive Models for Bone Remodeling and Mechanobiology

  • Conference paper
Computer Models in Biomechanics

  • 2443 Accesses

Abstract

In silico modeling is a powerful tool for the prediction of bone remodeling and mechanobiology. As the method is gaining popularity a standardized measure for the in vivo validation of the quality of the produced simulations is required. In this review, we discuss current validity assessment approaches, as well as the validation ‘gold standard’, in which the experimental and computational parts are carried out concomitantly, and by the same research team. A novel validation framework for the tissue level model, based on the true geometry is introduced.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adachi T, Tsubota K, Tomita Y, Hollister SJ (2001) Trabecular surface remodeling simulation for cancellous bone using microstructural voxel finite element models. J Biomech Eng 123:403–409

    Article  Google Scholar 

  • Anderson AE, Ellis BJ, Weiss JA (2007) Verification, validation and sensitivity studies in computational biomechanics. Comput Methods Biomech Biomed Eng 10:171–184

    Article  Google Scholar 

  • Anderson EJ, Knothe Tate ML (2008) Idealization of pericellular fluid space geometry and dimension results in a profound underprediction of nano-microscale stresses imparted by fluid drag on osteocytes. J Biomech 41:1736–1746

    Article  Google Scholar 

  • Bonivtch AR, Bonewald LF, Nicolella DP (2007) Tissue strain amplification at the osteocyte lacuna: a microstructural finite element analysis. J Biomech 40:2199–2206

    Article  Google Scholar 

  • Brekelmans W, Slooff T, Poort H (1972) New method to analyze mechanical behavior of skeletal parts. Acta Orthop Scand 43:301–317

    Article  Google Scholar 

  • Carter DR, Beaupré GS, Giori NJ, Helms JA (1998) Mechanobiology of skeletal regeneration. Clin Orthop Relat Res S355:S41–S55

    Article  Google Scholar 

  • Coelho PG, Fernandes PR, Rodrigues HC, Cardoso JB, Guedes JM (2009) Numerical modeling of bone tissue adaptation—a hierarchical approach for bone apparent density and trabecular structure. J Biomech 42:830–837

    Article  Google Scholar 

  • Engh CA, Mcgovern TF, Bobyn JD, Harris WH (1992) A quantitative-evaluation of periprosthetic bone-remodeling after cementless total hip-arthroplasty. J Bone Jt Surg, Am Vol 74:1009–1020

    Google Scholar 

  • Feldkamp LA, Goldstein SA, Parfitt AM, Jesion G, Kleerekoper M (1989) The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res 4:3–11

    Article  Google Scholar 

  • Frisch T, Thoumine O (2002) Predicting the kinetics of cell spreading. J Biomech 35:1137–1141

    Article  Google Scholar 

  • Fritton SP, McLeod KJ, Rubin CT (2000) Quantifying the strain history of bone: spatial uniformity and self-similarity of low-magnitude strains. J Biomech 33:317–325

    Article  Google Scholar 

  • Frost HM (1964) The laws of bone structure. Thomas, Springfield

    Google Scholar 

  • Gerhard FA, Webster DJ, van Lenthe GH, Müller R (2009) The relative significance of trabecular and cortical bone-density as a diagnostic index for osteoporosis. Philos Trans R Soc A 367:2011–2030

    Article  Google Scholar 

  • Goldstein SA, Matthews LS, Kuhn JL, Hollister SJ (1991) Trabecular bone remodeling—an experimental model. J Biomech 24:135–150

    Article  Google Scholar 

  • Guldberg RE, Richards M, Caldwell NJ, Kuelske CL, Goldstein SA (1997) Trabecular bone adaptation to variations in porous-coated implant topology. J Biomech 30:147–153

    Article  Google Scholar 

  • Hartmann MA, Dunlop JW, Brechet YJ, Fratzl P, Weinkamer R (2011) Trabecular bone remodelling simulated by a stochastic exchange of discrete bone packets from the surface. J Mech Beh Biomed Mat 4:879–887

    Article  Google Scholar 

  • Huiskes R (1997) Validation of adaptive bone-remodeling simulation models. Stud Health Technol Inform 40:33–48

    Google Scholar 

  • Huiskes R, Chao EYS (1983) A survey of finite element analysis in orthopedic biomechanics: the first decade. J Biomech 16:385–409

    Article  Google Scholar 

  • Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD, (2000) Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature 405:704–706

    Article  Google Scholar 

  • Isaksson H (2012) Recent advances in mechanobiological modeling of bone regeneration. Mech Res Commun 42:22–31

    Article  Google Scholar 

  • Isaksson H, Wilson W, van Donkelaar CC, Huiskes R, Ito K (2006) Comparison of biophysical stimuli for mechano-regulation of tissue differentiation during fracture healing. J Biomech 39:1507–1516

    Article  Google Scholar 

  • Jacobs CR, Kelly DJ (2011) Cell mechanics: the role of simulation. In: Fernandes PR, Bártolo PJ (eds) Advances on modeling in tissue engineering. Computational methods in applied sciences, vol. 20, pp 1–14

    Chapter  Google Scholar 

  • Kelly K (1998) The third culture. Science 279:992–993

    Article  Google Scholar 

  • Kerner J, Huiskes R, van Lenthe GH, Weinans H, van Rietbergen B, Engh CA, Amis AA (1999) Correlation between pre-operative periprosthetic bone density and post-operative bone loss in THA can be explained by strain-adaptive remodelling. J Biomech 32:695–703

    Article  Google Scholar 

  • Knothe Tate ML, Niederer P (1998) A theoretical FE-based model developed to predict the relative contribution of convective and diffusive transport mechanisms for the maintenance of local equilibria within cortical bone. In: Clegg S (ed) Advances in heat and mass transfer in biotechnology. The American Society of Mechanical Engineers, New York, pp 133–142

    Google Scholar 

  • Lacroix D, Prendergast PJ (2002) A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J Biomech 35:1163–1171

    Article  Google Scholar 

  • Landsberg C, Stenger F, Deutsch A, Gelinsky M, Rosen-Wolff A, Voigt A (2011) Chemotaxis of mesenchymal stem cells within 3D biomimetic scaffolds—a modeling approach. J Biomech 44:359–364

    Article  Google Scholar 

  • Leichter I, Bivas A, Giveon A, Margulies JY, Weinreb A (1987) The relative significance of trabecular and cortical bone-density as a diagnostic index for osteoporosis. Phys Med Biol 32:1167–1174

    Article  Google Scholar 

  • Lemaire V, Tobin FL, Greller LD, Cho CR, Suva LJ (2004) Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. J Theor Biol 229:293–309

    Article  MathSciNet  Google Scholar 

  • Lengsfeld M, Gunther D, Pressel T, Leppek R, Schmitt J, Griss P (2002) Validation data for periprosthetic bone remodelling theories. J Biomech 35:1553–1564

    Article  Google Scholar 

  • Lengsfeld M, Burchard R, Gunther D, Pressel T, Schmitt J, Leppek R, Griss P (2005) Femoral strain changes after total hip arthroplasty–patient-specific finite element analyses 12 years after operation. Med Eng Phys 27:649–654

    Article  Google Scholar 

  • Lio P, Merelli E, Paoletti N, Viceconti M (2011) A combined process algebraic and stochastic approach to bone remodeling. Electron Notes Theor Comput Sci 277:41–52

    Article  Google Scholar 

  • Loosli Y, Luginbuehl R, Snedeker JG (2010) Cytoskeleton reorganization of spreading cells on micro-patterned islands: a functional model. Philos Trans R Soc, Math Phys Eng Sci 368:2629–2652

    Article  Google Scholar 

  • McGarry JG, Klein-Nulend J, Mullender MG, Prendergast PJ (2005) A comparison of strain and fluid shear stress in stimulating bone cell responses—a computational and experimental study. FASEB J 19:482–484

    Google Scholar 

  • Müller R (2005) Long-term prediction of three-dimensional bone architecture in simulations of pre-, peri- and post-menopausal microstructural bone remodeling. Osteoporos Int 16:S25–S35

    Article  Google Scholar 

  • Müller R, Hayes WC (1997) Biomechanical competence of microstructural bone in the progress of adaptive bone remodeling. Proc SPIE 3149:69–81

    Article  Google Scholar 

  • Müller R, Rüegsegger P (1996) Analysis of mechanical properties of cancellous bone under conditions of simulated bone atrophy. J Biomech 29:1053–1060

    Article  Google Scholar 

  • Pivonka P, Zimak J, Smith DW, Gardiner BS, Dunstan CR, Sims NA, Martin TJ, Mundy GR (2008) Model structure and control of bone remodeling: a theoretical study. Bone 43:249–263

    Article  Google Scholar 

  • Potter LK, Greller LD, Cho CR, Nuttall ME, Stroup GB, Suva LJ, Tobin FL (2005) Response to continuous and pulsatile PTH dosing: a mathematical model for parathyroid hormone receptor kinetics. Bone 37:159–169

    Article  Google Scholar 

  • Roux W (1881) Der Kampf der Theile im Organismus. Ein Beitrag zur Vervollständigung der mechanischen Zweckmässigkeitslehre. Leipzig

    Google Scholar 

  • Ruffoni D, Fratzl P, Roschger P, Klaushofer K, Weinkamer R (2007) The bone mineralization density distribution as a fingerprint of the mineralization process. Bone 40:1308–1319

    Article  Google Scholar 

  • Ruimerman R, Hilbers P, van Rietbergen B, Huiskes R (2005a). A theoretical framework for strain-related trabecular bone maintenance and adaptation. J Biomech 38:931–941

    Article  Google Scholar 

  • Ruimerman R, van Rietbergen B, Hilbers P, Huiskes R (2005b). The effects of trabecular-bone loading variables on the surface signaling potential for bone remodeling and adaptation. Ann Biomed Eng 33:71–78

    Article  Google Scholar 

  • Sangiorgio SN, Longjohn DB, Dorr LD, Ebramzadeh E (2011) Challenges in relating experimental hip implant fixation predictions to clinical observations. J Biomech 44:235–243

    Article  Google Scholar 

  • Santos L, Romeu JC, Canhao H, Fonseca JE, Fernandes PR (2010) A quantitative comparison of a bone remodeling model with dual-energy X-ray absorptiometry and analysis of the inter-individual biological variability of femoral neck T-score. J Biomech 43:3150–3155

    Article  Google Scholar 

  • Schmitz MJ, Clift SE, Taylor WR, Hertig D, Warner MD, Ploeg HL, Bereiter H (2004) Investigating the effect of remodelling signal type on the finite element based predictions of bone remodelling around the thrust plate prosthesis: a patient-specific comparison. Proc Inst Mech Eng, H J Eng Med 218, pp 417–424

    Article  Google Scholar 

  • Schulte FA (2011) In silico bone biology in a murine model of bone adaptation. Diss. ETH No. 19679, Zurich

    Google Scholar 

  • Schulte FA, Lambers FM, Webster DJ, Kuhn G, Müller R (2011) In vivo validation of a computational bone adaptation model using open-loop control and time-lapsed micro-computed tomography. Bone 49:1166–1172

    Article  Google Scholar 

  • Silva MJ, Gibson LJ (1997) Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone 21:191–199

    Article  Google Scholar 

  • Sumner DR, Turner TM, Urban RM, Galante JO (1992) Remodeling and ingrowth of bone at two years in a canine cementless total hip-arthroplasty model. J Bone Jt Surg, Am Vol 74:239–250

    Google Scholar 

  • Taylor D, Hazenberg JG, Lee TC (2007) Living with cracks: damage and repair in human bone. Nat Mater 6:263–268

    Article  Google Scholar 

  • Testi D, Cappello A, Sgallari F, Rumpf M, Viceconti M (2004) A new software for prediction of femoral neck fractures. Comput Methods Programs Biomed 75:141–145

    Article  Google Scholar 

  • Van der Linden JC, Verhaar JAN, Weinans H (2001) A three-dimensional simulation of age-related remodeling in trabecular bone. J Bone Miner Res 16:688–696

    Article  Google Scholar 

  • Van der Meulen MCH, Huiskes R (2002) Why mechanobiology? A survey article. J Biomech 35:401–414

    Article  Google Scholar 

  • Webster D, Müller R (2011) In silico models of bone remodeling from macro to nano-from organ to cell. Wires Syst Biol Med 3:241–251

    Article  Google Scholar 

  • Weinbaum S, Cowin SC, Zeng Y (1994) A model for the excitation of ostecytes by mechanical loading-induced bone fluid shear stresses. J Biomech 27:339–360

    Article  Google Scholar 

  • Wolff J (1892) Das Gesetz der Transformation der Knochen. Hirschwald, Berlin

    Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge funding from the European Union for the Osteoporotic Virtual Physiological Human project (VPHOP FP7-ICT2008-223865) and computational time from the Swiss National Supercomputing Center (CSCS, Manno, Switzerland).

Author information

Authors and Affiliations

  1. ETH Zurich, Zurich, Switzerland

    Alina Levchuk & Ralph Müller

Authors
  1. Alina Levchuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ralph Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ralph Müller .

Editor information

Editors and Affiliations

  1. Institute of Biomechanics, Center of Biomedical Engineering, Graz University of Technology, Kronegasse 5-I, Graz, 8010, Austria

    Gerhard A. Holzapfel

  2. Dept. Mechanical Engineering, Dept. of Bioengineering (courtesy), Stanford University, Lomita Mall 496, Stanford, 94305-4040, California, USA

    Ellen Kuhl

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this paper

Cite this paper

Levchuk, A., Müller, R. (2013). In Vivo Validation of Predictive Models for Bone Remodeling and Mechanobiology. In: Holzapfel, G., Kuhl, E. (eds) Computer Models in Biomechanics. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5464-5_27

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-5464-5_27

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-5463-8

  • Online ISBN: 978-94-007-5464-5

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation