Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Hierarchical microimaging of bone structure and function

Abstract

With recent advances in molecular medicine and disease treatment in osteoporosis, quantitative image processing of three-dimensional bone structures is critical in the context of bone quality assessment. Biomedical imaging technology such as MRI or CT is readily available, but few attempts have been made to expand the capabilities of these systems by integrating quantitative analysis tools and by exploring structure–function relationships in a hierarchical fashion. Nevertheless, such quantitative end points are an important factor for success in basic research and in the development of novel therapeutic strategies. CT is key to these developments, as it images and quantifies bone in three dimensions and provides multiscale biological imaging capabilities with isotropic resolutions of a few millimeters (clinical CT), a few tens of micrometers (microCT) and even as high as 100 nanometers (nanoCT). The technology enables the assessment of the relationship between microstructural and ultrastructural measures of bone quality and certain diseases or therapies. This Review focuses on presenting strategies for three-dimensional approaches to hierarchical biomechanical imaging in the study of microstructural and ultrastructural bone failure. From this Review, it can be concluded that biomechanical imaging is extremely valuable for the study of bone failure mechanisms at different hierarchical levels.

Key Points

  • Over the last decade, microCT has been established as a quantitative microscope, especially for the assessment of hard tissues

  • MicroCT is fast, reliable and yields accurate and precise morphometric indices that are used for the diagnosis of disease and the monitoring of treatment regimens in both preclinical and clinical research

  • Biomechanical imaging (i.e. the combination of time-lapsed microCT imaging and concomitant mechanical testing) enables the study of bone failure initiation and propagation in a hierarchical fashion

  • Synchrotron radiation and advanced desktop nanoCT systems facilitate exploring the bone ultrastructure with submicrometer resolutions, enabling static quantitative morphometry of cortical bone canals and cell lacunae as well as biomechanical imaging of microcrack initiation and propagation

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic overview of hierarchical imaging with microCT and nanoCT.
Figure 2: Typical applications of microCT in the imaging of bone.
Figure 3: Ultrastructural representation of void spaces within cortical bone of a mouse femur.
Figure 4: Hierarchical imaging of bone function with synchrotron radiation CT.

Similar content being viewed by others

References

  1. Paulus, M. J., Gleason, S. S., Easterly, M. E. & Foltz, C. J. A review of high-resolution X-ray computed tomography and other imaging modalities for small animal research. Lab Anim. (NY) 30, 36–45 (2001).

    CAS  Google Scholar 

  2. Ritman, E. L. Micro-computed tomography-current status and developments. Annu. Rev. Biomed. Eng. 6, 185–208 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Badea, C. T., Fubara, B., Hedlund, L. W. & Johnson, G. A. 4-D micro-CT of the mouse heart. Mol. Imaging 4, 110–116 (2005).

    Article  PubMed  Google Scholar 

  4. Heinzer, S. et al. Hierarchical microimaging for multiscale analysis of large vascular networks. Neuroimage 32, 626–636 (2006).

    Article  PubMed  Google Scholar 

  5. Bullitt, E., Reardon, D. A. & Smith, J. K. A review of micro- and macrovascular analyses in the assessment of tumor-associated vasculature as visualized by MR. Neuroimage 37 (Suppl. 1), S116–S119 (2007).

    Article  PubMed  Google Scholar 

  6. Goldstein, S. A., Goulet, R. W. & McCubbrey, D. Measurement and significance of three-dimensional architecture to the mechanical integrity of trabecular bone. Calcif. Tissue Int. 53 (Suppl. 1), S127–S132 (1993).

    Article  PubMed  Google Scholar 

  7. Müller, R. & Rüegsegger, P. Micro-tomographic imaging for the nondestructive evaluation of trabecular bone architecture. Stud. Health Technol. Inform. 40, 61–79 (1997).

    PubMed  Google Scholar 

  8. Ito, M. et al. Analysis of trabecular microarchitecture of human iliac bone using microcomputed tomography in patients with hip arthrosis with or without vertebral fracture. Bone 23, 163–169 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Genant, H. K. et al. Advanced imaging of bone macro and micro structure. Bone 25, 149–152 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. McCreadie, B. R., Goulet, R. W., Feldkamp, L. A. & Goldstein, S. A., Hierarchical structure of bone and micro-computed tomography. Adv. Exp. Med. Biol. 496, 67–83 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Müller, R. The Zürich experience: one decade of three-dimensional high-resolution computed tomography. Top. Magn. Reson. Imaging 13, 307–322 (2002).

    Article  PubMed  Google Scholar 

  12. Link, T. M. & Majumdar, S. Current diagnostic techniques in the evaluation of bone architecture. Curr. Osteoporos. Rep. 2, 47–52 (2004).

    Article  PubMed  Google Scholar 

  13. Porter, B., Zauel, R., Stockman, H., Guldberg, R. & Fyhrie, D. 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. J. Biomech. 38, 543–549 (2005).

    Article  PubMed  Google Scholar 

  14. Wehrli, F. W. Structural and functional assessment of trabecular and cortical bone by micro magnetic resonance imaging. J. Magn. Reson. Imaging 25, 390–409 (2007).

    Article  PubMed  Google Scholar 

  15. Bouxsein, M. L. Technology insight: noninvasive assessment of bone strength in osteoporosis. Nat. Clin. Pract. Rheumatol. 4, 310–318 (2008).

    Article  PubMed  Google Scholar 

  16. McElhaney, J. H. et al. Mechanical properties of cranial bone. J. Biomech. 3, 495 (1970).

    Article  CAS  PubMed  Google Scholar 

  17. Carter, D. R. & Hayes, W. C. The compressive behavior of bone as a two-phase porous structure. J. Bone Joint Surg. Am. 59, 954–962 (1977).

    Article  CAS  PubMed  Google Scholar 

  18. Williams, J. L. & Lewis, J. L. Properties and an anisotropic model of cancellous bone from the proximal tibial epiphysis. J. Biomech. Eng. 104, 50–56 (1982).

    Article  CAS  PubMed  Google Scholar 

  19. Rice, J. C., Cowin, S. C. & Bowman, J. A. On the dependence of the elasticity and strength of cancellous bone on apparent density. J. Biomech. 21, 155–168 (1988).

    Article  CAS  PubMed  Google Scholar 

  20. Odgaard, A. & Linde, F. The underestimation of Young's modulus in compressive testing of cancellous bone specimens. J. Biomech. 24, 691–698 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Keller, T. S. Predicting the compressive mechanical behavior of bone. J. Biomech. 27, 1159–1168 (1994).

    Article  CAS  PubMed  Google Scholar 

  22. Keaveny, T. M., Guo, X. E., Wachtel, E. F., McMahon, T. A. & Hayes, W. C. Trabecular bone exhibits fully linear elastic behavior and yields at low strains. J. Biomech. 27, 1127–1136 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Ciarelli, M. J., Goldstein, S. A., Kuhn, J. L., Cody, D. D. & Brown, M. B. Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography. J. Orthop. Res. 9, 674–682 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Augat, P. & Schorlemmer, S. The role of cortical bone and its microstructure in bone strength. Age Ageing 35 (Suppl. 2), ii27–ii31 (2006).

    Article  PubMed  Google Scholar 

  25. Bouxsein, M. L. Bone quality: where do we go from here? Osteoporos. Int. 14 (Suppl. 5), S118–S127 (2003).

    Article  PubMed  Google Scholar 

  26. Felsenberg, D. & Boonen, S. The bone quality framework: determinants of bone strength and their interrelationships and implications for osteoporosis management. Clin. Ther. 27, 1–11 (2005).

    Article  PubMed  Google Scholar 

  27. Seeman, E. & Delmas, P. D. Bone quality—the material and structural basis of bone strength and fragility. N. Engl. J. Med. 354, 2250–2261 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. Turner, C. H. & Burr, D. B. Basic biomechanical measurements of bone: a tutorial. Bone 14, 595–608 (1993).

    Article  CAS  PubMed  Google Scholar 

  29. Bay, B. K., Yerby, S. A., McLain, R. F. & Toh, E. Measurement of strain distributions within vertebral body sections by texture correlation. Spine 24, 10–17 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Majumdar, S. Current technologies in the evaluation of bone architecture. Curr. Osteoporos. Rep. 1, 105–109 (2003).

    Article  PubMed  Google Scholar 

  31. van Lenthe, G. H. & Müller, R. CT-based visualization and quantification of bone microstructure in vivo. Bonekey Osteovision 5, 410–425 (2008).

    Google Scholar 

  32. Feldkamp, L. A., Goldstein, S. A., Parfitt, A. M., Jesion, G. & Kleerekoper, M. The direct examination of three-dimensional bone architecture in vitro by computed tomography. J. Bone. Miner. Res. 4, 3–11 (1989).

    Article  CAS  PubMed  Google Scholar 

  33. Rüegsegger, P., Koller, B. & Müller, R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif. Tissue Int. 58, 24–29 (1996).

    Article  PubMed  Google Scholar 

  34. Kuhn, J. L., Goldstein, S. A., Feldkamp, L. A., Goulet, R. W. & Jesion G. Evaluation of a microcomputed tomography system to study trabecular bone structure. J. Orthop. Res. 8, 833–842 (1990).

    Article  CAS  PubMed  Google Scholar 

  35. Uchiyama, T. et al. A morphometric comparison of trabecular structure of human ilium between microcomputed tomography and conventional histomorphometry. Calcif. Tissue Int. 61, 493–498 (1997).

    Article  CAS  PubMed  Google Scholar 

  36. Müller, R. et al. Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. Bone 23, 59–66 (1998).

    Article  PubMed  Google Scholar 

  37. Graichen, H. et al. A non-destructive technique for 3-D microstructural phenotypic characterisation of bones in genetically altered mice: preliminary data in growth hormone transgenic animals and normal controls. Anat. Embryol. (Berl.) 199, 239–248 (1998).

    Article  Google Scholar 

  38. Kapadia, R. D. et al. Applications of micro-CT and MR microscopy to study pre-clinical models of osteoporosis and osteoarthritis. Technol. Health Care 6, 361–372 (1998).

    CAS  PubMed  Google Scholar 

  39. Balto, K., Müller, R., Carrington, D. C., Dobeck, J. & Stashenko, P. Quantification of periapical bone destruction in mice by micro-computed tomography. J. Dent. Res. 79, 35–40 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Yamashita, T., Nabeshima, Y. & Noda, M. High-resolution micro-computed tomography analyses of the abnormal trabecular bone structures in klotho gene mutant mice. J. Endocrinol. 164, 239–245 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Goulet, R. W. et al. The relationship between the structural and orthogonal compressive properties of trabecular bone. J. Biomech. 27, 375–389 (1994).

    Article  CAS  PubMed  Google Scholar 

  42. Ulrich, D., van Rietbergen, B., Laib, A. & Ruegsegger, P. The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone. Bone 25, 55–60 (1999).

    Article  CAS  PubMed  Google Scholar 

  43. Yoshitake, H., Rittling, S. R., Denhardt, D. T. & Noda, M. Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption. Proc. Natl Acad. Sci USA 96, 8156–8160 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ding, M. & Hvid, I. Quantification of age-related changes in the structure model type and trabecular thickness of human tibial cancellous bone. Bone 26, 291–295 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Alexander, J. M. et al. Human parathyroid hormone 1–34 reverses bone loss in ovariectomized mice. J. Bone Miner. Res. 16, 1665–1673 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Dempster, D. W. et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J. Bone Miner. Res. 16, 1846–1853 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Borah, B. et al. Risedronate preserves trabecular architecture and increases bone strength in vertebra of ovariectomized minipigs as measured by three-dimensional microcomputed tomography. J. Bone Miner. Res. 17, 1139–1147 (2002).

    Article  CAS  PubMed  Google Scholar 

  48. Babij, P. et al. High bone mass in mice expressing a mutant LRP5 gene. J. Bone Miner. Res. 18, 960–974 (2003).

    Article  CAS  PubMed  Google Scholar 

  49. Borah, B. et al. Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone 34, 736–746 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Dedrick, D. K. et al. A longitudinal study of subchondral plate and trabecular bone in cruciate-deficient dogs with osteoarthritis followed up for 54 months. Arthritis Rheum. 36, 1460–1467 (1993).

    Article  CAS  PubMed  Google Scholar 

  51. Badger, A. M. et al. Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvant-induced arthritis. Arthritis Rheum. 43, 175–183 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Pettit, A. R. et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am. J. Pathol. 159, 1689–1699 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Day, J. S. et al. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage. J. Orthop. Res. 19, 914–918 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Turner, C. H. et al. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J. Bone Miner. Res. 15, 1126–1131 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Moutsatsos, I. K. et al. Exogenously regulated stem cell-mediated gene therapy for bone regeneration. Mol. Ther. 3, 449–461 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Bouxsein, M. L. et al. Mapping quantitative trait loci for vertebral trabecular bone volume fraction and microarchitecture in mice. J. Bone Miner. Res. 19, 587–599 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Huang, Y. C., Simmons, C., Kaigler, D., Rice, K. G. & Mooney, D. J. Bone regeneration in a rat cranial defect with delivery of PEI-condensed plasmid DNA encoding for bone morphogenetic protein-4 (BMP-4). Gene Ther. 12, 418–426 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Giesen, E. B. & van Eijden, T. M. The three-dimensional cancellous bone architecture of the human mandibular condyle. J. Dent. Res. 79, 957–963 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. Peters, O. A., Laib, A., Ruegsegger, P. & Barbakow, F. Three-dimensional analysis of root canal geometry by high-resolution computed tomography. J. Dent. Res. 79, 1405–1409 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Sasaki, H. et al. IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo. J. Immunol. 165, 3626–3630 (2000).

    Article  CAS  PubMed  Google Scholar 

  61. Duyck, J. et al. The influence of static and dynamic loading on marginal bone reactions around osseointegrated implants: an animal experimental study. Clin. Oral Implants Res. 12, 207–218 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Zeltinger, J., Sherwood, J. K., Graham, D. A., Müeller, R. & Griffith, L. G. Effect of pore size and void fraction on cellular adhesion, proliferation & matrix deposition. Tissue Eng. 7, 557–572 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Lin, A. S., Barrows, T. H., Cartmell, S. H. & Guldberg, R. E. Microarchitectural and mechanical characterization of oriented porous polymer scaffolds. Biomaterials 24, 481–489 (2003).

    Article  CAS  PubMed  Google Scholar 

  64. Lutolf, M. P. et al. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat. Biotechnol. 21, 513–518 (2003).

    Article  CAS  PubMed  Google Scholar 

  65. Jones, A. C. et al. Analysis of 3D bone ingrowth into polymer scaffolds via micro-computed tomography imaging. Biomaterials 25, 4947–4954 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Williams, J. M. et al. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials 26, 4817–4827 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Gluer, C. C., Wu, C. Y., Jergas, M., Goldstein, S. A. & Genant, H. K. Three quantitative ultrasound parameters reflect bone structure. Calcif. Tissue Int. 55, 46–52 (1994).

    Article  CAS  PubMed  Google Scholar 

  68. Nicholson, P. H. et al. Do quantitative ultrasound measurements reflect structure independently of density in human vertebral cancellous bone? Bone 23, 425–431 (1998).

    Article  CAS  PubMed  Google Scholar 

  69. Laib, A. & Rüegsegger, P. Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-microm-resolution microcomputed tomography. Bone 24, 35–39 (1999).

    Article  CAS  PubMed  Google Scholar 

  70. Engelke, K., Graeff, W., Meiss, L., Hahn, M. & Delling, G. High spatial resolution imaging of bone mineral using computed microtomography. Comparison with microradiography and undecalcified histologic sections. Invest. Radiol. 28, 341–349 (1993).

    Article  CAS  PubMed  Google Scholar 

  71. Bonse, U. et al. 3D computed X-ray tomography of human cancellous bone at 8 microns spatial and 10(−4) energy resolution. Bone Miner. 25, 25–38 (1994).

    Article  CAS  PubMed  Google Scholar 

  72. Salome, M. et al. A synchrotron radiation microtomography system for the analysis of trabecular bone samples. Med. Phys. 26, 2194–2204 (1999).

    Article  CAS  PubMed  Google Scholar 

  73. Stampanoni, M., Borchert, G., Abela, R. & Rüegsegger, P. Nanotomography based on double asymmetrical Bragg diffraction. Appl. Phys. Lett. 82, 2922–2924 (2003).

    Article  CAS  Google Scholar 

  74. Nuzzo, S. et al. Synchrotron radiation microtomography allows the analysis of three- dimensional microarchitecture and degree of mineralization of human iliac crest biopsy specimens: effects of etidronate treatment. J. Bone Miner. Res. 17, 1372–1382 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Borah, B. et al. The effect of risedronate on bone mineralization as measured by micro-computed tomography with synchrotron radiation: correlation to histomorphometric indices of turnover. Bone 37, 1–9 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Bousson, V. et al. Cortical bone in the human femoral neck: three-dimensional appearance and porosity using synchrotron radiation. J. Bone Miner. Res. 19, 794–801 (2004).

    Article  PubMed  Google Scholar 

  77. Matsumoto, T., Yoshino, M., Uesugi, K. & Tanaka, M. Biphasic change and disuse-mediated regression of canal network structure in cortical bone of growing rats. Bone 41, 239–246 (2007).

    Article  CAS  PubMed  Google Scholar 

  78. Schneider, P. et al. Ultrastructural properties in cortical bone vary greatly in two inbred strains of mice as assessed by synchrotron light based micro- and nano-CT. J. Bone Miner. Res. 22, 1557–1570 (2007).

    Article  PubMed  Google Scholar 

  79. Weiss, D. et al. Computed tomography of cryogenic biological specimens based on X-ray microscopic images. Ultramicroscopy 84, 185–197 (2000).

    Article  CAS  PubMed  Google Scholar 

  80. Thurner, P. J. et al. Time-lapsed investigation of three-dimensional failure and damage accumulation in trabecular bone using synchrotron light. Bone 39, 289–299 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Larrue, A., Rattner, A., Laroche, N., Vico, L. & Peyrin, F. Feasibility of micro-crack detection in human trabecular bone images from 3D synchrotron microtomography. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2007, 3918–3921 (2007).

    Google Scholar 

  82. Koester, K. J., Ager, J. W. 3rd & Ritchie, R. O. The true toughness of human cortical bone measured with realistically short cracks. Nat. Mater. 7, 672–677 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Parfitt, A. M. et al. Relationships between surface, volume & thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J. Clin. Invest. 72, 1396–1409 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hildebrand, T., Laib, A., Müller, R., Dequeker, J. & Rüegsegger, P. 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 (1999).

    Article  CAS  PubMed  Google Scholar 

  85. Odgaard, A. Three-dimensional methods for quantification of cancellous bone architecture. Bone 20, 315–328 (1997).

    Article  CAS  PubMed  Google Scholar 

  86. Hildebrand, T. & Rüegsegger, P. Quantification of bone microarchitecture with the structure model index. Comput. Methods Biomech. Biomed. Engin. 1, 15–23 (1997).

    Article  PubMed  Google Scholar 

  87. Whitehouse, W. J. The quantitative morphology of anisotropic trabecular bone. J. Microsc. 101, 153–168 (1974).

    Article  CAS  PubMed  Google Scholar 

  88. Odgaard, A. & Gundersen, H. J. Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions. Bone 14, 173–182 (1993).

    Article  CAS  PubMed  Google Scholar 

  89. Serra, J. Image Analysis and Mathematical Morphology (Academic Press, London, UK, 1982).

    Google Scholar 

  90. Gomberg, B. R., Saha, P. K. & Wehrli, F. W. Topology-based orientation analysis of trabecular bone networks. Med. Phys. 30, 158–168 (2003).

    Article  PubMed  Google Scholar 

  91. Stauber, M. & Müller, R. Volumetric spatial decomposition of trabecular bone into rods and plates—a new method for local bone morphometry. Bone 38, 475–484 (2006).

    Article  PubMed  Google Scholar 

  92. Stauber, M. & Müller, R. Age-related changes in trabecular bone microstructures: global and local morphometry. Osteoporos. Int. 17, 616–626 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Liu, X. S. et al. Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone. J. Bone Miner. Res. 23, 223–235 (2008).

    Article  PubMed  Google Scholar 

  94. Stauber, M., Rapillard, L., van Lenthe, G. H., Zysset, P. & Müller, R. Importance of individual rods and plates in the assessment of bone quality and their contribution to bone stiffness. J. Bone Miner. Res. 21, 586–595 (2006).

    Article  PubMed  Google Scholar 

  95. Cooper, D. M. et al. Age-dependent change in the 3D structure of cortical porosity at the human femoral midshaft. Bone 40, 957–965 (2007).

    Article  PubMed  Google Scholar 

  96. Voide, R., van Lenthe, G. H. & Müller, R. Bone morphometry strongly predicts cortical bone stiffness and strength, but not toughness, in inbred mouse models of high and low bone mass. J. Bone Miner. Res. 23, 1194–1203 (2008).

    Article  PubMed  Google Scholar 

  97. Turner, C. H. Bone strength: current concepts. Ann. NY Acad. Sci. 1068, 429–446 (2006).

    Article  PubMed  Google Scholar 

  98. Boivin, G. Y., Chavassieux, P. M., Santora, A. C., Yates, J. & Meunier, P. J. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27, 687–694 (2000).

    Article  CAS  PubMed  Google Scholar 

  99. Roschger, P., Paschalis, E. P., Fratzl, P. & Klaushofer, K. Bone mineralization density distribution in health and disease. Bone 42, 456–466 (2008).

    Article  CAS  PubMed  Google Scholar 

  100. Nazarian, A., Snyder, B. D., Zurakowski, D. & Muller, R. Quantitative micro-computed tomography: a non-invasive method to assess equivalent bone mineral density. Bone 43, 302–311 (2008).

    Article  PubMed  Google Scholar 

  101. Kazakia, G. J., Burghardt, A. J., Cheung, S. & Majumdar, S. Assessment of bone tissue mineralization by conventional x-ray microcomputed tomography: comparison with synchrotron radiation microcomputed tomography and ash measurements. Med. Phys. 35, 3170–3179 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Fajardo, R. J. et al. Specimen size and porosity can introduce error into microCT-based tissue mineral density measurements. Bone 44, 176–184 (2009).

    Article  PubMed  Google Scholar 

  103. Yang, G. et al. The anisotropic Hooke's law for cancellous bone and wood. J. Elast. 53, 125–146 (1998).

    Article  PubMed  Google Scholar 

  104. Müller, R., Hannan, M., Smith, S. Y. & Bauss, F. Intermittent ibandronate preserves bone quality and bone strength in the lumbar spine after 16 months of treatment in the ovariectomized cynomolgus monkey. J. Bone Miner. Res. 19, 1787–1796 (2004).

    Article  PubMed  CAS  Google Scholar 

  105. Hodgskinson, R. & Currey, J. D. 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. [H]. 204, 115 (1990).

    Article  CAS  Google Scholar 

  106. Hou, F. J., Lang, S. M., Hoshaw, S. J., Reimann, D. A. & Fyhrie, D. P. Human vertebral body apparent and hard tissue stiffness. J. Biomech. 31, 1009–1015 (1998).

    Article  CAS  PubMed  Google Scholar 

  107. Müller, R., Gerber, S. C. & Hayes, W. C. Micro-compression: a novel technique for the nondestructive assessment of local bone failure. Technol. Health Care 6, 433–444 (1998).

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  109. Müller, R. et al. Micromechanical evaluation of bone microstructures under load. In Developments in X-Ray Tomography III (Proceedings Volume 4503) (Ed. Bonse, U.) 189–200 (SPIE, San Diego, CA, 2002).

    Chapter  Google Scholar 

  110. Nagaraja, S., Couse, T. L. & Guldberg, R. E. Trabecular bone microdamage and microstructural stresses under uniaxial compression. J. Biomech. 38, 707–716 (2005).

    Article  PubMed  Google Scholar 

  111. Hulme, P. A., Ferguson, S. J. & Boyd, S. K. Determination of vertebral endplate deformation under load using micro-computed tomography. J. Biomech. 41, 78–85 (2008).

    Article  CAS  PubMed  Google Scholar 

  112. Thurner, P. J. et al. High-speed photography of compressed human trabecular bone correlates whitening to microscopic damage. Eng. Fract. Mech. 74, 1928–1941 (2007).

    Article  Google Scholar 

  113. Weiner, S., Traub, W. & Wagner, H. D. Lamellar bone: structure-function relations. J. Struct. Biol. 126, 241–255 (1999).

    Article  CAS  PubMed  Google Scholar 

  114. Voide, R. et al. Functional microimaging: a hierarchical investigation of bone failure behavior. J. Jpn. Soc. Bone Morphom. 18, 9–21 (2008).

    Google Scholar 

  115. Nalla, R. K., Stolken, J. S., Kinney, J. H. & Ritchie, R. O. Fracture in human cortical bone: local fracture criteria and toughening mechanisms. J. Biomech. 38, 1517–1525 (2005).

    Article  CAS  PubMed  Google Scholar 

  116. Di Michiel, M. et al. Fast microtomography using high energy synchrotron radiation. Rev. Sci. Instrum. 76, 043702 (2005).

    Article  CAS  Google Scholar 

  117. Meier, M., Vogel, P., Voide, R., Schneider, P. & Müller, R. Investigation of microdamage in murine bone under dynamic load. J. Biomech. 41 (Suppl. 1), S76 (2008).

    Article  Google Scholar 

Download references

Acknowledgements

The author would like to acknowledge support from the Swiss National Science Foundation. Special thanks to Drs. T. Kohler, T. L. Mueller, P. Schneider, G. H. van Lenthe and R. Voide for generously providing images.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ralph Müller.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Müller, R. Hierarchical microimaging of bone structure and function. Nat Rev Rheumatol 5, 373–381 (2009). https://doi.org/10.1038/nrrheum.2009.107

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2009.107

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing