Assessing Skeletal Risk During Rehabilitation in Patients after Chronic Disuse

描述（由申请人提供）： 废用性骨质疏松症，一种由慢性固定引起的病症，导致固定肢体的骨强度降低和骨折风险的相应增加（Frisbie，1997;加兰等人，1992; Smith，2011）。废用性骨质疏松症与脊髓损伤、中风、多发性硬化症、帕金森病（第五期）、肌萎缩性侧索硬化症、脊髓灰质炎、布朗-斯夸德综合征、脑瘫、创伤性脑损伤以及更普遍的情况下，专门使用轮椅移动或无法离开病床的个人有关。在一项对VA的脊髓损伤患者的研究中，这些脊髓损伤性骨折的治疗所需的平均住院时间是非骨折住院患者的7倍（莫尔斯等人，2009年）。同时，治疗并发症（即，骨不连、压疮、疼痛、自主神经反射障碍、异位骨化）。考虑到日常和/或治疗活动导致的大部分骨折（Fattal等人，二〇一一年; Ragnarsson & Sell，1981）以及与废用性骨折相关的大量并发症，预防几乎被普遍推荐为最重要的临床干预（加兰等人，1992; Bauman等人，2009; Logan等人，2008年）。该项目的长期目标是减少 废用性骨质疏松症患者的骨折，特别是通过解决未回答的临床问题，“一个特定的病人的骨骼足够强壮，参加规定的活动，锻炼，或治疗？（Kiratli，2001）。 为了实现这一目标，必须解决以下未满足的需求：1）准确估计废用性骨质疏松症患者特定骨强度的有效方法; 2）量化施加于风险患者的内力。 在日常活动和治疗相关活动中的骨骼部位。本研究将通过扩展双能X射线吸收测定法（DXA）（用于诊断骨质疏松症的前哨技术）的临床能力来解决第一个未满足的需求，以计算与骨强度相关的基于力学的参数。受弯曲和扭转载荷（即，废用性骨质疏松症患者最常见的骨折部位和骨折形式）将通过对65具尸体股骨的力学测试进行评价。我们期望得到的结构参数与绝对骨强度良好相关，如先前使用基于力学的方法和非侵入性成像技术在其他骨骼部位所证明的那样（Eckstein等人，2004; Moisio等人，2003; Siu等人，2003年）。 在本试点研究的结论中，1）通过开发和验证一种从两种常见DXA扫描技术的原始DXA数据重建逐像素骨骼图的方法，将消除使用DXA技术推导基于结构的指标的关键障碍扫描技术（笔形和扇形束扫描器）; 2）使用单个，垂直，将确定相同骨骼的三重定向DXA扫描;以及3）将定义使用DXA衍生的基于工程的度量来估计股骨中段和远端区域的测量弯曲和扭转强度的预测强度。用于估计患者特异性骨强度的基于力学的方法有可能提高在参与常见康复活动时识别有骨关节炎风险的个体的特异性。我们希望个性化医疗方法在帮助临床医生确定治疗和活动方面具有最大的益处， 将有益于患者健康，并且还具有在给定患者中引起骨折的低风险。最终，我们相信这项研究将导致废用性骨质疏松症患者骨折发生率降低。 公共卫生相关性： 废用性骨质疏松症患者（如脊髓损伤患者）的骨折主要发生在日常活动、被动伸展运动或其他康复治疗期间，这些骨折的治疗具有高并发症风险。虽然骨折预防是最广泛接受的临床干预措施，但目前还没有临床方法来评估患者的骨骼是否足够强壮以参与规定的活动。该项目的最终目标是为废用性骨质疏松症患者的特定骨折强度的诊断评估提供一种经过验证的临床工具，以评估特定日常和治疗相关活动的安全参与。该研究将直接影响专门使用轮椅的退伍军人，以及那些无法离开病床的人。我们相信VA可以并且应该在骨质疏松症研究中发挥核心作用，特别是在帮助维持生活质量方面，这可能会在废用性骨质疏松性骨折后受到严重影响。

DESCRIPTION (provided by applicant): Disuse osteoporosis, a condition caused by chronic immobilization, results in decreased bone strength of the immobilized limb(s) and a corresponding increase in the risk of fracture (Frisbie, 1997; Garland et al., 1992; Smith, 2011). Disuse osteoporosis has been associated with individuals with spinal cord injury, stroke, multiple sclerosis, Parkinson's disease (Stage V), amyotrophic lateral sclerosis, poliomyelitis, Brown-S¿quard syndrome, cerebral palsy, traumatic brain injury, and more generally, individuals who exclusively use wheelchairs for mobility or are unable to leave their bed. In a study of individuals with spinal cord injury at the VA, treatment o these osteoporotic fractures required a mean hospital stay seven times longer than hospital stays for non-fracture admissions (Morse et al., 2009). Concurrently, treatment complications (i.e., non-union, pressure ulcers, pain, autonomic dysreflexia, heterotopic ossification) were observed in over half of all fracture cases. Considering the large proportion of fractures resultin from daily and/or therapeutic activities (Fattal et al., 2011; Ragnarsson & Sell, 1981) and the abundance of complications associated with disuse osteoporotic fractures, prophylaxis is nearly universally recommended as the paramount clinical intervention (Garland et al., 1992; Bauman et al., 2009; Logan et al., 2008). The long-term goal of this project is to reduce the incidence of fracture in individuals with disuse osteoporosis, specifically by addressing the unanswered clinical question, "Are a particular patient's bones strong enough to participate in a prescribed activity, exercise, or therapy?" (Kiratli, 2001). To address this goal, the following unmet need must be resolved: 1) a validated method for accurately estimating patient-specific bone strength for individuals with disuse osteoporosis; and 2) quantifying the internal forces imposed on at-risk skeletal sites during common daily and therapy-related activities. This study will address the firs unmet need by expanding the clinical capability of Dual energy X-ray Absorptiometry (DXA), the sentinel technology used for diagnosing osteoporosis, to compute mechanics-based parameters related to bone strength. Estimates of DXA-derived bone strength of the midshaft and distal femur subjected to bending and torsional loading (i.e., the most common fracture sites and fracture modalities observed for individuals with disuse osteoporosis) will be evaluated with mechanical testing of 65 cadaveric femora. We expect the derived structural parameters to be well correlated with absolute bone strength, as has been previously demonstrated at other skeletal sites using a mechanics-based approach and non-invasive imaging technology (Eckstein et al., 2004; Moisio et al., 2003; Siu et al., 2003). At the conclusion of this pilot sudy, 1) a critical barrier to progress in using DXA technology for deriving structural-based metrics will be eliminated by developing and validating a method for reconstructing pixel-by- pixel bone maps from raw DXA data for two common DXA scanning technologies (pencil and fan beam scanners); 2) the accuracy and precision of reconstructing engineering-based bone strength metrics using single, perpendicular, and triple-oriented DXA scans of the same bone will be determined; and 3) the predictive strength of using DXA-derived engineering-based metrics for estimating the measured bending and torsional strength of the midshaft and distal regions of the femur will be defined. A mechanics-based approach for estimating patient-specific bone strength has the potential to improve the specificity of identifying individuals at- risk of fractue when participating in common rehabilitation activities. We expect the personalized medicine approach to have the most benefit in aiding clinicians in identifying therapies and activities that will benefit patient health and also be of low-risk for causing a fracture in a given patient. Ultimately we believe this research will lead to a reduced fracture incidence in individuals with disuse osteoporosis. PUBLIC HEALTH RELEVANCE: Fractures in individuals with disuse osteoporosis, such as individuals with a spinal cord injury, predominantly occur during routine daily activities, passive stretching exercises, or other rehabilitation therapies and treatment of those fractures poses a high risk of complication. Although fracture prevention is the most widely accepted clinical intervention, there is currently no clinical method for assessing whether a patient's bones are strong enough to participate in a prescribed activity. The ultimate goal of this project is to produce a validated clinical tool for he diagnostic assessment of patient-specific fracture strength of individuals with disuse osteoporosis for evaluating the safe participation in specific daily and therapy-related activities This research will directly impact veterans who exclusively use wheelchairs for mobility, as well as those who are unable to leave their bed. We believe that the VA can and should play a central role in osteoporosis research, particularly in helping maintain quality of life, which can e severely affected following a disuse osteoporotic fracture.