Anorexia nervosa is an increasingly common disorder in adolescent girls with a prevalence of 0.2 to 1.0% in Western societies. Adolescence is a critical time for bone mineral accretion as between 60-90% of peak bone mass is established during this time and peak bone mass is a major determinant of osteoporosis and fracture risk throughout life. Osteopenia is a complication of anorexia nervosa in more than half of affected women and is associated with clinical fractures. Little is known about the pathogenesis of osteopenia in adolescents and there are no established therapies to maximize peak bone mass and prevent fractures. Although anorexia nervosa is associated with profound estrogen deficiency and estrogen is known to be a critical factor in bone development, the effects of estrogen administration have not been investigated in adolescents with this disorder. In the current proposal, disordered bone metabolism and body composition will be investigated and the effects of anorexia nervosa on growth hormone and nutritionally dependent endpoints will be examined. In the first Specific Aim we will prospectively investigate the disordered state of bone mineral accretion in pubertal adolescents with anorexia nervosa. Predictive factors leading to low bone density will be studied as well as the effect of anorexia nervosa on linear growth, predicted height and growth hormone secretion. In the second Aim we will investigate the hypothesis that estrogen administration given to adolescents with anorexia nervosa, in a bone-age, dose-dependent manner will increase bone density during the development of peak bone mass, stimulate IGF-I levels and stimulate linear growth in girls with immature bone age. These studies will be essential in developing strategies to address the profound loss of bone accrual seen in this large population of adolescent girls at high fracture risk.
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