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MRI Assessment of Hip Fracture Risk and Therapy Response in HIV/HCV Coinfection

HIV/HCV 合并感染髋部骨折风险和治疗反应的 MRI 评估

基本信息

批准号：
10666414
负责人：
Chamith Sudesh Rajapakse
金额：
$ 47.11万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-11 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10666414
关键词：
Address Affect Antiviral Agents Antiviral Therapy Assessment tool Bone Density Bone Diseases Chronic Chronic Hepatitis C Clinical Clinical Management Clinical Trials Consensus Data Development Dual-Energy X-Ray Absorptiometry Evaluation Fatty acid glycerol esters Femur Fracture Funding Future HIV Hepatitis C virus Hip Fractures Hip region structure Imaging Device Impairment Individual Infection Institution Intervention Ionizing radiation Knowledge Light Magnetic Resonance Imaging Marrow Measures Mediating Methodology Modality Modeling Osteoporosis Participant Patients Persons Pharmaceutical Preparations Population Porosity Protocols documentation Research Personnel Risk Risk Factors Site Structure Testing Time United States National Institutes of Health Viral Virus Virus Diseases Walking Work antiretroviral therapy bone bone health bone metabolism bone strength chronic inflammatory disease clinically significant co-infection cohort fracture risk fragility fracture hip bone imaging modality improved innovation men mortality new therapeutic target novel prevent skeletal tool treatment response viral RNA

项目摘要

Project Summary Within a year of hip fracture 20-30% of patients die, and 50% percent lose the ability to walk. A consensus exists that infection with the human immunodeficiency virus (HIV) or the hepatis C virus (HCV) increases the likelihood of fracture risk. Co-infection with HIV and HCV is prevalent - - one third of infected HIV patients are also infected with HCV) - - thus the risk of hip fracture in this population is greatly pronounced. Evidence suggests that current standard modalities used to measure bone strength, dual energy X-ray absorptiometry (DXA) and the Fracture Risk Assessment Tool (FRAX), underestimate this risk in HIV+/HCV+ patients. To address this issue, we will apply novel magnetic resonance imaging (MRI) methods to the proximal femur (i.e., hip) in three patient cohorts available through a recently funded NIH project in order to determine how MRI analyzes bone deficits inaccessible by BMD/FRAX scores, how the methodology may provide clinical tools useful for future HIV+/HCV+ trials, and how direct-acting antiviral (DAA) treatment of HCV affects bone strength in light of possible future treatment innovations for fracture risk in HIV+/HCV+ and HCV+ patients. In this work, the investigators propose to test and compare bone strength, trabecular microstructure, cortical porosity, and marrow fat using MRI of the proximal femur in HIV+/HCV+ patients, in HCV+ patients, and in unaffected individuals. HIV+/HCV+ coinfection is predicted to decrease bone strength, present abnormal trabecular structure, increase cortical porosity, and present abnormal marrow fat fraction, in comparison to the HCV+ and uninfected cohorts. Group differences are predicted to be less pronounced in BMD as assessed by DXA and FRAX scores. Identical parameters will be tested for each of the three cohorts 18 months after initiation of a 12-week treatment of DAA therapy in HIV+/HCV+ and HCV+ individuals. Treating HIV with antiretroviral therapy (ART) is known to have immediate negative effects on overall bone strength, but less information exists about bone deficit changes following HCV cure with DAA treatment. Cure of HCV is predicted to result in increased bone strength, improved trabecular microstructure, decreased cortical porosity, and improved marrow fat fraction in the HCV+ and HIV+/HCV+ cohorts, but again predicted to be less pronounced as assessed by DXA and FRAX scores. The HCV+ cohort is predicted to have larger positive changes concerning these parameters in comparison to the HIV+/HCV+ group. The proposed project has the potential to change and improve how bone disease is clinically managed and to reduce the burdens of hip fractures in patients infected with HIV and HCV.

项目摘要在髋部骨折的一年内，20-30%的患者死亡，50%的患者失去行走能力。存在共识感染人类免疫缺陷病毒（HIV）或丙型肝炎病毒（HCV）会增加骨折风险。艾滋病毒和丙型肝炎病毒的合并感染很普遍-三分之一的艾滋病毒感染者同时感染 HCV感染）- -因此，这一人群中髋部骨折的风险非常明显。有证据表明，目前用于测量骨强度的标准模式，双能X射线吸收法（DXA）和骨折风险评估工具（FRAX），低估了HIV+/HCV+患者的这种风险。为了解决这个问题，我们将应用新的磁共振成像（MRI）的方法对股骨近端 (i.e.,髋关节）在三个患者队列，通过最近资助的NIH项目，以确定如何MRI 分析BMD/FRAX评分无法达到的骨缺损，该方法如何提供有用的临床工具，未来的HIV+/HCV+试验，以及HCV的直接作用抗病毒（DAA）治疗如何影响骨强度， HIV+/HCV+和HCV+患者骨折风险的未来可能的治疗创新。在这项工作中，研究人员建议测试和比较骨强度，骨小梁显微结构，皮质骨，使用MRI对HIV+/HCV+患者、HCV+患者和不受影响的个人。预计HIV+/HCV+合并感染会降低骨强度，骨小梁结构，增加皮质孔隙度，并存在异常的骨髓脂肪分数，相比， HCV+和未感染队列。通过以下评估，预测组间BMD差异不太明显： DXA和FRAX评分。将在开始12周治疗后18个月对三个队列中的每个队列检测相同的参数。 DAA疗法在HIV+/HCV+和HCV+个体中的治疗。用抗逆转录病毒疗法（ART）治疗艾滋病毒是已知对整体骨强度有直接的负面影响，但关于骨缺损的信息较少用DAA治疗HCV治愈后的变化。HCV的治愈预计会导致骨强度增加， HCV+患者的小梁显微结构改善，皮质孔隙率降低，骨髓脂肪分数改善和HIV+/HCV+队列，但再次预测不太明显，如DXA和FRAX评分所评估的。预计HCV+队列在这些参数方面的积极变化大于 HIV+/HCV+组。拟议的项目有可能改变和改善骨骼疾病的临床管理方式，减少HIV和HCV感染患者髋部骨折的负担。