Boyd Steven K, Davison Peter, Müller Ralph, Gasser Jürg A
Department of Mechanical and Manufacturing Engineering, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
Bone. 2006 Oct;39(4):854-62. doi: 10.1016/j.bone.2006.04.017. Epub 2006 Jun 6.
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.
去卵巢（OVX）大鼠是骨质疏松症研究中一个成熟的模型。体内微型计算机断层扫描（micro-CT）的最新发展为长期监测个体骨骼变化提供了新的可能性。本研究的目的是确定OVX大鼠模型中骨质流失的正常时间进程，并与在每个时间点处死动物的横断面研究设计相比，确定在体内检测形态学变化的能力。将8月龄雌性Wistar大鼠随机分为两组之一：OVX组（N = 10）或假手术组（N = 10）。对右侧胫骨近端干骺端进行体内micro-CT扫描，每隔1个月进行一次，共6个月。在每个时间点对每只动物进行形态学分析，并使用重复测量的双向方差分析来分析数据。作为横断面研究设计，进行了第二次无重复测量的统计分析。与横断面研究分析相比，重复测量分析对早期变化更敏感。通过纵向分析在假手术组和OVX组动物中随时间检测到变化（P < 0.001），假手术组动物的小梁间距除外。相对于基线测量，OVX组动物在1个月后骨体积比降低了33%，在3个月后降低了72%。使用纵向分析早期检测到骨体积比、小梁数量和间距的显著变化，因此体内评估完全有能力研究早期治疗方案对骨骼结构的影响。体内分析发现假手术组动物有显著变化，而横断面分析未检测到，并且更早检测到OVX组动物形态的变化。在同质性大鼠组中观察到基线形态测量的显著差异以及对OVX的反应，因此强调了进行体内分析的优势，即每只动物自身作为对照。这些数据为OVX后个体骨骼变化提供了新的见解，并可作为设计未来体内研究的基线信息。
