Project 3: Beta blockers and their impact on fracture risk in nursing home residents taking atypical antipsychotics

非典型抗精神病药物(AAs)，被广泛用于治疗精神和行为 在养老院环境中的老年人的症状与骨骼风险增加有关 骨折。AAS增加骨折风险的机制尚不清楚，尽管最近 有证据表明，导致骨质丢失的分子机制。β阻滞剂(BBS)，广泛应用于 给疗养院居民开的治疗心脏病和高血压的处方，有 证明了降低骨折风险的效果。风险降低的规模已经被发现是 依赖于BB级，β1选择性阻滞剂在大多数情况下显示出最大的保护作用 学习。BBS对骨折风险的保护作用也得到了动物研究的支持，其中一些研究 已由团队成员和项目负责人完成(K.Motyl，项目4)。 我们的主要假设是，在事件AA用户中并发使用BB将导致 我们进一步假设，这种影响的大小将随着β1选择性的不同而变化。 我们提出了一项大型观察性研究，以衡量同时使用BB对骨折风险的影响。 养老院老年居民发起AAS。我们的临床研究将得到相关人员的支持 研究(K.Motyl)在小鼠模型中的骨生理学。我们将分析大量的数据， 全国养老院居民数据与临床特征挂钩数据库最小 来自联邦医疗保险A、B和D部分的数据集以及诊断和药物数据，适用于大多数美国长期- 留下来当居民。在我们的第一个特定目标中，我们将测试患者启动再生障碍性贫血(称为 AA初学者)在疗养院同时暴露于BBS将降低骨折风险。 我们的主要结果将是髋部骨折，而主要的骨质疏松性骨折将是次要结果。 我们还将分析跌倒是导致骨折的另一个次要结果。 我们将针对BB用户和BB用户之间不平衡的患者特征做出适当调整 非用户使用倾向评分方法，并使用新的事件间隔时间方法，该方法允许 对与时间相关的苯系物暴露进行建模，以便准确估计使用苯系物的影响。在我们的 第二个具体目标，我们将估计BB对骨折和跌倒的影响的类内差异。 作为β1-选择性类与非选择性类的函数。在这项研究结束时，我们将发现 BB暴露是否降低了AA治疗相关的骨折风险，并展示了其影响 根据BB类药物的不同而不同。这项研究将为动物模型研究提供信息，并提供初步数据 关于疗养院环境中AA引起的骨折风险的基于BB的治疗机制。

Atypical antipsychotics (AAs), which are widely prescribed to manage psychiatric and behavioral symptoms in elderly adults in nursing home settings, are associated with an increased risk of bone fracture. The mechanism by which AAs increase fracture risk is not well understood, although recent evidence suggests molecular mechanisms that result in bone loss. β-blockers (BBs), which are widely prescribed to nursing home residents to manage cardiac disease and high blood pressure, have demonstrated effects to reduce fracture risk. The size of the risk reduction has been found to be dependent on BB class, with β1 selective blockers showing the greatest protective effect in most studies. The protective effect of BBs on fracture risk is also supported by animal studies, some of which have been completed by fellow team member and project leader in this COBRE (K. Motyl, Project 4). Our primary hypothesis is that concurrent BB use in incident AA users will result in a reduction in fracture risk, and we further hypothesize that the magnitude of this effect will vary with β1 selectivity. We propose a large observational study to measure the effect of concurrent BB use on fracture risk in elderly nursing home residents initiating AAs. Our clinical study will be supported by concomitant studies (K. Motyl) addressing bone physiology in a mouse model. We will analyze data from a large, national database of nursing home resident data with linked clinical characteristics from the Minimum Data Set and diagnosis and drug data from Medicare Parts A, B, and D for the majority of U.S. long- stay residents. In our first specific aim, we will test the hypothesis that patients initiating AA (termed AA initiates) in the nursing home with concurrent exposure to BBs will have a reduced risk of fracture. Our primary outcome will be hip fracture, and major osteoporotic fractures will be a secondary outcome. We will also analyze falls as another secondary outcome that lies along the causal pathway to fracture. We will make appropriate adjustments for imbalanced patient characteristics between BB users and non-users using propensity score methods, and use a novel time-to-event method that allows for modeling time-dependent exposure to BBs to allow for precise estimates of the effect of BB use. In our second specific aim we will estimate the within-class variation in the effect of BB on fractures and falls as a function of β1-selective vs. non-selective class. At the conclusion of this study we will discover whether BB exposure mitigates fracture risk associated with AA treatment, and show how that effect varies by class of BB drug. This study will inform animal model research and provide preliminary data for BB-based mechanisms for the treatment of AA-induced fracture risk in the nursing home setting.