心血管代谢危险因素在儿童至成年肥胖影响骨量过程中的多重中介效应：基于结构方程模型的生命历程研究

Childhood and adolescence are critical periods for the accrual of bone minerals, and an accumulation of childhood risk factors is associated with the increased risk of osteoporosis in adulthood. Previous studies have demonstrated that childhood obesity is associated with adult bone mass, and the potential mediating effects of cardiovascular disorders on fat-bone relations. However, data regarding the association of long-term burden and trajectory patterns of multiple childhood to adulthood adiposity measures with adult bones is limited. Also, the mediation effects of cardiovascular disorders were sparsely reported..In the present project, we plan to invite all participants from the Beijing Blood Pressure cohort study (baseline in 1987, n=3198, 6-18y; followed 10 times) to have a clinical examination during 2020-2022. During the follow-up survey, bone mass (including bone mineral content and density), body composition, cardiovascular disorders and bone metabolic markers will be measured..A mixed-effect model will be used to investigate the association of curve parameters of adiposity measures from childhood to adulthood, and effects of cumulative burden, long-term variation, and obesity type on adult bone mass. In addition, based on structural functional models, we will use mediation analysis to investigate the indirect effect of cardiovascular disorders on the above associations and its potential mechanisms. The results from this project are expected to provide evidence-based strategies for early prevention of osteoporosis.

儿童青少年时期是骨骼发育的重要阶段，该时期不良因素的积累将增加日后骨质疏松发生风险。前期研究发现儿童肥胖可以预测成年期骨量水平，而心血管代谢状态可能影响肥胖与骨量之间的关联，但既往研究中肥胖指标的选择较为单一，且缺乏对心血管危险因素中介效应的定量评估。.本项目拟于2020-2022年对“北京儿童血压队列”人群（基线：1987年，n=3198，6-18岁；已随访10次）进行临床随访，内容包括骨量（骨矿物质含量与密度）与体成分测量、心血管代谢异常和骨代谢指标的检测等。.本研究拟利用既往获得的肥胖指标（体质指数、皮褶厚度、腰围、体脂百分比），采用混合效应模型多角度评估儿童至成人肥胖的累积效应、变异程度和肥胖类型与成年骨量的关系；同时，采用结构方程模型的多重中介效应分析方法，定量评估心血管代谢危险因素对上述关系中介作用并探讨其潜在机制，以期为骨质疏松的早期防治提供基于流行病学的循证依据。

【背景】儿童青少年时期是骨骼发育的重要阶段，该时期不良因素的积累将增加日后骨密度（BMD）降低甚至骨质疏松的发生风险。【研究内容与方法】本项目通过对北京儿童血压队列的前瞻性随访，评估了儿童至成年体重和体脂肪水平的变化对成年腰椎和全髋BMD的影响，并探讨了心血管代谢异常在儿童体重／体脂肪与成年骨密度关联中的作用。本项目采用双能X线吸收法测量腰椎和全髋BMD，基于儿童期体质指数（BMI）和皮褶厚度（SF）的多时点测量数据，采用混合效应模型构建个体儿童期BMI和SF生长曲线并计算累积负担、累积增长与变异度，采用结构方程模型评估成年心血管代谢异常对儿童BMI/SF→成年BMD的中介/遮掩效应及潜在机制通路。【重要结果及关键数据】1）儿童期BMI和SF的基线水平和累积负担与成年期腰椎和全髋BMD正相关；2）儿童-成年BMI/体脂肪持续偏高组较儿童-成年BMI/体脂肪持续正常组成年腰椎BMD和全髋BMD均增加，但血清维生素D和骨钙素水平偏低；3）在男性中发现，儿童期BMI/SF的增加与成年血压、血糖和血脂指标的增加正相关，其中成年期收缩压和舒张压的升高遮掩了20.8～31.8%的“儿童期BMI/SF→成年腰椎BMD”正向关联；尽管在女性中也发现了儿童期BMI/SF的增加与成年心血管代谢指标的正向关联，但未发现各项新血管代谢危险因素对儿童BMI／SF-成年各部位BMD的中介/遮掩作用。鉴于肥胖、心血管疾病和骨质疏松均为影响我国居民健康的重大公共卫生问题，且低龄化趋势不断加剧。本研究结果强调了干预儿童-成年期（尤其是男性人群）持续性期肥胖以及相关心血管代谢异常可能会减缓未来骨质疏松发生风险，为实现成人慢性病的“前移”与“共防共治”提供重要的流行病学证据。