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: 10706659
• 负责人: Annette L Adams
• 金额: $ 102.13万
• 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/10706659
• 关键词: Accounting; Address; Adverse event; Benefits and Risks; Bone Density; California; Case Study; Characteristics; Clinical; Cohort Studies; Communication; Data; Data Pooling; Decision Making; Development; Drug usage; Epidemiology; Equation; Equilibrium; Ethnic Origin; Etiology; Femoral Fractures; Fracture; Fright; Funding; Goals; 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; adjudication; adverse outcome; analytical method; bisphosphonate; clinical decision-making; clinical practice; clinical risk; cohort; comorbidity; data harmonization; design; epidemiology study; evidence base; falls; 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 用于预防骨折的双膦酸盐（BP）药物的使用正在下降，部分原因是患者和 提供者担心发生非典型股骨骨折（AFF），这显然与长期- 术语双膦酸盐使用。许多人选择根本不使用这些药物，而不是冒险 有这种罕见的结果。这一决定可能使个人处于发病和死亡的高风险之中。平衡 典型的骨质疏松相关骨折的风险，如髋关节或椎骨骨折，与罕见的风险 AFF是医生和患者关于药物使用决策的重要组成部分。此外，本发明还 了解哪些女性亚组可能有更大或更小的AFF风险将是有用的， 做出关于开始用药、治疗持续时间和休药期使用的临床决定。的 一项拟议的研究将通过结合来自三个大型的、基于人群的 放射学证实的AFFS队列研究，全面纵向药物暴露，数据 统一其他协变量的定义，并集中协调统计方案编制。我们将 专注于两个具体目标。在目标1中，我们将研究长期使用BP的风险， 通过确定BP治疗和停药期对AFF风险的独立影响，包括 假期前治疗持续时间和假期持续时间之间的潜在相互作用。在小说探索 分析，我们将确定停药期后重新开始BP治疗的影响。我们还将评估 AFF风险与使用其他骨折预防药物之间的关系（例如，静脉内BP， 地舒单抗和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，我们将使用来自3个队列的汇总数据来开发和验证预测 结合长期BP治疗模式、休药期和临床风险因素的模型， 对个体患者的预期骨折保护和潜在伤害进行全面建模并评估 AFF风险和骨关节炎相关骨折预防之间的组水平平衡。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。开发这些预测工具和解决 与BP治疗、休药期和重新开始BP或其他抗骨质疏松药物相关的科学证据 药物治疗将通过鼓励和 改善骨质疏松症药物的最佳使用。