Estrogen - Bone Blood Flow and Bone Mechanical Properties

Fleming, John

Abstract

Osteoporosis and the high incidence of bone fractures among women is a major public health issue. Among aged women, the rate of bone lose has been correlated with a decline in blood flow, suggesting that a decrease in bone blood flow contributes to the development of osteoporosis. This study will test the hypothesis that the decrease in bone blood flow with age is due to a dysfunctional vascular endothelium resulting from a decrease in estrogen levels. We propose the following: as estrogen level among females decrease with age, bone vascular endothelial cell function decreases, bone arterioles become more reactive to physiologic constrictor stimuli resulting in a decrease in bone blood flow and subsequently a decrease in bone density. This hypothesis will be tested by assessing bone vascular endothelial cell function among young (2 months), middle aged (5 months) and old (15 months) female rats, either treated or untreated with estrogen. Bone vascular endothelial cell function will be correlated with: (1) basal bone blood flow, (2) bone blood vessel vasoconstrictor reactivity, (3) plasma estrogen levels, and (4) bone biomechanical properties.
Specific Aim #1 is to assess bone vascular endothelial cell function among female rats at three ages (2, 5 and 15 months).
Specific Aim #2 is to assess the vasoconstrictor reactivity of bone arterioles from female rats at the same three ages, before and after removing the endothelium to evaluate the ability of the endothelium to produce dilator products in response to constrictor agonists.
Specific Aim #3 is to determine if estrogen treatment will preserve vascular endothelial cell function, basal bone blood flow, vascular reactivity and bone mechanical properties among aging female rats.
Specific Aim #4 is to determine if estrogen improves endothelial cell function by increasing the expression of nitric oxide synthase in the bone vasculature.