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.

项目摘要 使用双膦酸盐（BP）药物预防骨折，部分原因是患者和 提供者担心非典型股骨骨折（AFF）的发生，显然与长期有关 用双膦酸盐使用。许多人选择根本不使用这些药物而不是风险 有这种罕见的结果。该决定可能会使个人处于发病和死亡率的高风险。平衡 典型的骨质疏松相关骨折的风险，例如臀部或椎骨骨折，并有稀有的风险 AFF是医生和患者对药物使用的决策的重要组成部分。更远， 了解哪些女性亚组可能面临AFF的风险或多或少会有用 就药物的开始，治疗持续时间和药物假期的使用做出临床决策。这 拟议的研究将通过结合来自三个基于人群的大型，基于人群的个人级别数据来解决这些问题 X射线照相验证的AFF，全面的纵向药物暴露，数据的队列研究 对其他协方差的协调定义，以及中央协调的统计编程。我们会的 专注于两个具体目标。在AIM 1中，我们将研究长期使用BP进行预防的风险 通过确定BP治疗和药物假期对AFF风险的独立影响，包括 节日前治疗时间与假期期间之间的潜在相互作用。在新颖的探索性中 分析，我们将确定毒品假期后BPS重新定型的影响。我们还将评估 AFF风险与其他骨折预防药物的使用之间的关系（例如静脉注射BPS， Denosumab和Serms），其他潜在的危险因素（例如体育活动，骨矿物质密度（BMD），种族）， 和合并症。在AIM 2中，我们将使用来自3个同类群体的汇总数据来开发和验证预测 结合长期BP治疗，药物假期和临床风险因素模式的模型， 全面地对单个患者的预期断裂保护和潜在危害进行全面建模并评估 AFF风险和与骨质疏松相关的骨折预防之间的群体水平平衡。这些模型将允许 临床医生量化个性化风险，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差距 与BP治疗，药物假期和BP或其他抗骨质疏松症的重新定型有关的科学证据 药物将通过鼓励和 改善骨质疏松药物的最佳使用。