Role of local strain in osteogenic response to vibration therapy in humans

局部应变在人体对振动疗法的成骨反应中的作用

• 批准号: 8682886
• 负责人: Chamith Sudesh Rajapakse
• 金额: $ 8.22万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8682886
• 关键词: Address; Adherence; Adverse effects; Affect; Alternative Therapies; Animal Model; Biomechanics; Bone Density; Bone Diseases; Bone Growth; Bone Resorption; Bone remodeling; Calcium; Cell Culture Techniques; Child; Chronic Kidney Failure; Clinical; Clinical Trials; Data; Dependence; Development; Dialysis patients; Dialysis procedure; Disease; Distal; Double-Blind Method; Dual-Energy X-Ray Absorptiometry; Effectiveness; Elements; End stage renal failure; Exercise; FDA approved; Failure; Fracture; General Population; Human; Image; Intervention; Kidney Diseases; Knowledge; Lead; Life Style; Light; Location; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Mechanical Stimulation; Mechanics; Metaphysis; Methodology; Methods; Modeling; Monitor; Motor; Osteogenesis; Osteoporosis; Outcome; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Population; Population Study; Postmenopause; Prevalence; Prevention; Preventive Intervention; Radial; Randomized; Renal Osteodystrophy; Reporting; Research; Resolution; Risk; Risk Factors; Role; Sheep; Site; Skeleton; Solutions; Staging; Stimulus; Structure; Techniques; Testing; Translations; Treatment Efficacy; United States; Vitamin D; Weight-Bearing state; Woman; Work; aging population; alternative treatment; base; bone; bone loss; bone strength; career; cohort; cost; disability; experience; fibula; foot sole; improved; inorganic phosphate; mortality; non-invasive imaging; osteogenic; public health relevance; response; sedentary; substantia spongiosa; theories; tibia; tool; treatment effect; two-dimensional; vibration; young woman

DESCRIPTION (provided by applicant): Renal osteodystrophy (ROD) is a multifactorial and pervasive disorder of bone remodeling in chronic kidney disease (CKD). The prevalence CKD in the United States is estimated at 15.1% in 2011. With the aging population, the number of patients affected by ROD, therefore, is expected to increase. Despite the widespread use of therapies, such as phosphate binders, calcium, and vitamin D, bone-fracture rates and mortality risk following fractures are markedly greater in patients on dialysis, compared with the general population. Furthermore, the effectiveness of treating dialysis patients with conventional osteoporosis drugs is not established. The high cost and numerous side effects of drug therapies have spurred the search for alternative treatment options for ROD. It has recently been shown that low-magnitude mechanical stimulation (LMMS) is osteogenic. Although many theories exist, the mechanism of action of LMMS is not well established. A more precise understanding of how vibrations work is needed to optimize the efficacy of LMMS treatment and increase its appeal as a viable non-pharmacological solution to the problem of weak bone. One major hurdle in monitoring efficacy of treatment to LMMS in particular and other interventions in general is the lack of non-invasive tools to study the anabolic response at micro-structural levels in humans. All LMMS trials conducted to date use BMD as the outcome variable, an approach which has many limitations. In high-turnover ROD, for example, increased trabecular bone volume may offset cortical bone loss, resulting in normal or increased areal-BMD despite poor bone strength. The proposed project focuses on overcoming a critical barrier towards understanding the mechanism of action of LMMS therapy in humans by developing a non-invasive high-resolution imaging based biomechanics technique to study the dependence of local-strain on bone formation at the microstructural level in response to LMMS intervention in dialysis patients. If the aims of this project are achieved, scientific knowledge of LMMS treatment in humans and technical capabilities to monitor bone's anabolic response to treatment will be improved. Most importantly, the successful completion of the aims has the potential to change the current paradigm of managing ROD by adapting LMMS as an attractive and preventive intervention.

描述（由申请人提供）：肾脏骨营养不良（ROD）是慢性肾脏病（CKD）中骨重塑的多因素和普遍性疾病。 2011年，美国的患病率CKD估计为15.1％。随着人口老龄化，受ROD影响的患者人数有望增加。尽管广泛使用疗法，例如磷酸盐粘合剂，钙和维生素D，但与一般人群相比，透析患者的骨折后骨骼骨折率和死亡率的风险明显更大。此外，尚未确定治疗常规骨质疏松药物的透析患者的有效性。药物疗法的高成本和许多副作用刺激了寻找杆的替代治疗选择。 最近已经显示，低稳定性机械刺激（LMM）是成骨的。尽管存在许多理论，但LMM的作用机理尚未确定。更精确地了解需要如何进行振动，以优化LMMS治疗的功效，并增加其作为对弱骨骼问题的可行的非药理学解决方案的吸引力。 监测对LMM的治疗疗效的一个主要障碍，通常是其他干预措施的是缺乏无创的工具来研究微观结构水平的合成代谢响应 在人类中。迄今为止进行的所有LMMS试验都使用BMD作为结果变量，这种方法具有许多局限性。例如，在高转向杆中，小梁骨体积的增加可能会抵消皮质骨质的流失，尽管骨强度较差，但仍会导致正常或增加的面积-BMD。 拟议的项目着重于克服关键的障碍，以通过开发非侵入性高分辨率成像生物力学技术来理解人类中LMMS治疗的作用机制，以研究局部构造对透析患者LMMS干预响应的微观结构水平骨骼形成的依赖。 如果实现了该项目的目的，将改善人类LMMS治疗的科学知识以及监测骨骼对治疗的合成代谢反应的技术能力。最重要的是，成功完成目标有可能通过将LMMS调整为有吸引力的预防性干预来改变当前管理RAD的范式。