Background: While physiologic
estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with
anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14−25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral
progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite
element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were −1.13 (−1.58, −0.38) in AN-E+ vs. 0.08 (−0.40, 0.84) in HC (p < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic
estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue
mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic
estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue
mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for
estrogen replacement effectively mimics the effects of endogenous
estrogen on bone structure and estimated strength.