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

• 批准号: 10017007
• 负责人: Chamith Sudesh Rajapakse
• 金额: $ 53.66万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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/10017007
• 关键词: Address; Affect; Antiviral Agents; Antiviral Therapy; Assessment tool; Bone Density; Bone Diseases; Chronic; Chronic Hepatitis C; Clinical; 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; base; 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; response; skeletal; tool; viral RNA

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，患者有20-30％死亡，而50％的患者失去了行走的能力。存在共识 感染人类免疫缺陷病毒（HIV）或HEPATIS C病毒（HCV）增加了可能性 裂缝风险。与HIV和HCV的共同感染很普遍 - 三分之一的感染HIV患者也被感染 使用HCV） - 因此，该人群中髋部骨折的风险非常明显。证据表明目前 用于测量骨骼强度，双能X射线吸收法（DXA）和断裂的标准方式 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，我们将对股骨近端应用新颖的磁共振成像（MRI）方法 （即髋关节）通过最近资助的NIH项目可用的三个患者队列，以确定MRI 分析BMD/FRAX评分无法访问的骨缺陷，该方法可以提供有用的临床工具 对于未来的HIV+/HCV+试验，以及直接作用抗病毒（DAA）的HCV处理如何影响光中的骨骼强度 HIV+/HCV+和HCV+患者骨折风险的未来治疗创新。 在这项工作中，研究人员建议测试和比较骨强度，小梁微结构，皮质 使用HIV+/HCV+患者，HCV+患者和IN中的股骨近端股骨的MRI和骨髓脂肪和骨髓脂肪 未受影响的人。 HIV+/HCV+共感染预计会降低骨强度，呈异常 小梁结构，增加皮质孔隙度，并呈现异常的骨髓脂肪级分，与 HCV+和未感染的队列。预计BMD的群体差异不太明显。 DXA和FRAX分数。 在12周开始18个月后，将对三个队列中的每个人群中的每个参数进行测试相同的参数 HIV+/HCV+和HCV+个体中DAA治疗的治疗。用抗逆转录病毒治疗（ART）治疗HIV是 已知对整体骨骼强度有立即的负面影响，但有关骨不足的信息较少 HCV治疗后DAA治疗后的变化。预测HCV的治疗将导致骨强度提高， 提高小梁微观结构，皮质孔隙率降低，并改善了HCV+的骨髓脂肪分数 和HIV+/HCV+队列，但预计由DXA和FRAX评分评估不那么明显。 与HCV+队列相比，HCV+队列在这些参数方面具有更大的正变化 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和 为了减轻感染HIV和HCV的患者的髋部骨折负担。