Teenage girls with anorexia nervosa (AN) are at risk for low bone density and low rates of
bone accrual, raising concerns regarding acquisition of peak bone mass, an important
determinant of future bone health and fracture risk. Important factors contributing to low
bone density in AN include low levels of estrogen and insulin like growth factor-1 (IGF-1).
While estrogen is important for preventing bone loss, IGF-1 is important for optimizing bone
formation. We have shown in a previous study that replacement of estrogen is effective in
increasing bone density in teenage girls with AN; however, this increase in bone density
remains lower than that seen in normal-weight controls over the same duration, and residual
deficits persist. Importantly, the impact of administering replacement doses of IGF-1 with
estrogen replacement has not been studied in teenagers with AN.
This study will examine the impact of administering recombinant human (rh) insulin like
growth factor-1 (rhIGF-1) with estrogen (to mimic pubertal levels of these hormones) versus
administration of estrogen alone on bone metabolism in adolescent girls with anorexia nervosa
(AN).
One aim of this proposal is to investigate whether co-administration of insulin like growth
factor-1 (rhIGF-1) with physiologic estradiol replacement to adolescent girls with AN will
increase BMD (bone mineral density) more than estrogen monotherapy, and whether bone mass
will approach that seen in healthy adolescent girls. An additional aim is to determine
whether co-administration of rhIGF-1 with estradiol to mimic the normal pubertal milieu
stimulates bone formation through an IGF-1 mediated anabolic effect, increases bone density
to a greater extent than estrogen monotherapy, and improves bone mass accrual to approach
that in healthy controls. The impact of rhIGF-1 +estradiol versus estradiol alone on bone
microarchitecture will also be assessed.