Bone quality and marrow adiposity in subjects with HIV

HIV 感染者的骨质量和骨髓肥胖

• 批准号: 9271800
• 负责人: GALATEIA J KAZAKIA
• 金额: $ 55.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9271800
• 关键词: Adipocytes; Affect; Age; Age-Related Bone Loss; Aging; Biological; Biological Markers; Biomechanics; Bone Density; Bone Marrow; Cell Differentiation process; Cell Lineage; Chromosome Fragile Sites; Competence; Control Groups; Cross-Sectional Studies; Data; Data Quality; Deterioration; Distal; Enrollment; Equilibrium; Etiology; Fatty acid glycerol esters; Femur; Fracture; Functional disorder; Future; General Population; HIV; HIV Infections; HIV therapy; Health; Health Care Costs; High Prevalence; Hip region structure; Human; Image; Imaging Techniques; Incidence; Individual; Inflammation; Kidney; Knowledge; Limb structure; Lipids; Magnetic Resonance Imaging; Marrow; Mechanics; Mission; Monitor; Morbidity - disease rate; Obesity; Osteoblasts; Osteoporosis; Pathway interactions; Patients; Peripheral; Play; Population; Public Health; Race; Radial; Reporting; Research; Resolution; Risk Assessment; Role; Serum; Site; Societies; Stromal Cells; Structure; Testing; Therapeutic; Translating; United States National Institutes of Health; Vertebral column; Visceral; WNT Signaling Pathway; Woman; Work; X-Ray Computed Tomography; adipocyte differentiation; aged; aging population; antiretroviral therapy; base; bone; bone cell; bone geometry; bone health; bone loss; bone quality; bone turnover; cost; density; disability; drug development; experience; fracture risk; fragility fracture; high resolution imaging; immune activation; improved; in vivo; innovation; lipid biosynthesis; mechanical properties; men; mortality; novel; novel strategies; sex; skeletal; subcutaneous; therapeutic target; tibia; treatment strategy

HIV-infected individuals experience up to 4-fold higher annual rates of fragility fractures than the general population. As HIV-infected individuals live longer through effective antiretroviral therapy (ART), fracture rates are expected to further increase in the future. While several studies have emphasized an increased fracture incidence in HIV-infected patients, this increased fracture incidence is not explained by differences in bone mineral density (BMD) between HIV-infected individuals and healthy controls. An emerging explanation for this paradox is that HIV infection and treatment are associated with bone quality changes – including changes in bone geometry and microstructure – that do not impact BMD but do increase fracture risk. To date, only a few studies have investigated bone quality and only at the distal extremities. However, the proximal femur is an important site for fragility fracture. Hence, a critical gap in knowledge is whether bone quality at central skeletal sites, including the spine and hip, is similarly affected by HIV infection and therapy. Thus, a critical barrier to progress in the field is a lack of understanding of bone quality changes in HIV infected subjects. A potential mechanism influencing low bone quality in HIV could be an imbalance in bone and fat cell differentiation. Thus, bone marrow fat (BMF) could potentially be another important biomarker for bone health. A better understanding of these relationships could translate into new approaches for fracture risk assessment, drug development, and therapy monitoring in HIV-infected patients. We have identified three working hypotheses: (1) Significant micro-structural deterioration and reduction in biomechanical competence will be detected in HIV-infected patients at both peripheral and central sites and will reveal larger differences between HIV-infected and control groups than BMD data from DXA alone; (2) Increased BMF will be detected in HIV-infected patients compared to healthy controls and will be associated with increased visceral adiposity and decreased HIV-associated subcutaneous adiposity; and (3) Increased BMF will partially explain the association of HIV with poor bone quality. These hypotheses will be tested by pursuing the following Specific Aims: (1) Quantify differences in bone density, structure, and mechanical properties between HIV-infected patients and uninfected controls; (2) Determine differences in BMF between HIV-infected patients and uninfected controls; and (3) Determine the relationship between BMF and bone quality in HIV-infected patients. The approach is innovative because it combines novel in-vivo MRI and HR-pQCT imaging techniques to determine relationships between bone features and BMF with voxel based morphormetry. The proposed research is significant because the associations between bone quality and BMF have not yet been assessed in HIV-infected subjects. These relationships may reveal pathobiological mechanisms at play in HIV, and identify potential therapeutic targets for improving skeletal health in the HIV-infected population.

HIV感染者的脆性骨折年发生率比一般人高4倍 人口随着艾滋病毒感染者通过有效的抗逆转录病毒治疗（ART）寿命延长， 预计未来利率将进一步上升。虽然一些研究强调， HIV感染患者骨折发生率的增加，不能用差异来解释 HIV感染者和健康对照者的骨密度（BMD）。一个新兴 对这一矛盾的解释是，艾滋病毒感染和治疗与骨质变化有关- 包括骨几何结构和微观结构的变化-不影响BMD，但会增加骨折 风险迄今为止，只有少数研究调查了骨骼质量，并且仅在远端四肢。然而，在这方面， 股骨近端是脆性骨折的重要部位。因此，一个关键的知识差距是， 包括脊柱和髋关节在内的中央骨骼部位的骨质同样受到HIV感染的影响， 疗法因此，该领域进展的关键障碍是缺乏对骨质量变化的理解， 艾滋病毒感染者。影响HIV患者低骨质量的一个潜在机制可能是 骨和脂肪细胞分化。因此，骨髓脂肪（BMF）可能是另一个重要的 骨骼健康的生物标志物。更好地理解这些关系可以转化为新的 HIV感染者骨折风险评估、药物开发和治疗监测的方法 患者我们已经确定了三个工作假设：（1）显着的微观结构恶化， 在HIV感染患者中，外周和外周的生物力学能力将降低， 与BMD数据相比，HIV感染组和对照组之间的差异更大 （2）与健康对照组相比，HIV感染患者的BMF增加 并将与内脏肥胖增加和艾滋病毒相关的皮下 肥胖;（3）BMF增加将部分解释HIV与骨质不良的关系。这些 将通过追求以下特定目的来检验假设：（1）量化骨密度的差异， 结构和机械性能之间的HIV感染患者和未感染的对照;（2）确定 HIV感染患者和未感染对照之间的BMF差异;以及（3）确定 HIV感染者BMF与骨质量的关系这种方法是创新的，因为它 结合了新的体内MRI和HR-pQCT成像技术，以确定骨之间的关系 特征和BMF与基于体素的形态学。这项研究意义重大，因为 尚未在HIV感染者中评估骨质量和BMF之间的相关性。这些 关系可能揭示在HIV中起作用的病理生物学机制，并确定潜在的治疗方法。 改善艾滋病毒感染人群骨骼健康的目标。