Rates and determinants of decreased bone health among HIV-infected patients

HIV 感染者骨骼健康状况下降的比率和决定因素

• 批准号: 8590186
• 负责人: Roger Bedimo
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8590186
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Age; Aging; Analysis of Variance; Anti-Retroviral Agents; Body mass index; Bone Density; Caring; Chronic; Clinical; Code; Confounding Factors (Epidemiology); Control Groups; Cox Proportional Hazards Models; Cross-Sectional Studies; Data; Databases; Drug usage; Dyslipidemias; Endocrine system; Evaluation; Evaluation of Risk Factors; Fracture; Gender; General Population; Gonadal Hormones; Guidelines; HIV; HIV Infections; HIV Seropositivity; Health; Healthcare Systems; Hepatitis C; Hepatitis C virus; High Prevalence; Highly Active Antiretroviral Therapy; Hyperglycemia; ICD-9; Incidence; Infection; Inflammatory; Insulin Resistance; Knowledge; Lead; Malnutrition; Mediating; Metabolic; Modeling; Mono-S; Morbidity - disease rate; Osteoporosis; Outcome; Pathogenesis; Patients; Population; Race; Registries; Risk; Risk Factors; Role; Smoking; Source; Steroids; Subgroup; Survival Analysis; Testing; Texas; Time; Veterans; Vitamin D; Work; aging population; antiretroviral therapy; bone health; bone loss; bone mass; bone turnover; clinical risk; cohort; cytokine; data registry; health administration; high risk; improved; mortality; osteoporosis with pathological fracture; screening; trend; Acquired Immunodeficiency Syndrome; Address; Affect; Age; Aging; Analysis of Variance; Anti-Retroviral Agents; Body mass index; Bone Density; Caring; Chronic; Clinical; Code; Confounding Factors (Epidemiology); Control Groups; Cox Proportional Hazards Models; Cross-Sectional Studies; Data; Databases; Drug usage; Dyslipidemias; Endocrine system; Evaluation; Evaluation of Risk Factors; Fracture; Gender; General Population; Gonadal Hormones; Guidelines; HIV; HIV Infections; HIV Seropositivity; Health; Healthcare Systems; Hepatitis C; Hepatitis C virus; High Prevalence; Highly Active Antiretroviral Therapy; Hyperglycemia; ICD-9; Incidence; Infection; Inflammatory; Insulin Resistance; Knowledge; Lead; Malnutrition; Mediating; Metabolic; Modeling; Mono-S; Morbidity - disease rate; Osteoporosis; Outcome; Pathogenesis; Patients; Population; Race; Registries; Risk; Risk Factors; Role; Smoking; Source; Steroids; Subgroup; Survival Analysis; Testing; Texas; Time; Veterans; Vitamin D; Work; aging population; antiretroviral therapy; bone health; bone loss; bone mass; bone turnover; clinical risk; cohort; cytokine; data registry; health administration; high risk; improved; mortality; osteoporosis with pathological fracture; screening; trend

DESCRIPTION (provided by applicant): With the improved survival of HIV-infected patients since the introduction of Highly Active Antiretroviral Therapy (HAART), low bone mass and osteoporotic fractures seem to be emerging as important chronic problems that affect the aging HIV-positive population. Furthermore, an estimated 15 to 30% of HIV-infected patients are co-infected with hepatitis C (HCV), also associated with osteoporosis. For a given decrease in bone mineral density (BMD), the fracture risk increases dramatically with age in the general population. Despite this fact, trends in fracture risk in a large HIV cohort have never been evaluated to determine whether this is a growing problem among HIV-infected patients nor has an in-depth evaluation of risk factors been conducted, including type and duration of antiretroviral therapy (ART) and HCV co-infection. Furthermore, factors associated with HCV infection that might mediate a higher risk of decreased bone density and osteoporotic fractures - either decreased formation or increased resorption - among HIV-infected patients have not been elucidated. Finally, the impact of osteoporotic fractures on AIDS-related and non-AIDS-related morbidity and mortality is not known. We propose to help bridge these gaps in knowledge with a combination of: 1) a retrospective analysis of osteoporotic fracture risk, their predictors and outcomes in the Veterans Health Administration (VHA) Clinical Case Registry (CCR) which contains data on close to 60,000 current and former patients followed since 1984, provides an excellent source for addressing these important questions; and 2) a cross-sectional study comparing BMD and bone turnover markers (BTMs) between HIV/HCV co-infected, HIV and HCV mono-infected patients receiving care at the VA North Texas Health Care System (VANTHCS), with 650 current HIV patients (1/3 co-infected with HCV) and close to 5000 HCV patients. The current proposed work will address three specific aims: 1) To determine the impact of ART on bone health in HIV-infected patients. Using the CCR, osteoporotic fractures will be identified by ICD-9 code. Age-adjusted standardized incidence rates (SIRs) of osteoporotic fractures will be calculated and compared between the pre-HAART (1984-1995) and HAART (1996-2009) eras. Survival analyses will then be performed predicting onset of fractures among HIV-infected patients with various ARTexposure as time-dependent variables; 2) To determine the impact of HCV co-infection on bone health in HIV patients. We will assess BMD, BTMs, calciotropic and gonadal hormones and inflammatory cytokines in HIV/HCV co-infected patients and age-, gender-, and race-matched HIV mono-infected patients and HCV mono-infected patients receiving care at the VANTHCS. The ANOVA analysis will be conducted to detect difference among the three groups of patients. Age-adjusted SIRs of osteoporotic fractures will be computed and compared between HIV/HCV co- infected and HIV-only infected patients. We will further compare the SIRs within the pre-HAART and HAART eras; 3) To determine the association of decreased bone health and osteoporotic fractures with morbidity and mortality of HIV-infected patients. In the cross-sectional analysis, we will evaluate the correlation of dyslipidemia, insulin resistance and hyperlactatemia with BMD and BTMs. Furthermore, we will use the CCR data to explore whether dyslipidemia, hyperglycemia and hyperlactemia predict the onset of osteoporotic fractures by including them into the Cox survival model as time-dependent covariates. Finally, survival models will be constructed from CCR data to explore the association of osteoporotic fractures with all- cause mortality, AIDS and non-AIDS-related mortality.

描述（由申请人提供）： 自从引入高度活跃的抗逆转录病毒疗法（HAART）以来，艾滋病毒感染患者的存活率提高，低骨量和骨质疏松性骨折似乎正在成为影响HIV阳性人群衰老的重要慢性问题。此外，估计有15至30％的HIV感染患者与丙型肝炎（HCV）共感染，也与骨质疏松症有关。对于给定的骨矿物质密度（BMD）的降低，裂缝风险随着普通人群的年龄而大大增加。尽管这一事实，从未评估过大型艾滋病毒队列中骨折风险的趋势，以确定这是否是艾滋病毒感染患者的日益严重的问题，也对危险因素进行了深入评估，包括抗逆转录病毒疗法的类型和持续时间（ART）（ART）和HCV共同感染。此外，在HIV感染的患者中，与HCV感染有关的因素可能介导较高的骨密度和骨质疏松性骨折的风险较高 - 形成或吸收增加 - 尚未阐明。最后，尚不清楚骨质疏松性裂缝对与艾滋病相关和非AID相关的发病率和死亡率的影响。我们建议通过以下组合来帮助弥合知识的差距：1）对骨质疏松性断裂风险的回顾性分析，其预测因素和退伍军人卫生管理局（VHA）临床病例注册表（CCR），其中包含自1984年以来紧随其后的60,000名现任和前任患者的数据，提供了解决这些重要问题的良好来源；和2）一项横断面研究，比较了HIV/HCV共感染，HIV和HCV单单感染的患者在VA North Texas Health Care System（VANTHCS）中接受护理的患者，与650名当前HIV患者（与HCV共同感染）和接近5000 HCV的HIV患者（1/3共同感染），在HIV/HCV共感染，HIV和HCV单一感染的患者中进行了比较BMD和骨转换标记（BTM）（BTM）（BTM）（1/HCV），与HIV/HCV共同感染的患者（与HIV和HCV单单相）之间进行了比较，2）2）当前建议的工作将针对三个具体目标： 1）确定ART对HIV感染患者的骨骼健康的影响。使用CCR，将通过ICD-9代码识别骨质疏松骨折。在Haart（1984-1995）和Haart（1996-2009）ERAS（1984-1995）和Haart（1996-2009）ERAS（1984-1995）和HAART（1996-2009）时期，将计算出年龄调整的标准化发病率（SIRS）。然后将进行生存分析，以预测具有各种ART曝光的HIV感染患者中骨折的发作。 2）确定HCV共感染对HIV患者骨骼健康的影响。我们将评估HIV/HCV共感染的患者以及年龄，性别 - 和种族匹配的HIV单感染的患者以及HCV一单位感染的患者接受护理的HIV/HCV共同感染的患者，BMD，BTMS，BTMS，钙调子和性腺激素以及炎症细胞因子。将进行方差分析分析以检测三组患者之间的差异。将计算骨质疏松骨折的年龄调整后的SIRS，并比较HIV/HCV感染和仅HIV感染的患者。我们将进一步比较前哈特和哈特时代内的sir; 3）确定减少骨骼健康和骨质疏松性骨折与HIV感染患者的发病率和死亡率的关联。在横截面分析中，我们将评估血脂异常，胰岛素抵抗和多氨基血症与BMD和BTM的相关性。此外，我们将使用CCR数据来探讨血脂异常，高血糖和高乳酸血症是否通过将骨质疏松性骨折作为时间依赖性协变量来预测骨质疏松性骨折的发作。最后，将从CCR数据构建生存模型，以探讨骨质疏松性骨折与全部导致死亡率，艾滋病和非AID相关死亡率的关联。