Lifespan Psychosocial Profiles and Biological Pathways to Bone Strength

描述（由申请人提供）：骨骼强度，或抗骨折的能力，严重依赖于青年和中年的骨骼健康-年轻时达到的峰值骨量越高，晚年患骨质疏松症的可能性越低。我们假设，在整个生命周期中，社会和心理因素通过影响青年时期达到的峰值强度水平、成年中期骨骼强度的维持以及老年时骨骼强度下降的速度来影响骨骼强度。我们的具体目标是：目标1。确定长期社会心理特征和骨骼强度之间的关联强度。目标2。确定生物系统失调与骨强度之间的关联强度。目标3。确定假定的生物学途径在多大程度上调解长期社会心理特征和骨强度之间的关联。该项目将借鉴三项队列研究（美国中年研究、威斯康辛晚年恢复力研究和麦克阿瑟成功衰老研究），这些研究共有来自24岁及以上成年人的数据，并有9年或更长时间的随访。该项目对本论文进行了独特的优化，因为：1)除了使用标准的骨矿物质密度评估外，我们将扩展骨健康结果，包括骨强度和骨代谢平衡的综合评估。2)我们将确定社会逆境和心理不健康以及社会优势和心理健康对骨骼结果的影响。3)将采用寿命视角，其中长期社会心理影响将被用作成人骨强度的预测因子。这个项目将是第一个全面的尝试，描述在生命过程中（包括早期生活经历）多种社会心理领域对骨骼强度的影响，并确定这些影响施加的生物学途径。它的优势在于三个队列研究中无与伦比的社会心理和生物学评估的广度、深度和纵向方面，三个研究中评估骨骼结果的广度和深度是互补的，随访时间长，年龄跨度大，以及研究问题的新方法：采用更适当的生活历史方法来估计社会心理对骨骼强度的影响，平等考虑社会心理优势和逆境，以及超越通常的骨密度强度度量的创新和全面的骨骼强度评估。公共卫生相关性：该项目将确定骨骼强度（即骨骼抗骨折的能力）如何受到社会经济地位（经济状况和社会地位），社会关系（与父母，配偶，朋友，孩子等）和心理健康（积极方面，如幸福，生活满意度，个人成长和生活目的，以及消极方面，如抑郁和焦虑）的生活史的影响。我们还将研究哪些生物变化可能解释这些对骨骼健康的社会和心理影响。这些对骨强度的影响和生物学机制的发现将意味着我们可以识别和针对骨折高风险人群进行早期筛查和干预，最终目标是减轻骨质疏松症（低骨强度）对生活质量和死亡率的负担。

DESCRIPTION (provided by applicant): Bone strength, or the ability to resist fractures, is critically dependent on bone health in young and middle years - the higher the peak bone mass achieved in younger years, the lower the likelihood of developing osteoporosis in later life. We postulate that social and psychological factors over the lifespan affect bone strength by influencing the level of peak strength achieved in young adulthood, the maintenance of bone strength through middle adulthood, and the rate of decline in older ages. Our specific aims are to: Aim 1. Determine the strength of the association between long-term psychosocial profiles and bone strength. Aim 2. Determine the strength of the association between biological system dysregulation and bone strength. Aim 3. Determine the extent to which the putative biological pathways mediate the associations between long- term psychosocial profiles and bone strength. The project will draw on three cohort studies (Midlife in the United States, the Wisconsin Study of Late Life Resilience, and the MacArthur Study of Successful Aging) that together, have data from adults, ages 24 and up, and have 9 or more years of follow up. This project is uniquely optimized to explore this thesis because: 1) In addition to using standard bone mineral density assessments, we will expand bone health outcomes to include comprehensive assessments of bone strength and bone metabolic balance. 2) We will determine the influence not only of social adversity and psychological ill-health but also of social advantage and psychological well-being on bone outcomes. 3) A lifespan perspective will be adopted, wherein long-term psychosocial influences will be used as predictors of adult bone strength. This project will be the first comprehensive attempt to delineate the influences of multiple psychosocial domains over the life course (including early life experiences) on bone strength, and to identify the biological pathways through which these influences are exerted. Its strengths lie in the unmatched breadth, depth, and longitudinal aspect of psychosocial and biological assessments in the 3 cohort studies, the complementary breadth and depth of bone outcomes assessed across the 3 studies, the lengths of follow up, the large range of ages spanned, and the novel approach to the research questions: the adoption of the more appropriate life- history approach to estimating psychosocial influences on bone strength, the equal consideration given to psychosocial advantage and adversity, and the innovative and comprehensive assessment of bone strength, that goes beyond the usual bone density metric of strength. PUBLIC HEALTH RELEVANCE: This project will determine how bone strength (i.e., bone's ability to resist fracture) is affected by life histories of socioeconomic status (financial condition and social status), social relationships (with parents, spouse, friends, children, etc.), and psychological health (both positive aspects such as happiness, life satisfaction, personal growth and purpose in life, and negative ones, such as depression and anxiety). We will also examine which biological changes might explain these social and psychological effects on bone health. Discovery of these effects on bone strength and the biological mechanisms will mean that we can identify and target those at high risk for fractures for early screening and interventions, with the eventual goal of reducing the burden of osteoporosis (low bone strength) on quality of life and mortality.