Long-Term Approaches to Treating Osteoporosis

项目概要/摘要 骨质疏松症是一种以骨强度受损和骨折风险增加为特征的骨骼疾病， 影响了美国1000万老年人。大约50%的绝经后妇女和25%的 60岁以上的白色男性在其一生中将经历骨质疏松性骨折， 而且成本很高，而且随着美国人口的老龄化，成本预计还会增加。有许多有效 骨质疏松症的药理学治疗选择，其大致属于抗吸收剂的类别 抑制骨骼分解和合成代谢物质来构建骨骼。然而，个体骨质疏松症 虽然骨质疏松症是一种慢性疾病， 需要长期管理，以维持降低的脆性骨折风险。因此，治疗 一生中的骨质疏松症涉及药剂之间的转换。骨质疏松症的序贯使用 药物是一个新的和重要的研究领域，需要进一步研究。另夕h 使用多种药物的联合治疗方案是另一个重要的感兴趣的主题， 对于某些骨质疏松症患者， 骨折风险。目前，几乎没有科学证据可以指导医生和患者 骨质疏松症的最佳策略之间的过渡药物的长期治疗，这 已被确定为一个关键的知识差距，在该领域的专业协会和国家卫生研究院。与 在本申请中提出的工作，我们的目标是通过评估许多不同的长期 骨质疏松症的治疗策略，包括序贯疗法和联合疗法，以确定最佳治疗方案。 治疗方法在一生中。为此，我们建议首先进行临床荟萃分析， 序贯疗法和联合疗法治疗骨质疏松症的疗效研究（目的1）。后续我们将 进行全面的成本效益分析，比较各种长期治疗策略， 包括序贯和联合治疗方案，以及使用单一治疗剂， 间歇性药物假期，运动疗法和常规护理（仅钙和维生素D）， 骨质疏松症和不同的临床特征（目的2）。我们的研究结果将阐明 骨质疏松症的治疗策略是最有效和成本效益的个人与各种临床 因此，直接解决了医生面临的最大挑战之一， 治疗骨质疏松症患者。这项创新的调查将有助于提供证据的框架- 为数百万美国骨质疏松症患者提供基于基础的个性化治疗过渡管理。

Project Summary/Abstract Osteoporosis, a skeletal disease characterized by compromised bone strength and increased risk of fracture, affects 10 million older adults in the United States. Approximately 50% of postmenopausal women and 25% of white men over age 60 will experience an osteoporotic fracture in their lifetimes, and the morbidity, mortality, and costs are high and projected to increase with the aging of the U.S. population. There are many effective pharmacological treatment options for osteoporosis, which broadly fall into categories of antiresorptive agents that inhibit bone breakdown and anabolic agents that build bone. However, individual osteoporosis therapies are not recommended for indefinite use, although osteoporosis is a chronic disease that requires long-term management to maintain reduced risk of fragility fracture. Thus, treatment of osteoporosis over the lifetime involves transitions between agents. Sequential use of osteoporosis medications is a novel and important area of investigation that requires further examination. Additionally, the use of combination treatment regimens with multiple medications is another important topic of interest that may be effective and appropriate short-term therapy for some individuals with osteoporosis at particularly high fracture risk. Currently, there is little scientific evidence to guide physicians and patients with osteoporosis on best strategies for transitions between medications for long-term treatment, and this has been identified as a key knowledge gap in the field by professional societies and the NIH. With the work proposed in this application we aim to address this knowledge gap by evaluating many different long-term treatment strategies for osteoporosis, including sequential and combination therapies, to identify the best therapeutic approaches over the lifetime. To do so, we propose to first perform meta-analyses of clinical studies on the efficacy of sequential and combination therapies for osteoporosis (Aim 1). Subsequently, we will perform comprehensive cost-effectiveness analyses comparing various long-term treatment strategies, including sequential and combination therapy regimens, as well as the use of single therapeutic agents with intermittent drug holidays, exercise therapy, and usual care (calcium and vitamin D only) for patients with osteoporosis and different clinical characteristics (Aim 2). Our research findings will elucidate which osteoporosis treatment strategies are most effective and cost-effective for individuals with various clinical characteristics over the lifetime, and thus directly address one of the biggest challenges facing physicians who treat patients with osteoporosis. This innovative investigation will help provide the framework for evidence- based and individualized management of transitions of therapy for millions of Americans with osteoporosis.