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

描述（由申请方提供）：肾性骨营养不良（ROD）是一种慢性肾脏疾病（CKD）中的多因素和广泛性骨重建疾病。2011年，美国CKD的患病率估计为15.1%。因此，随着人口老龄化，预计受ROD影响的患者数量将增加。尽管广泛使用的治疗，如磷酸盐结合剂，钙，维生素D，骨折后骨折的发生率和死亡风险显着更高的透析患者，与一般人群相比。此外，使用常规骨质疏松症药物治疗透析患者的有效性尚未确定。药物治疗的高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，低强度机械刺激（LMMS）是成骨的。尽管存在许多理论，但LMMS的作用机制尚未完全确定。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，并增加其作为弱骨问题的可行的非药物解决方案的吸引力。 监测LMMS治疗效果和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。迄今为止进行的所有LMMS试验都使用BMD作为结果变量，这种方法有许多局限性。例如，在高转换ROD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积BMD，尽管骨强度差。 拟议项目的重点是通过开发一种基于生物力学技术的非侵入性高分辨率成像来研究局部应变对透析患者在微观结构水平上响应LMMS干预的骨形成的依赖性，从而克服理解LMMS治疗在人类中的作用机制的关键障碍。 如果该项目的目标得以实现，人类LMMS治疗的科学知识和监测骨骼对治疗的合成代谢反应的技术能力将得到提高。最重要的是，目标的成功完成有可能改变目前的模式管理ROD适应LMMS作为一个有吸引力的和预防性的干预措施。

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.