Low Magnitude Mechanical Stimulation to Improve BMD

描述(申请人提供)：骨质疏松症是老年人群中的一种主要健康并发症，其治疗方案仅限于药物干预，其中大部分是抗吸收的。在这项修订的应用中，我们建议评估一种独特的、基于生物力学的治疗方法对骨丢失的疗效；低强度机械刺激。这一修订后的申请回应了所有审查者的关切。在动物(小鼠、大鼠、火鸡、绵羊)和人类(绝经后3-8年的妇女、有残疾的儿童、10-13岁的低骨密度(BMD)女孩、有骨折病史和低BMD的16-21岁女孩)中的初步数据表明，高频、低幅度的机械刺激(LMM)可以保护BMD免受全身对骨吸收的压力(例如，废弃、衰老)，并能刺激新骨形成。组织形态计量学评估表明，这种作用主要是通过增强骨骼的形成活性来实现的，并且在低骨密度的动物/人身上效果最好。为了证实和扩展这些观察结果，我们提议在200名老年女性和男性(65岁及以上)中进行为期两年的双盲、随机、安慰剂对照的LMMS临床试验，髋部的体重指数为27 kg/m2，T评分为-1至-2.5。位于马萨诸塞州波士顿的一个临床中心将从地理上邻近的六个独立生活设施中招募受试者，为2082名居民服务，所有数据将由数据协调中心处理 (马里兰医学研究所)。在与不活动的振动平台进行了两周的磨合后， 符合纳入/排除标准的参与者将被随机分为以下两组：每天短暂接触 LMMS(10分钟/天，0.3g@30赫兹；1g=地球引力场=9.8m/s2)在振动平台或 安慰剂平台超过两年。所有参与者将获得500毫克的元素钙和400国际单位的 每天补充维生素D。主要终点将是通过定量计算机断层扫描脊柱和髋部的体积小梁骨密度的变化。次要结果将是骨形成(前胶原1N端肽和骨特异性碱性磷酸酶)和吸收(I型胶原的C端端肽)的生化标记物的变化。不良事件将在整个研究期间由调查人员和数据和安全监测委员会进行监测。这项研究并不是为了解决骨折问题。在这项研究中，我们召集了国际知名的涉及老年人的骨质疏松症专家的合作，以及一个受人尊敬和经验丰富的协调中心。基于强大的初步数据，这项研究将提供关于低幅度高频机械刺激对骨骼的作用的新的重要信息。

DESCRIPTION (provided by applicant): The treatment options for osteoporosis, a major health complication in the aged population, are limited to pharmacologic interventions, the majority of which are antiresorptive. In this revised application, we propose to evaluate the efficacy of a unique, biomechanically based treatment for bone loss; low magnitude mechanical stimulation. This revised application responds to all reviewers concerns. Preliminary data in the animal (mouse, rat, turkey, sheep) and human (women 3-8 years past the menopause, children with disabling conditions, 10-13 year old girls with low bone mineral density (BMD), 16-21 year old girls with a fracture history and low BMD) demonstrate that high frequency, low magnitude mechanical stimulation (LMMS) can preserve BMD against systemic pressures to resorb (e.g., disuse, aging), and can stimulate new bone formation. Histomorphometric evaluation demonstrates that this effect is achieved primarily by enhancing the formative activity of the skeleton, and that it is most efficacious in animals/humans with low BMD. To confirm and extend these observations, we are proposing a two-year, double-blind, randomized, placebo-controlled clinical trial of LMMS in 200 elderly women and men (65 years of age and older), with body mass index < 27 kg/m2) and low T-scores from -1 to -2.5) at the hip. A clinical center located in Boston, MA will recruit subjects from six independent living facilities in close geographic proximity serving a population of 2,082 residents, and all data will be handled by a Data Coordinating Center (Maryland Medical Research Institute). Following a two-week run-in with an inactive vibrating platform, participants meeting the inclusion/exclusion criteria will be randomized to either brief daily exposure to LMMS (10 min/d of 0.3g @ 30Hz; 1g = Earth's gravitational field = 9.8 m/s2) on a vibrating platform or a placebo platform over two years. All participants will receive 500 mg of elemental calcium and 400 IU of vitamin D per day. The primary endpoints will be changes in volumetric trabecular BMD of the spine and hip by quantitative computed tomography. The secondary outcome will be the change in biochemical markers of bone formation (Procollagen type 1 N-terminal peptide and Bone Specific Alkaline Phosphatase) and resorption (C-terminal Telopeptide of type I collagen). Adverse events will be monitored throughout the study by the investigators and a Data and Safety Monitoring Board. This study is not powered to address fracture. For this study we have assembled a collaboration of internationally known experts in osteoporosis involving older persons, together with a respected and experienced coordinating center. Based on strong preliminary data, this study will provide new and important information about the role of low magnitude high frequency mechanical stimulation on the skeleton.