Bone Accrual and Hormones in Response to Lactation

描述(由申请人提供)： 这笔职业发展补助金将为候选人实现她的目标做好准备，即成为一名独立资助的院士，致力于研究绝经前骨骼健康的决定因素，以及将保持年轻女性健康骨骼重塑的预防性努力。本申请中提出的这项新颖的研究得益于一个强大的、多学科的高级研究团队的指导，并将哺乳作为雌激素缺乏期间骨丢失的生理模型，并在断奶后随后恢复骨密度。通过对哺乳期的研究，有机会确定骨量重塑和形成的最佳条件。这一建议的总体假设是：1)骨骼对哺乳期的反应是通过一种或多种合成激素的形成以及雌二醇的恢复来调节的；以及2)这些事件导致骨骼的数量(BMD)和质量(骨骼几何)变化，这可能为以后的女性提供结构优势。在目标1中，将在产后妇女中进行一项前瞻性队列研究，以评估骨密度丢失和恢复的激素决定因素，并使用双能X射线吸收法(DXA)评估骨结构参数。目标1将利用一个大型的、建立良好的临床队列，在UNC-CH(PIN研究)招募孕妇。在目标2中，将使用1978年首次收集的队列(NIEHS-绝经时间研究)来研究哺乳期与晚年骨密度之间的关系。这一群体的优势是在过去有很好的哺乳史记录。 除了指导研究外，候选人还将接受流行病学、生物统计学和结果研究方面的正式高级培训，这将使她能够巩固自己在临床研究和流行病学原理方面的基础。该应用程序得益于内分泌科、综合临床研究中心和北卡罗来纳大学公共卫生学院提供的强大的研究密集型环境和资源，以及确保能够接触到这两个大型、成熟的队列的临床人群。将受保护的时间用于指导研究和教学是理想的，并将使她发展经验、技能和初步数据，以发展为一名独立的临床科学家。

DESCRIPTION (provided by applicant): This career development grant will prepare the candidate to pursue her goal of becoming an independently funded academician devoted to investigating pre- menopausal determinants of bone health and the preventive efforts that will maintain healthy bone remodeling in young women. The novel research proposed in this application benefits from mentoring by a strong, multidisciplinary team of senior investigators and uses lactation as a physiological model of bone loss during estrogen deficiency and subsequent recovery of bone density after weaning. By studying lactation, there is the opportunity to identify optimal conditions for bone mass remodeling and formation. The overall hypotheses of this proposal are that 1) the skeletal response to lactation is mediated through the elaboration of one or more anabolic hormones in conjunction with the return of adequate estradiol production; and 2) these events lead to both quantitative (BMD) and qualitative (bone geometry) changes in the skeleton that may confer a structural advantage for women later in life. In aim 1, a prospective cohort study will be conducted in postpartum women to assess hormonal determinants of bone density losses and recovery and an assessment of bone structural parameters usingdual-energy x-ray absorptiometry (DXA). Aim 1 will utilize a large, well-established clinical cohort enrolling pregnant women at UNC-CH (PIN Study). In aim 2, the association of lactation duration and bone mineral density later in life will be examined using a cohort originally assembled in 1978 (NIEHS - Timing of Menopause Study). This cohort has the advantage of having lactation history well documented in the past. In addition to the mentored research, the candidate will undertake formal advanced training in epidemiology, biostatistics and outcomes research that will allow her to solidify her foundation in clinical research and epidemiological principles. The application benefits from the robust, research-intensive environment and resources provided by the Division of Endocrinology, the General Clinical Research Center, and the School of Public Health at UNC as well as assured access to the clinical populations of the two large, well-established cohorts. The combination of protected time for mentored research and didactics are ideal and will allow her to develop the experience, skills and preliminary data to develop as an independent clinician-scientist.