Application of micro-CT assessment of 3-D bone microstructure in preclinical and clinical studies
Application of micro-CT assessment of 3-D bone microstructure in preclinical and clinical studies
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DOI：
10.1007/bf03026336
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Genant, HK
中科院分区：
文献类型：
--
作者：
Jiang, YB;Zhao, J;Genant, HK
由于骨小梁的机械能力是其表观密度和三维分布的函数，因此评估三维骨小梁结构特征可以提高我们了解骨质疏松症病理生理学、测试药物干预效果以及评估骨质疏松症的能力。骨生物力学特性。我们研究了卵巢切除术引起的大鼠骨质疏松症及其用雌激素和氟化钠等药物的治疗。我们已经证明，3-D微计算机断层扫描（mu CT）可以直接量化小鼠骨小梁和皮质骨结构，各向同性分辨率为6 μ m（3）。μ CT还可用于研究小鼠的骨质疏松症和基因操作小鼠的表型，例如SHIP敲除小鼠，其由于高吸收破骨细胞数量增加而严重骨质疏松，PTHrP异质性缺失小鼠和Zmpste 24缺陷小鼠。μ CT可以量化小鼠Ilizarov腿延长程序中的骨生成、大鼠颅骨缺损模型中的骨传导以及关节炎兔、大鼠和小鼠中的结构变化。在临床研究中，我们评估了髂嵴的纵向变化。同一绝经前后妇女的成对骨活检显示三维骨小梁结构的变化，如骨小梁厚度减少，骨小梁由板状结构向杆状结构转变，骨小梁各向异性程度降低。绝经后骨质疏松症妇女接受PTH治疗后，骨小梁形态显著改善，骨小梁结构向板状结构转变，骨小梁连接密度增加，皮质厚度增加。绝经后骨质疏松妇女在开始雌激素替代治疗前和开始雌激素替代治疗后平均2年的髂嵴配对骨活检标本表明，治疗后活检显示板与杆的比例有显著变化，其他3-D小梁参数的变化无统计学意义。因此，mu CT可以表征各种动物模型的3-D结构，以及在绝经期恶化的3-D骨微结构完整性的纵向变化，在绝经后妇女中，HRT可以保留这些变化，而PTH治疗可以改善这些变化。
As the mechanical competence of trabecular bone is a function of its apparent density and 3-D distribution, assessment of 3-D trabecular structural characteristics may improve our ability to understand the pathophysiology of osteoporosis, to test the efficacy of pharmaceutical intervention, and to estimate bone biomechanical properties. We have studied ovariectomy-induced osteopenia in rats and its treatment with agents such as estrogen and sodium fluoride. We have demonstrated that 3-D micro-computed tomography (mu CT) can directly quantify mouse trabecular and cortical bone structure with an isotropic resolution of 6 mu m(3). mu CT is also useful for studying osteoporosis in mice and phenotypes of mice with gene manipulation, such as SHIP-knockout mice, which are severely osteoporotic due to increased numbers of hyperresorptive osteoclasts, PTHrP heterozygous-null mice, and mice with Zmpste24 deficiency. mu CT can quantify osteogenesis in mouse Ilizarov leg-lengthening procedures, osteoconduction in a rat cranial defect model, and structural changes in arthritic rabbits, rats, and mice. In clinical studies, we evaluated longitudinal changes in the iliac crests. Paired bone biopsies from the same premenopausal and postmenopausal women showed the changes in 3-D trabecular structure, such as decreased trabecular thickness, shifting of trabecular model from platelike structure to rodlike structure, and decreased degree of anisotropy were remarkable. Treatment with PTH in postmenopausal women with osteoporosis significantly improved trabecular morphology with a shift toward a more platelike structure, increased trabecular connectivity density, and increased cortical thickness. Paired bone biopsy specimens from the iliac crest in postmenopausal women with osteoporosis before and an average of 2 years after beginning of estrogen replacement therapy demonstrated that posttreatment biopsies showed a significant change in the ratio of plates to rods and statistically insignificant changes in other 3-D trabecular parameters. Thus, mu CT can characterize 3-D structure of various animal models, and the longitudinal changes in 3-D bone microarchitectural integrity that deteriorates in the transmenopausal period, is preserved with HRT, and is improved with PTH treatment in postmenopausal women.