Oral immune activation and alveolar bone loss in HIV-infected postmenopausal women

感染艾滋病毒的绝经后妇女的口腔免疫激活和牙槽骨丢失

• 批准号: 9320344
• 负责人: Sunil Wadhwa
• 金额: $ 45.2万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9320344
• 关键词: Address; Affect; Age; Alveolar; Alveolar Bone Loss; Attenuated; Biological Markers; Bone Density; Bone Resorption; Clinical; Controlled Study; Cross-Sectional Studies; Data; Dental; Dental Hygiene; Disease Progression; Estrogens; Experimental Models; Fracture; Frequencies; Gene Expression; Gingiva; Gingival Crevicular Fluid; Gingivitis; Goals; HIV; HIV Infections; Health; Height; Hip region structure; Hormone replacement therapy; Immune; Immune response; Individual; Inflammation; Inflammatory; Inflammatory Response; Instruction; Intervention; Intervention Studies; Knowledge; Maintenance; Measures; Mediating; Menopause; Modeling; Morbidity - disease rate; Oral; Oral health; Osteoporosis; Outcome; Pathogenesis; Periodontal Diseases; Periodontitis; Population; Postmenopause; Premenopause; Prevalence; Prospective Studies; Resolution; Risk; Salivary; Selective Estrogen Receptor Modulators; Serum; Severities; Skeletal bone; TNF gene; Testing; Tissues; Tooth Cervix; Tooth Loss; Tooth structure; United States; Vertebral column; Woman; Women' s Group; alveolar bone; antiretroviral therapy; bone loss; cone-beam computed tomography; cytokine; defined contribution; immune activation; older women; pathogen; prevent; rate of change; response; scaling and root planing; skeletal; standard of care; therapy development; trend

PROJECT SUMMARY There are very few controlled studies on the oral health of older HIV-infected individuals, especially postmenopausal women. This is of particular concern in the U.S, where more than half of HIV-infected individuals are over age 50. Our group has previously demonstrated that skeletal bone loss at the spine and hip is greater and fracture rates higher in HIV-infected than uninfected women after menopause. Our preliminary data also show that HIV-infected women over age 50 had greater alveolar bone loss and a trend for fewer teeth compared to age-matched uninfected controls. However, the separate and/or combined contribution of HIV infection and estrogen deficiency to oral immune activation and the observed alveolar bone loss is uncertain. Therefore, the goal of this study is to determine the extent and progression of periodontal disease in HIV-infected pre- and postmenopausal women on cART and to investigate the contribution of periodontal immune activation to its pathogenesis. We hypothesize that HIV-infection is associated with increased oral immune activation. Loss of the beneficial immune-modulatory effects of estrogen results in an increased inflammatory response to periodontal pathogens, and greater alveolar bone loss after menopause. In order to examine this, we propose three Specific Aims. Aim 1: To determine the impact of HIV infection and menopause on periodontal health in a cross sectional study 240 HIV-infected and uninfected pre- and post- menopausal women. HIV-infected postmenopausal women will have evidence of worsened clinical periodontal parameters, higher GCF inflammatory biomarkers, greater alveolar bone loss and fewer teeth than uninfected post-menopausal women, and both HIV-infected and uninfected pre-menopausal women. Aim 2: To define the oral immune response in HIV-infected and uninfected postmenopausal women during the induction and resolution of gingival inflammation using the experimental gingivitis model. The clinical, GCF and gingival tissue cytokine response during induction of gingivitis will be greater, and the resolution of the inflammatory response more attenuated in HIV-infected post-menopausal women compared to uninfected postmenopausal women or HIV-infected women on hormone replacement therapy. Aim 3: To delineate the clinical, oral immune, and alveolar bone response to standard-of-care periodontal treatment in HIV-infected and uninfected postmenopausal women with moderate periodontitis. Improvements in clinical periodontal parameters, GCF biomarkers, and alveolar bone density and microarchitecture will be less in HIV-infected than uninfected postmenopausal women with moderate periodontitis in response to oral hygiene instruction, scaling/root planing and periodontal maintenance. If proven correct, these studies provide rationale for investigating use of a selective estrogen receptor modulator (SERM), as a safe and testable intervention to prevent periodontal disease progression and/or alveolar bone loss in HIV-infected postmenopausal women.

项目摘要 很少有关于老年艾滋病毒感染者口腔健康的对照研究，特别是 绝经后妇女。这在美国尤其令人担忧，在美国，超过一半的艾滋病毒感染者 个人年龄超过50岁。我们的研究小组先前已经证明， 绝经后感染艾滋病毒的妇女比未感染艾滋病毒的妇女髋关节更大，骨折率更高。我们 初步数据还显示，50岁以上感染艾滋病毒的妇女有更大的牙槽骨损失， 与年龄匹配的未感染对照组相比，然而，单独的和/或组合的 HIV感染和雌激素缺乏对口腔免疫激活和观察到的牙槽骨的贡献 损失不确定。因此，本研究的目的是确定牙周炎的程度和进展， 接受cART治疗的绝经前和绝经后HIV感染妇女的疾病，并调查 牙周免疫激活对其发病机制的影响。我们假设艾滋病毒感染与 增强口服免疫激活。雌激素的有益免疫调节作用的丧失导致 增加对牙周病原体的炎症反应，以及绝经后更大的牙槽骨丢失。 为此，我们提出三个具体目标。目标1：确定艾滋病毒感染的影响， 在一项横断面研究中，240名艾滋病毒感染者和未感染者在绝经前后 更年期妇女HIV感染的绝经后妇女将有临床牙周恶化的证据 参数，更高的GCF炎症生物标志物，更大的牙槽骨丢失和更少的牙齿比未感染 绝经后妇女，以及HIV感染和未感染的绝经前妇女。目标2：定义 诱导期间HIV感染和未感染的绝经后妇女的口服免疫应答， 使用实验性牙龈炎模型解决牙龈炎症。临床、龈沟液和牙龈 在诱导牙龈炎期间的组织细胞因子反应将更大，并且炎症性细胞因子的消退将更快。 与未感染的绝经后妇女相比，HIV感染的绝经后妇女的反应更弱 妇女或接受激素替代疗法的艾滋病毒感染妇女。目的3：描述临床、口腔、 HIV感染者和未感染者对标准牙周治疗的免疫和牙槽骨反应 中度牙周炎的绝经后妇女。临床牙周参数的改善 生物标志物、牙槽骨密度和微结构在HIV感染者中将低于未感染者 中度牙周炎的绝经后妇女对口腔卫生指导的反应，刮治/根治 刨平和牙周维护。如果被证明是正确的，这些研究为研究使用 选择性雌激素受体调节剂（SERM），作为一种安全和可测试的干预措施，以防止牙周炎 HIV感染的绝经后妇女的疾病进展和/或牙槽骨丢失。