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

项目摘要 髋部骨折一年内，20%-30%的患者死亡，50%的患者失去行走能力。共识是存在的 感染人类免疫缺陷病毒(HIV)或丙型肝炎病毒(HCV)会增加 有骨折的风险。艾滋病毒和丙型肝炎病毒混合感染很普遍--三分之一的艾滋病毒感染者也感染了 因此，在这一人群中，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、双能X射线吸收测量仪(DXA)和骨折的标准模式 风险评估工具(FRAX)，低估了艾滋病毒+/丙型肝炎+患者的这种风险。 为了解决这个问题，我们将把新的磁共振成像(Mri)方法应用于股骨近端。 (即髋关节)，通过最近资助的NIH项目提供的三个患者队列中，以确定MRI如何 分析BMD/FRAX评分无法获得的骨缺陷，该方法学如何提供有用的临床工具 关于未来的HIV+/丙型肝炎病毒+试验，以及丙型肝炎病毒的直接作用抗病毒(DAA)治疗如何影响骨强度。 针对HIV+/丙型肝炎病毒阳性和丙型肝炎病毒阳性患者的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、骨小梁微结构、皮质 HIV+/丙型肝炎病毒阳性患者、丙型肝炎病毒阳性患者和男性患者股骨近端的MRI孔隙率和骨髓脂肪 未受影响的个体。HIV+/丙型肝炎病毒+混合感染预计会降低骨强度，出现异常 骨小梁结构，皮质孔隙率增加，并出现异常的骨髓脂肪分数，与 丙型肝炎病毒阳性和未感染的队列。据预测，根据以下评估，BMD在群体中的差异不那么明显 DXA和FRAX评分。 在为期12周的试验开始18个月后，将对三个队列中的每一个进行相同的参数测试 人类免疫缺陷病毒/丙型肝炎病毒阳性和丙型肝炎病毒阳性患者的DAA治疗用抗逆转录病毒疗法(ART)治疗艾滋病毒 已知对整体骨骼强度有直接的负面影响，但关于骨骼缺陷的信息较少 丙型肝炎病毒DAA治疗治愈后的变化。丙型肝炎病毒的治愈被预测会导致骨骼强度的增加， 改善了小梁结构，减少了皮质孔隙率，并改善了丙型肝炎病毒阳性患者的骨髓脂肪含量 和HIV+/丙型肝炎病毒+队列，但根据DXA和FRAX评分再次预测不太明显。 预测与丙型肝炎病毒+队列相比，在这些参数方面有更大的积极变化 HIV+/丙型肝炎病毒阳性组。 拟议的项目有可能改变和改善骨病的临床管理和治疗方式 减轻感染艾滋病毒和丙型肝炎患者髋部骨折的负担。

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.