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)：肾性骨营养不良(Rod)是慢性肾脏疾病(CKD)中的一种多因素和普遍存在的骨重建障碍。2011年，美国慢性肾脏病的患病率估计为15.1%。因此，随着人口老龄化，预计受ROD影响的患者数量将会增加。尽管广泛使用磷酸盐粘合剂、钙和维生素D等治疗方法，但与普通人群相比，接受透析的患者骨折发生率和骨折后死亡风险明显更高。此外，用传统的骨质疏松症药物治疗透析患者的有效性还没有确定。药物疗法的高昂成本和众多副作用促使人们寻找Rod的替代治疗方案。最近的研究表明，低幅度机械刺激(LMMS)具有成骨作用。虽然存在多种理论，但LMM的作用机制还不是很成熟。需要更精确地了解振动是如何工作的，以优化LMMS治疗的疗效，并增加其作为解决骨质脆弱问题的可行非药物解决方案的吸引力。监测LMM治疗效果和一般其他干预措施的一个主要障碍是缺乏在微观结构水平上研究合成代谢反应的非侵入性工具 在人类身上。到目前为止进行的所有LMMS试验都使用BMD作为结果变量，这一方法有许多局限性。例如，在高周转率的棒中，增加的骨小梁体积可以抵消皮质骨丢失，导致正常或增加的面骨密度，尽管骨强度较低。这项拟议的项目致力于克服理解LMMS治疗在人类中作用机制的关键障碍，开发一种基于非侵入性高分辨率成像的生物力学技术，在微观结构水平上研究透析患者LMMS干预后局部应变对骨形成的依赖性。如果该项目的目标得以实现，将提高人类对LMMS治疗的科学知识，并提高监测骨骼对治疗的合成代谢反应的技术能力。最重要的是，AIMS的成功完成有可能改变目前管理Rod的模式，使LMM成为一种有吸引力的预防性干预措施。