IMPACT OF A PROTEIN SUPPLEMENT ON BONE MASS IN OLDER WOMEN

描述（由申请人提供）：骨质疏松症和骨质减少是影响超过4400万美国人的主要健康问题，主要是老年妇女。营养在骨骼健康中起着至关重要的作用，但其在骨丢失的发病机制和预防中的作用尚不完全清楚。我们已经发现，膳食蛋白质是钙稳态的主要调节剂，但其对骨骼健康的影响仍然存在争议。 已知增加膳食蛋白质会增加尿钙排泄，并且广泛持有的观点是，这种额外的钙部分来自骨骼。然而，最近的流行病学研究发现，较高的蛋白质摄入量与较高（而不是较低）的骨矿物质密度和较低（而不是较高）的骨丢失率相关。使用钙动力学方法，我们发现当健康女性的膳食蛋白质增加时，肠道钙吸收显著增加，并且几乎占尿钙增加的全部。此外，当女性食用高蛋白饮食时，来自骨骼的尿钙百分比降低，骨转换也略有降低。我们假设，蛋白质补充剂添加到习惯性低正常蛋白质饮食的健康老年妇女的饮食中，将改善骨健康和骨代谢的激素指数（与安慰剂对照相比）。 为了验证这一假设，我们将使用耶鲁大学和康涅狄格大学健康中心的综合临床研究中心进行一项为期18个月的双盲，安慰剂对照，膳食蛋白补充剂试验。将从康涅狄格州中部招募200名至少60岁的健康女性。受试者将入组自然摄入适度低（但足够）水平的膳食蛋白（0.6-1 g/kg）。（大约30-40%的美国妇女超过60岁属于这一组）。基线测量后，受试者将随机接受安慰剂（麦芽糊精）或40 g蛋白质补充剂，持续18个月。本试验的主要结局指标是通过DEXA评估的脊柱骨密度。次要结局将包括通过QCT测量的脊柱和髋关节BMD、矿物质稳态和骨转换的血清指标以及体能评估。这些研究将更好地为最佳骨骼健康提供膳食蛋白质建议，如果我们的假设是正确的，则为年龄相关的骨质流失提供新的治疗方法。

DESCRIPTION (provided by applicant): Osteoporosis and osteopenia are major health problems affecting over 44 million Americans, primarily older women. Nutrition, plays a critical role in bone health but its role in the pathogenesis and prevention of bone loss is incompletely understood. We have found that dietary protein is a major regulator of calcium homeostasis, yet its impact on skeletal health remains controversial. Increasing dietary protein is known to increase urinary calcium excretion and a widely held view is that this extra calcium originates, in part, from bone. However, recent epidemiologic studies have found that higher protein intakes are associated with higher (not lower) bone mineral density and lower (not higher) rates of bone loss. Using calcium kinetic methodology, we have found that when dietary protein is increased in healthy women, intestinal calcium absorption increases significantly and accounts for almost all of the increase in urinary calcium. Further, when women consumed a high protein diet, the percentage of urinary calcium originating from bone is reduced and bone turnover is also slightly reduced. We hypothesize that a protein supplement added to the diets of healthy older women with habitually a low-normal protein diet, will improve bone health and hormonal indices of bone metabolism (in comparison to a placebo control). To test this hypothesis, we will conduct an 18-month, double-blind, placebo-controlled, dietary protein supplementation trial using the General Clinical Research Centers at Yale University and the University of Connecticut Health Center. Two hundred healthy women at least 60 yrs. of age will be recruited from central Connecticut. Subjects will be enrolled who naturally consume a moderately low (yet adequate) level of dietary protein (0.6-1 g/kg). (Approximately 30-40% of US women over the age of 60 y fall into this group). After baseline measurements, subjects will be randomized to receive either a placebo (maltodextrin) or a 40 g protein supplement for 18 months. The primary outcome measure in this trial is spinal bone density as assessed by DEXA. Secondary outcomes will include BMD at the spine and hip measured by QCT, serum measures of mineral homeostasis and bone turnover, and an assessment of physical performance. These studies will better inform dietary protein recommendations for optimal skeletal health and, if our hypothesis is correct, provide a new therapeutic approach to age-related bone loss.