Pooling International Cohort Studies of Long-Term Bisphosphonate Use and Atypical Femur Fractures

长期使用双膦酸盐和非典型股骨骨折的汇集国际队列研究

• 批准号: 10516684
• 负责人: Annette L Adams
• 金额: $ 113.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516684
• 关键词: Accounting; Address; Adverse event; Benefits and Risks; Bone Density; California; Case Study; Characteristics; Clinical; Cohort Studies; Data; Data Pooling; Decision Making; Development; Drug usage; Epidemiology; Equation; Equilibrium; Ethnic Origin; Etiology; Femoral Fractures; Fracture; Fright; Funding; Goals; Gold; Hip Fractures; Holidays; Individual; International; Intravenous; Joints; Longitudinal cohort study; Measures; Medication Management; Modeling; Morbidity - disease rate; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Needs Assessment; Osteoporosis; Osteoporotic; Outcome; Patient Care; Patients; Pattern; Pharmaceutical Preparations; Pharmacy facility; Physical activity; Physicians; Policy Maker; Population Study; Prevention; Provider; Publishing; Race; Radiology Specialty; Recommendation; Records; Reporting; Risk; Risk Assessment; Risk Factors; Safety; Sampling; Selective Estrogen Receptor Modulators; Spinal Fractures; Stress Fractures; Subgroup; Woman; adjudicate; adverse outcome; analytical method; base; bisphosphonate; clinical decision-making; clinical practice; clinical risk; cohort; comorbidity; data harmonization; design; epidemiology study; evidence base; fracture risk; high risk; improved; individual patient; mortality; novel; osteoporosis with pathological fracture; population based; predictive modeling; predictive tools; programs; radiological imaging; risk prediction; risk prediction model; targeted treatment; tool; treatment duration; treatment guidelines; treatment strategy; trend

Project Summary Use of bisphosphonate (BP) medications for the prevention of fractures is declining, partially due to patient and provider fears about the occurrence of atypical femur fractures (AFF), which are clearly associated with long- term bisphosphonate use. Many individuals are choosing to not use these medications at all rather than risk having this rare outcome. This decision may leave individuals at high risk of morbidity and mortality. Balancing the risk of typical osteoporosis-related fractures, such as hip or vertebral fractures, with the risk of the much rarer AFF, is an important component of decision-making by physicians and patients about medication use. Further, an understanding of which subgroups of women may be at greater or lesser risk of AFF will be useful when making clinical decisions about initiation of medication, duration of treatment, and use of drug holidays. The proposed study will address these issues by combining individual-level data from three large, population-based cohort studies with radiographically verified AFFs, comprehensive longitudinal medication exposure, data harmonized definitions of other covariables, and centrally coordinated statistical programming. We will be focusing on two Specific Aims. In Aim 1, we will examine the risks of long-term use of BP for the prevention of AFF by determining the independent effects of BP treatment and drug holidays on AFF risk, including the potential interplay between pre-holiday duration of treatment and duration of holiday. In novel exploratory analyses, we will determine the effects of re-initiation of BPs after a drug holiday. We will also evaluate the relationships between AFF risk and the use of other fracture prevention medications (e.g., intravenous BPs, denosumab and SERMs), other potential risk factors (e.g., physical activity, bone mineral density (BMD), race), and comorbidities. In Aim 2, we will use the pooled data from our 3 cohorts to develop and validate predictive models incorporating patterns of long-term BP treatment, drug holidays and clinical risk factors, to comprehensively model the expected fracture protection and potential harms for individual patients and evaluate the group-level balance between AFF risk and osteoporosis-related fracture prevention. These models will allow clinicians to quantify individualized risk, balancing the benefits and harms of bisphosphonate treatment accounting for other risk factors. Development of these predictive tools and addressing important gaps in the scientific evidence related to BP treatment, drug holidays, and re-initiation of BP or other anti-osteoporosis medications will have an immediate positive impact on clinical practice and patient care by encouraging and improving the optimal use of osteoporosis medications.

项目概要 用于预防骨折的双膦酸盐 (BP) 药物的使用正在减少，部分原因是患者和 提供者担心非典型股骨骨折（AFF）的发生，这显然与长期骨折有关 术语双膦酸盐的使用。许多人选择根本不使用这些药物，而不是冒险 才有这个罕见的结果。这一决定可能会使个人面临发病和死亡的高风险。平衡 典型的骨质疏松症相关骨折的风险，例如髋部或椎骨骨折，以及更罕见的风险 AFF 是医生和患者用药决策的重要组成部分。更远， 了解哪些女性亚群患 AFF 的风险较高或较低，在以下情况下会很有用： 就开始用药、治疗持续时间和药物假期的使用做出临床决定。这 拟议的研究将通过结合来自三个大型、基于人口的个人数据来解决这些问题 队列研究采用放射学验证的 AFF、综合纵向药物暴露、数据 统一其他协变量的定义，并集中协调统计规划。我们将会 重点关注两个具体目标。在目标 1 中，我们将检查长期使用 BP 预防疾病的风险 通过确定 BP 治疗和药物假期对 AFF 风险的独立影响，包括 AFF 节前治疗持续时间和假期持续时间之间潜在的相互作用。在小说探索中 通过分析，我们将确定药物假期后重新开始 BP 的效果。我们还将评估 AFF 风险与使用其他骨折预防药物（例如静脉注射 BP、 地诺塞麦和 SERM）、其他潜在风险因素（例如体力活动、骨矿物质密度 (BMD)、种族）、 和合并症。在目标 2 中，我们将使用 3 个队列的汇总数据来开发和验证预测 模型结合了长期血压治疗、药物假期和临床危险因素的模式， 全面模拟个体患者的预期骨折保护和潜在危害并进行评估 AFF 风险与骨质疏松相关骨折预防之间的群体层面平衡。这些模型将允许 临床医生量化个体化风险，平衡双膦酸盐治疗的益处和危害 考虑其他风险因素。开发这些预测工具并解决重要的差距 与血压治疗、药物假期以及重新开始血压或其他抗骨质疏松药物相关的科学证据 通过鼓励和治疗，药物将对临床实践和患者护理产生直接的积极影响 改善骨质疏松症药物的最佳使用。