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(BP)药物的使用率正在下降，部分原因是患者和 提供者担心非典型股骨骨折(AFF)的发生，这显然与长时间的 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 有这种罕见的结果。这一决定可能会使个人面临发病率和死亡率的高风险。平衡 典型的骨质疏松相关骨折的风险，如髋部或脊椎骨折，风险要罕见得多 AFF是医生和患者进行用药决策的重要组成部分。此外， 在以下情况下，了解哪些子组的妇女患AFF的风险可能更高或更低将是有用的 就开始用药、疗程和用药节假日作出临床决定。这个 拟议的研究将通过结合来自三个大型、以人口为基础的 放射学验证的AFF的队列研究，全面的纵向药物暴露，数据 其他协变量的统一定义，以及中央协调的统计方案编制。我们会的 着眼于两个具体目标。在目标1中，我们将研究长期使用BP预防高血压的风险 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》中 分析，我们将确定在毒品假期后重新启动BPS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BPS， Denosumab和SERM)，其他潜在危险因素(例如，体力活动、骨密度、种族)， 以及合并症。在目标2中，我们将使用来自3个队列的汇集数据来开发和验证预测性 包含长期BP治疗模式、药物假期和临床风险因素的模型，以 对单个患者的预期骨折保护和潜在危害进行综合建模和评估 AFF风险和骨质疏松相关骨折预防之间的组水平平衡。这些型号将允许 临床医生对个性化风险进行量化，平衡双磷酸盐治疗的好处和坏处 考虑到其他风险因素。开发这些预测工具并解决在以下方面的重要差距 与BP治疗、停药和重新启动BP或其他抗骨质疏松症相关的科学证据 药物将立即对临床实践和患者护理产生积极影响，因为它鼓励和 提高骨质疏松症药物的优化使用。