Low Magnitude Mechanical Stimulation to Improve BMD

描述（由申请人提供）：骨质疏松症是老年人的主要健康并发症，其治疗选择仅限于药物干预，其中大多数是抗再吸收的。在这个修订后的申请中，我们建议评估一种独特的、基于生物力学的治疗骨质流失的疗效；低强度的机械刺激。这个修改后的应用程序回应了所有审稿人的关注。动物（小鼠、大鼠、火鸡、羊）和人类（绝经后3-8岁的妇女、残疾儿童、10-13岁的低骨密度女孩、16-21岁有骨折史和低骨密度的女孩）的初步数据表明，高频、低强度的机械刺激（LMMS）可以保护骨密度免受全身压力的吸收（例如，废弃、衰老），并可以刺激新骨的形成。组织形态计量学评估表明，这种效果主要是通过增强骨骼的形成活性来实现的，并且在骨密度低的动物/人类中最有效。为了证实和扩展这些观察结果，我们提出了一项为期两年、双盲、随机、安慰剂对照的LMMS临床试验，研究对象为200名老年女性和男性（65岁及以上），体重指数< 27 kg/m2)，臀部t评分从-1到-2.5。位于马萨诸塞州波士顿的一个临床中心将从六个地理位置接近的独立生活设施中招募受试者，为2,082名居民提供服务，所有数据将由数据协调中心处理

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.