膳食及体内黄酮类化合物与中老年女性髋骨骨折的关系及机制研究

Hip fracture (HF) is the most serious consequence of osteoporosis. Studies in vitro and in vivo indicated that several subclasses of flavonoids could modulate the bone metabolisms via suppressing inflammation and oxidative stress. Except for isoflavone, only a few human studies have performed to explore the association between other subclasses of flavonoids and bone mineral density. Based on a large cross-sectional study, we have found that women consumed higher total flavonoids and its several subtypes like flavonols and flavanols exhibited better bone mineral status. However, up to now, there are no studies have exerted to investigate the association between different subclasses of flavonoids consumption and HF. Additionally, no study has detected whether the potential effects of flavonoids on HF might be attributed to their anti-inflammation and antioxidant ability. Different subclasses of flavonoids are varied in their bioavailability and bioefficacy. Thus, blood and urinary concentrations of flavonoids may reflect intake levels of these compounds much more accurately compared with dietary assessment. It is uncertain that whether circulating flavonoids are correlated with the risk of HF. To address those issues, we proposed a 1:1 case-control study, including 600 pairs of new cases of HF and community-derived controls, to obtain the information of dietary intakes and physical activities et al using questionnaire, to collect blood and 24-h urine samples. The circulating level (blood and 24-h urine) of selected flavonoids (Flavanols, Flavonols, Flavanones, Isoflavone) will be measured using liquid chromatography-tandem mass spectrometry. Dietary consumption of flavonoids and its subclasses will be assessed. Measurement of inflammatory cytokines and oxidative damage markers will be performed. Univariate and multivariate conditional logistic regressions analysis will be applied to test the relationship between different level and different subclasses of flavonoids and the risk of HF. To address the potential mechanism of HF, path analysis will be used to determine the role of inflammatory cytokines and markers of oxidative damage in the causal chain between flavonoids and the risk of HF. Those results will provide the scientific evidence for preventing HF via dietary approach or developing new nutritional products for HF.

髋骨骨折（HF）是骨质疏松最重要的临床结局。细胞和动物研究提示黄酮类化合物（FV）可调节骨代谢，本人亦发现膳食FV越高人体骨密度越好。但迄今尚无研究探讨和比较不同种类FV 摄入水平对HF的影响，也无报道其机制是否与抑制炎症反应及氧化应激有关。本研究拟采用病例对照设计，招募600例新发HF女性病例和600例匹配的社区对照，收集膳食资料并计算FV摄入量，检测空腹血及24小时尿中黄烷醇，黄酮醇，黄烷酮与异黄酮等FV的含量，及炎性因子和氧化应激水平，分析膳食和体内FV、炎性因子、氧化应激水平与HF间的关联，拟解答下列关键问题：膳食及体内FV是否与HF有关？如有，与哪种FV关联较强？FV是否是通过降低炎性反应及氧化应激来降低HF风险？研究结果在理论上可丰富和补充FV的生物学作用及作用机制；在实践上可为制订HF的膳食防治措施及开发FV类相关功能产品奠定科学依据，因此，具有理论和实践的双重价值。

髋部骨折(HF)是骨质疏松症最严重的临床结局。细胞及动物模型显示，黄酮类化合物（FV)可通过其很好的抗炎及抗氧化效应延缓骨量减少，然而人群研究甚少；且FV种类繁多，极有必要阐明不同的黄酮类化合物效应是否有所差异。本研究采用病例对照设计，招募1050例新发HF病例和1050例匹配的社区对照，用含79个条目的膳食频率问卷收集膳食资料并计算膳食营养素摄入量，并超出原计划对对照组研究对象进行骨密度进行测量并随访；采用液相色谱-质谱联用法检测尿液大豆苷元（Daidzein）；染料木素（Genistein）；柚皮素（Naringenin）；异鼠李素（Isorhamnetin）；山柰酚（Kaempferol）；槲皮素（Quercetin）；表儿茶素（Epicatechin）含量，测定血液IL1-β，TNF-α及氧化应激水平指标（GSH，TAC）。研究结果显示矫正混杂因素后，较高的膳食炎症指数，较低的膳食总黄酮及不同亚类黄酮类化合物的摄入是HF及的危险因素；较高的尿液表儿茶素水平对骨骼具有保护作用；而较高的异鼠李素及槲皮素对个别部位BMD流失具有有害性关联。血液较高水平的IL1-β，TNF-α是骨健康的危险因素，但其不能解释黄酮类化合物对骨健康的效应。本项目研究结果在理论上可丰富和补充FV的生物学作用及作用机制；在实践上可为制订HF的膳食防治措施及开发FV类相关功能产品奠定科学依据，具有理论和实践的双重价值。本项目资助下已发表4 SCI论文，另有3篇论文在投稿中。