Mechanical stress and skeletal plasticity after spinal cord injury in humans

人类脊髓损伤后的机械应力和骨骼可塑性

• 批准号: 8302328
• 负责人: RICHARD K. SHIELDS
• 金额: $ 29.88万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-24 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8302328
• 关键词: 18 year old; Acute; American; Animal Model; Animals; Autonomic Dysreflexia; Biological Preservation; Body Weight; Bone Density; Bone Tissue; Chronic; Clinical; Communities; Dose; Effectiveness; Electric Stimulation; Event; Fracture; Frequencies; Future; Goals; Health; Human; Incidence; Individual; Injury; Intervention; Isometric Exercise; Kidney; Knowledge; Lateral; Lead; Leg; Lesion; Limb structure; Longitudinal Studies; Lower Extremity; Mechanical Stress; Mechanics; Methods; Modeling; Morbidity - disease rate; Motor Neurons; Muscle; Muscle Contraction; Muscular Atrophy; Musculoskeletal System; Osteoblasts; Osteoporosis; Outcome Study; Paralysed; Peripheral Nerves; Physiological; Population; Process; Property; Protocols documentation; Public Health; Quality of life; Rehabilitation therapy; Relative (related person); Reporting; Research; Risk; Savings; Signal Transduction; Site; Skeletal system; Societies; Soleus Muscle; Source; Spinal cord injury; Stimulus; Stress; Testing; Therapeutic; Time; Training; Translating; Variant; Work; base; bone; bone loss; bone mass; bone preservation; cost; design; effective intervention; expectation; experience; hazard; improved; injured; injury and repair; limb bone; mortality; motor neuron injury; muscle stress; novel; novel strategies; prevent; public health relevance; rehabilitation science; skeletal; standard of care; substantia spongiosa; therapy development; tibia; vibration

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.

描述（由申请人提供）：长期目标是预防完全脊髓损伤（SCI）后出现有害的骨骼继发并发症。每年有多达两万名美国人患有 SCI，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会导致骨折和肾脏并发症，每年给社会造成 4 至 70 亿美元的损失。一种预防 SCI 后骨质流失的方法不仅可以节省大量资金，还可以深刻改善 SCI 患者的生活质量，并使他们成为未来治疗的可行候选者。最近，我们证实一定剂量的肌肉应力可以在 SCI 后 3 年内保留小腿骨骼。不幸的是，许多 SCI 患者由于下运动神经元损伤、慢性瘫痪引起的严重骨质疏松或刺激引起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颖的方法来单独或组合施加机械压缩应力和振荡（振动）应力，以确定是否可以使慢性瘫痪患者的骨骼恢复并预防急性瘫痪患者的骨骼。三个具体目标将使用伺服控制振动台和气动控制压缩负载来测试这些假设。每次干预都是单侧的，因此另一条腿作为对照。目标 1 将确定 SCI 后一年内规定剂量的机械负荷对胫骨骨密度的影响。目标 2 将确定 SCI 后 1 年内低负载振动机械应力（30 Hz，0.6 g）对胫骨骨密度的影响。目标 3 将确定 SCI 后第一年压缩负荷和振动输入对骨密度的影响。这项研究的一个新颖之处是它分解了肌肉抵抗收缩过程中可能存在的压力。我们假设振动和压缩负载条件相结合将诱发最大的成骨细胞活性，从而使受训肢体的骨密度增加 20% 以上。与组合条件相比，机械压缩载荷和振动应力对骨密度的影响较小。这项研究有可能迅速转化为临床环境，以影响 SCI 后的健康质量。所提出的方法不仅具有出色的疗效潜力，而且可能经济且易于融入 SCI 患者的日常生活中 公共健康相关性：本研究探讨了高机械诱导压缩负荷和低振动负荷对脊髓损伤 (SCI) 患者骨密度的影响。我们最近对电诱导肌肉收缩的发现提出了一种可能性，即防止骨质流失的肌肉应力由振荡（振动）和压缩力包络线组成。在这个项目中，我们分解了压力信号，并开发了一种对患有 SCI 的人应用振动和压缩的方法，其中许多人无法使用电刺激。