Low Magnitude Mechanical Stimulation to Improve BMD

骨质疏松症是老年人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。在这份修订后的申请中，我们建议 评估一种独特的、以生物力学为基础的治疗骨丢失的疗效；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。 动物(小鼠、大鼠、火鸡、绵羊)和人类(妇女3-8年后)的初步数据 更年期，残疾儿童，10-13岁骨密度低的女孩，16- 有骨折病史和低骨密度的21岁女孩)表明高频率、低幅度 机械刺激(LMM)可以保护BMD免受全身对吸收的压力(例如，废弃， 衰老)，并能刺激新骨形成。组织形态计量学评价表明，这一效应 主要是通过加强骨骼的形成活动来实现的，而且它在 低骨密度的动物/人。为了证实和扩大这些观察，我们提议在两年内， 200名老年男性和女性的双盲、随机、安慰剂对照临床试验(年龄65岁) 年龄及以上)，身体质量指数&lt；27公斤/平方米)，臀部T-分数从-1到-2.5)。一家诊所 位于马萨诸塞州波士顿的中心将从地理位置接近的六个独立生活设施中招募受试者 近距离服务于2,082名居民，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。主要终点将是脊柱和髋部体积骨小梁BMD的变化 通过定量计算机断层扫描。次要结果将是生化标记物的变化。 骨形成(前胶原1型N端肽和骨特异性碱性磷酸酶)和 吸收(I型胶原的C端端肽)。不良事件将在整个 由调查人员和数据和安全监测委员会进行的研究。这项研究不能解决 骨折。 在这项研究中，我们召集了一批国际知名的骨质疏松症专家 让老年人参与，以及一个受人尊敬和经验丰富的协调中心。基于强大的 初步数据显示，这项研究将提供有关低震级高压作用的新的重要信息 骨骼的频率机械刺激

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 atwo-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