Benefits and Harms of Long-term Osteoporosis Pharmacotherapy: Impact of Treatment Length, Type, Switching, and Holidays

长期骨质疏松症药物治疗的好处和坏处：治疗长度、类型、转换和假期的影响

• 批准号: 10515946
• 负责人: Suzanne Cadarette
• 金额: $ 63.7万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10515946
• 关键词: Address; Adherence; Adverse event; Age; Alendronate; Algorithms; Benefits and Risks; Canada; Cessation of life; Characteristics; Clinical; Clinical Trials; Clinical assessments; Communities; Data; Data Set; Data Sources; Decision Making; Drug usage; Educational workshop; Elderly; Electronic Health Record; Exposure to; Femoral Fractures; Forteo; Fracture; Future; Geographic Locations; Goals; Guidelines; Harm Reduction; Health; Healthcare; Hip Fractures; Holidays; Individual; International; Joints; Knowledge; Length; Life Expectancy; Link; Long-Term Effects; Longitudinal Studies; Medicare; Medicare claim; Methods; Modeling; National Institute on Aging; Nursing Homes; Ontario; Oral; Osteoporosis; Outcome; Pain; Pathway interactions; Patient risk; Patient-Focused Outcomes; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacotherapy; Population; Prevention; Raloxifene; Recommendation; Recording of previous events; Research; Research Personnel; Risk; Subgroup; System; Time; Woman; Work; Zoledronate; adverse event risk; aged; bisphosphonate; comparative; data cleaning; disability; epidemiology study; evidence base; experience; follow-up; fracture risk; frailty; high risk; human old age (65+); improved; individualized medicine; men; novel; osteoporosis with pathological fracture; patient subsets; personalized medicine; prediction algorithm; premature; prevent; randomized trial; risk benefit ratio; risk minimization; risk prediction model; secondary analysis; sex; side effect; study population; therapy duration; treatment strategy

Project Summary Sixty percent of older adults who start osteoporosis drug therapy (ODT) with an oral bisphosphonate (BP) have long-term exposure (3 or more years with 80% or higher adherence). Although a minimum of 6 to 12 months of BP treatment is required to reduce fracture risk, BPs have extended half-lives and can provide benefits long after discontinuation. Clinical trials have identified little difference in fracture risk for women who stopped versus continued BP after 3 to 5 years. Further, prolonged BP use has been linked to adverse events like atypical femoral fracture (AFF). Thus, guidelines recommend a drug holiday (pause in therapy) for most patients after 3 to 5 years of BP use. Patients at high fracture risk are recommended to continue BP or switch to another ODT, like denosumab, teriparatide, abaloparatide, or raloxifene. Several critical gaps in knowledge exist about the risks and benefits of long-term BP use, drug holidays, ODT switching on clinical outcomes and adverse events, particularly in groups with limited representation in trials like men and nursing home (NH) residents. This proposal has three specific aims: (1) Among community-dwelling older adults with at least 3 years of BP use, examine the effects of BP drug holidays and ODT switching on fractures, fracture sequelae (e.g., death, entry into NH), and AFF. (2) Among NH residents with at least 3 years of ODT, compare the effects of discontinuing versus continuing ODT on fractures/sequelae and patient-centered outcomes (e.g., functioning, pain); and (3) Develop and validate clinical prediction algorithms for osteoporotic fracture and AFF to guide clinicians making decisions on whether to initiate a drug holiday. Our central hypothesis is that the effects of long-term ODT strategies will be dependent on treatment length, type, and patient characteristics. The rigorous studies we propose will use multinational linked administrative and clinical datasets. The study population will comprise older adults aged 66 years or older in the US and Ontario, Canada who have at least 3 years of long-term ODT. Data for this study will come from 1) Linked, universal healthcare and medication claims data for all people (community-dwelling and NH) aged ≥65 years in Ontario; 2) U.S. Medicare claims on community-dwelling older adults; and 3) Electronic health record (EHR) data for up to 10,000 NHs linked to Medicare claims. We will implement a validated data cleaning algorithm for osteoporosis medication claims and novel rolling window method to capture long-term ODT. Time-varying propensity score approaches and novel causal inference methods like target trial emulation will be employed. This project will generate critical, generalizable evidence to guide long-term ODT, prevent fractures, and minimize AFF among older adults. This research will directly address RFA-AG-22-018, the Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention Pathways to Prevention Workshop Panel Recommendations 1 and 4, and Strategic Goal C of the National Institute on Aging. Additionally, the project will create an international data partnership to leverage EHR and universal healthcare data to answer emerging research questions on ODT.

项目概要 开始服用口服双膦酸盐 (BP) 的骨质疏松症药物治疗 (ODT) 的老年人中有 60% 患有骨质疏松症 长期暴露（3年或更长时间，80%或更高的依从性）。尽管至少需要 6 至 12 个月 需要进行 BP 治疗以降低骨折风险，BP 的半衰期较长，可以提供长期益处 停药后。临床试验发现，停止治疗的女性骨折风险几乎没有差异。 与 3 至 5 年后的持续血压比较。此外，长期使用血压与不良事件有关，例如 非典型股骨骨折（AFF）。因此，指南建议大多数人休药（暂停治疗）。 使用 BP 3 至 5 年后的患者。建议骨折风险高的患者继续降压或换药 另一种 ODT，如狄诺塞麦、特立帕肽、阿巴洛帕肽或雷洛昔芬。知识方面的几个关键差距 存在长期使用血压、药物假期、ODT 转换对临床结果的风险和益处，以及 不良事件，特别是在试验中代表性有限的群体，如男性和疗养院 (NH) 居民。该提案有三个具体目标： (1) 在社区居住的老年人中，至少有 3 使用 BP 年数，检查 BP 药物假期和 ODT 转换对骨折、骨折后遗症的影响 （例如，死亡、进入新罕布什尔州）和 AFF。 (2) 在接受过至少 3 年 ODT 的 NH 居民中，比较 停止与继续 ODT 对骨折/后遗症和以患者为中心的结果的影响（例如， 功能、疼痛）； (3) 开发并验证骨质疏松性骨折和 AFF 的临床预测算法 指导临床医生决定是否启动药物假期。我们的中心假设是 长期 ODT 策略的效果将取决于治疗长度、类型和患者特征。 我们建议的严格研究将使用跨国链接的管理和临床数据集。研究 人口将包括美国和加拿大安大略省 66 岁或以上的老年人，他们至少拥有 3年长期ODT。本研究的数据将来自 1) 关联的全民医疗保健和药物治疗 安大略省所有年龄 ≥ 65 岁的人（社区居民和非居民）的索赔数据； 2) 美国医疗保险索赔 社区居住的老年人； 3) 最多 10,000 个 NH 的电子健康记录 (EHR) 数据 医疗保险索赔。我们将为骨质疏松症药物索赔实施经过验证的数据清理算法 以及新颖的滚动窗口方法来捕获长期 ODT。随时间变化的倾向得分接近和 将采用目标试验仿真等新颖的因果推理方法。该项目将产生关键的、 指导老年人长期 ODT、预防骨折和尽量减少 AFF 的普遍证据。这 研究将直接解决 RFA-AG-22-018，骨质疏松症药物治疗的适当使用 预防骨折的途径研讨会小组建议 1 和 4 以及战略目标 C 国家老龄化研究所。此外，该项目将建立国际数据合作伙伴关系 利用 EHR 和全民医疗保健数据来回答有关 ODT 的新兴研究问题。