Osteoporosis treatment response assessed by micromechanical modeling of MRI data.

通过 MRI 数据的微机械模型评估骨质疏松症治疗反应。

• 批准号: 8297424
• 负责人: Felix W Wehrli
• 金额: $ 43.22万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-07 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8297424
• 关键词: Address; Adherence; Adipocytes; Adverse effects; Affect; Age; Aging; Alternative Therapies; American; Animal Model; Biomechanics; Bone Density; Bone Marrow; Bone Resorption; Cells; Competence; Data; Diagnosis; Disease; Distal; Double-Blind Method; Down-Regulation; Dual-Energy X-Ray Absorptiometry; Electronics; Elements; Equilibrium; Estrogens; Exercise; Failure; Fatty acid glycerol esters; Feedback; Fracture; Frequencies; Gender; Gene Expression; Hip region structure; Human; Image; Intervention; Laboratories; Life Style; Magnetic Resonance Imaging; Maintenance; Marrow; Measurement; Measures; Mechanical Stimulation; Mechanics; Menopause; Mesenchymal Stem Cells; Methodology; Methods; Modeling; Monitor; Nuclear Hormone Receptors; Obesity; Osteoblasts; Osteocytes; Osteogenesis; Osteoporosis; Outcome; Patients; Peripheral; Peroxisome Proliferator-Activated Receptors; Pharmaceutical Preparations; Placebos; Play; Postmenopause; Predisposition; Prevalence; Prevention; Property; Protocols documentation; Public Health; Radial; Randomized; Relative (related person); Reporting; Resolution; Risk Factors; Sheep; Signaling Molecule; Site; Staging; Stromal Cells; Tissues; Vertebral column; Woman; Work; aged; base; bone; bone loss; bone mass; bone strength; cohort; cost; density; effective therapy; follow-up; imaging modality; improved; insight; lipid biosynthesis; lumbar vertebra bone structure; magnetic resonance spectroscopic imaging; men; osteogenic; peer; prophylactic; randomized placebo controlled trial; response; sedentary; skeletal; skeletal disorder; spectroscopic imaging; spine bone structure; substantia spongiosa; tibia; treatment response; vibration; young woman

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. PUBLIC HEALTH RELEVANCE: Osteoporosis and low bone mass are major public health issues affecting a significant portion of older Americans, in particular women after menopause. While effective drug treatment is now available, it is expensive, associated with significant side effects and indicated only at a late stage of the disease at which point it is no longer reversible Mechanical stimulation is a new, entirely noninvasive form of nonpharmacologic intervention, but its effect in terms of conferring bone strength is not known. By evaluating changes in bone mechanical competence in early postmenopausal women undergoing mechanical stimulation via image-based computational biomechanics, this project focuses on prevention rather than treatment.

描述（由申请人提供）：骨质疏松症和低骨质量估计是近4400万名50岁及50岁以上的美国男性的主要公共卫生威胁。尽管这种疾病影响了这两种性别，但患有这种疾病的人中约有80％是女性。更年期和雌激素水平的伴随下降后，骨发生结构变化和组织量密度的降低，导致强度降低和骨折易感性增加。即使有有效的治疗方法，抗吸收和合成代谢药物的高成本和许多副作用刺激了寻找替代疗法。然而，同样重要的是，在受试者发展到与骨质疏松症的诊断相称的骨密度水平之前，通常不会表明药理干预。 最近已经显示，在赫尔兹数十亿的频率下，低稳定性的机械刺激（LMM）是成骨的，大概是通过下调核激素受体的下调，PPAR，导致骨髓基质细胞优先区分朝骨细胞的骨髓细胞而不是脂肪细胞毛线。该竞争性更新项目旨在进一步开发基于图像的微元素元素建模的方法，用于量化骨骼机械能力的各种特性，以及改进的方法，用于对高分辨率结构磁共振（MR）皮质和小梁骨的高分辨率结构性磁共振（MR）成像，以及通过MR Spectroscopic ImageTroscosic ImageTroscopic ImageTroscopic Imageing bone骨髓组成的测量。 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. 该项目的成功完成将为监测预防性干预的基于图像的计算生物力学的潜力提供新的见解。 公共卫生相关性：骨质疏松症和低骨量是影响大部分美国人的主要公共卫生问题，尤其是更年期后的妇女。尽管现在可以使用有效的药物治疗，但它很昂贵，与重大副作用相关，并且仅在疾病的后期才表明它不再是可逆的机械刺激是一种新的，完全无创的非药物干预形式，但在赋予骨骼强度方面的作用尚不清楚。通过评估通过基于图像的计算生物力学进行机械刺激的早期骨骼机械能力的变化，该项目的重点是预防而不是治疗。