NUTRITIONAL REGULATION OF BONE TURNOVER

骨转换的营养调节

• 批准号: 2053599
• 负责人: Sue Amy Shapses
• 金额: $ 12.37万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2053599
• 关键词: biomarker; biomechanics; blood chemistry; bone density; bone fracture; caloric dietary content; dietary calcium; dietary supplements; estrogens; female; hormone regulation /control mechanism; human subject; laboratory rat; nutrition related tag; osteocalcin; parathyroid hormones; photon absorptiometry; physiologic bone resorption; postmenopause; pyridine; reducing diet; starvation; urinalysis; weight loss; young adult human (21-34)

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.

骨质疏松症影响20%的65岁以上女性人口， 有80%的额外死亡率后，一个脊椎骨骨折。的 保持骨量以及达到峰值骨量是 这是预防这种疾病的根本。骨质疏松症的风险 低体重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， 中度体重减轻后，矿物质密度（BMD）降低。这些发现 由于大量的美国妇女（最多 40%）正在遵循减肥方案。在减肥过程中， 瘦体重的减少取决于总热量不足和 蛋白质摄入量关于其他损失的信息有限。 蛋白质，如胶原蛋白，它构成了大约三分之一的 蛋白质在体内，主要存在于骨骼中。胶原蛋白具有缓慢的 因此，一般认为，在半年度期间， 饥饿然而，我们的初步数据却恰恰相反。我们发现 胶原蛋白交联排泄率（作为胶原蛋白的量度 代表骨吸收的骨转换）在中等体重期间加倍 约1100千卡/天的损失方案。此外，增加的骨密度 绝经后妇女的骨吸收大于绝经前妇女。科目 被建议每天摄入约800毫克的钙，但他们的实际摄入量 平均摄入量约为500 mg/d。因此，尚不清楚卡路里是否 和/或钙可能是造成骨中 再吸收这项研究将探讨营养 在适度减肥期间调节骨转换。具体地说， 我们将检验一个假设，即在体重增加过程中低钙摄入量 减少加速骨转换的速率。最近开发的两个 测量骨转换、胶原交联排泄和血清 骨钙素水平，这两个都是敏感和具体的短期 研究，将用于检查骨吸收和合成， 分别我们将确定是否减肥的速度， 绝对体重减轻，或钙摄入量的水平会影响 骨转换和BMD。此外，为了解决机制问题， 其中骨转换被改变，减肥和钙的影响 将评估摄入量对骨转换激素调节剂的影响。 在大鼠模型中的补充研究将用于进一步探索如何 营养参数调节骨成分、组织学和 生物力学性能重要的是，这些啮齿动物研究将直接 评估骨生化指标与临床指标之间的关系 健康与骨折的发生率有关。长期目标是 研究计划是确定营养对软骨的影响， 可应用于预防和治疗 骨质疏松