Development and Validation of a Novel and HIV-Relevant Prediction Model for Fracture

摘要 艾滋病毒(PWH)患者中的脆性骨折(骨折)每年造成9900万美元的额外费用 在美国。我们先前的研究表明，在PWH中，骨折的年发生率要高得多 -大多数是中年人-与未感染的人(2.0%对1.4%)相比。这样的骨折是 与住院率和疗养院入院率上升、长期身体残疾、 社会孤立和死亡。因为中年是人们在经济上和社会上最 多产，在生命的这个时期骨折为经济困难和较差的健康结果奠定了基础，如 这些人会变老。有非常有效的方法来防止脆性骨折，通过 25%-50%。然而，目前还没有可靠的风险预测模型来确定威尔斯亲王面临的最大风险。 裂缝风险评估工具(FRAX)是预测裂缝的最广泛的模型 普通人口。它结合了人口统计数据(年龄、性别、种族)和关键风险因素(体重指数、 既往骨折、父母骨折、当前吸烟、使用糖皮质激素、类风湿性关节炎、继发性 骨质疏松症和危险饮酒)。对于可用双能X射线吸收法的设置， 通过在算法中加入骨密度(BMD)，可以提高FRAX的灵敏度。然而，我们的 先前的研究表明，FRAX在PWH中表现不佳，表现出较差的辨别力(C统计0.59) 灵敏度(0.06)。我们认为这是因为FRAX没有考虑到对 威尔斯亲王医院。例如，FRAX没有考虑跌倒、丙型和乙肝病毒、药物使用障碍、 多发病、多药联用、使用其他与骨折相关的药物或生理性虚弱--所有这些 这与PWH中的骨折有关。最后，FRAX不能解释抗逆转录病毒 治疗(ART)使用。个人艺术和艺术课程都与骨折有独立的联系。 利用优秀的协作者团队和研究平台，我们将开发、验证和 发布基于FRAX但包含HIV相关风险的骨折风险评估计算器 系数(FRAC-HIV)，以计算下一年威尔斯亲王医院发生骨折的可能性。我们有大量的 参与退伍军人老龄化队列研究(VAS)的经验，这是北方最大的威斯康星医院队列研究 美国，它将作为我们的发展队列。为了评估通用性，我们将从外部验证 使用耶鲁纽黑文医疗保健系统和波士顿医疗集团的电子健康记录数据的模型 中心。我们的最终目标是通过开发一个 基于Web的骨折风险预测计算器，它将直接从以下提供商的见解中获得信息 关爱威尔斯亲王医院。FRAC-HIV将重新定义和促进骨折预防的临床决策 通过强调临床可改变的危险因素的作用。我们的发现将为未来的发展奠定基础 将FRAC-HIV纳入临床护理算法的干预试验，以防止PWH中的骨折。

ABSTRACT Fragility fractures (fractures) among persons with HIV (PWH) account for $99 million in excess costs each year in the United States. Our prior research has shown a significantly higher annual rate of fractures among PWH – most of whom are middle-aged – compared with uninfected individuals (2.0% vs 1.4%). Such fractures are associated with increased rates of hospitalization and nursing home admissions, long-term physical disability, social isolation, and death. Because middle-age is a time when people are most economically and socially productive, fractures at this time of life set the stage for economic hardship and poorer health outcomes as these individuals grow older. Highly effective methods exist for preventing fragility fractures, reducing rates by 25%-50%. However, there are no risk prediction models that reliably identify PWH at greatest risk. The Fracture Risk Assessment Tool (FRAX) is the most widely used model for predicting fractures in the general population. It incorporates demographics (age, sex, race) and key risk factors (body mass index, previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, and hazardous alcohol use). For settings where dual-energy x-ray absorptiometry is available, sensitivity of FRAX can be improved by adding bone mineral density (BMD) to the algorithm. However, our prior studies suggest that FRAX underperforms among PWH, exhibiting poor discrimination (C statistic 0.59) and sensitivity (0.06). We believe this is because FRAX does not account for risk factors that are important to PWH. For example, FRAX does not account for falls, hepatitis C and B viruses, substance use disorder, multimorbidity, polypharmacy, use of other medications associated with fractures, or physiologic frailty – all of which have been associated with fractures among PWH. Finally, FRAX does not account for antiretroviral therapy (ART) use. Individual ART as well as ART classes have been independently associated with fracture. Leveraging an outstanding team of collaborators and research platforms, we will develop, validate and disseminate a Fracture Risk Assessment Calculator based on FRAX but that incorporates HIV-relevant risk factors (FRAC-HIV) to calculate the probability of a fracture among PWH in the next year. We have extensive experience working with the Veterans Aging Cohort Study (VACS), the largest cohort of PWH in North America, which will serve as our development cohort. To assess generalizability, we will externally validate the model using electronic health record data from Yale New Haven Healthcare System and Boston Medical Center. Our final aim sets the stage for the implementation of this predictive model via the development of a web-based fracture risk prediction calculator, which will be directly informed by insights from providers who care for PWH. FRAC-HIV will reconceptualize and facilitate clinical decision-making for fracture prevention in PWH by emphasizing the role of clinically modifiable risk factors. Our findings will lay the foundation for future intervention trials that will incorporate FRAC-HIV into clinical care algorithms to prevent fractures among PWH.