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 关于老年艾滋病毒感染者的口腔健康的对照研究很少，尤其是 绝经后妇女。在美国特别关注的是，其中超过一半的艾滋病毒感染者 个人已超过50岁。我们的小组以前已经证明了脊柱的骨骼骨质流失， HIV感染的HIP率高，而更年期后的未感染妇女的骨折率高。我们的 初步数据还表明，50岁以上的艾滋病毒感染的妇女具有更大的肺泡骨质流失和趋势 与年龄匹配的未感染对照相比，牙齿较少。但是，单独和/或组合 HIV感染和雌激素缺乏对口服免疫激活的贡献以及观察到的肺泡骨 损失不确定。因此，这项研究的目的是确定牙周的程度和进展 hiv感染的艾滋病毒前和绝经后妇女的疾病，并调查 牙周免疫激活其发病机理。我们假设HIV感染与 口服免疫激活增加。雌激素的有益免疫调节作用的丧失导致 炎症对牙周病原体的炎症反应增加，更年期后的肺泡骨质损失更大。 为了检查这一点，我们提出了三个具体目标。目标1：确定艾滋病毒感染的影响和 一项横断面研究的牙周健康的更年期 更年期的妇女。艾滋病毒感染的绝经后妇女将有临床牙周恶化恶化的证据 参数，GCF较高的炎症生物标志物，牙槽骨质流失更大，牙齿少于未感染 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 在诱导期间，艾滋病毒感染和未感染的绝经后妇女的口服免疫反应 使用实验性牙龈炎模型解决牙龈炎症。临床，GCF和牙龈 诱导牙龈炎期间的组织细胞因子反应将更大，并且炎症的分辨率 与未感染的绝经后的艾滋病毒感染后妇女的反应更为衰减 妇女或感染HIV的妇女接受激素替代疗法。目标3：描绘临床，口腔 免疫和肺泡骨对艾滋病毒感染和未感染的牙周治疗的牙齿骨反应 绝经后妇女中度牙周炎。临床牙周参数的改进，GCF 生物标志物，牙槽骨密度和微体系结构的HIV感染将少于未感染 响应口服卫生指导，缩放/根的绝经后妇女 计划和牙周维护。如果被证明是正确的，这些研究为调查使用的使用提供了理由 选择性雌激素受体调节剂（SERM），作为一种安全且可测试的干预措施，以防止牙周 疾病进展和/或肺泡的绝经后妇女的肺泡损失。