Three-dimensional dynamic bone histomorphometry

Authors

  • Craig R Slyfield,

    1. Biomedical Mechanics Laboratories, Sibley School of Mechanical and Aerospace Engineering and Biomedical Engineering, Cornell University, Ithaca, NY, USA
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  • Evgeniy V Tkachenko,

    1. Biomedical Mechanics Laboratories, Sibley School of Mechanical and Aerospace Engineering and Biomedical Engineering, Cornell University, Ithaca, NY, USA
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  • David L Wilson,

    1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
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  • Christopher J Hernandez

    Corresponding author
    1. Biomedical Mechanics Laboratories, Sibley School of Mechanical and Aerospace Engineering and Biomedical Engineering, Cornell University, Ithaca, NY, USA
    • 219 Upson Hall, Cornell University, Ithaca, NY 14853, USA.
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Abstract

Dynamic bone histomorphometry is the standard method for measuring bone remodeling at the level of individual events. Although dynamic bone histomorphometry is an invaluable tool for understanding osteoporosis and other metabolic bone diseases, the technique's two-dimensional nature requires the use of stereology and prevents measures of individual remodeling event number and size. Here, we used a novel three-dimensional fluorescence imaging technique to achieve measures of individual resorption cavities and formation events. We performed this three-dimensional histomorphometry approach using a common model of postmenopausal osteoporosis, the ovariectomized rat. The three-dimensional images demonstrated the spatial relationship between resorption cavities and formation events consistent with the hemiosteonal model of cancellous bone remodeling. Established ovariectomy was associated with significant increases in the number of resorption cavities per unit bone surface (2.38 ± 0.24 mm−2 sham surgery versus 3.86 ± 0.35 mm−2 bilateral ovariectomy [OVX], mean ± SD, p < 0.05) and total volume occupied by cavities per unit bone volume (0.38% ± 0.06% sham versus 1.12% ± 0.18% OVX, p < 0.001), but there was no difference in surface area per resorption cavity, maximum cavity depth, or cavity volume. In addition, we found that established ovariectomy is associated with increased size of bone formation events because of the merging of formation events (23,700 ± 6,890 µm2 sham verusus 33,300 ± 7,950 µm2 OVX). No differences in mineral apposition rate (determined in 3D) were associated with established ovariectomy. That established estrogen depletion is associated with increased number of remodeling events with only subtle changes in remodeling event size suggests that circulating estrogens may have their primary effect on the origination of new basic multicellular units with relatively little effect on the progression and termination of active remodeling events. © 2012 American Society for Bone and Mineral Research

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