Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography

Boyd, Steven K.<sup>1</sup>; Davison, Peter<sup>1</sup>; Müller, Ralph<sup>2</sup>; Gasser, Jürg A.<sup>3</sup>

Affiliations

¹Department of Mechanical and Manufacturing Engineering, University of Calgary, 2500 University Drive, N.W., Calgary, Alberta, Canada T2N 1N4

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

³Novartis Institutes for Biomedical Research, Basel, Switzerland

Abstract and keywords

The ovariectomized (OVX) rat is a well established model for osteoporosis research. The recent development of in vivo micro-computed tomography (micro-CT) provides new possibilities to monitor individual bone changes over time. The purpose of this study was to establish the normal time course of bone loss in the OVX rat model, and to determine the ability to detect morphological changes in vivo compared to cross-sectional study designs where animals are sacrificed at each time point. Eight-month-old female Wistar rats were randomly assigned to one of two groups: OVX (N = 10) or sham-operated (N = 10). In vivo micro-CT scanning of the right proximal tibial metaphyses occurred at 1-month intervals for 6 months. Morphological analyses were performed at each time step for every animal, and a two-way ANOVA with repeated measures was used to analyze the data. A second statistical analysis was performed without repeated measures for analysis as a cross-sectional study design. The repeated measures analysis was more sensitive to early changes than the cross-sectional study analysis. Changes were detected by longitudinal analysis in the sham-operated and OVX animals over time (P < 0.001) with the exception of trabecular separation in the sham animals. The OVX animals had decreases of bone volume ratio of 33% after 1 month, and 72% after 3 months relative to baseline measurements. Significant changes in bone volume ratio, trabecular number and separation were detected early using a longitudinal analysis, thus in vivo assessment is well poised to enable the study of early treatment protocols on the effects of bone architecture. The in vivo analysis found significant changes in the sham animals which were not detected by the cross-sectional analysis, and the changes to the OVX animal morphology was detected sooner. A substantial variation of baseline morphometry within the homogenous group of rats and response to OVX was observed, thus emphasizing the advantage of performing in vivo analysis where each animal acts as its own control. These data provide new insight into individual bone changes following OVX, and can be used as baseline information upon which future in vivo studies can be designed.

Keywords: Osteoporosis; Osteopenia; Bone histomorphometry; Rat; Tibial metaphyses; Micro-computed tomography; Histomorphometry

Links

DOI: 10.1016/j.bone.2006.04.017

PubMed: 16757220

WoS: 000240792700019

History

Received: 2006-02-12

Revised: 2006-03-30

Accepted: 2006-04-07

Online: 2006-06-06

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