NUTRITIONAL REGULATION OF BONE TURNOVER

骨质疏松症影响20%的65岁以上女性人口和 骨质疏松性骨折后有80%的超额死亡率。这个 保持骨量以及达到峰值骨量是 对预防这种疾病状态至关重要。骨质疏松症的风险 低体重女性或有体重史的女性增加 损失。此外，最近的研究表明，在肥胖受试者中，骨骼 在适度减肥后，骨密度(BMD)会下降。这样的发现 由于大量的美国妇女(高达 40%)正在遵循减肥方案的人。在减重过程中， 瘦体重的减少取决于总的卡路里赤字和 蛋白质摄入量。关于其他人的损失的信息有限 蛋白质，如胶原蛋白，它约占 蛋白质存在于体内，主要存在于骨骼中。胶原蛋白的速度很慢 成交额，因此通常被认为是不会在半 饿死了。然而，我们的初步数据显示，情况恰恰相反。我们发现 胶原蛋白的交联率(作为衡量胶原蛋白的指标 成交量(代表骨吸收)在中等体重时翻倍 每天约1100千卡的减量方案。此外，骨量增加 绝经后妇女的吸收率高于绝经前妇女。科目 被建议每天摄入大约800毫克的钙，但他们的实际情况是 平均每天摄入约500毫克。因此，目前还不清楚卡路里是否 和/或钙可能是骨量显著增加的原因 再吸收。拟议的调查将探索营养 中度减重过程中骨转换的调节。具体来说， 我们将检验这一假设，即体重期间低钙摄入量 减少会加快骨骼的周转速度。两个最新开发的 骨转换、胶原交联物排泄和血清指标 骨钙素水平，两者在短期内都是敏感和特异的 研究，将用于检查骨吸收和合成， 分别进行了分析。我们将确定体重减轻的速度， 绝对减重，或钙摄入量的水平会影响 骨转换和骨密度。此外，为了通过以下方式处理这些机制 哪些骨骼的转换被改变，体重减轻和钙的影响 将评估摄入量对骨转换的激素调节作用。 在老鼠模型中的补充研究将被用来进一步探索如何 营养参数调节骨骼成分、组织学和 生物力学特性。重要的是，这些啮齿动物研究将直接 评价骨生化指标与临床指标的关系 健康与骨折发生率的关系。这样做的长期目标是 研究项目是确定营养对软骨的影响 可用于预防和治疗糖尿病的组织 骨质疏松。

Osteoporosis affects 20% of the female population over 65 years of age and there is an 80% excess mortality after an osteoporotic fracture. The preservation of bone mass as well as achieving a peak bone mass are fundamental to preventing this disease state. The risk of osteoporosis increases in women of low body weight or those who have a history of weight loss. In addition, recent studies have shown that in obese subjects, bone mineral density (BMD) decreases after moderate weight loss. Such findings are of particular concern due to the large number of American women (up to 40%) who are following a weight loss regimen. During weight reduction, the loss in lean body mass is dependent on the total caloric deficit and the protein intake. There is limited information about the loss of other proteins, such as collagen, which makes up approximately one third of the protein in the body and is primarily in bone. Collagen has a slow rate of turnover and therefore has generally been thought to be spared during semi- starvation. Our preliminary data, however, suggest the Opposite. We found that the rate of collagen cross-link excretion (as a measure of collagen turnover which represents bone resorption) doubles during a moderate weight loss regimen of about 1100 kcal/d. Moreover, the increased rate of bone resorption was greater in postmenopausal than premenopausal women. Subjects were counseled to consume about 800 mg of calcium/d, however their actual intake averaged about 500 mg/d. Thus, it is not clear whether calories and/or calcium might be responsible for the marked increased in bone resorption. The proposed investigation will explore the nutritional regulation of bone turnover during moderate weight reduction. Specifically, we will test the hypothesis that a low calcium intake during weight reduction accelerates the rate of bone turnover. Two recently developed measures of bone turnover, collagen cross-link excretion and serum osteocalcin levels, both of which are sensitive and specific for short-term studies, will be used to examine bone resorption and synthesis, respectively. We will determine whether the rate of weight loss, the absolute weight loss, or the level of calcium intake influence the rate of bone turnover and BMD. In addition, in order to address the mechanisms by which bone turnover is altered, the effect of weight loss and calcium intake on the hormonal regulators of bone turnover will be assessed. Complementary studies in a rat model will be used to further explore how nutritional parameters regulate bone composition, histology, and biomechanical properties. Importantly, these rodent studies will directly assess the relationship between biochemical and clinical indexes of bone health with the incidence of bone fractures. The long-term goals of this research program are to determine nutritional influences on cartilaginous tissues which can be applied in the prevention and treatment of osteoporosis.