Fluoride & Other Factors in Childhood and Adolescent Bone Development

描述（由申请人提供）：摘要对于儿童和青少年时期可改变和不可改变因素对骨骼发育的影响，以及早期骨骼健康对常见成人疾病（如骨质疏松症和骨折）风险的影响，我们的理解仍有许多空白。很少有儿科研究纵向评估骨累积和骨几何形状的变化。即使是体力活动和众所周知的饮食因素，如氟化物、钙和维生素D，也没有大规模的儿童队列来描述从出生到青春期后期的骨骼发育。爱荷华州骨骼发育研究（IBDS）已进入第11个年头，是一项纵向队列调查，研究行为、选定的身体特征和遗传因素对骨骼发育的影响。我们的目标是通过将我们的评估扩展到青春期后期（15岁和17岁）来增加对儿童/青少年骨骼发育和骨骼健康决定因素的理解，从而允许从5岁开始对骨骼发育进行全面评估。据估计，到17岁时，男孩和女孩的骨量分别达到总峰值的86%和93%。我们在5岁（n=470）、8岁（n=539）和11岁（n=483）的队列中使用双能x线吸收仪（DXA）和外周定量计算机断层扫描（pQCT）评估了骨骼测量；13岁的评估几乎完成（n=466）；15岁开始进行检查（n=111）。从出生开始就收集氟化物摄入量和饮食数据；身体活动评估继续通过加速度计和问卷；与骨矿化、基质结构和生长有关的候选基因也得到了研究。我们还对队列成员的父母进行了类似的解释和骨骼结果测量。在这次更新中，我们将收集15岁和17岁的骨骼、氟化物摄入量和饮食、酒精、烟草、身体活动、成熟度和身体成分数据。我们建议：1)评估和确定氟摄入对17岁时骨量和几何形状以及5 - 17岁纵向骨发育的时间特异性和累积效应。2)评估和定义行为（饮食模式、饮酒、吸烟和体育活动）和身体属性（性别、生长发育、身体组成和肌肉力量）对17岁时骨量和几何形状以及5岁至17岁纵向骨发育的时间特异性和累积效应。3)基于上述目标1和2所获得的结果，评估和定义行为、身体属性和遗传因素以及相互作用效应（环境x环境基因4环境和基因4基因）对17岁时骨量和几何形状以及5岁至17岁纵向骨骼发育的时间特异性和累积效应。该队列的持续随访将导致对氟化物和这些其他因素对骨骼发育的相对重要性及其最大影响的时间的重要见解，从而提高我们对优化骨骼健康的最佳策略的理解。公共卫生相关性：虽然骨质疏松症通常被认为是成年人的疾病，但人们越来越认识到儿童和青少年时期充足的骨质积累对于预防以后的骨质疾病的重要性。我们对儿童/青少年时期骨骼发育的理解仍有许多空白，包括可改变和不可改变因素的影响。爱荷华骨发育研究队列持续随访至17岁，提供了一个独特的机会来评估氟化物和其他饮食、身体活动、性成熟、身体组成和遗传因素对骨发育和累积的相对重要性。研究结果将提高我们对优化骨骼健康和预防未来骨骼疾病的最佳策略的理解。

DESCRIPTION (provided by applicant): Abstract A number of gaps remain in our understanding of the effects of modifiable and non-modifiable factors on bone development during childhood and adolescence, and the impact of early bone health on the risk for common adult conditions such as osteoporosis and bone fractures. Few pediatric studies have longitudinally assessed bone accrual and changes in bone geometry. Even for physical activity and well-known dietary factors such as fluoride, calcium, and vitamin D, no large cohort of children has been followed to describe bone development from birth through later adolescence. The Iowa Bone Development Study (IBDS), in its 11th year, is a longitudinal cohort investigation of the effects of behaviors, selected physical attributes, and genetic factors on bone development. Our goal is to increase the understanding of childhood/adolescent bone development and determinants of bone health by extending our assessments into later adolescence (ages 15 and 17), thus allowing a comprehensive assessment of bone development from age 5. It has been estimated that by age 17, approximately 86 and 93% of total peak bone mass has accrued for boys and girls, respectively. We have assessed bone measures using dual energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) for our cohort at 5 (n=470), 8 (n=539), and 11 (n=483) years of age; age 13 assessments are nearly complete (n=466 to date); and age 15 exams have been initiated (n=111). Fluoride intake and dietary data have been collected from birth; physical activity assessment continues by accelerometry and questionnaire; and candidate genes involved in bone mineralization, matrix structure, and growth have been studied. We also have analogous explanatory and bone outcome measures for parents of cohort members. In this renewal, we will collect age 15 and 17 bone, fluoride intake and dietary, alcohol, tobacco, physical activity, maturity, and body composition data. We propose to: 1) Assess and define the time-specific and cumulative effects of fluoride intake on bone mass and geometry at age 17 and bone development longitudinally from age 5 to age 17. 2) Assess and define the time-specific and cumulative effects of behaviors (dietary patterns, alcohol intake, tobacco use, and physical activity) and physical attributes (gender, growth and development, body composition, and muscle strength) on bone mass and geometry at age 17 and bone development longitudinally from age 5 to age 17. and 3) Assess and define the time-specific and cumulative effects of behaviors, physical attributes, and genetic factors, as well as interaction effects (environment x environment gene 4 environment, and gene 4 gene), on bone mass and geometry at age 17 and bone development longitudinally from age 5 to age 17, building on the results obtained by addressing aims #1 and 2 above. Continued follow-up of this cohort will lead to major insights into the relative importance of fluoride and these other factors on bone development and the times of their greatest impact, thus improving our understanding of the best strategies to optimize skeletal health. PUBLIC HEALTH RELEVANCE: Although osteoporosis is generally considered a disease of adults, there is increased recognition of the importance of adequate bone accrual in childhood and adolescence for prevention of bone disease later in life. Many gaps remain in our understanding of how bone develops during childhood/adolescence, including the effects of modifiable and non-modifiable factors. Continued follow-up of the Iowa Bone Development Study cohort to age 17 provides a unique opportunity to assess the relative importance of fluoride and other dietary, physical activity, sexual maturation, body composition, and genetic factors on bone development and accrual. Findings will improve our understanding of the best strategies to optimize skeletal health and prevent future bone disease.