Osteoporosis Treatment and Drug Holiday Duration

骨质疏松症治疗和药物假期持续时间

基本信息

批准号：
9569267
负责人：
Smita Nayak
金额：
$ 15.96万
依托单位：
BERKELEY MADONNA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-21 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9569267
关键词：
Activities of Daily Living Acute Address Adult Adverse event Affect Affinity Aftercare Age Aging Alendronate American Binding Bone Density Bone necrosis Bone remodeling Cerebrovascular Disorders Cessation of life Clinical Collaborations Computer Simulation Elderly Expert Opinion FDA approved Femoral Fractures Fracture Future Hip Fractures Hip region structure Holidays Ibandronate Individual Intravenous Jaw Knowledge Length Literature Medical Medicare Meta-Analysis Modeling Morbidity - disease rate Myocardial Infarction Nursing Homes Oral Osteoclasts Osteoporosis Patients Pharmaceutical Preparations Pharmacology Placebos Pneumonia Population Recommendation Recording of previous events Relative Risks Research Residual state Risedronate Risk Risk Reduction Safety Serious Adverse Event Spinal Fractures Suggestion Time Translating Uncertainty United States Woman Work Zoledronic Acid base bisphosphonate bone chronic pain clinical care clinical practice comparative effectiveness compare effectiveness cost cost effective cost effectiveness effective therapy evidence base experience fracture risk high risk human old age (65+)inhibitor/antagonist men models and simulation mortality osteoporosis with pathological fracture spine bone structure systematic review therapy duration treatment duration

项目摘要

Project Summary/Abstract Osteoporosis is highly prevalent among older adults in the United States, with approximately 10 million people affected. Nearly 50% of women over age 50 years and 25% of white men over age 60 years will suffer an osteoporotic fracture in their lifetimes, with significant consequences including death, difficulty in performing activities of daily living, loss of ambulatory ability, nursing home placement, and chronic pain. Bisphosphonates, a class of medications that are strong inhibitors of osteoclast bone remodeling, are effective for reducing fracture risk and the most commonly prescribed medications for osteoporosis treatment. FDA- approved bisphosphonates for treatment of osteoporosis include alendronate, risedronate, ibandronate, and zoledronic acid. These medications should not be continued indefinitely due to an increased risk of rare serious adverse events, such as atypical femoral fracture or osteonecrosis of the jaw, with therapy duration beyond 5 years. However, there is uncertainty with respect to the optimal duration of bisphosphonate therapy for individuals with osteoporosis. Furthermore, for individuals who stop treatment, the optimal duration of the “drug holiday”, or period of time in which treatment is stopped before restarting treatment, is unknown. Bisphosphonates bind to bone and can remain bound for many years, thus resulting in residual pharmacological activity for years after discontinuation. However, binding affinity to bone varies among the bisphosphonates, and thus it is likely that the optimal drug holiday duration may vary depending on the particular bisphosphonate. The purpose of this proposed research is to systematically review the evidence on the duration of treatment for which fracture risk reduction has been demonstrated for each of the FDA- approved bisphosphonates for osteoporosis treatment and associated fracture risk reduction efficacy and change in bone mineral density (BMD) on bisphosphonate treatment, the impact of drugs holidays on fracture risk and BMD, and the safety (adverse events rates) associated with different durations of treatment (Aim 1); and to compare the effectiveness and cost-effectiveness of different treatment and drug holiday durations for each bisphosphonate for U.S. adults with osteoporosis (Aim 2). Our analyses would address key osteoporosis clinical care knowledge gaps and provide evidence to guide treatment duration and drug holiday duration decisions in clinical practice; and help enable a future R01 proposal to investigate approaches to translate findings about best treatment practices to the clinical setting to reduce osteoporosis-related morbidity and mortality. Our research team is ideally suited to perform this work; we have substantial experience and expertise in osteoporosis, systematic reviews/meta-analysis, and cost-effectiveness modeling, and a track record of successful collaboration.

项目概要/摘要骨质疏松症在美国老年人中非常普遍，约有 1000 万人近 50% 的 50 岁以上女性和 25% 的 60 岁以上白人男性将受到影响。一生中发生骨质疏松性骨折，造成严重后果，包括死亡、表演困难日常生活活动、行走能力丧失、疗养院安置和慢性疼痛。双膦酸盐是一类破骨细胞骨重塑的强抑制剂药物，非常有效用于降低骨折风险和骨质疏松症治疗最常用的处方药物。批准用于治疗骨质疏松症的双膦酸盐包括阿仑膦酸盐、利塞膦酸盐、伊班膦酸盐和这些药物不应无限期持续使用，因为会增加罕见严重并发症的风险。不良事件，如非典型股骨骨折或颌骨坏死，治疗持续时间超过5年然而，双膦酸盐治疗的最佳持续时间尚不确定。此外，对于停止治疗的个体，“药物的最佳持续时间”。 “假期”，或在重新开始治疗之前停止治疗的时间段，尚不清楚。双膦酸盐与骨结合并可以保持结合多年，从而导致残留停药后数年仍具有药理活性，但不同药物对骨的结合亲和力各不相同。双膦酸盐，因此最佳药物假期持续时间可能会根据情况而变化这项研究的目的是系统地审查有关双膦酸盐的证据。 FDA 已证明可降低骨折风险的治疗持续时间批准的双膦酸盐用于骨质疏松症治疗和降低相关骨折风险的功效和双膦酸盐治疗引起的骨密度 (BMD) 变化、药物假期对骨折的影响风险和 BMD，以及与不同治疗持续时间相关的安全性（不良事件发生率）（目标 1）；并比较不同治疗方法和药物假期持续时间的有效性和成本效益每种双磷酸盐对患有骨质疏松症的美国成年人（目标 2）。临床护理知识差距并提供证据来指导治疗持续时间和药物假期持续时间临床实践中的决策；并帮助未来的 R01 提案研究转化方法关于临床环境中减少骨质疏松症相关发病率的最佳治疗实践的发现我们的研究团队非常适合开展这项工作；我们拥有丰富的经验和能力。骨质疏松症、系统评价/荟萃分析和成本效益模型方面的专业知识以及跟踪成功合作的记录。