Long-Term Approaches to Treating Osteoporosis

项目摘要/摘要 骨质疏松症是一种骨骼疾病，其特征是骨骼强度下降，骨折风险增加， 影响着美国1000万老年人。约50%的绝经后女性和25%的 60岁以上的白人男性一生中将经历骨质疏松性骨折，发病率、死亡率、 而且成本很高，预计会随着美国人口老龄化而增加。有很多有效的方法 骨质疏松症的药物治疗选择，骨质疏松症大致属于抗吸收药物类别 抑制骨骼分解和形成骨骼的合成代谢剂。然而，个体骨质疏松症 尽管骨质疏松症是一种慢性疾病，但不建议无限期地使用治疗方法。 需要长期的管理，以保持降低的脆性骨折风险。因此，治疗 终生的骨质疏松症涉及到药物之间的转换。骨质疏松症的序贯使用 药物是一个新的和重要的调查领域，需要进一步检查。此外， 使用多种药物的联合治疗方案是另一个令人感兴趣的重要话题，可能 对某些骨质疏松症患者进行有效和适当的短期治疗 骨折风险。目前，几乎没有科学证据来指导医生和患者 关于骨质疏松症在长期治疗药物之间过渡的最佳策略，以及 已被专业协会和美国国立卫生研究院确定为该领域的关键知识缺口。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项目来解决这一知识差距 骨质疏松症的治疗策略，包括序贯疗法和联合疗法，以确定最佳方案 终生的治疗方法。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(目标1)。随后，我们将 对各种长期治疗策略进行全面的成本-效果分析， 包括序贯疗法和联合疗法，以及使用单一的治疗药物 间歇性用药假期、运动疗法和常规护理(仅限钙和维生素D) 骨质疏松症与不同临床特征(目标2)。我们的研究结果将阐明 骨质疏松症的治疗策略对不同临床症状的人来说是最有效和最具成本效益的 特征，从而直接解决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为证据提供框架- 对数百万患有骨质疏松症的美国人的治疗过渡进行基于和个性化的管理。

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.