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Objective Transdermal, but not oral, estrogen replacement improves bone mineral density (BMD) in athletes with oligoamenorrhea (OA). Our objective was to determine mechanisms that may explain the impact of route of estrogen administration on bone outcomes. Methods Seventy-three participants with OA between 14 and 25 years old received (i) a 17β-estradiol transdermal patch continuously with cyclic oral micronized progesterone (PATCH), (ii) a combined ethinyl estradiol and desogestrel pill (PILL), or (iii) no estrogen/progesterone (NONE) for 12 months. We evaluated morning fasting levels of a marker of bone formation [N-terminal propeptide of type 1 procollagen (P1NP)], a marker of bone resorption (N-telopeptide), IGF-1, insulinlike growth factor binding protein 3, total testosterone, estradiol, SHBG, sclerostin, preadipocyte factor-1 (Pref-1), brain-derived neurotrophic factor (BDNF), calcium, 25(OH) vitamin D, and PTH levels at baseline and 12 months. Results Groups did not differ for age, weight, exercise activity, or markers of bone formation at baseline. Over 12 months, P1NP decreased the most in the PILL group (P = 0.03) associated with a decrease in IGF-1 levels (r = 0.37; P = 0.003). Sclerostin, Pref-1, and BDNF decreased in the PATCH group over 12 months. PATCH had the greatest increases in estradiol (P ≤ 0.0001), and estradiol increases were associated with increases in bone density. Conclusion Transdermal 17β-estradiol given over 12 months does not cause the decrease in IGF-1 observed with oral ethinyl estradiol. It also leads to decreases in sclerostin, Pref-1, and BDNF, which may mediate the beneficial effects of estrogen.

AN is deleterious to bone at all sites and both bone compartments. A high stress fracture rate in OAs, who have comparable WBLH and hip aBMD measures to controls, indicates that BMD in these women may need to be even higher to avoid fractures.

Background: Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normalweight controls. Whereas bone parameters that increase fracture risk are well characterized in anorexia nervosa (AN), the other end of nutritional spectrum, these data are lacking in adolescents with obesity. Objective: Our objective was to compare bone parameters in adolescent girls across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. Methods: We assessed bone endpoints in 153 adolescent girls 14-21 years old: 50 OB, 48 controls and 55 AN. We used (i) DXA to assess aBMD at the lumbar spine, proximal femur and whole body, and body composition, (ii) high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and (iii) finite element

Context Sleeve gastrectomy (SG), the most common metabolic and bariatric surgery in adolescents, is associated with bone loss. Marrow adipose tissue (MAT) is a dynamic endocrine organ that responds to changes in nutrition and might serve as a novel biomarker for bone health. Two types of MAT have been described which differ in anatomic location, proximal regulated MAT vs distal constitutive MAT. Objective To determine the effects of SG on volumetric BMD (vBMD) and MAT in adolescents with obesity. We hypothesized that SG would lead to a decrease in vBMD and differential changes in MAT. Design 12-month prospective study in 52 adolescents with moderate-to-severe obesity (38F, mean age:17.5±2.2 years, mean BMI:45.2±7.0 kg/m 2), 26 subjects before and after SG and 26 nonsurgical controls. Main outcome measures Lumbar vBMD by QCT; MAT of the lumbar spine, femur and tibia by 1H-MRS; abdominal fat and thigh muscle by MRI Results Adolescents lost 34.1±13.1 kg after SG vs 0.3±8.4 kg in the control group (p&0.001). Lumbar vBMD decreased in the SG group (p=0.04) and this change was associated with a reduction in weight and muscle area (p&0.05) and an increase in lumbar MAT (p=0.0002). MAT of the femur and tibia decreased after SG vs. controls (p&0.05), however, the differences were no longer significant after controlling for change in weight. Conclusion SG in adolescents decreased lumbar vBMD associated with an increase in lumbar MAT and decrease in extremity MAT. This demonstrates differential changes of regulated MAT in the lumbar spine and constitutive MAT in the distal skeleton in adolescents in response to SG.

Context Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health. Objective To evaluate the effect of VSG on bone health in youth. Design Observational 2-year study Setting Tertiary care center Participants 66 subjects ages 13-24 years with moderate-to-severe obesity meeting criteria for VSG Exposure VSG (n = 30) or non-surgical (n = 36) management per decision of patient and clinical team Main outcome measures: Dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture. Results VSG subjects achieved 25.3 ± 2.0% weight loss at two years (p < 0.001) while control subjects gained 4.0 ± 2.0% (p = 0.026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (p < 0.001), with similar results at the femoral neck (p < 0.001). Total volumetric BMD (vBMD) decreased at both the distal radius and tibia following VSG (p < 0.001) driven primarily by trabecular vBMD loss (p < 0.001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG at both the radius and tibia (p = 0.048 and p < 0.001). Cortical thickness increased in controls but not in VSG (p = 0.022 and p = 0.002 for between-group comparisons at the radius and tibia respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls. Conclusions VSG leads to progressive changes in bone health over two years, and may lead to increased skeletal fragility in adolescents and young adults.

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