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Grant Abstract

Grant Number: 5R01AR053701-03

Abstract: 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.

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