Context Sleeve gastrectomy (SG) improves metabolic endpoints but is associated with impaired bone outcomes. Objective To determine mechanisms contributing to impaired bone health in youth following SG. Methods 12-month longitudinal observational study in a multidisciplinary tertiary-care hospital, including 64 youth 13-25 years old with moderate-to-severe obesity (51 females); 30 underwent SG and 34 were nonsurgical (NS) controls. SG was undertaken after a combined decision-making process between treatment team and patient. The main outcome measures were fasting blood for enteric peptides, sex steroids, sclerostin, and bone turnover markers (N-terminal propeptide of type 1 procollagen [P1NP] and C-terminal cross-linking telopeptide [CTX]); dual-energy X-ray absorptiometry measures of areal bone mineral density (aBMD) and body composition; high resolution peripheral quantitative computed tomography; measures of volumetric BMD (vBMD); microfinite element analysis of strength estimates (distal radius and tibia). Results SG had greater reductions in body mass index (BMI) z-scores, serum estrone, and the free androgen index (FAI) (P ≤ .046), and greater increases in sclerostin, P1NP, and CTX (P ≤ .010) than NS controls. Fasting ghrelin decreased in SG vs NS (P < .0001); fasting peptide YY did not change. Most changes were driven by female SG participants. Among females (the majority of study participants), after controlling for baseline age and race, reductions in total hip aBMD Z-scores were positively associated with changes in BMI, lean mass, estrone, FAI, and ghrelin, and inversely with changes in sclerostin.. Decreases in total vBMD of the radius and tibia were associated positively with decreases in BMI. Increases in CTX were associated with decreases in BMI, lean mass, and ghrelin, and increases in sclerostin. Conclusion Bone loss after SG in youth is associated with changes in body composition, sex steroids, sclerostin, and enteric peptides. These are potential targets for future preventative or therapeutic strategies.

Context Female athletes, particularly runners, with insufficient caloric intake for their energy expenditure (low energy availability or relative energy deficiency) are at risk for impaired skeletal integrity. Data are lacking in male runners. Objective To determine whether male runners at risk for energy deficit have impaired bone mineral density (BMD), microarchitecture, and estimated strength Design Cross-sectional Setting Clinical research center Participants 39 men (20 runners, 19 controls), ages 16-30y Main Outcome Measures Areal BMD (DXA); tibia and radius volumetric BMD and microarchitecture (high resolution peripheral quantitative CT); failure load (microfinite element analysis); serum testosterone, estradiol, leptin; energy availability (EA) Results Mean age (24.5 ± 3.8y), lean mass, testosterone, and estradiol levels were similar; BMI, percent fat mass, leptin, and lumbar spine BMD Z-score (-1.4 ± 0.8 vs. -0.8 ± 0.8) lower (p < 0.05); and calcium intake and running mileage higher (p ≤ 0.01) in runners vs. controls. Runners with EA < median had lower lumbar spine (-1.5 ± 0.7, p = 0.028), while runners with EA ≥ median had higher hip (0.3 ± 0.7 vs. -0.4 ± 0.5, p = 0.002), BMD Z-scores vs. controls. After adjusting for calcium intake and running mileage, runners with EA < median had lower mean tibial total and trabecular volumetric BMD, trabecular bone volume fraction, cortical porosity, and apparent modulus vs. controls (p < 0.05). Appendicular lean mass and serum estradiol (R ≥ 0.45, p ≤ 0.046), but not testosterone, were positively associated with tibial failure load among runners. Conclusions Despite weight-bearing activity, skeletal integrity is impaired in male runners with lower caloric intake relative to exercise energy expenditure, which may increase bone stress injury risk. Lower estradiol and lean mass are associated with lower tibial strength in runners.

Female athletes with low energy availability are at risk for impaired bone microarchitecture and strength associated with hypogonadism. Data are lacking for bone outcomes in male athletes. We studied 31 men 16-30 years (n=15 runners with mean (±SD) mileage 43±4 miles/week, n=16 non-athlete controls). We assessed distal tibia and radius volumetric BMD (vBMD) and microarchitecture by high resolution peripheral quantitative CT (HRpQCT), estimated bone strength by microfinite element analysis and body composition by DXA. Testosterone, estradiol (by LC-MS) and leptin (by electrochemiluminescence) were measured. Groups did not differ for mean age (24.5±3.6y), BMI (22.2±2.6 kg/m2), lean mass, or testosterone or estradiol levels. Mean tibial cortical vBMD was lower and porosity higher in athletes than controls (p<0.01). In contrast, mean tibial trabecular vBMD and number were higher, and separation lower, in athletes (p<0.02). Athletes with BMI ≤ 21 kg/m2 had lower tibial failure load (bone strength estimate) than those with BMI >21 kg/m2 (p=0.007). Lean mass (R=0.85, p<0.0001), serum leptin (R=0.59, p=0.046) and estradiol (R=0.66, p=0.007), but not testosterone, were associated with tibial failure load in athletes. Athlete and control groups did not differ for HRpQCT variables at the radius. Despite weight-bearing activity, male runners have impaired tibial cortical BMD and microarchitecture, which may increase their risk for bone stress injuries. Lower leptin (reflecting lower fat mass) and estradiol (converted from testosterone in adipose tissue), as well as lean mass, are determinants of lower tibial strength in these athletes, suggesting that low energy availability is a risk factor for impaired bone strength in male runners. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.

ImportanceIndividuals with anorexia nervosa maintain extremely low body weights despite elevations in the circulating orexigenic hormone ghrelin. Whether circulating levels of endogenous ghrelin are associated with weight gain in anorexia nervosa is unknown.ObjectiveTo examine the association between baseline ghrelin and future weight change in individuals with anorexia nervosa.Design, Setting, and ParticipantsThis prospective cohort study was conducted between April 1, 2014, and March 31, 2020, in the US. Girls and women aged 10 to 22 years were recruited from the greater Boston area from community and area treatment centers, enrolled, and followed up for 18 months. Statistical analyses were performed between January and August 2022.ExposuresPresence or absence of anorexia nervosa and elevations in endogenous ghrelin.Main Outcomes and MeasuresChanges in age- and sex-standardized body mass index percentiles from baseline to 9- and 18-month follow-up were the main outcomes of interest.ResultsA total of 68 girls and young women (11 [16%] Asian, 4 [6%] Hispanic or Latina, 51 [75%] White [non–Hispanic or Latina], and 2 [3%] other race or ethnicity), including 35 with anorexia nervosa and 33 healthy controls of similar Tanner stage, were included in this study. Anorexia nervosa and healthy control groups were not statistically different by race and ethnicity, Tanner stage, number completing follow-up visits, and the duration between baseline and follow-up visits. At baseline, individuals with anorexia nervosa were slightly older (median [IQR], 20.1 [18.5-21.0] vs 18.7 [14.7-19.4] years; P = .005), had lower body mass index percentiles (median [IQR], 2.4 [0.3-4.7] vs 52.9 [40.4-68.3]; P < .001), and had elevated circulating ghrelin area under the curve composite index (median [IQR], 1389.4 [1082.5-1646.4] vs 958.5 [743.0-1234.5] pg/mL; P = .003) compared with healthy individuals. In linear mixed-effects regression analyses, baseline ghrelin was associated with prospective weight gain after adjusting for diagnosis, age, race, and duration of follow-up (odds ratio, 2.35; 95% CI, 1.43-3.73; P = .004).Conclusions and RelevanceIn this cohort study, endogenous ghrelin was associated with longitudinal weight gain in individuals with anorexia nervosa. Further studies are warranted to confirm this result and examine its potential clinical utility in treatment development.