Low Magnitude Mechanical Stimulation to Improve BMD

描述（由申请人提供）：骨质疏松症是老年人群的一种主要健康并发症，其治疗选择仅限于药物干预，其中大部分为抗吸收药物。在本修订申请中，我们建议评价一种独特的、基于生物力学的骨丢失治疗方法的有效性;低强度机械刺激。这个修订后的应用程序回应了所有审查员的关注。 动物中的初步数据（小鼠、大鼠、火鸡、绵羊）和人（绝经后3-8年的妇女、患有残疾状况的儿童、具有低骨矿物质密度（BMD）的10-13岁女孩、具有骨折史和低BMD的16-21岁女孩）的研究表明，高频率、低幅度的机械刺激（LMMS）可以保护BMD抵抗再吸收的全身压力（例如，废用、老化），并且可以刺激新骨形成。组织形态学评价表明，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BMD的动物/人中最有效。为了证实和扩展这些观察结果，我们建议在200名老年女性和男性（65岁及以上）中进行一项为期两年的双盲、随机、安慰剂对照的LMMS临床试验，这些老年女性和男性的体重指数< 27 kg/m2，髋关节的T评分从-1到-2.5。位于马萨诸塞州波士顿的临床中心将从地理位置接近的六个独立生活设施招募受试者，为2，082名居民提供服务，所有数据将由数据协调中心处理 （马里兰州医学研究所）。在与一个不活跃的振动平台进行了两周的磨合之后， 符合入选/排除标准的受试者将随机接受每日短暂暴露， LMMS（10 min/d，0.3g@30Hz; 1g =地球重力场= 9.8 m/s2），在振动平台上或 安慰剂平台超过两年。所有参与者将接受500 mg的元素钙和400 IU的 每天补充维生素D。主要终点是通过定量计算机断层扫描测量的脊柱和髋关节骨小梁BMD的体积变化。次要结局将是骨形成（1型前胶原N-末端肽和骨特异性碱性磷酸酶）和骨吸收（I型胶原C-末端肽）的生化标志物的变化。研究者和数据和安全性监查委员会将在整个研究期间对不良事件进行监查。本研究不足以解决骨折问题。 在这项研究中，我们聚集了国际知名的老年人骨质疏松症专家，以及一个受人尊敬和经验丰富的协调中心。基于强有力的初步数据，这项研究将提供有关低幅度高频机械刺激对骨骼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.