X-Treme CT Equipment Grant

描述(申请人提供)：目前，在骨质疏松症和其他代谢性骨疾病的人体研究中，评估骨骼健康和预测骨折风险的金标准是用双能X射线骨密度仪(DXA)测量面骨密度(BMD)。然而，DXA存在重大的科学和技术限制。从科学角度来看，DXA仅提供面骨密度测量，不提供有关骨结构的信息，如骨小梁数量、骨小梁厚度、骨小梁连通性或皮质厚度。这些影响骨质量的参数可能至少部分解释了以下观察结果：许多骨折发生在骨密度正常的患者中，抗吸收治疗后面骨密度的微小变化导致骨折风险的降低大于预期，以及抗吸收治疗后骨密度的变化解释了骨折风险降低的一小部分差异。从技术角度来看，DXA不能测量真实密度，可被脊柱退行性疾病(尤其是男性和老年受试者)显著改变，受周围软组织的数量和分布的强烈影响，并且无法分离皮质和松质骨。目前，评估皮质和小梁微结构的金标准是髂骨顶活组织检查。这一过程是非常有侵入性的，以至于很少有受试者愿意接受一次，更不用说在长期研究中反复进行了。此外，骨组织形态计量学的重复性较差，进一步限制了其在纵向骨研究中的应用。XtremeCT是一种新技术，它可以产生高分辨率的骨骼图像，允许对皮质骨和骨小梁微结构进行非侵入性评估。本质上，XtremeCT是一种虚拟的骨活检，可以在有限的X射线曝光下进行，并且具有高度的重复性。因此，作为DXA的补充，在代谢性骨病的研究中，它是一种理想的技术，可以提供有关骨结构变化的关键信息，并绕过许多关键人群中DXA的限制。目前，美国只有3台XtremeCT机器，新英格兰一台也没有。随着技术的进步，XtremeCT似乎将成为代谢性骨病最先进的临床研究中不可或缺的工具。我们建议将XtremeCT用于广泛的骨骼疾病研究，这些研究跨越多个学科，并为波士顿和整个新英格兰的广泛研究人员提供服务。

DESCRIPTION (provided by applicant): Currently, the gold standard for evaluating skeletal health and predicting fracture risk in human studies of osteoporosis and other metabolic bone diseases is measurement of areal bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA). However, there are major scientific and technical limitations to DXA. From a scientific perspective, DXA provides only areal BMD measurements and does not provide information about bone architecture such as trabecular number, trabecular thickness, trabecular connectivity, or cortical thickness. These parameters, which contribute to bone quality, are likely responsible, at least in part, for the observations that many fractures occur among patients with normal BMD, that small changes in areal BMD with antiresorptive therapy result in greater than expected reductions in fracture risk, and that changes in BMD following antiresorptive therapy explain a small proportion of the variance in fracture risk reduction. From a technical perspective, DXA does not measure true density, can be markedly altered by degenerative disease in the spine (particularly in men and elderly subjects), is strongly affected by the amount and distribution of surrounding soft tissue, and cannot separate cortical from trabecular bone. Currently, the gold standard for assessing cortical and trabecular microarchitecture is iliac crest biopsy. This procedure is quite invasive so that few subjects are willing to undergo it once, let alone repeatedly in long-term studies. Moreover, reproducibility of bone histomorphometry is poor further limiting its utility in longitudinal bone studies. XtremeCT is a new technique that produces high resolution images of bone that allow a non- invasive assessment of cortical and trabecular microstructure. In essence, XtremeCT is a virtual bone biopsy that can be performed with limited x-ray exposure and is highly reproducible. Thus, it is an ideal technique to use in studies of metabolic bone disease as a complement to DXA to provide critical information about changes in bone architecture and to circumvent limitations of DXA in many key populations. Currently, there are only 3 XtremeCT machines in the US and none in New England. With advances in technology, it appears likely that XtremeCT will be an indispensable tool for state-of-the-art clinical research in metabolic bone disease. We propose to use XtremeCT in a wide range of studies of bone disease that span a multitude of disciplines and serve a wide range of investigators in Boston and throughout New England.