Osteoporosis treatment response assessed by micromechanical modeling of MRI data.

描述（由申请人提供）：骨质疏松症和低骨量目前估计是近4400万50岁及以上美国女性和男性的主要公共健康威胁。虽然这种疾病影响到两种性别，但大约80%的患者是女性。绝经后和伴随的雌激素水平下降，骨发生结构变化和组织体积密度降低，导致强度降低和骨折易感性增加。尽管有效的治疗是可用的，抗吸收和合成代谢药物的高成本和众多的副作用刺激了替代疗法的研究。然而，同样重要的是，在受试者的骨密度进展到与骨质疏松症诊断相称的水平之前，通常不需要药物干预。 最近的研究表明，低强度的机械刺激（LMMS）在几十赫兹的频率是成骨的，大概是通过下调核激素受体，过氧化物酶体增殖物激活受体，导致骨髓基质细胞向成骨细胞，而不是脂肪细胞谱系的优先分化。该竞争性更新项目旨在进一步开发基于图像的微观有限元建模方法，用于量化骨骼机械能力的各种特性，沿着改进皮质骨和松质骨的高分辨率结构磁共振（MR）成像方法，以及通过MR光谱成像测量骨髓成分。将在随后的随机、双盲、平移患者研究中应用所得到的方案，以评价以下假设：早期绝经后女性，每天接受10分钟LMMS治疗，持续一年，将显示骨小梁和皮质刚度以及胫骨失效强度的改善，沿着，相对于安慰剂治疗的同龄人，脊椎骨髓脂肪减少。 该项目的成功完成将为基于图像的计算生物力学监测预防性干预的潜力提供新的见解。

DESCRIPTION (provided by applicant): Osteoporosis and low bone mass are currently estimated to be a major public health threat for almost 44 million U.S. women and men aged 50 and older. While the disorder affects both genders, approximately 80% of those having the condition are women. After menopause and the concomitant decline in estrogen levels, bone undergoes structural changes and reduction in tissue volume density resulting in reduced strength and increased fracture susceptibility. Even though effective treatment is available, the high cost and numerous side effects of antiresorptive and anabolic drugs have spurred the search for alternative therapies. Equally important, however, is that pharmacologic intervention is generally not indicated until subjects have progressed to a level of bone density commensurate with the diagnosis of osteoporosis. It has recently been shown that low-magnitude mechanical stimulation (LMMS) at frequencies of tens of Hertz is osteogenic, presumably via downregulation of the nuclear hormone receptor, PPAR, resulting in preferential differentiation of marrow stromal cells toward the osteoblastic instead of the adipocytic lineage. This competing renewal project seeks to further develop methods for image-based micro-finite-element modeling for quantifying various properties of skeletal mechanical competence, along with improved methods for high-resolution structural magnetic resonance (MR) imaging of cortical and trabecular bone, and measurement of bone marrow composition by MR spectroscopic imaging. The resulting protocol will be applied in a subsequent randomized, double-blinded, translational patient study to evaluate the hypothesis that early postmenopausal women, subjected to a daily 10-minute treatment of LMMS for one year, will show an improvement in trabecular and cortical stiffness and failure strength at the tibia, along with a reduction in vertebral marrow adiposity relative to their placebo-treated peers. The successful completion of the project will provide new insight into the potential for image-based computational biomechanics for monitoring prophylactic intervention.