Disclosure: M. Misra: Regeneron Pharmaceuticals, Consultant, Amgen Inc, Drug Donation, Up To Date, Contributor. S. Nimmala: None. V. Singhal: None. A.P. Lopez Lopez: None. D.M. Mitchell: None. M. Bouxsein: None. H. Lee: None. E.W. Yu: None. M. Bredella: None. Data are lacking regarding effects of Roux-en-Y gastric bypass (RYGB) on skeletal outcomes in youth. We examined the impact of RYGB vs. sleeve gastrectomy (SG) and no surgery (NS) on trabecular (Trab) structure in youth with moderate to severe obesity aged 14-26 years. We hypothesized that RYGB would result in the greatest deleterious effects on Trab parameters. 79 subjects were enrolled (30 undergoing SG, 13 RYGB and 36 NS controls) (mean: 18.5±0.3 years). 12-month (12M) data were available for 24, 10 and 20 subjects, and 24M data for 29, 10 and 18 subjects respectively. We assessed Trab parameters at the distal tibia (weight-bearing site) and radius (non-weight-bearing site) using high resolution peripheral quantitative CT (HR-pQCT) and individual trabecula segmentation (ITS), and report data for percent change over time. JMP software (v18) was used for analysis. RYGB and SG had higher BMI at baseline than NS, with greater BMI reductions over 24M than NS (-33.7±2.8 and -25.7±2.4 vs. 2.9±1.5%, p<0.0001). At the tibia, over 12M, decreases were greater for RYGB vs. NS for Trab BMD (p=0.001), and for RYGB and SG vs. NS for Trab number (p≤0.01). Over 24M, both RYGB and SG had greater reductions in Trab BMD and number vs. NS (p<0.0001), with greater reductions following RYGB than SG for Trab BMD (p=0.02), even after adjusting for weight change (p=0.004). Reductions in rod BV/TV were greater following both RYGB and SG vs. NS at 12 and 24M (p≤ 0.013). Groups did not differ for changes in plate and axial BV/TV and Trab thickness. At the radius, decreases were greater for SG vs. NS at 12M for Trab BMD (p=0.025), and for both RYGB and SG vs. NS at 24M (p≤0.0002); decreases were greater after RYGB than SG (p=0.025), even after adjusting for weight change (p=0.01). The RYGB group had reductions in Trab number vs. NS at 12M (p=0.031), and vs. SG and NS at 24M (p≤0.012). Reductions in rod BV/TV were greater following RYGB vs. SG and NS at 24M (p≤ 0.017). SG (but not RYGB) had reductions in plate BV/TV at 24M (p=0.002). Groups did not differ for changes in axial BV/TV or trab thickness. Percent change in BMI correlated with percent change in radius Trab number, BMD and rod BV/TV in the surgical groups (r≥0.45, p≤0.02). RYGB and SG in youth result in deleterious Trab outcomes at weight-bearing and non-weight-bearing sites related to reductions in BMI; RYGB has a greater impact than SG. Further studies are necessary to devise preventative and therapeutic strategies. Presentation: Monday, July 14, 2025

Context Low vitamin D status is common and is associated with various common medical conditions.Objective To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease.Methods We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence.Results Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D.Conclusion The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals' and providers' values and preferences and other important decisional and contextual factors to develop clinical recommendations.

Background Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain.Objective To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing.Methods A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D.Results The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity.Conclusion The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

A 10-month-old boy was admitted to the hospital because of vomiting and weight loss. The calcium level was 13.2 g per deciliter (range, 8.5 to 10.5). Radiographs of the wrists and knees were normal. A diagnosis was made.

Abstract Background Hypoparathyroidism (HP) is a rare endocrine disease commonly caused by the removal or damage of parathyroid glands during surgery and resulting in transient (tHP) or chronic (cHP) disease. cHP is associated with multiple complications and comorbid conditions; however, the economic burden has not been well characterized. The objective of this study was to evaluate the healthcare resource utilization (HCRU) and costs associated with post-surgical cHP, using tHP as a reference. Methods This analysis of a US claims database included patients with both an insurance claim for HP and thyroid/neck surgery between October 2014 and December 2019. cHP was defined as an HP claim ≥ 6 months following surgery and tHP was defined as only one HP claim < 6 months following surgery. The cHP index date was the first HP diagnosis claim following their qualifying surgery claim, whereas the tHP index date was the last HP diagnosis claim following the qualifying surgery claim. Patients were continuously enrolled at least 1 year pre- and post-index. Patients’ demographic and clinical characteristics, all-cause HCRU, and costs were descriptively analyzed. Total all-cause costs were calculated as the sum of payments for hospitalizations, emergency department, office/clinic visits, and pharmacy. Results A total of 1,406 cHP and 773 tHP patients met inclusion criteria. The average age (52.1 years cHP, 53.5 years tHP) and representation of females (83.2% cHP, 81.2% tHP) were similar for both groups. Neck dissection surgery was more prevalent in cHP patients (23.6%) than tHP patients (5.3%). During the 1–2 year follow-up period, cHP patients had a higher prevalence of inpatient admissions (17.4%), and emergency visits (26.0%) than the reference group -tHP patients (14.4% and 21.4% respectively). Among those with a hospitalization, the average number of hospitalizations was 1.5-fold higher for cHP patients. cHP patients also saw more specialists, including endocrinologists (28.7% cHP, 15.8% tHP), cardiologists (16.7% cHP, 9.7% tHP), and nephrologists (4.6% cHP, 3.3% tHP). Conclusion This study demonstrates the increased healthcare burden of cHP on the healthcare system in contrast to patients with tHP. Effective treatment options are needed to minimize the additional resources utilized by patients whose HP becomes chronic.

Context Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease.Methods We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n = 21) and associated controls (n = 12). Groups were well matched for age, height, strength, and physical activity.Results By high-resolution peripheral quantitative computed tomograpy, participants with T1D had lower trabecular bone volume fraction at the distal radius (-14.6%, P-adj = .095) and the tibia (-12.8%, P-adj = .017) and decreased trabecular thickness (-8.3% radius, P-adj = .007; -7.5% tibia, P-adj = .034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (P-adj = .024) and porosity was decreased by 52.9% with T1D (P-adj = .012). There were no significant differences in bone density by dual-energy x-ray absorptiometry. Participants with T1D also had lower circulating levels of osteocalcin (-30%, P = .057), and type I collagen cross-linked C-telopeptide (-36%, P = .035), suggesting low bone formation and turnover in T1D. Based on the Michigan Neuropathy Screening Instrument, 9.5% of those with T1D had clinical evidence of diabetic peripheral neuropathy. However, consideration of neuropathy status failed to explain the widespread T1D-associated changes in bone.Conclusion Our study defines early deficits in trabecular bone microarchitecture, decreased cortical porosity in the tibia, and suppression of biomarkers of bone turnover in adolescent girls with T1D, prior to the onset of symptomatic peripheral neuropathy. These findings inform our understanding of the rapid progression of skeletal disease in young girls with T1D and suggests that early detection and management strategies may help to prevent fracture and related comorbidities later in life.

Abstract Disclosure: K.L. Deering: None. Q. Harshaw: None. D.M. Mitchell: None. N.J. Larsen: None. B. Weiss: None. P. Loustau: None. S. Allas: None. Objectives: Emerging evidence regarding optimal treatment for patients with chronic hypoparathyroidism (cHP) has led to the development of updated evaluation and management guidelines. The goal of this study was to determine how current practice patterns for individuals with cHP compare with these guidelines. Methods: We extracted data from a large US claims database (130 million patients) from Oct 2014 to Dec 2019. cHP was defined as an HP diagnosis claim ≥6 months following neck surgery or ≥2 claims ≥6 months apart. Patient data were extracted from 1 year prior to surgery (if applicable) and up to 2 years following their qualifying HP claim. Additionally, a panel comprised of 103 endocrinologists and nephrologists (US=40, UK=21, France=21, Germany=21) was assembled and conducted chart reviews with each participant contributing data for 5 patients with cHP in their practice. Results: 5,302 patients met criteria for cHP from the claims database, while the physician panel chart review included 515 cHP patients. In the claims database, 33.0% saw an endocrinologist and 9.4% or less saw a nephrologist during the 1-year follow-up. Panel physicians reported being the decision maker for 93% of their cHP patients and 90% of the patients were seen at least twice per year. Guidelines recommend all new and established cHP patients be monitored for key laboratory values every 3-12 months. Overall, while neither study found monitoring practices consistent with guidelines, there was less laboratory monitoring in the database study than in the physician panel: serum magnesium (36.6%; 57%), serum phosphorous (36.8%; 90%), urine calcium (10.0%; 57%), and renal imaging (20.9%; 34%). Additionally, patients were monitored for bone health in the database study and physician panel (bone mineral density: 10.7%; 44%; bone markers: 5.2%; 25%). Conclusion: Real-world practice patterns vary from guideline recommendations; however, the practice patterns from the physician panel study align more closely with recommendations than the claims database study. This discrepancy may be due to patients less frequently utilizing physicians specialized in cHP in the database study. Our data underscore challenges with optimizing care for patients with this rare disorder. In addition, they suggest that ongoing efforts to educate both patients and physicians about management guidelines may improve care and ultimately enhance health and quality of life in cHP. Presentation: Saturday, June 17, 2023

To understand whether the bone loss which occurs after vertical sleeve gastrectomy increases the risk of fracture, we used an engineering model to estimate risk in participants before and after surgery. We found that estimated risk decreased 1 year after surgery and remained lower, though had rebounded, at year 2. Vertical sleeve gastrectomy (VSG) improves metabolic health in young people with obesity but is accompanied by substantial loss of bone mass and estimated bone strength. We thus estimated fracture risk following VSG using the load-to-strength ratio (LSR), which integrates bone strength estimates with the predicted force of a fall. Prospective 2-year study of youth ages 13–24 years with obesity undergoing VSG (n = 24) or lifestyle therapy (n = 34). We performed high-resolution peripheral quantitative computed tomography of the distal radius and microfinite element analysis to estimate bone strength and calculated LSR. VSG participants lost 26.4 ± 8.1

OBJECTIVE:To determine mechanisms contributing to impaired bone health in youth 24 months following sleeve gastrectomy (SG).DESIGN:Twenty-four-month longitudinal observational study.METHODS:Participants included 23 youth undergoing SG and 30 non-surgical controls (NS) 13-25 years old with moderate-to-severe obesity. Subjects underwent fasting labs for bone turnover markers (N-terminal propeptide of type 1 procollagen, C-telopeptide (CTX)), sex hormones, sex hormone binding globulin (SHBG), and enteric peptides, DXA for areal bone mineral density (aBMD) and body composition, high-resolution peripheral quantitative CT for volumetric BMD (vBMD) at the distal radius and tibia, and microfinite element analysis for strength estimates.RESULTS:Groups did not differ for mean age or BMI z-scores. Over 24 months, compared to NS, SG had greater reductions in BMI z-scores, and spine, hip, and femoral neck aBMD Z-scores (P ≤ .012), greater increases in serum CTX and SHBG (P ≤ .039), and greater decreases in estrone and ghrelin (P ≤ .021). Among females, estrone and free androgen index (FAI) decreased (P ≤ .022) in SG vs NS groups. After controlling for age and sex, decreases in BMI and lean mass were associated with decreases in total hip and femoral neck aBMD Z-scores, and decreases in radial total and trabecular vBMD and failure load, and tibial total and trabecular vBMD. Among females, after controlling for age, decreases in estrone were associated with decreases in spine aBMD Z-scores and radial total and trabecular vBMD, and decrease in FAI with decreases in radial failure load.CONCLUSION:Reductions in BMI, lean mass, and sex steroids over 24 months post-SG are associated with bone loss and could be targeted for preventative or therapeutic interventions. Clinical trial registration number: The study is registered in ClinicalTrials.gov (NCT02557438).

ABSTRACT Type 1 diabetes (T1D) confers an increased risk of fracture and is associated with lower bone mineral density (BMD) and altered microarchitecture compared with controls. Adequate calcium (Ca) intake promotes bone mineralization, thereby increasing BMD. The objective of this analysis was to evaluate the associations of total daily Ca intake with bone outcomes among youth with T1D. This was a cross‐sectional analysis of girls ages 10–16 years with (n = 62) and without (n = 60) T1D. We measured Ca intake with a validated food‐frequency questionnaire and BMD, microarchitecture, and strength estimates with dual‐energy X‐ray absorptiometry and high‐resolution peripheral quantitative computed tomography. Total daily Ca intake did not differ between groups (950 ± 488 in T1D versus 862 ± 461 mg/d in controls, p = 0.306). Serum 25OHD was lower in T1D (26.3 ± 7.6 versus 32.6 ± 9.0 ng/mL, p = <0.001), and parathyroid hormone (PTH) was higher in T1D (38.9 ± 11 versus 33.4 ± 9.7 pg/mL, p = 0.004). Trabecular volumetric BMD and thickness at the tibia were lower in T1D (p = 0.013, p = 0.030). Ca intake correlated with trabecular BMD at the radius and tibia among T1D participants (β = 0.27, p = 0.047, and β = 0.28, p = 0.027, β = 0.28, respectively) but not among controls (pinteraction = 0.009 at the radius, pinteraction = 0.010 at the tibia). Similarly, Ca intake was associated with estimated failure load at the tibia in T1D but not control participants (p = 0.038, β = 0.18; pinteraction = 0.051). We observed the expected negative association of Ca intake with parathyroid hormone in controls (p = 0.022, β = −0.29) but not in T1D participants (pinteraction = 0.022). Average glycemia as measured by hemoglobin A1c did not influence the relationship of Ca and PTH among participants with T1D (pinteraction = 0.138). These data suggest that youth with T1D may be particularly vulnerable to dietary Ca insufficiency. Increasing Ca intake may be an effective strategy to optimize bone health in this population. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

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 This work aimed to evaluate the effect of VSG on bone health in youth. Methods An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included 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 patients achieved 25.3 +/- 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 +/- 2.0% (P = .026). Total hip BMD declined 8.5 +/- 1.0% following VSG compared with 0.1 +/- 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .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. Conclusion VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.

Background/Objective:Genetic variants in hepatic nuclear factor 1α (HNF1A) cause maturity-onset diabetes of the young (MODY). We sought to examine whether HNF1A MODY variants also cause neonatal hypoglycemia.Case Report:We present 3 infants with variants in HNF1A shared with their mothers. The infants experienced neonatal hypoglycemia, 2 extending beyond 1 year and the third resolving by 28 days, and all were large for gestational age (birth weights of >99th percentile). In 2 cases, genetic testing for neonatal hypoglycemia revealed pathogenic variants in HNF1A; 1 mother was previously diagnosed with HNF1A MODY, and the other's genetic testing and ultimate MODY diagnosis were prompted by her child's hypoglycemia workup. In the third case, the infant's persistent hypoglycemia prompted genetic testing, revealing an HNF1A variant of uncertain significance, which was then identified in the mother.Discussion:Genetic variants causing HNF1A MODY have not been definitively linked to neonatal hypoglycemia or fetal overgrowth in utero. MODY caused by HNF1A is clinically similar to that caused by HNF4A, for which a causal relationship with neonatal hypoglycemia is more certain. Case reports have previously implicated variants in HNF1A in congenital hyperinsulinism; however, these cases have generally not been in families with MODY. The cases presented here suggest that HNF1A variants causing MODY may also cause neonatal hypoglycemia.Conclusion:Although confounding factors make the assessment of neonatal hypoglycemia challenging, these cases offer potential support for single genetic variants in HNF1A causing both MODY and neonatal hypoglycemia, with associated fetal overgrowth in utero.

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.

Background: Among adolescents with extremity fractures, individuals with obesity have greater representation compared with individuals of normal-weight, despite having higher areal and volumetric bone mineral density (aBMD, vBMD) than their normal-weight counterparts. The relative increase in BMD in individuals with obesity may thus be insufficient to support the greater force generated upon falling. The load-to-strength ratio is a biomechanical approach for assessing the risk of fracture by comparing applied force to bone strength, with higher load-to-strength ratios indicating higher fracture risk. Objective: To assess the load-to-strength ratio at the distal radius in adolescent and young adult females with severe obesity (OB) compared with normal-weight healthy controls (HC). We hypothesized that OB have a higher load-to-strength ratio compared to HC. Methods: We examined bone parameters in 65 girls 14-21 years old: 33 OB and 32 HC. We used dual-energy X-ray absorptiometry (DXA) to assess body composition, high resolution peripheral quantitative CT (HR-pQCT) to estimate vBMD, and microfinite element analysis (mu FEA) to assess bone strength at the distal radius. To quantify fracture risk, we computed the load-to-strength ratio, where the numerator is defined as the load applied to the outstretched hand during a forward fall and the denominator is the bone strength, as estimated by mu FEA. Results: Although OB had higher total vBMD than HC (368.3 vs. 319.9 mgHA/cm(3), p = 0.002), load-to-strength ratio at the radius was greater in OB than HC after controlling for age and race (0.66 vs. 0.54, p < 0.0001). In OB, impact force and load-to-strength ratio were associated negatively with % lean mass (r = -0.49; p = 0.003 and r = -0.65; p < 0.0001 respectively) and positively with visceral fat (r = 0.65; p < 0.0001 and r = 0.36; p = 0.04 respectively). Conclusions: Adolescent and young adult females with obesity have higher load-to-strength ratio at the distal radius due to higher forces applied to bone in a fall combined with incomplete adaptation of bone to increasing body weight. This is differentially affected by lean mass, fat mass, and visceral fat mass.