Methods in Bone Biology in Animals: Imaging



Animal models are essential research tools for investigating the musculoskeletal system. Analysis of bone morphology and bone density can provide information about skeletal phenotypes, including characterization of the skeletal effects of aging, disease, and dietary, genetic, pharmacologic, or mechanical interventions.


Cortical Bone Trabecular Bone Skeletal Site Large Animal Model Bone Morphology 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors acknowledge funding from NIH (AR053986, AR057522, AR058389 and AG023480). The authors would like to thank Alison Cloutier and Rajaram Manoharan for assistance with preparation of figures.


  1.  1.
    Parfitt AM, Drezner MK, Glorieux FH, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomen­clature Committee. J Bone Miner Res. 1987;2(6):595-610.PubMedCrossRefGoogle Scholar
  2.  2.
    Binkley N, Dahl DB, Engelke J, Kawahara-Baccus T, Krueger D, Colman RJ. Bone loss detection in rats using a mouse densitometer. J Bone Miner Res. 2003;18(2):370-375.PubMedCrossRefGoogle Scholar
  3.  3.
    Brochmann EJ, Duarte ME, Zaidi HA, Murray SS. Effects of dietary restriction on total body, femoral, and vertebral bone in SENCAR, C57BL/6, and DBA/2 mice. Metabolism. 2003;52(10):1265-1273.PubMedCrossRefGoogle Scholar
  4.  4.
    Iida-Klein A, Hughes C, Lu SS, et al. Effects of cyclic versus daily hPTH(1-34) regimens on bone strength in association with BMD, biochemical markers, and bone structure in mice. J Bone Miner Res. 2006;21(2):274-282.PubMedCrossRefGoogle Scholar
  5.  5.
    Masinde GL, Li X, Gu W, Wergedal J, Mohan S, Baylink DJ. Quantitative trait loci for bone density in mice: the genes determining total skeletal density and femur density show little overlap in F2 mice. Calcif Tissue Int. 2002;71(5):421-428.PubMedCrossRefGoogle Scholar
  6.  6.
    Reed DR, Bachmanov AA, Tordoff MG. Forty mouse strain survey of body composition. Physiol Behav. 2007;91(5):593-600.PubMedCrossRefGoogle Scholar
  7.  7.
    Nagy TR, Clair AL. Precision and accuracy of dual-energy X-ray absorptiometry for determining in vivo body composition of mice. Obes Res. 2000;8(5):392-398.PubMedCrossRefGoogle Scholar
  8.  8.
    Kolta S, De Vernejoul MC, Meneton P, Fechtenbaum J, Roux C. Bone mineral measurements in mice: comparison of two devices. J Clin Densitom. 2003;6(3):251-258.PubMedCrossRefGoogle Scholar
  9.  9.
    Brommage R. Validation and calibration of DEXA body composition in mice. Am J Physiol Endocrinol Metab. 2003;285(3):E454-E459.PubMedGoogle Scholar
  10. 10.
    Johnston SL, Peacock WL, Bell LM, Lonchampt M, Speakman JR. PIXImus DXA with different software needs individual calibration to accurately predict fat mass. Obes Res. 2005;13(9):1558-1565.PubMedCrossRefGoogle Scholar
  11. 11.
    Gasser JA, Ingold P, Venturiere A, Shen V, Green JR. Long-term protective effects of zoledronic acid on cancellous and cortical bone in the ovariectomized rat. J Bone Miner Res. 2008;23(4):544-551.PubMedCrossRefGoogle Scholar
  12. 12.
    Armamento-Villareal R, Sheikh S, Nawaz A, et al. A new selective estrogen receptor modulator, CHF 4227.01, preserves bone mass and microarchitecture in ovariectomized rats. J Bone Miner Res. 2005;20(12):2178-2188.PubMedCrossRefGoogle Scholar
  13. 13.
    Silva MJ, Touhey DC. Bone formation after damaging in vivo fatigue loading results in recovery of whole-bone monotonic strength and increased fatigue life. J Orthop Res. 2007;25(2):252-261.PubMedCrossRefGoogle Scholar
  14. 14.
    McCann RM, Colleary G, Geddis C, et al. Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model. J Orthop Res. 2008;26(3):384-393.PubMedCrossRefGoogle Scholar
  15. 15.
    Beamer WG, Donahue LR, Rosen CJ, Baylink DJ. Genetic variability in adult bone density among inbred strains of mice. Bone. 1996;18(5):397-403.PubMedCrossRefGoogle Scholar
  16. 16.
    Breen SA, Loveday BE, Millest AJ, Waterton JC. Stimulation and inhibition of bone formation: use of peripheral quantitative computed tomography in the mouse in vivo. Lab Anim. 1998;32(4):467-476.PubMedCrossRefGoogle Scholar
  17. 17.
    Schmidt C, Priemel M, Kohler T, et al. Precision and accuracy of peripheral quantitative computed tomography (pQCT) in the mouse skeleton compared with histology and microcomputed tomography (microCT). J Bone Miner Res. 2003;18(8):1486-1496.PubMedCrossRefGoogle Scholar
  18. 18.
    Martin-Badosa E, Amblard D, Nuzzo S, Elmoutaouakkil A, Vico L, Peyrin F. Excised bone structures in mice: imaging at three-dimensional synchrotron radiation micro CT. Radiology. 2003;229(3):921-928.PubMedCrossRefGoogle Scholar
  19. 19.
    Fajardo RJ, Cory E, Patel ND, et al. Specimen size and porosity can introduce error into microCT-based tissue mineral density measurements. Bone. 2009;44(1):176-184.PubMedCrossRefGoogle Scholar
  20. 20.
    Kapadia RD, Stroup GB, Badger AM, et al. Applications of micro-CT and MR microscopy to study pre-clinical models of osteoporosis and osteoarthritis. Technol Health Care. 1998;6(5–6):361-372.PubMedGoogle Scholar
  21. 21.
    Bonnet N, Laroche N, Vico L, Dolleans E, Courteix D, Benhamou CL. Assessment of trabecular bone microarchitecture by two different x-ray microcomputed tomographs: a comparative study of the rat distal tibia using Skyscan and Scanco devices. Med Phys. 2009;36(4):1286-1297.PubMedCrossRefGoogle Scholar
  22. 22.
    Waarsing JH, Day JS, Weinans H. An improved segmentation method for in vivo microCT imaging. J Bone Miner Res. 2004;19(10):1640-1650.PubMedCrossRefGoogle Scholar
  23. 23.
    Alexander JM, Bab I, Fish S, et al. Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice. J Bone Miner Res. 2001;16(9):1665-1673.PubMedCrossRefGoogle Scholar
  24. 24.
    Muller R, Van Campenhout H, Van Damme B, et al. Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. Bone. 1998;23(1):59-66.PubMedCrossRefGoogle Scholar
  25. 25.
    Fanuscu MI, Chang TL. Three-dimensional morphometric analysis of human cadaver bone: microstructural data from maxilla and mandible. Clin Oral Implants Res. 2004;15(2):213-218.PubMedCrossRefGoogle Scholar
  26. 26.
    Chappard D, Retailleau-Gaborit N, Legrand E, Basle MF, Audran M. Comparison insight bone measurements by ­histomorphometry and microCT. J Bone Miner Res. 2005;20(7):1177-1184.PubMedCrossRefGoogle Scholar
  27. 27.
    Hankenson KD, Hormuzdi SG, Meganck JA, Bornstein P. Mice with a disruption of the thrombospondin 3 gene differ in geometric and biomechanical properties of bone and have accelerated development of the femoral head. Mol Cell Biol. 2005;25(13):5599-5606.PubMedCrossRefGoogle Scholar
  28. 28.
    von Stechow D, Zurakowski D, Pettit AR, et al. Differential transcriptional effects of PTH and estrogen during anabolic bone formation. J Cell Biochem. 2004;93(3):476-490.CrossRefGoogle Scholar
  29. 29.
    Christiansen BA, Silva MJ. The effect of varying magnitudes of whole-body vibration on several skeletal sites in mice. Ann Biomed Eng. 2006;34(7):1149-1156.PubMedCrossRefGoogle Scholar
  30. 30.
    Squire M, Donahue LR, Rubin C, Judex S. Genetic variations that regulate bone morphology in the male mouse skeleton do not define its susceptibility to mechanical unloading. Bone. 2004;35(6):1353-1360.PubMedCrossRefGoogle Scholar
  31. 31.
    Uthgenannt BA, Silva MJ. Use of the rat forelimb compression model to create discrete levels of bone damage in vivo. J Biomech. 2007;40(2):317-324.PubMedCrossRefGoogle Scholar
  32. 32.
    Naik AA, Xie C, Zuscik MJ, et al. Reduced COX-2 expression in aged mice is associated with impaired fracture healing. J Bone Miner Res. 2009;24(2):251-264.PubMedCrossRefGoogle Scholar
  33. 33.
    Gardner MJ, Ricciardi BF, Wright TM, Bostrom MP, van der Meulen MC. Pause insertions during cyclic in vivo loading affect bone healing. Clin Orthop Relat Res. 2008;466(5):1232-1238.PubMedCrossRefGoogle Scholar
  34. 34.
    Duvall CL, Taylor WR, Weiss D, Wojtowicz AM, Guldberg RE. Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice. J Bone Miner Res. 2007;22(2):286-297.PubMedCrossRefGoogle Scholar
  35. 35.
    Shen X, Wan C, Ramaswamy G, et al. Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J Orthop Res. 2009;27(10):1298-1305.PubMedCrossRefGoogle Scholar
  36. 36.
    Gerstenfeld LC, Sacks DJ, Pelis M, et al. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res. 2009;24(2):196-208.PubMedCrossRefGoogle Scholar
  37. 37.
    Morgan EF, Mason ZD, Chien KB, et al. Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function. Bone. 2009;44(2):335-344.PubMedCrossRefGoogle Scholar
  38. 38.
    Duvall CL, Taylor WR, Weiss D, Guldberg RE. Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury. Am J Physiol Heart Circ Physiol. 2004;287(1):H302-H310.PubMedCrossRefGoogle Scholar
  39. 39.
    Duvall CL, Weiss D, Robinson ST, Alameddine FM, Guldberg RE, Taylor WR. The role of osteopontin in recovery from hind limb ischemia. Arterioscler Thromb Vasc Biol. 2008;28(2):290-295.PubMedCrossRefGoogle Scholar
  40. 40.
    Chen RR, Snow JK, Palmer JP, et al. Host immune competence and local ischemia affects the functionality of engineered vasculature. Microcirculation. 2007;14(2):77-88.PubMedCrossRefGoogle Scholar
  41. 41.
    Guldberg RE, Lin AS, Coleman R, Robertson G, Duvall C. Microcomputed tomography imaging of skeletal development and growth. Birth Defects Res C Embryo Today. 2004;72(3):250-259.PubMedCrossRefGoogle Scholar
  42. 42.
    Wang Y, Wan C, Deng L, et al. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest. 2007;117(6):1616-1626.PubMedCrossRefGoogle Scholar
  43. 43.
    Abruzzo T, Tumialan L, Chaalala C, et al. Microscopic computed tomography imaging of the cerebral circulation in mice: feasibility and pitfalls. Synapse. 2008;62(8):557-565.PubMedCrossRefGoogle Scholar
  44. 44.
    Suo J, Ferrara DE, Sorescu D, Guldberg RE, Taylor WR, Giddens DP. Hemodynamic shear stresses in mouse aortas: implications for atherogenesis. Arterioscler Thromb Vasc Biol. 2007;27(2):346-351.PubMedCrossRefGoogle Scholar
  45. 45.
    Awad HA, Zhang X, Reynolds DG, Guldberg RE, O’Keefe RJ, Schwarz EM. Recent advances in gene delivery for structural bone allografts. Tissue Eng. 2007;13(8):1973-1985.PubMedCrossRefGoogle Scholar
  46. 46.
    Rai B, Oest ME, Dupont KM, Ho KH, Teoh SH, Guldberg RE. Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. J Biomed Mater Res A. 2007;81(4):888-899.PubMedGoogle Scholar
  47. 47.
    Palmer AW, Guldberg RE, Levenston ME. Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography. Proc Natl Acad Sci USA. 2006;103(51):19255-19260.PubMedCrossRefGoogle Scholar
  48. 48.
    Waarsing JH, Day JS, van der Linden JC, et al. Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data. Bone. 2004;34(1):163-169.PubMedCrossRefGoogle Scholar
  49. 49.
    Boyd SK, Moser S, Kuhn M, et al. Evaluation of three-dimensional image registration methodologies for in vivo micro-computed tomography. Ann Biomed Eng. 2006;34(10):1587-1599.PubMedCrossRefGoogle Scholar
  50. 50.
    Boyd SK, Davison P, Muller R, Gasser JA. Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography. Bone. 2006;39(4):854-862.PubMedCrossRefGoogle Scholar
  51. 51.
    Campbell GM, Buie HR, Boyd SK. Signs of irreversible architectural changes occur early in the development of experimental osteoporosis as assessed by in vivo micro-CT. Osteoporos Int. 2008;19(10):1409-1419.PubMedCrossRefGoogle Scholar
  52. 52.
    Buie HR, Moore CP, Boyd SK. Postpubertal architectural developmental patterns differ between the L3 vertebra and proximal tibia in three inbred strains of mice. J Bone Miner Res. 2008;23(12):2048-2059.PubMedCrossRefGoogle Scholar
  53. 53.
    Brouwers JE, Lambers FM, Gasser JA, van Rietbergen B, Huiskes R. Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized wistar rats assessed by in vivo micro-computed tomography. Calcif Tissue Int. 2008;82(3):202-211.PubMedCrossRefGoogle Scholar
  54. 54.
    Brouwers JE, van Rietbergen B, Huiskes R, Ito K. Effects of PTH treatment on tibial bone of ovariectomized rats assessed by in vivo micro-CT. Osteoporos Int. 2009;20(11):1823-1835.PubMedCrossRefGoogle Scholar
  55. 55.
    McErlain DD, Appleton CT, Litchfield RB, et al. Study of subchondral bone adaptations in a rodent surgical model of OA using in vivo micro-computed tomography. Osteoarthritis Cartilage. 2008;16(4):458-469.PubMedCrossRefGoogle Scholar
  56. 56.
    Morenko BJ, Bove SE, Chen L, et al. In vivo micro computed tomography of subchondral bone in the rat after ­intra-articular administration of monosodium iodoacetate. Contemp Top Lab Anim Sci. 2004;43(1):39-43.PubMedGoogle Scholar
  57. 57.
    Dare A, Hachisu R, Yamaguchi A, Yokose S, Yoshiki S, Okano T. Effects of ionizing radiation on proliferation and differentiation of osteoblast-like cells. J Dent Res. 1997;76(2):658-664.PubMedCrossRefGoogle Scholar
  58. 58.
    Klinck RJ, Campbell GM, Boyd SK. Radiation effects on bone architecture in mice and rats resulting from in vivo micro-computed tomography scanning. Med Eng Phys. 2008;30(7):888-895.PubMedCrossRefGoogle Scholar
  59. 59.
    Nuzzo S, Lafage-Proust MH, Martin-Badosa E, 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. 2002;17(8):1372-1382.PubMedCrossRefGoogle Scholar
  60. 60.
    Burghardt AJ, Wang Y, Elalieh H, et al. Evaluation of fetal bone structure and mineralization in IGF-I deficient mice using synchrotron radiation microtomography and Fourier transform infrared spectroscopy. Bone. 2007;40(1):160-168.PubMedCrossRefGoogle Scholar
  61. 61.
    Matsumoto T, Yoshino M, Asano T, Uesugi K, Todoh M, Tanaka M. Monochromatic synchrotron radiation muCT reveals disuse-mediated canal network rarefaction in cortical bone of growing rat tibiae. J Appl Physiol. 2006;100(1):274-280.PubMedCrossRefGoogle Scholar
  62. 62.
    Raum K, Hofmann T, Leguerney I, et al. Variations of microstructure, mineral density and tissue elasticity in B6/C3H mice. Bone. 2007;41(6):1017-1024.PubMedCrossRefGoogle Scholar
  63. 63.
    Schneider P, Stauber M, Voide R, Stampanoni M, Donahue LR, Muller R. 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. 2007;22(10):1557-1570.PubMedCrossRefGoogle Scholar
  64. 64.
    Kinney JH, Ryaby JT, Haupt DL, Lane NE. Three-dimensional in vivo morphometry of trabecular bone in the OVX rat model of osteoporosis. Technol Health Care. 1998;6(5–6):339-350.PubMedGoogle Scholar
  65. 65.
    Muller R, Koller B, Hildebrand T, Laib A, Gianolini S, Ruegsegger P. Resolution dependency of microstructural properties of cancellous bone based on three-dimensional mu-tomography. Technol Health Care. 1996;4(1):113-119.PubMedGoogle Scholar
  66. 66.
    Brodt MD, Pelz GB, Taniguchi J, Silva MJ. Accuracy of peripheral quantitative computed tomography (pQCT) for assessing area and density of mouse cortical bone. Calcif Tissue Int. 2003;73(4):411-418.PubMedCrossRefGoogle Scholar
  67. 67.
    Hamrick MW, Pennington C, Newton D, Xie D, Isales C. Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone. 2004;34(3):376-383.PubMedCrossRefGoogle Scholar
  68. 68.
    Glatt V, Canalis E, Stadmeyer L, Bouxsein ML. Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res. 2007;22(8):1197-1207.PubMedCrossRefGoogle Scholar
  69. 69.
    Judex S, Garman R, Squire M, Donahue LR, Rubin C. Genetically based influences on the site-specific regulation of trabecular and cortical bone morphology. J Bone Miner Res. 2004;19(4):600-606.PubMedCrossRefGoogle Scholar
  70. 70.
    Ridler T, Calvard S. Picture thresholding using an iterative selection method. IEEE Trans Syst Man Cybern. 1978;SMC-8(8):630-632.Google Scholar
  71. 71.
    Meinel L, Fajardo R, Hofmann S, et al. Silk implants for the healing of critical size bone defects. Bone. 2005;37(5):688-698.PubMedCrossRefGoogle Scholar
  72. 72.
    Tommasini SM, Hu B, Nadeau JH, Jepsen KJ. Phenotypic integration among trabecular and cortical bone traits establishes mechanical functionality of inbred mouse vertebrae. J Bone Miner Res. 2009;24(4):606-620.PubMedCrossRefGoogle Scholar
  73. 73.
    Davey RA, MacLean HE, McManus JF, Findlay DM, Zajac JD. Genetically modified animal models as tools for studying bone and mineral metabolism. J Bone Miner Res. 2004;19(6):882-892.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  1. 1.Department of OrthopaedicsUniversity of California-Davis Medical CenterSacramentoUSA

Personalised recommendations