Combining Imaging and Modeling in Osteoporosis Fracture Risk Assessment

结合成像和建模进行骨质疏松症骨折风险评估

• 批准号: 7888181
• 负责人: Gary Beaupre
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7888181
• 关键词: Activities of Daily Living; Adult; Affect; Age; Aging; American; Bone Density; Cadaver; Clinic; Clinical; Clinical Research; Colles' Fracture; Computational Technique; Data; Databases; Densitometry; Development; Devices; Diagnosis; Disadvantaged; Disease; Disease Progression; Distal; Drug Prescriptions; Dual-Energy X-Ray Absorptiometry; Elderly; Engineering; Epidemiologic Studies; Female; Femur; Financial cost; Forearm; Fosamax; Foundations; Fracture; Future; Generic Drugs; Goals; Health; Health Policy; High Resolution Computed Tomography; Hip Fractures; Hip region structure; Image; Image Analysis; Individual; Intervention; Lead; Legal patent; Life Style; Link; Measurement; Measures; Methods; Modeling; Morbidity - disease rate; Names; Osteopenia; Osteoporosis; Patients; Peripheral; Pharmaceutical Preparations; Physicians' Offices; Play; Postmenopause; Prevalence; Primary Care Physician; Quality-Adjusted Life Years; Radial; Research; Research Personnel; Resolution; Risk; Risk Assessment; Risk Estimate; Roentgen Rays; Role; Scanning; Scientist; Sentinel; Site; Societies; Spinal Fractures; Techniques; Technology; Testing; Time; Tomography, Computed, Scanners; Translating; Vertebral column; Veterans; Woman; World Health Organization; Wrist; X-Ray Computed Tomography; abstracting; analytical tool; base; bone; bone imaging; bone mass; bone strength; clinical application; clinically relevant; computerized data processing; computerized tools; cost; demographics; epidemiology study; experience; improved; in vivo; male; men; mortality; portability; prognostic value; research study; skeletal; statistics; tool; wrist fracture; young adult

DESCRIPTION (provided by applicant): 6. Project Summary/Abstract Osteoporosis is a major and growing US heath concern. The National Osteoporosis Foundation estimates that 44 million Americans have osteoporosis or low bone mass. For many of these individuals a fragility fracture will be the first indication that they have the disease. These fractures are associated with morbidity, limitations in the activities of daily living, increased mortality, particularly in the case of hip fractures, and a financial cost to society that is estimated at $19 billion per year or more than $52 million per day. Although osteoporosis is perceived by many as a disease primarily affecting post-menopausal females, it has recently been estimated that one out of eight older male veterans has osteoporosis. This translates to a prevalence of nearly 1.2 million male veterans with osteoporosis. Based on fracture statistics and veterans demographics (more than 12 male veterans for every female veteran), approximately three times as many male veterans as female veterans are expected to experience a fragility fracture. Given these facts we believe the VA has an important responsibility to be a leading stakeholder in osteoporosis research, especially given the number of male veterans likely to experience an osteoporosis-related fractures. The most common method for osteoporosis assessment uses an X-ray based technique called Dual- energy X-ray Absorptiometry, or DXA for short. The default DXA measurements were originally proposed for use in large epidemiology studies and were not intended to be used for diagnosis or treatment of individual patients. Nevertheless, these DXA measures are routinely used by primary care physicians in osteoporosis diagnosis and treatment even though these DXA measures are not accurate predictors of bone strength or fracture risk in an individual patient. The goal of this project is to develop more accurate approaches for estimating bone strength using newly developed engineering-based techniques. The project will examine three X-ray based technologies currently used for osteoporosis assessment. For each of these technologies we will quantify the accuracy with which they can predict the experimentally measured strength of cadaver bones from 25 male and 25 female donors. For each technology we will first assess the accuracy of estimating bone strength using the default measures available for that technology. We will then used new analytical and computational tools that we have developed that we believe will result in substantial improvements in estimating bone strength and that can be used in future clinical and research studies to more accurately predict bone strength in vivo. The specific densitometry technologies to be assessed were chosen so that the results will have the broadest possible impact for clinicians, clinician scientists and researchers. The ultimate goal of this research is to provide additional and better ways to identify individuals with low bone strength who would benefit from pharmacological interventions or lifestyle changes, thereby reducing both the near-term and long-term risks and costs of osteoporosis-related fractures. PUBLIC HEALTH RELEVANCE: 7. Project Narrative Many of the 44 million American who have osteoporosis or low bone mass are at an increased risk for a fragility fracture. Osteoporosis is often referred to as a "silent" diseases, because a fracture is often the first indication that an individual has the disease. Although osteoporosis is commonly viewed as a disease largely restricted to post-menopausal women, a recent study of VA patients suggests that one out of eight male veterans has osteoporosis. In addition to this alarmingly high rate of osteoporosis in male veterans, statistics indicate that fragility fractures occur more frequently among male veterans than among female veterans. This conclusion is based on the ratio of female/male fractures at the hip (3 to 1) and wrist (5 to 1) in older adults, combined with the current ratio of male/female veterans of 12.3 to 1. Taken together, these statistics support the surprising conclusion that between 2.5 and 4.1 times as many male veterans as female veterans are predicted to experience osteoporosis-related wrist and hip fractures. Thus, a substantial number of older male veterans can be expected to experience osteoporosis-related fractures. One key to reducing the number of fragility fractures in veterans is to identify individuals with low bone strength prior to fracture and to prescribe drug treatment or lifestyle changes that will alter the progression of the disease. The goal of the proposed study is to develop new techniques for more accurate assessment of individuals at risk of osteoporosis, specifically analysis techniques that focus on bone strength as a direct indicator of fracture risk. If the creation of new osteoporosis assessment tools that focus on bone strength results in a higher percentage of male veterans for whom treatment is indicated, the VA could be faced with the question of whether the increase in treatment can be justified from a cost perspective. One of the leading bone anti- resorption drugs (Fosamax) used to treat osteoporosis lost US patent protection in February of 2008. Since the high cost of brand name osteoporosis drugs is considered an impediment to widespread treatment, the recent introduction of generic forms of this drug should make increased treatment of men much more easily justified in terms of the cost per quality-adjusted life-year gained. As a result it is likely that the clinical application of positive results of the proposed study should not be impeded by considerations related to the cost of treating more veterans. Based on all of the above, we believe that the VA can and should play a central role in osteoporosis research, especially given the potential for a large number of aging male veterans to experience an osteoporosis-related fracture.

描述（由申请人提供）： 6. 项目摘要/摘要 骨质疏松症是美国日益严重的一个主要健康问题。国家骨质疏松症基金会估计，4400 万美国人患有骨质疏松症或骨量低。对于其中许多人来说，脆性骨折将是他们患有这种疾病的第一个迹象。这些骨折与发病率、日常生活活动受限、死亡率增加（尤其是髋部骨折）以及每年给社会造成的经济损失估计为 190 亿美元或每天超过 5200 万美元有关。 尽管骨质疏松症被许多人认为是一种主要影响绝经后女性的疾病，但最近估计八分之一的老年男性退伍军人患有骨质疏松症。这意味着近 120 万男性退伍军人患有骨质疏松症。根据骨折统计数据和退伍军人人口统计数据（超过 12 名男性退伍军人与一名女性退伍军人），预计遭受脆性骨折的男性退伍军人数量大约是女性退伍军人的三倍。鉴于这些事实，我们认为退伍军人管理局有重要责任成为骨质疏松症研究的主要利益相关者，特别是考虑到可能经历骨质疏松症相关骨折的男性退伍军人数量。 最常见的骨质疏松症评估方法是使用基于 X 射线的技术，称为双能 X 射线吸收测定法，简称 DXA。默认 DXA 测量最初建议用于大型流行病学研究，并不打算用于个体患者的诊断或治疗。然而，尽管这些 DXA 测量不能准确预测个体患者的骨强度或骨折风险，但初级保健医生在骨质疏松症诊断和治疗中常规使用这些 DXA 测量。该项目的目标是使用新开发的基于工程的技术开发更准确的方法来估计骨骼强度。 该项目将研究目前用于骨质疏松症评估的三种基于 X 射线的技术。对于每一项技术，我们都将量化其预测 25 名男性和 25 名女性捐赠者尸体骨骼强度的实验测量强度的准确性。对于每种技术，我们将首先使用该技术可用的默认测量来评估估计骨强度的准确性。然后，我们将使用我们开发的新分析和计算工具，我们相信这些工具将在估计骨强度方面带来实质性改进，并可用于未来的临床和研究，以更准确地预测体内骨强度。选择要评估的具体密度测定技术，以便其结果能够对临床医生、临床科学家和研究人员产生尽可能广泛的影响。这项研究的最终目标是提供额外的、更好的方法来识别骨强度低的个体，这些个体将受益于药物干预或生活方式的改变，从而降低骨质疏松症相关骨折的近期和长期风险和成本。 公共卫生相关性： 7. 项目叙述 4400 万美国人患有骨质疏松症或骨量低，其中许多人发生脆性骨折的风险增加。骨质疏松症通常被称为“沉默”的疾病，因为骨折通常是个体患有这种疾病的第一个迹象。尽管骨质疏松症通常被认为是一种主要局限于绝经后女性的疾病，但最近对退伍军人事务部患者的一项研究表明，八分之一的男性退伍军人患有骨质疏松症。除了男性退伍军人骨质疏松症发病率高得惊人之外，统计数据还表明，男性退伍军人比女性退伍军人更容易发生脆性骨折。这一结论是基于老年人中女性/男性髋部骨折（3比1）和手腕骨折（5比1）的比例，加上目前男女退伍军人的比例为12.3比1。总而言之，这些统计数据支持了一个令人惊讶的结论，即预计男性退伍军人中患有骨质疏松症相关手腕和髋部骨折的人数是女性退伍军人的2.5至4.1倍。因此，大量老年男性退伍军人预计会经历与骨质疏松症相关的骨折。 减少退伍军人脆性骨折数量的关键之一是在骨折前识别骨强度较低的人，并开出药物治疗或改变生活方式以改变疾病的进展。拟议研究的目标是开发新技术，更准确地评估有骨质疏松症风险的个体，特别是专注于骨强度作为骨折风险直接指标的分析技术。 如果专注于骨强度的新骨质疏松症评估工具的创建导致需要治疗的男性退伍军人比例更高，那么退伍军人管理局可能会面临这样的问题：从成本角度来看，增加治疗是否合理。用于治疗骨质疏松症的一种主要抗骨吸收药物 (Fosamax) 于 2008 年 2 月失去了美国专利保护。由于骨质疏松症品牌药物的高成本被认为是广泛治疗的障碍，因此最近推出的该药物的仿制药形式应该使男性增加的治疗从获得的每质量调整生命年的成本方面更容易证明是合理的。因此，拟议研究的积极结果的临床应用可能不会因与治疗更多退伍军人的费用相关的考虑而受到阻碍。 基于上述所有内容，我们认为退伍军人管理局可以而且应该在骨质疏松症研究中发挥核心作用，特别是考虑到大量老年男性退伍军人可能会经历骨质疏松症相关的骨折。