Mechanical stress and skeletal plasticity after spinal cord injury in humans

描述(由申请人提供)：长期目标是预防完全性脊髓损伤(SCI)后有害的骨骼继发并发症。每年有多达两万美国人患有脊髓损伤，这使其成为首要的公共卫生问题。骨质疏松症的继发性并发症导致骨折和肾脏并发症，每年给社会造成40至70亿美元的损失。一种预防脊髓损伤后骨丢失的方法不仅可以节省大量资金，还可以显著提高脊髓损伤患者的生活质量，使他们成为未来治疗的可行对象。最近，我们证实了一定剂量的肌肉应力能使脊髓损伤后的小腿骨保存3年。不幸的是，许多SCI患者由于低位运动神经元损伤、慢性瘫痪导致的严重骨质疏松或刺激导致的自主神经反射障碍而无法激活肌肉。因此，我们建议使用一种新的方法，分别和联合施加机械压缩应力和振荡(振动)应力，以确定慢性瘫痪患者的骨骼是否可以恢复，而急性瘫痪患者的骨骼是否可以预防。三个特定的目标将使用伺服控制的振动台和气动控制的压缩载荷来测试这些假设。每一次干预都是单方面的，因此另一条腿起到了控制作用。目的1研究脊髓损伤后1年内规定剂量的机械负荷对胫骨骨密度的影响。目的研究低负荷振动机械应力(30 Hz，0.6g)对脊髓损伤后1年以上胫骨骨密度的影响。目标3将确定压缩负荷和振动输入对脊髓损伤后第一年骨密度的影响。这项研究的一个新组成部分是它分解了抵抗肌肉收缩时可能存在的压力。我们假设，振动和压缩负荷的组合将诱导最大的成骨细胞活动，导致训练肢体的骨密度增加20%以上。与组合状态相比，机械压缩载荷和振动应力对骨密度的影响都较小。这项研究有可能迅速转化为临床环境，以影响脊髓损伤后的健康质量。建议的方法不仅有很好的疗效潜力，而且很可能是经济的，很容易融入脊髓损伤患者的日常生活。 公共卫生相关性：这项研究考察了高机械诱导压缩负荷和低振动负荷对患有脊髓损伤(SCI)的人类骨密度的影响。我们最近关于电诱导肌肉收缩的发现提出了这样一种可能性，即防止骨丢失的肌肉应力既由振荡(振动)组成，也由压缩压力包络组成。在这个项目中，我们分解了应力信号，并开发了一种方法，在患有脊髓损伤的人类中同时施加振动和压迫，其中许多人不能使用电刺激。

DESCRIPTION (provided by applicant): The long-term goal is to prevent the deleterious skeletal secondary complications that follow complete spinal cord injury (SCI). As many as twenty thousand Americans sustain an SCI each year, making it a public health concern of primary importance. Secondary complications from osteoporosis leads to bone fractures and renal complications that cost society between 4 and 7 billion dollars annually. A method to prevent bone loss after SCI would not only provide substantial savings, but could also profoundly improve the quality of life of people with SCI and keep them as viable candidates for the future cure. Recently, we verified that a certain dose of muscle stress preserved bone in the lower leg for 3 years following SCI. Unfortunately, many individuals with SCI cannot activate their muscles due to lower motor neuron injuries, too severe osteoporosis from chronic paralysis, or stimulation induced autonomic dysreflexia. Accordingly, we propose to use a novel approach to apply mechanical compressive stress and oscillatory (vibratory) stress both individually and in combination to determine if bone can be recovered in those with chronic paralysis and prevented in those with acute paralysis. Three specific aims will test these hypotheses using a servo-controlled vibration table and a pneumatically controlled compressive load. Each intervention will be unilateral so the opposite leg serves as a control. Aim 1 will determine the effects of a prescribed dose of mechanical load on bone density of the tibia over 1 year following SCI. Aim 2 will determine the effects of low load vibratory mechanical stress (30 Hz, 0.6 g,) on bone density of the tibia over 1 year following SCI. Aim 3 will determine the effects of both compressive load and vibratory input on bone density over the first year following SCI. A novel component of this study is it decomposes the stresses that may be present during resisted muscle contractions. We hypothesize the combined vibration and compressive load condition will induce the greatest osteoblast activity leading to over 20% more bone density in the trained limb. The mechanical compressive load and the vibratory stress will each have a lesser effect on bone density when compared to the combined condition. This research has the potential to rapidly translate to the clinical milieu to influence health quality after SCI. The proposed method not only has excellent potential for efficacy, but is also likely to be economical and easily integrated into the daily lives of people with SCI PUBLIC HEALTH RELEVANCE: This study examines the effects of high mechanically induced compressive loads and low vibratory loads on bone density in humans with spinal cord injury (SCI). Our recent findings with electrically induced muscle contractions raised the possibility that muscle stress that prevents bone loss is composed of both an oscillation (vibration) and a compressive force envelope. In this project, we decompose the stress signal and develop a method to apply both vibration and compression in humans with SCI, many of whom cannot use electrical stimulation.