Nutritional Regulation of bone

描述（由申请人提供）：骨质疏松和肥胖都是重要的公共卫生问题。体重（wt）的减少是建议减少肥胖相关的并发症，但会导致骨质流失（即使有足够的钙摄入），绝经后妇女。虽然一些研究已经开始讨论热量限制（CR）期间饮食成分对代谢参数的影响，但实际上对其对骨量和质量的作用一无所知。这一建议将解决几个主要的差距，我们的知识关于饮食组成在体重损失期间，因为它影响骨骼健康。我们将特别讨论膳食蛋白质（pro）水平，以及维生素D （vit D）在钙吸收中的作用。在wt稳定的成年人中有证据表明，较高的饮食pro增加了胰岛素样生长因子-1和钙的吸收，并可能有助于提高骨量和降低骨折风险。相反，高的pro摄入量也被证明会增加酸负荷，导致高钙尿和潜在的骨质流失。目前尚不清楚高pro饮食如何影响CR期间的骨密度或骨质量。此外，在胃旁路手术（GB）后严重的wt丢失期间，pro摄入水平可能尤其重要，因为通常在手术后缺乏pro摄入（而不是Ca和维生素D），可能会加剧骨质流失。此外，由于血清甲状旁腺激素（PTH）解释了CR期间观察到的钙吸收减少的部分原因（400IU维生素D /天），因此通过饮食增加血清25-羟基维生素D水平可能会减弱血清甲状旁腺激素（PTH）并增强真正的部分钙吸收（TFCA）。本研究的目的是：1)在控制正常钙和维生素D摄入的情况下，研究与标准高碳水化合物（HC）减肥饮食相比，高pro饮食如何影响绝经后妇女的骨转换、骨量和骨质量；2)在严重wt丢失的GB妇女中检查正常和较高pro摄入量的骨骼；3)确定高维生素D摄入量（1200 lU/ D）是否会增加绝经后妇女在标准HC减脂饮食中的TFCA。总的来说，近%的定期节食的美国人需要预防骨质流失的基本建议。老年人口将在短短几十年内翻一番，而wt损失是骨质流失、骨折风险和最终死亡率的主要决定因素。因此，这些研究对于确定饮食成分如何预防老年人骨质流失的重要性既重要又及时。

DESCRIPTION (provided by applicant): Osteoporosis and obesity are both important public health problems. Weight (wt) reduction is recommended to reduce obesity-related complications, but induces bone loss (even with adequate Ca intake) in post- menopausal women. Although several studies have begun to address the effects of diet composition during caloric restriction (CR) on metabolic parameters, virtually nothing is known its role on bone mass and quality. This proposal will address several major gaps in our knowledge concerning dietary composition during wt loss as it impacts bone health. In particular we will address dietary protein (pro) levels, and the role of vitamin D (vit D) in Ca absorption. Evidence in wt-stable adults shows that higher dietary pro increases insulin-like growth factor-1 and Ca absorption and may contribute to a higher bone mass and reduced fracture risk. In contrast, a high pro intake has also been shown to increase the acid load, leading to hypercalciuria, and potential bone loss. It is currently not known how a high pro diet affects bone density or quality during CR. In addition, the level of pro intake may be especially important during severe wt loss after gastric bypass surgery (GB), because of the deficient pro intake (rather than Ca and vit D) that typically follows the procedure that may exacerbate bone loss. Furthermore, because serum parathyroid hormone (PTH) explains part of the reduction in Ca absorption observed during CR (400IU vit D /day), it is possible that increasing serum 25-hydroxy-vit D levels through diet will attenuate serum PTH and enhance true fractional Ca absorption (TFCA). The aims of this proposal are: 1) to examine how a high-pro diet compared to a standard high-carbohydrate (HC) wt loss diet affects bone turnover, mass and quality in post- menopausal women, while controlling for normal Ca and vit D intake; 2) to examine bone with usual and higher pro intake during severe wt loss in women with GB; and 3) to determine if a high vit D intake (1200 lU/d) can increase TFCA in postmenopausal women during a standard HC wt-loss diet. Overall, rationale recommendations for the prevention of bone loss are needed for nearly % of the US population that is regularly dieting. The older population is going to double in only a few decades, and wt loss is a major determinant of bone loss, fracture risk, and ultimately mortality. Thus, the importance of these studies for identifying how diet composition can prevent bone loss in the older population is both critical and timely.