膳食模式、炎性因子、氧化应激及其相关基因对中老年居民骨质疏松影响的前瞻性研究

Osteoporosis is closely related to nutritional/dietary and genetic factors. In vitro studies showed that oxidative stress and inflammation might play a key role in osteoporotic progress. However, up to date, no large prospective study has examined the overall effect of multiple nutritional/dietary factors and polymorphisms of candidate genes in Chinese populations. To address this issue, we proposed this study based on a community cohort of 2924 Guangzhou residents (50-70y) established during 2007-2009, subjects completed baseline survey and will completed two follow-ups during 2010-2012 (~2000 subjects) and 2013-2015 (~1600 subjects). Nutritional and dietary factors would and will be collected using food frequency questionnaire and blood or urinary analyses. Blood inflammatory cytokines and oxidative/anti-oxidative factors will be determined. Gene polymorphisms related to some inflammatory cytokines and anti-oxidative enzymes will be assessed. Bone mineral density and content at the whole body, lumbar spine and left hip sites were/will be determined using due-energy X-ray densitometry. Speed of sound at the distal 1/3 of radius and middle tibia using an ultrasound device (Omnisense?7000S) were/will be determined. The associations of various nutritional and dietary factors (including but not limited to dietary pattern and dietary quality indices), blood inflammatory cytokines and oxidative/anti-oxidative factors, and the polymorphisms of their related candidate genes with the changes in bone density and risk of osteoporosis will be determined using univariate and multivariate analyses. The validity of dietary patterns and dietary quality indices related to osteoporotic fractures obtained from our previous case-control study will be validated in this study. Predictive model of nutritional/dietary factors and dietary quality index will be established for the prediction of the changes in bone density and risk of osteoporosis, and these results will provide the scientific evidence for making the dietary guideline for the osteoporosis prevention in Chinese. To address the potential mechanism of osteoporosis, path analysis will be used to determine the role of inflammatory cytokines and oxidative/anti-oxidative factors in the causal chain between nutritional/dietary factors and bone density and risk of osteoporosis. Interaction analyses of nutritional/dietary factors and genes will be conducted to identify the susceptibility genes, and these results will form the foundation for individualized measures of osteoporosis prevention via dietary approach.

骨质疏松（OS）与营养膳食及基因密切相关，体外实验提示氧化应激与炎性反应为OS重要潜在原因。然而迄今我国尚无大样本前瞻性研究来验证多种营养因素与多基因对OS的综合影响以及氧化应激与炎性反应在其中所起的作用。为此，本研究拟利用2007-09年建立的2924名50-70岁广州社区居民队列，通过基线及2010-12年与2013-15年两次随访调查共6年的前瞻性研究，分析营养膳食因素、炎性反应及氧化应激水平，炎性因子与抗氧化酶相关基因多态性等因素与骨密度变化及OS发病风险的关联。验证本人前期病例对照研究中所获膳食模式的效度；建立对骨密度变化及OS预测的营养膳食模型及膳食质量评估体系，为制订OS膳食防治指南提供科学依据；检验氧化应激及炎性反应是否为营养膳食因素影响人群骨健康的关键环节以阐明作用机制；通过营养与基因交互作用分析，筛查具有调节作用的相关基因型，为我国OS个体化营养膳食预防提供科学依据。

背景：骨质疏松（OS）与营养膳食及基因密切相关，体外实验提示氧化应激与炎性反应为OS重要潜在原因。然而迄今我国尚无较大样本的前瞻性研究来验证膳食及体内多种氧化及炎性相关的营养因素、氧化应激与炎性反应及其相关基因对OS的综合影响。目的：检验膳食及体内氧化营养物质、营养及炎性水平以及其相关及基因多态性与骨密度及OS的关系。研究内容：本项目基于前期建立的约4100人40-80岁的社区居民队列平台进行研究。该队列于基线（2007-2010年）招募和访问了3216人，第2次（2010-2013年）访问随访了2580人和新招募了870人，第3次（2014-2017年）访问随访了2776人。每次访问调查了研究的一般情况、详细的膳食资料、运动情况和健康相关行为等因素。检测了身高、体重等体格指标。于第2次和第3次访问采用DXA检测了全身、腰椎和股骨的骨密度（BMD）。（3）采用HPLC法检测了基线3120人血清抗氧化营养成分（视黄醇、-和β-胡萝卜素、番茄红素、叶黄素和玉米黄质、β-隐黄质和维生素E，尿酸）；测量了约3200人晨尿中钠和钾浓度，约1840人血清氧化应激指标(SOD、谷胱甘肽、丙二醛和总抗氧化指数，1563人血清炎性因子（MCP1、IL6、IL1、TNF、CRP和sVCAM_1），以及约2000人炎性因子（CRP、IL-6、IL-10、TNFR2、TNFSF11）和SOD2基因等候选基因多态性。结果：与骨密度或OS有保护性关联的因素有：地中海膳食模式，膳食中抗氧化成分（VC、VE、β-胡萝卜素和硒、视黄醇当量，膳食总黄酮及其部分亚类），水果与蔬菜；血液抗氧化营养成分（视黄醇、-胡萝卜素、β-胡萝卜素、番茄红素和β-隐黄质，抗氧化物质总分）和抗氧化代谢物（尿酸）。危害性关联的因素有：尿钠钾比和尿钠，部分炎性因子、血液谷胱甘肽、TNFRSF11B基因的RS3134069位点带有“C”碱基。未发现其他血液氧化应激指标及所测候选基因多态性与骨密度或OS之间的统计学关联。意义：结果提示增加蔬菜水果和膳食中的抗氧化营养成分的摄入，提高血液该类营养物质的含量，降低炎性水平有助于改善骨健康。为制订我国人群OS预防措施提供了科学依据。