Skip to main content
SpringerLink
Log in

Bone Volume Fraction Explains the Variation in Strength and Stiffness of Cancellous Bone Affected by Metastatic Cancer and Osteoporosis

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Preventing nontraumatic fractures in millions of patients with osteoporosis or metastatic cancer may significantly reduce the associated morbidity and reduce health-care expenditures incurred by these fractures. Predicting fracture occurrence requires an accurate understanding of the relationship between bone structure and the mechanical properties governing bone fracture that can be readily measured. The aim of this study was to test the hypothesis that a single analytic relationship with either bone tissue mineral density or bone volume fraction (BV/TV) as independent variables could predict the strength and stiffness of normal and pathologic cancellous bone affected by osteoporosis or metastatic cancer. After obtaining institutional review board approval and informed consent, 15 patients underwent excisional biopsy of metastatic prostate, breast, lung, ovarian, or colon cancer from the spine and/or femur to obtain 41 metastatic cancer specimens. In addition, 96 noncancer specimens were excised from 43 age- and site-matched cadavers. All specimens were imaged using micro-computed tomography (micro-CT) and backscatter emission imaging and tested mechanically by uniaxial compression and nanoindentation. The minimum BV/TV, measured using quantitative micro-CT, accounted for 84% of the variation in bone stiffness and strength for all cancellous bone specimens. While relationships relating bone density to strength and stiffness have been derived empirically for normal and osteoporotic bone, these relationships have not been applied to skeletal metastases. This simple analytic relationship will facilitate large-scale screening and prediction of fracture risk for normal and pathologic cancellous bone using clinical CT systems to determine the load capacity of bones altered by metastatic cancer, osteoporosis, or both.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Michaeli DA, Inoue K, Hayes WC, Hipp JA (1999) Density predicts the activity-dependent failure load of proximal femora with defects. Skeletal Radiol 28:90–95

    Article  PubMed  CAS  Google Scholar 

  2. Hipp JA, Springfield DS, Hayes WC (1995) Predicting pathologic fracture risk in the management of metastatic bone defects. Clin Orthop Relat Res 312:120–135

    PubMed  Google Scholar 

  3. Snyder BD, Hauser-Kara DA, Hipp JA, Zurakowski D, Hecht AC, Gebhardt MC (2006) Predicting fracture through benign skeletal lesions with quantitative computed tomography. J Bone Joint Surg Am 88:55–70

    Article  PubMed  Google Scholar 

  4. Hong J, Cabe GD, Tedrow JR, Hipp JA, Snyder BD (2004) Failure of trabecular bone with simulated lytic defects can be predicted non-invasively by structural analysis. J Orthop Res 22:479–486

    Article  PubMed  Google Scholar 

  5. Keyak JH, Kaneko TS, Tehranzadeh J, Skinner HB (2005) Predicting proximal femoral strength using structural engineering models. Clin Orthop Relat Res 437:219–228

    Article  PubMed  Google Scholar 

  6. Kaneko TS, Bell JS, Pejcic MR, Tehranzadeh J, Keyak JH (2004) Mechanical properties, density and quantitative CT scan data of trabecular bone with and without metastases. J Biomech 37:523–530

    Article  PubMed  Google Scholar 

  7. Kaneko TS, Pejcic MR, Tehranzadeh J, Keyak JH (2003) Relationships between material properties and CT scan data of cortical bone with and without metastatic lesions. Med Eng Phys 25:445–454

    Article  PubMed  Google Scholar 

  8. Bevill G, Eswaran SK, Gupta A, Papadopoulos P, Keaveny TM (2006) Influence of bone volume fraction and architecture on computed large-deformation failure mechanisms in human trabecular bone. Bone 39:1218–1225

    Article  PubMed  Google Scholar 

  9. Whealan KM, Kwak SD, Tedrow JR, Inoue K, Snyder BD (2000) Noninvasive imaging predicts failure load of the spine with simulated osteolytic defects. J Bone Joint Surg Am 82:1240–1251

    PubMed  CAS  Google Scholar 

  10. Hayes WC, Bouxsein ML (1997) Biomechanics of cortical and trabecular bone: implication for assessment of fracture risk. In: Mow VC, Hayes WC (eds) Basic orthopaedic biomechanics. Lippincott-Raven, Philadelphia, pp 69–112

    Google Scholar 

  11. Homminga J, McCreadie BR, Weinans H, Huiskes R (2003) The dependence of the elastic properties of osteoporotic cancellous bone on volume fraction and fabric. J Biomech 36:1461–1467

    Article  PubMed  Google Scholar 

  12. Keller TS (1994) Predicting the compressive mechanical behavior of bone. J Biomech 27:1159–1168

    Article  PubMed  CAS  Google Scholar 

  13. Carter DR, Hayes WC (1976) Bone compressive strength: the influence of density and strain rate. Science 194:1174–1176

    Article  PubMed  CAS  Google Scholar 

  14. Rice JC, Cowin SC, Bowman JA (1988) On the dependence of the elasticity and strength of cancellous bone on apparent density. J Biomech 21:155–168

    Article  PubMed  CAS  Google Scholar 

  15. Kowalczyk P (2003) Elastic properties of cancellous bone derived from finite element models of parameterized microstructure cells. J Biomech 36:961–972

    Article  PubMed  Google Scholar 

  16. Kowalczyk P (2006) Orthotropic properties of cancellous bone modelled as parameterized cellular material. Comput Methods Biomech Biomed Eng 9:135–147

    Article  Google Scholar 

  17. Bourne BC, van der Meulen MC (2004) Finite element models predict cancellous apparent modulus when tissue modulus is scaled from specimen CT-attenuation. J Biomech 37:613–621

    Article  PubMed  Google Scholar 

  18. Hernandez CJ, Beaupre GS, Keller TS, Carter DR (2001) The influence of bone volume fraction and ash fraction on bone strength and modulus. Bone 29:74–78

    Article  PubMed  CAS  Google Scholar 

  19. Gibson LJ (1997) Cellular solids. Cambridge University Press, New York

    Google Scholar 

  20. Parfitt A, Drezner M, Glorieux F, Kanis J, Recker R (1987) Bone histomorphometry: standardization of nomenclature, symbols and units. J Bone Miner Res 2:595–610

    PubMed  CAS  Google Scholar 

  21. Pattijn V, Van Cleynenbreugel T, Vander Sloten J, Van Audekercke R, Van der Perre G, Wevers M (2001) Structural and radiological parameters for the nondestructive characterization of trabecular bone. Ann Biomed Eng 29:1064–1073

    Article  PubMed  CAS  Google Scholar 

  22. Szejnfeld VL, Monier-Faugere MC, Bognar BJ, Ferraz MB, Malluche HH (1997) Systemic osteopenia and mineralization defect in patients with ankylosing spondylitis. J Rheumatol 24:683–688

    PubMed  CAS  Google Scholar 

  23. Nazarian A, Muller R (2004) Time-lapsed microstructural imaging of bone failure behavior. J Biomech 37:55–65

    Article  PubMed  Google Scholar 

  24. Nazarian A, Stauber M, Muller R (2005) Design and implementation of a novel mechanical testing system for cellular solids. J Biomed Mater Res B Appl Biomater 73:400–411

    PubMed  Google Scholar 

  25. Muller R, Gerber SC, Hayes WC (1998) Micro-compression: a novel technique for the nondestructive assessment of local bone failure. Technol Health Care 6:433–444

    PubMed  CAS  Google Scholar 

  26. Timoshenko S, Goodier JN (1970) Theory of elasticity, 3rd edn. McGraw-Hill, New York

    Google Scholar 

  27. Keaveny TM, Borchers RE, Gibson LJ, Hayes WC (1993) Theoretical analysis of the experimental artifact in trabecular bone compressive modulus. J Biomech 26:599–607

    Article  PubMed  CAS  Google Scholar 

  28. Richy F, Gourlay ML, Garrett J, Hanson L, Reginster JY (2004) Osteoporosis prevalence in men varies by the normative reference. J Clin Densitom 7:127–133

    Article  PubMed  Google Scholar 

  29. Oliver WC, Pharr GM (1992) An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res 7(6):1564–1583

    Article  CAS  Google Scholar 

  30. Rho J-Y, Tsui TY, Pharr GM (1998) Elastic properties of human cortical and trabecular lamellar bone measured by nanoindentation. Biomaterials 18:1325–1330

    Article  Google Scholar 

  31. Keaveny TM, Pinilla TP, Crawford RP, Kopperdahl DL, Lou A (1997) Systematic and random errors in compression testing of trabecular bone. J Orthop Res 15:101–110

    Article  PubMed  CAS  Google Scholar 

  32. Keaveny TM, Borchers RE, Gibson LJ, Hayes WC (1993) Trabecular bone modulus and strength can depend on specimen geometry. J Biomech 26:991–1000

    Article  PubMed  CAS  Google Scholar 

  33. Nazarian A, Müller R (2004) Time-lapsed microstructural imaging of bone failure behavior. J Biomech 37:55–65

    Article  PubMed  Google Scholar 

  34. Ruegsegger P, Koller B, Muller R (1996) A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 58:24–29

    Article  PubMed  CAS  Google Scholar 

  35. Hildebrand T, Laib A, Muller R, Dequeker J, Ruegsegger P (1999) Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res 14:1167–1174

    Article  PubMed  CAS  Google Scholar 

  36. Lorensen WE, Cline HE (1987) Marching cubes: a high resolution 3D surface construction algorithm. Comput Graph 21:163–169

    Article  Google Scholar 

  37. Laird NM, Ware JH (1982) Random-effects models for longitudinal data. Biometrics 38:963–974

    Article  PubMed  CAS  Google Scholar 

  38. Schwarz G (1978) Estimating the dimension of a model. Ann Stat 6:461–464

    Article  Google Scholar 

  39. Gibson LJ (2005) Biomechanics of cellular solids. J Biomech 38:377–399

    Article  PubMed  Google Scholar 

  40. Snyder BD, Piazza S, Edwards WT, Hayes WC (1993) Role of trabecular morphology in the etiology of age-related vertebral fractures. Calcif Tissue Int 53:S14–S22

    Article  PubMed  Google Scholar 

  41. Meng XW, Rosenthal R, Rubin DB (1992) Comparing correlated correlation coefficients. Quant Methods Psychol 111:172

    Google Scholar 

  42. Dunn OJ, Clark V (1969) Correlation coefficients measured on the same individuals. J Am Stat Assoc 64:366–377

    Article  Google Scholar 

  43. Lane JM, Nydick M (1999) Osteoporosis: current modes of prevention and treatment. J Am Acad Orthop Surg 7:19–31

    PubMed  CAS  Google Scholar 

  44. Riggs BL, Melton LJIII (1986) Involutional osteoporosis. N Engl J Med 314:1676–1686

    PubMed  CAS  Google Scholar 

  45. Kim DG, Hunt CA, Zauel R, Fyhrie DP, Yeni YN (2007) The effect of regional variations of the trabecular bone properties on the compressive strength of human vertebral bodies. Ann Biomed Eng 35:1907–1913

    Article  PubMed  Google Scholar 

  46. Cody D, Goldstein S, Flynn M, Brown E (1991) Correlations between vertebral regional bone mineral density (rBMD) and whole bone fracture load. Spine 16:146–154

    PubMed  CAS  Google Scholar 

  47. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM (1993) Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 341:72–75

    CAS  Google Scholar 

  48. Hui SL, Slemenda CW, Carey MA, Johnston CC Jr (1995) Choosing between predictors of fractures. J Bone Miner Res 10:1816–1822

    PubMed  CAS  Google Scholar 

  49. 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  PubMed  CAS  Google Scholar 

  50. Ford CM, Keaveny TM (1996) The dependence of shear failure properties of trabecular bone on apparent density and trabecular orientation. J Biomech 29:1309–1317

    Article  PubMed  CAS  Google Scholar 

  51. Goulet R, Goldstein S, Ciarelli M, Kuhn J, Brown M, Feldkamp L (1994) The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech 27:375–389

    Article  PubMed  CAS  Google Scholar 

  52. Hodgskinson R, Currey JD (1990) The effect of variation in structure on the Young’s modulus of cancellous bone: a comparison of human and non-human material. Proc Inst Mech Eng 204:115–121

    CAS  Google Scholar 

  53. McBroom RJ, Hayes WC, Edwards WT, Goldberg RP, White AA (1985) Prediction of vertebral body compressive fracture using quantitative computed tomography. J Bone Joint Surg Am 67:1206–1214

    PubMed  CAS  Google Scholar 

  54. Silva M, Keaveny T, Hayes W (1997) Load sharing between the shell and centrum in the lumbar vertebral body. Spine 22:140–150

    Article  PubMed  CAS  Google Scholar 

  55. Yeni YN, Dong XN, Fyhrie DP, Les CM (2004) The dependence between the strength and stiffness of cancellous and cortical bone tissue for tension and compression: extension of a unifying principle. Biomed Mater Eng 14:303–310

    PubMed  Google Scholar 

  56. Keaveny TM, Wachtel EF, Zadesky SP, Arramon YP (1999) Application of the Tsai-Wu quadratic multiaxial failure criterion to bovine trabecular bone. J Biomech Eng 121:99–107

    Article  PubMed  CAS  Google Scholar 

  57. Currey J (1986) Effects of porosity and mineral content on the Young’s modulus of bone. In: European Society of Biomechanics. 5th ESB Conference, Berlin, p 104

  58. Yeni Y, Brown C, Wang Z, Norman T (1997) The influence of bone morphology on fracture toughness of the human femur and tibia. Bone 21:453–459

    Article  PubMed  CAS  Google Scholar 

  59. Currey JD (1984) Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci 304:509–518

    Article  PubMed  CAS  Google Scholar 

  60. Viguet-Carrin S, Garnero P, Delmas PD (2006) The role of collagen in bone strength. Osteoporos Int 17:319–336

    Article  PubMed  CAS  Google Scholar 

  61. Zioupos P, Currey JD, Hamer AJ (1999) The role of collagen in the declining mechanical properties of aging human cortical bone. J Biomed Mater Res 45:108–116

    Article  PubMed  CAS  Google Scholar 

  62. Diab T, Vashishth D (2005) Effects of damage morphology on cortical bone fragility. Bone 37:96–102

    Article  PubMed  CAS  Google Scholar 

  63. Mayhew PM, Thomas CD, Clement JG, Loveridge N, Beck TJ, Bonfield W, Burgoyne CJ, Reeve J (2005) Relation between age, femoral neck cortical stability, and hip fracture risk. Lancet 366:129–135

    Article  PubMed  Google Scholar 

  64. Wang XF, Duan Y, Beck TJ, Seeman E (2005) Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone 36:978–986

    Article  PubMed  Google Scholar 

  65. Turner CH (2002) Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int 13:97–104

    Article  PubMed  CAS  Google Scholar 

  66. Carter DR, Hayes WC (1977) The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg Am 59:954–962

    PubMed  CAS  Google Scholar 

  67. Keaveny TM, Wachtel EF, Ford CM, Hayes WC (1994) Differences between the tensile and compressive strengths of bovine tibial trabecular bone depend on modulus. J Biomech 27:1137–1146

    Article  PubMed  CAS  Google Scholar 

  68. Hou FJ, Lang SM, Hoshaw SJ, Reimann DA, Fyhrie DP (1998) Human vertebral body apparent and hard tissue stiffness. J Biomech 31:1009–1015

    Article  PubMed  CAS  Google Scholar 

  69. Schaffler MB, Burr DB (1988) Stiffness of compact bone: effects of porosity and density. J Biomech 21:13–16

    Article  PubMed  CAS  Google Scholar 

  70. Turner CH, Cowin SC, Rho JY, Ashman RB, Rice JC (1990) The fabric dependence of the orthotropic elastic constants of cancellous bone. J Biomech 23:549–561

    Article  PubMed  CAS  Google Scholar 

  71. Van Rietbergen B, Odgaard A, Kabel J, Huiskes R (1998) Relationships between bone morphology and bone elastic properties can be accurately quantified using high-resolution computer reconstructions. J Orthop Res 16:23–28

    Article  PubMed  Google Scholar 

  72. Cowin SC (1985) The relationship between the elasticity tensor and the fabric tensor. Mech Mater 4:137–147

    Article  Google Scholar 

  73. Kabel J, van Rietbergen B, Odgaard A, Huiskes R (1999) Constitutive relationships of fabric, density, and elastic properties in cancellous bone architecture. Bone 25:481–486

    Article  PubMed  CAS  Google Scholar 

  74. Hipp JA, Rosenberg AE, Hayes WC (1992) Mechanical properties of trabecular bone within and adjacent to osseous metastases. J Bone Miner Res 7:1165–1171

    Article  PubMed  CAS  Google Scholar 

  75. McBroom RJ, Cheal EJ, Hayes WC (1988) Strength reductions from metastatic cortical defects in long bones. J Orthop Res 6:369–378

    Article  PubMed  CAS  Google Scholar 

  76. McBroom RJ, Hayes WC, Edwards WT, Goldberg RP, White AA 3rd (1985) Prediction of vertebral body compressive fracture using quantitative computed tomography. J Bone Joint Surg Am 67:1206–1214

    PubMed  CAS  Google Scholar 

  77. Wehrli FW, Saha PK, Gomberg BR, Song HK, Snyder PJ, Benito M, Wright A, Weening R (2002) Role of magnetic resonance for assessing structure and function of trabecular bone. Top Magn Reson Imaging 13:335–355

    Article  PubMed  Google Scholar 

  78. Newitt DC, Majumdar S, van Rietbergen B, von Ingersleben G, Harris ST, Genant HK, Chesnut C, Garnero P, MacDonald B (2002) In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius. Osteoporos Int 13:6–17

    Article  PubMed  CAS  Google Scholar 

  79. Hong J, Hipp JA, Mulkern RV, Jaramillo D, Snyder BD (2000) Magnetic resonance imaging measurements of bone density and cross-sectional geometry. Calcif Tissue Int 66:74–78

    Article  PubMed  CAS  Google Scholar 

  80. Crawford RP, Cann CE, Keaveny TM (2003) Finite element models predict in vitro vertebral body compressive strength better than quantitative computed tomography. Bone 33:744–750

    Article  PubMed  Google Scholar 

  81. Nazarian A, Stauber M, Müller R (2005) Design and implementation of a novel mechanical testing system for cellular solids. J Biomed Mater Res B Appl Biomater 73:400–411

    PubMed  Google Scholar 

  82. Michel M, Guo X, Gibson L, McMahon T, Hayes W (1993) Compressive fatigue behavior of bovine trabecular bone. J Biomech 26:453–463

    Article  PubMed  CAS  Google Scholar 

  83. Galasko CS (1976) Mechanisms of bone destruction in the development of skeletal metastases. Nature 263:507–508

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was funded by National Institutes of Health grant CA40211 (to B. D. S.), Susan G. Komen grant BCTR0403271 (to B. D. S.), Swiss National Science Foundation grants FP 620–58097.99 and PP-104317/1 (to R. M.), and a Fulbright Full Grant for Graduate Study and Research Abroad (to A. N.). The authors acknowledge Dr. Marc Grynpas for BSE microscopy imaging, Dr. Zaifeng Fan for nanoindentation, Dr. Andrew Rosenberg for providing histological confirmation of skeletal metastasis in bone specimens, and Dr. Martin Stauber for assistance in image visualization. Additionally, they acknowledge Dr. Evan Snyder from Burnham Institute for Medical Research for reviewing the manuscript and providing helpful comments.

Author information

Authors and Affiliations

  1. Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    Ara Nazarian, Dietrich von Stechow & Brian D. Snyder

  2. Institute for Biomedical Engineering, University and ETH Zürich, Zürich, 8044, Switzerland

    Ara Nazarian

  3. Institute for Biomechanics, ETH Zürich, Zürich, 8044, Switzerland

    Ralph Müller

  4. Department of Orthopedic Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA

    David Zurakowski & Brian D. Snyder

  5. Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN115, Boston, MA, 02215, USA

    Brian D. Snyder

Authors
  1. Ara Nazarian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dietrich von Stechow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Zurakowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ralph Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Brian D. Snyder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian D. Snyder.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nazarian, A., von Stechow, D., Zurakowski, D. et al. Bone Volume Fraction Explains the Variation in Strength and Stiffness of Cancellous Bone Affected by Metastatic Cancer and Osteoporosis. Calcif Tissue Int 83, 368–379 (2008). https://doi.org/10.1007/s00223-008-9174-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-008-9174-x

Keywords

Search

Navigation