NUTRITIONAL REGULATION OF BONE TURNOVER

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Osteoporosis affects approximately 28 million Americans, and is a leading cause of death among older men and women. It has been estimated that in women (50+ years), up to 50% have osteopenia (low bone mass) and 18% have osteoporosis. The risk of osteoporosis increases in women of low body weight or those who have a history of weight loss. In addition, the PIs have shown that moderate weight loss results in bone mobilization and loss in obese women. Moreover, studies of involuntary wt loss show that the magnitude of the bone loss is greater in thinner than heavier women. Hence, these studies will address whether bone mobilization and loss is greater in overweight (body mass index, BMI 25-29.9) than obese (BMI more than 30 ) pre- and post menopausal women during moderate voluntary wt loss. Our data show that an increase in serum parathyroid hormone (PTH) and a decrease in sex hormones may be regulating the rise in bone turnover with wt loss. It is hypothesized that a reduced calcium absorption during caloric restriction is responsible for the rise in PTH. We propose to study the basis for the rise in turnover and PTH during caloric restriction by examining total fractional calcium absorption during wt loss. In obese women, the PIs found that 1.6 mg/d of Ca can suppress the bone mobilization and loss associated with wt loss. However, it is not known if this level of Ca intake can suppress bone mobilization in "thinner" overweight women during caloric restriction. Also, it is possible that the current recommended level of intake (1-1.2 g/d) is not adequate during wt loss based on studies of wt loss induced bone loss by others. Therefore, these studies will examine bone turnover and mass during caloric restriction at 2 levels of Ca intake (adequate or high) to determine optimal levels for wt loss. Importantly, rat studies show that fracture risk is increased with caloric restriction (despite adequate Ca intake). To understand how the quality of bone is altered with wt loss, and whether it is dependent on initial body wt, we will examine the ultrastructural properties of bone after chronic caloric restriction in obese and lean rats. Long-term goals of these studies are to determine nutritional influences on bone which can be applied in the prevention and treatment of osteoporosis.