Total Body Dual-energy X-ray Research Articles

The Subcutaneous Adipose Microenvironment as a Determinant of Body Fat Development in Polycystic Ovary Syndrome.

Adipose steroid metabolism modifies body fat development in polycystic ovary syndrome (PCOS). To determine whether subcutaneous (SC) abdominal adipose aldo-keto reductase 1C3 (AKR1C3; a marker of testosterone generation) is increased in normal-weight women with PCOS vs age- and body mass index (BMI)-matched normoandrogenic ovulatory women (controls) and is related to SC abdominal adipose activator protein-1 (AP-1; a marker of adipocyte differentiation) and/or androgen receptor (AR) protein expression in predicting fat accretion. Prospective cohort study. Academic center. Eighteen normal-weight PCOS women; 17 age- and BMI-matched controls. Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy, immunohistochemistry. Clinical characteristics, hormonal concentrations, body fat distribution, SC adipose AKR1C3, AR, and AP-1 protein expression. Women with PCOS had significantly higher serum androgen levels and greater android/gynoid fat mass ratios than controls. SC adipose AKR1C3, AR, and AP-1 protein expressions were comparable between the study groups, but groups differed in correlations. In PCOS women vs controls, SC adipose AKR1C3 protein expression correlated positively with android and gynoid fat masses and negatively with SC adipose AP-1 protein expression. SC adipose AR protein expression correlated negatively with fasting serum free fatty acid and high-density lipoprotein levels. In both study groups, SC adipose AKR1C3 protein expression negatively correlated with serum cortisol levels. In normal-weight PCOS women, SC abdominal adipose AKR1C3 protein expression, in combination with intra-adipose AP-1 and AR-dependent events, predicts fat accretion in the presence of physiological cortisol levels.

Bone Density in Transgender Youth on Gender-Affirming Hormone Therapy.

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was -0.10 [-0.8, 0.4] (AFAB, female norms) and -0.65 [-1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score -0.2 [-0.5, 0] (male norms) and 0.4 [-0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score -0.4 [-1.1, 0.3] (male norms) and -0.2 [-0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = -0.5, P = .005; female norms: r = -0.4, P = .029) and positively correlated with BMI (male norms: r = 0.4, P = .003; female norms: r = 0.4, P = .004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy.

Plasma microRNA signature associated with skeletal muscle wasting in post-menopausal osteoporotic women.

Skeletal muscle mass wasting almost invariably accompanies bone loss in elderly, and the coexistence of these two conditions depends on the tight endocrine crosstalk existing between the two organs, other than the biomechanical coupling. Since the current diagnostics limitation in this field, and given the progressive population aging, more effective tools are needed. The aim of this study was to identify circulating microRNAs (miRNAs) as potential biomarkers for muscle mass wasting in post-menopausal osteoporotic women. One hundred seventy-nine miRNAs were assayed by quantitative real-time polymerase chain reaction in plasma samples from 28 otherwise healthy post-menopausal osteoporotic women (73.4±6.6years old). The cohort was divided in tertiles based on appendicular skeletal muscle mass index (ASMMI) to better highlight the differences on skeletal muscle mass (first tertile: n=9, ASMMI=4.88±0.40kg·m-2; second tertile: n=10, ASMMI=5.73±0.23kg·m-2; third tertile: n=9, ASMMI=6.40±0.22kg·m-2). Receiver operating characteristic (ROC) curves were calculated to estimate the diagnostic potential of miRNAs. miRNAs displaying a statistically significant fold change≥±1.5 and area under the curve (AUC)>0.800 (P<0.05) between the first and third tertiles were considered. A linear regression model was applied to estimate the association between miRNA expression and ASMMI in the whole population, adjusting for body mass index, age, total fat (measured by total-body dual-energy X-ray absorptiometry [DXA]) and bone mineral density (measured by femur DXA). Circulating levels of adipo-myokines were evaluated by bead-based immunofluorescent assays and enzyme-linked immunosorbent assays. Five miRNAs (hsa-miR-221-3p, hsa-miR-374b-5p, hsa-miR-146a-5p, hsa-miR-126-5p and hsa-miR-425-5p) resulted down-regulated and two miRNAs (hsa-miR-145-5p and hsa-miR-25-3p) were up-regulated in the first tertile (relative-low ASMMI) compared with the third tertile (relative-high ASMMI) (fold change≥±1.5; P-value<0.05). All the corresponding ROC curves had AUC>0.8 (P<0.05). Two signatures hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p showed the highest AUC, 0.914 (sensitivity=77.78%; specificity=100.00%) and 0.901 (sensitivity=88.89%; specificity=100.00%), respectively. In this study, we identified, for the first time, two miRNA signatures, hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p, specifically associated with muscle mass wasting in post-menopausal osteoporotic women.

Effect of six weeks of resistance training on bone preservation in older adults: a randomized control trial.

It has been established that chronic resistance exercise contributes to positive changes to bone in older adults. This study evaluated the effect of 6weeks of resistance exercise with either elastic bands or dumbbells vs. a control period on bone morphology of older adults. Fifty-seven adults (mean ± SD; age = 66.5 ± 7.09 yrs; height = 165.2 ± 10.6cm; body mass = 74.5 ± 14.6kg) were randomized into three groups (dumbbell, elastic, or control). Participants underwent a total body dual-energy X-ray absorptiometry (DXA) scan for total body and segmental bone mineral content (BMC) and bone mineral density (BMD) before and following 6-week intervention. Age-matched Z-scores for BMD and BMC were recorded. Data were analyzed using two-way repeated measures ANOVAs and 0.05 significance level. BMCarm improved for the dumbbell group (p = 0.016) after the training, with no change in BMD for any group (p > 0.05). Additionally, significant (time x treatment group) interaction (p = 0.024) of age-matched Z-scores indicated an improvement in only the dumbbell group after 6weeks (p = 0.015), with no change in the elastic group despite them having greater Z-scores than the control group. This study is the first to demonstrate acute normative adaptations as dumbbell-based programs may promote positive maintenance of bone metrics over 6weeks, despite the lack of significant change in absolute BMC or BMD. Adults did not lose relative bone mass with acute exercise using dumbbells as the external load applied and this may lead to positive changes following chronic training. There was no bone-related impact from elastic bands, suggesting a weighted load or force produced relative to gravity is beneficial.

SAT399 Are Gender-affirming Hormone Therapy Duration And Body Mass Index Associated With Bone Mineral Density In Transgender And Gender Diverse Adults?

Abstract Disclosure: S.J. Iwamoto: None. J.D. Rice: None. N.J. Nokoff: None. K.L. Moreau: None. M. Cornier: None. M.E. Wierman: None. M.P. Mancuso: None. M.S. Rothman: None. Background: Sex steroids play crucial roles in bone mineral density (BMD) accrual and maintenance. Data on gender-affirming hormone therapy’s (GAHT) bone effects in transgender and gender diverse (TGD) adults have been limited to non-U.S. cohorts with higher gonadectomy and smoking rates. A higher prevalence of low BMD has been seen in TGD adults prior to initiating feminizing, compared to masculinizing, GAHT (fGAHT, mGAHT). Both fGAHT and mGAHT maintain lumbar spine (LS) BMD and increase Z-scores. Adult femoral neck (FN) and total hip (TH) site data are limited. The associations of GAHT duration and body mass index (BMI) with bone health among U.S. TGD adults are understudied. Objectives: To evaluate the associations between BMDs and Z-scores with GAHT duration and BMI among nonsmoking TGD adults aged 18-40 years, without prior gonadectomy, taking estrogen+spironolactone (fGAHT) or testosterone (mGAHT) for &amp;gt;1 year. Hypotheses: BMDs and Z-scores among fGAHT and mGAHT are within expected male and female reference ranges. Increasing GAHT duration and BMI are each associated with increasing BMDs and Z-scores at FN, TH and LS sites. Methods: Cross-sectional study of FN, TH, and LS bone density outcomes measured by total body dual-energy X-ray absorptiometry (DXA) in 30 adults receiving GAHT within a metropolitan area. Means±standard deviations were calculated. Associations between BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated for each of the three sites using linear regression. Results: Among fGAHT (n=15, n=0 non-White or Hispanic, age 28.7±4.8 years, GAHT 3.1±2.1 years, estradiol 189.7±119.6 pg/mL, total testosterone 97.6±99.5 ng/dL), mean BMI was in the overweight range (27.6±6.4 kg/m2) and mean total body percent fat was 33.7±7.3%. Among mGAHT (n=15, n=3 non-White, n=2 Hispanic, age 28.5±5.7 years, GAHT 4.0±2.0 years, estradiol 46.8±24.0 pg/mL, total testosterone 544.6±332.8 ng/dL), mean BMI was also in the overweight range (BMI 25.3±5.9 kg/m2) and mean total body percent fat was 29.8±7.1%. Both fGAHT and mGAHT groups had BMDs and Z-scores within expected male and female reference ranges at all three sites. Increasing BMI among mGAHT, but not fGAHT, was associated with increasing FN and TH, not LS, BMDs and Z-scores using male and female references (p&amp;lt;0.05). GAHT duration was not associated with BMDs or Z-scores. Conclusions: Z-scores in nonsmoking TGD adults taking fGAHT or mGAHT for &amp;gt;1 year, without prior gonadectomy, and with average BMIs in the overweight range, were reassuringly within the expected ranges for age. Increasing BMI, but not GAHT duration, was associated with higher FN and TH, but not LS, BMDs and Z-scores among mGAHT only. Larger studies, especially prospective, are needed to understand the associations between body composition changes (for example, lean mass and fat mass), normal or low BMIs, and gonadectomy with BMDs and Z-scores. Presentation: Saturday, June 17, 2023

OR35-05 Interaction of Cortisol with Testosterone Predicts Abdominal Fat Mass in Normal-weight Polycystic Ovary Syndrome Women with Normal Serum 11-Oxygenated Androgens

Abstract Disclosure: D.A. Dumesic: Consulting Fee; Self; Ferring Pharmaceuticals, Precede Biosciences, Inc, Spruce Biosciences, Inc. Grant Recipient; Self; National Institutes of Health. A.F. Turcu: None. H. Liu: None. T.R. Grogan: None. D.H. Abbott: None. G. Lu: None. D. Dharanipragada: None. G.D. Chazenbalk: None. Adrenal and ovarian steroidogenesis are interwoven with endocrine-metabolic dysfunction into polycystic ovary syndrome (PCOS). Women with PCOS and normal weight have androgen excess along with preferential abdominal adipose deposition (1,2), which is partially reversed by androgen receptor blockade (3). The role of adrenal steroids in this relationship, however, remains unclear. The present study examines whether serum levels of 11-oxygenated adrenal androgens, cortisol and/or cortisone differ between normal-weight PCOS women and body mass index (BMI)/age-matched normo-androgenic ovulatory women (controls) and whether adrenal steroids associate with abdominal adipose deposition. Twenty normal-weight PCOS women and 20 age- and BMI-matched controls underwent circulating hormone/metabolic determinations, intravenous glucose tolerance testing and total-body dual-energy x-ray absorptiometry. Clinical characteristics and hormonal values were compared between PCOS and control subjects. An unpaired Student’s t-test and Pearson correlation coefficients, adjusting for serum cortisol, were used as appropriate. Serum total/free testosterone (T) and androstenedione (A4) levels, and android/gynoid fat mass ratio, were greater in PCOS women with low-normal insulin sensitivity than in controls (all androgens P&amp;lt;0.001; android/gynoid fat mass ratio, P=0.026). A positive correlation of serum androgens with android/gynoid fat mass ratio was observed in all women combined (total T: R=+0.41, P=0.013; free T: R=+0.49, P=0.003; A4: R=+0.45, P=0.006). Serum 11ß-hydroxyA4 (11OHA4), 11-ketoA4 (11KA4), 11ß-hydroxyT (11OHT) and 11-ketoT (11KT), cortisol and cortisone levels were comparable between PCOS women and controls, and were unrelated to body fat distribution. Serum 11-oxygenated adrenal androgens correlated negatively with % total body fat (11OHA4: R=-0.42, P=0.011; 11KA4: R=-0.34, P=0.046; 11OHT: R=-0.36, P=0.031; 11KT: R=-0.37, P=0.027), but were no longer significant when adjusting for a concomitant negative relationship of serum cortisol with % total body fat (R=-0.45, P=0.006). Serum cortisol levels also correlated negatively with android fat mass in all women combined (R=-0.38, P=0.021) and were accompanied by a trend (P=0.075) towards reduced serum cortisol to cortisone ratio, as a marker of reduced 11β-hydroxysteroid dehydrogenase type 1 (HSD11ß1) conversion of cortisone to cortisol, in PCOS women versus controls (P=0.075). Ratios of 11KT/11KA4 and 11KT/11OHT as markers of AKR1C3and HSD11ß2 activities, respectively, did not differ by female type (both enzyme markers, P=nonsignificant). Conclusion: Reduced cortisol action, mediated in part through decreased HSD11ß1, interacts with an elevated androgens pathway to determine abdominal fat mass in normal-weight PCOS women with normal serum 11-oxygenated androgens.

A nude mutant rat derived from Sprague Dawley-National Institute of Nutrition rat colony with normal thymus: A potential model for noncommunicable diseases.

A spontaneous mutant rat with a hairless phenotype and an intact thymus was discovered in a long-standing Sprague Dawley-National Institute of Nutrition (SD/NIN) rat colony at a national animal resource facility. We conducted extensive phenotypic and biochemical analyses on this mutant strain to determine its suitability as a preclinical model for immunocompetent testing in noncommunicable disease research. We subjected the mutant rats to strict and frequent phenotypic and genetic surveillance to accomplish this objective. The animals were assessed for food intake, body weight, blood cell profile, clinical chemistry, adipose tissue deposition, and bone mineral density (BMD) using total electrical body conductance (TOBEC) and dual-energy X-ray absorptiometry (DXA) analysis. Initially, only two hairless mutant rats, a male and a female, were born from a single dam in the SD/NIN rat strain. However, the results indicate that the mutant colony propagated from these unique pups displayed distinct phenotypic features and exhibited differences in feeding behavior, weight gain, and clinical biochemistry. The food conversion rate was significantly higher in nude females (2.8-fold) while 26% lower in nude males. Both sexes of nude rats had significantly higher triglycerides and lower glucose levels in females. However, glucose levels did not change in male nude rats. Furthermore, nude female and male rats had significantly lower fat (TOBEC) and bone mineral content (DXA). Nonetheless, BMD was only slightly lower (7%-8%) compared to the heterozygous groups. These findings indicate that the spontaneous mutant rat has the potential to serve as an immunopotent and modulatory testing system in pharmacokinetics/pharmacodynamics and toxicology, which can be further explored for therapeutic drug discovery.

Automated measurement of size of spinal curve in population-based cohorts: Validation of a method based on total body dual energy X-ray absorptiometry scans.

Scoliosis is spinal curvature that may progress to require surgical stabilisation. Risk factors for progression are little understood due to lack of population-based research, since radiographs cannot be performed on entire populations due to high levels of radiation. To help address this, we have previously developed and validated a method for quantification of spinal curvature from total body dual energy X-ray absorptiometry (DXA) scans. The purpose of this study was to automate this quantification of spinal curve size from DXA scans using machine learning techniques. To develop the automation of curve size, we utilised manually annotated scans from 7298 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 9 and 5122 at age 15. To validate the automation we assessed (1) agreement between manual vs automation using the Bland-Altman limits of agreement, (2) reliability by calculating the coefficient of variation, and (3) clinical validity by running the automation on 4969 non-annotated scans at age 18 to assess the associations with physical activity, body composition, adipocyte function and backpain compared to previous literature. The mean difference between manual vs automated readings was less than one degree, and 90.4% of manual vs automated readings fell within 10°. The coefficient of variation was 25.4%. Clinical validation showed the expected relationships between curve size and physical activity, adipocyte function, height and weight. We have developed a reasonably accurate and valid automated method for quantifying spinal curvature from DXA scans for research purposes.

Interplay of Cortisol, Testosterone, and Abdominal Fat Mass in Normal-weight Women With Polycystic Ovary Syndrome.

Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production. To compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition. Prospective, cross-sectional, cohort study. Academic medical center. Twenty normal-weight women with PCOS and 20 body mass index-/age-matched controls. Blood sampling, IV glucose tolerance testing, and total-body dual-energy x-ray absorptiometry. Clinical characteristics, hormonal concentrations, and body fat distribution. Women with PCOS had higher serum total/free testosterone (T) and androstenedione (A4) levels and a greater android/gynoid fat mass than controls (androgens P < .001; android/gynoid fat mass ratio, P = .026). Serum total/free T and A4 levels correlated positively with android/gynoid fat mass ratio in all women combined (P < .025, all values). Serum 11ß-hydroxyA4, 11-ketoA4, 11ß-hydroxyT, 11-ketoT, cortisol, and cortisone levels were comparable between female types and unrelated to body fat distribution. Serum 11-oxyandrogens correlated negatively with % total body fat, but lost significance adjusting for cortisol. Serum cortisol levels, however, correlated inversely with android fat mass (P = .021), with a trend toward reduced serum cortisol to cortisone ratio in women with PCOS vs controls (P = .075), suggesting diminished 11β-hydroxysteroid dehydrogenase activity. Reduced cortisol may protect against preferential abdominal fat mass in normal-weight PCOS women with normal serum 11-oxyandrogens.

Influence of sex hormones status and type of training on regional bone mineral density in exercising females

ABSTRACT The primary objective of this study was to examine the influence of hormonal ovarian profile and training characteristics on spine, pelvis, and total body bone mineral density (BMD) in a group of well-trained females. Forty-two eumenorrheic females, twenty-eight monophasic oral contraceptive (OC) users and thirteen postmenopausal females participated in this study. Body composition was measured by total body dual-energy X-ray absorptiometry (DXA) to determine BMD of the areas of interest. Endurance-trained premenopausal females showed lower spine BMD compared to resistance-trained premenopausal females (1.03 ± 0.1 vs. 1.09 ± 0.09 g/cm2; p = 0.025). Postmenopausal females reported lower BMD level in comparison to eumenorrheic females in pelvis (1.079 ± 0.082 vs 1.19 ± 0.115 g/cm2; p = 0.005), spine (0.969 ± 0.097 vs 1.069 ± 0.109 g/cm2; p = 0.012) and total (1.122 ± 0.08 vs 1.193 ± 0.077 g/cm2; p = 0.018) and OC users whose duration of OC use was less than 5 years (OC < 5) in pelvis (1.235 ± 0.068 g/cm2; p < 0.001) and spine (1.062 ± 0.069 g/cm2; p = 0.018). In addition, lower BMD values were found in OC users who had been using OC for more than 5 years (OC ≥ 5) than eumenorrheic females in pelvis (1.078 ± 0.086 g/cm2; p = 0.029) and spine (0.966 ± 0.08 g/cm2; p = 0.05). Likewise, OC ≥ 5 showed lower values than and OC < 5 in pelvis (p = 0.004) and spine (p = 0.047). We observed a lower spine BMD value in premenopausal endurance-trained females compared to premenopausal resistance-trained females. Moreover, this research observed that prolonged use of OCs may reduce bone mass acquisition in the spine and pelvis, even in well-trained females. Finally, postmenopausal showed lower BMD despite being exercising women. Trial registration: ClinicalTrials.gov identifier: NCT04458662. Highlights Ovarian hormonal profile should be considered when assessing BMD in female athletes. The duration of oral contraceptive use influences spine and pelvis regional BMD in exercising females. Postmenopausal women show lower BMD when compared to premenopausal females despite being exercising females.

Sex differences in muscle SIRT1 and SIRT3 and exercise + weight loss effects on muscle sirtuins.

The sirtuins, SIRT1 and SIRT3, are involved in the control of cellular processes to maintain metabolic homeostasis. The purpose of this study was to determine the effects of a 6-month aerobic training + weight loss program and hyperinsulinemia on SIRT1 and SIRT3 expression in skeletal muscle and to compare their expression between men and women. Thirty-five adult men (n = 18) and postmenopausal women (n = 17), (X ± SEM, age: 61 ± 1 years, BMI: 31.3 ± 0.7 kg/m2) completed 6 months 3×/week of aerobic exercise and 1×/week dietary instruction to induce weight loss (EX + WL). Participants had a VO2max test, vastus lateralis muscle biopsies at baseline and 2 h into a hyperinsulinemic-euglycemic clamp, a total body dual-energy X-ray absorptiometry scan, and abdominal computed tomography scan. Skeletal muscle SIRT1, SIRT3, and PGC1-α mRNA expression were quantified by qRT-PCR. Skeletal muscle SIRT1 and SIRT3 mRNA expression are higher in women than men (P < 0.005). Body weight, body fat, and abdominal obesity decreased and VO2max and glucose utilization (M) increased after EX + WL (P < 0.001). Basal SIRT1 decreased following EX + WL (P < 0.05). This change in basal SIRT1 was not related to changes in VO2max, M or fat mass, nor was it different by gender. Insulin stimulation increased SIRT1 expression (P < 0.001) and PGC1-α expression (P < 0.01) following EX + WL (insulin-basal post). Sex differences in the levels of these sirtuins did not affect changes with EX + WL. Skeletal muscle SIRT1 decreases after a long-term combined exercise and weight loss program in middle-aged and older adults.

Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children

ObjectiveTo identify novel candidate genes whose expression is associated with bone mineral density (BMD) and body lean mass (LM) in children.MethodsA tissue-specific transcriptome-wide association study (TWAS) was conducted utilizing a large-scale genome-wide association study (GWAS) dataset associated with BMD and LM and involving 10,414 participants. The measurement of BMD and LM phenotypes was made based on total-body dual-energy X-ray absorptiometry (TB-DXA) scans. TWAS was conducted by using FUSION software. Reference panels for muscle skeleton (MS), peripheral blood (NBL) and whole blood (YBL) were used for TWAS analysis. Functional enrichment and protein–protein interaction (PPI) analyses of the genes identified by TWAS were performed by using the online tool Metascape (http://metascape.org).ResultsFor BMD, we identified 174 genes with P < 0.05, such as IKZF1 (P = 1.46 × 10−9) and CHKB (P = 8.31 × 10−7). For LM, we identified 208 genes with P < 0.05, such as COPS5 (P = 3.03 × 10−12) and MRPS33 (P = 5.45 × 10−10). Gene ontology (GO) enrichment analysis of the BMD-associated genes revealed 200 GO terms, such as protein catabolic process (Log P = −5.09) and steroid hormone-mediated signaling pathway (Log P = −3.13). GO enrichment analysis of the LM-associated genes detected 287 GO terms, such as the apoptotic signaling pathway (Log P = −8.08) and lipid storage (Log P = −3.55).ConclusionThis study identified several candidate genes for BMD and LM in children, providing novel clues to the genetic mechanisms underlying the development of childhood BMD and LM.

OR13-4 Bone Mineral Density in Transgender Youth on Gender Affirming Therapies

Abstract Background 2% of youth identify as transgender. Many have puberty blocked with gonadotropin-releasing hormone analogues (GnRHa), followed by testosterone (T) or estradiol (E2). Bone mineral density (BMD) effects of these therapies are understudied. Objective For youth on GnRHa alone or T or E2 +/- GnRHa, to evaluate: (1) BMD z-scores; (2) BMD z-score differences for those +/-GnRHa; and (3) associations between GnRHa duration and BMD z-score. Methods Cross-sectional study of transgender youth (n=56 age 10.4-19.8 years, 53% female sex assigned at birth) undergoing total body dual-energy X-ray absorptiometry (Hologic Discovery A). Data are presented as median and interquartile range, group differences evaluated with Mann Whitney U tests and associations with Spearman correlations. Results BMD z-scores on GnRHa alone (n=19) were -0.5 (-1.4, 0.3) using male norms and -0.8 (-1.7, 0.3) using female norms. BMD z-score for transgender males (TM) on T (n=21, 5 with past GnRHa): -0.2 (-0.6, 0.0) using male norms, 0.4 (-0.3, 0.8) using female norms. BMD z-score for transgender females (TF) on E2 (n=16, 6 on current/past GnRHa): -0.4 (-1.2, 0.3) using male norms, -0.2 (-1.0, 0.7) using female norms. TM on T with prior GnRHa had significantly lower BMD z-scores than TM on T alone (p=0.004); but no differences for TF on E2 +/- GnRHa. GnRHa duration was inversely correlated with BMD z-score (male norms: r=-0.5, p=0.005, female norms: r=-0.4, p=0.029). BMD z-score was unrelated to length of T/E2 therapy or sex steroid concentrations. Conclusions Longer durations of GnRHa therapy were associated with worse BMD z-scores. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

A 4-Yr Mixed Longitudinal Study of Health Behaviors and Fat Mass Accrual during Adolescence and Early Adulthood.

Physical activity (PA), sedentary time (SED), and energy intake (EI) are associated with fat mass accrual in children and youth. Previous studies relied primarily on cross-sectional designs and proxy measures of body composition such as body mass index. We aimed to prospectively investigate associations between PA, SED, EI, and total body fat mass accrual using dual-energy x-ray absorptiometry. This analysis of the mixed longitudinal Healthy Bones III Study included data from 312 participants (138 boys age 9 to 21 yr at baseline). For each participant, we acquired a maximum of four annual total body dual-energy x-ray absorptiometry scans from which we determined fat mass (in kilograms; n = 748 observations). We assessed total PA, moderate-to-vigorous PA (MVPA) and SED with accelerometers (ActiGraph GT1M) and measured EI via 24-h dietary recall. We fit sex-specific multilevel models adjusting for maturity (years from age at peak height velocity (APHV)), weight status, ethnicity, total PA, MVPA, SED, and EI. Boys and girls demonstrated divergent trajectories of fat mass accrual; rate of fat mass accrual in girls was four times greater than boys at APHV and increased across adolescence, whereas boys' fat mass plateaued after APHV. In boys, within-person change in MVPA negatively predicted fat mass independent of SED; each annual increase in MVPA of 6 min·d -1 was associated with a 0.21-kg lower fat mass. In girls, between-person average MVPA negatively predicted fat mass accrual independent of SED; greater MVPA of 4 min·d -1 across adolescence was associated with a 0.31-kg lower fat mass. MVPA demonstrates an independent and negative effect on fat mass in boys and girls. Given different trajectories of fat mass accrual and movement behaviors between boys and girls, PA interventions aimed at preventing obesity in youth may benefit from a sex and gendered approach.

Changes in Bone Mineral Density of the Femur and Tibia Before Injury to 2 Years After Anterior Cruciate Ligament Reconstruction in Division I Collegiate Athletes

Background: Osteoarthritis (OA) is a significant long term concern after anterior cruciate ligament (ACL) reconstruction (ACLR). A low bone mineral density (BMD), particularly in the subchondral region, has been associated with the development of OA and is evident at the knee in patients long after ACLR. It is unknown if persistent BMD deficits are present in high level collegiate athletes. Purpose/Hypothesis: The purpose of this study was to evaluate bilateral changes in the BMD of the femur and tibia from before the injury to 24 months after ACLR in collegiate athletes. We hypothesized that the BMD of both the distal femur and the proximal tibia would be significantly reduced within the surgical limb initially postoperatively but return to preinjury levels by 24 months after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 33 Division I collegiate athletes were identified between 2010 and 2021 (13 female) who underwent total body dual-energy X-ray absorptiometry (DXA) before sustaining an ACL injury. DXA was repeated at 6, 12, and 24 months after ACLR. Linear mixed effects models assessed differences in the BMD at 5%, 15%, and 50% of the femur's length (F5, F15, F50) and at 5%, 15%, and 50% of the tibia's length (T5, T15, T50) within each limb from before the injury to 24 months after ACLR, reported as Tukey-adjusted P values. Results: Compared with before the injury, the BMD at F5 of the surgical limb was reduced by 0.15 g/cm2 (SE, 0.02 g/cm2) at 6 months (P < .001). The BMD at F15 of the surgical limb was reduced by 0.06 g/cm2 (SE, 0.01 g/cm2), 0.09 g/cm2 (SE, 0.01 g/cm2), and 0.09 g/cm2 (SE, 0.01 g/cm2) at 6, 12, and 24 months, respectively (all P < .001). The BMD at T5 of the nonsurgical limb was reduced by 0.07 g/cm2 (SE, 0.02 g/cm2) at 12 months (P = .02) and 0.10 g/cm2 (SE, 0.02 g/cm2) at 24 months (P = .001). The BMD at T15 of the surgical limb was reduced by 0.07 g/cm2 (SE, 0.01 g/cm2) at 6 months and 0.08 g/cm2 (SE, 0.02 g/cm2) at 12 months (P < .001). Conclusion: BMD deficits at F15 of the surgical limb persisted out to 24 months (–7.1%) after ACLR compared with before the injury in collegiate athletes. The BMD at F5 and T15 of the surgical limb was reduced at 6 and 12 months but not at 24 months compared with preinjury levels. For the nonsurgical limb, no significant differences were detected, except for the T5 region at 12 months (–5.1%) and 24 months (–7.2%). The BMD at F50 and T50 of both limbs was not significantly different than preinjury levels at any time after ACLR.

Predictive Equations Overestimate Resting Metabolic Rate in Survivors of Chronic Stroke

ObjectiveTo measure resting metabolic rate (RMR) in survivors of chronic (>3 months prior) stroke (mean ± SEM age, 61±7.5 years) and to compare to predicted RMR using predictive equations in adults without stroke. DesignCross-sectional study. SettingHospital. ParticipantsSurvivors of stroke (N=71). InterventionNot applicable. Main Outcome MeasuresRMR was measured by indirect calorimetry. Participants underwent a total body dual-energy x-ray absorptiometry scan and treadmill test for peak oxygen consumption (V̇o2peak). RMR was calculated using 9 established equations. ResultsRMR measured (1552±319 kcal/d) was significantly lower than 9 predicted RMR values (all P<.001), with the best being McArdle-Katch (1652±233 kcal/d), Livingston (1677±230 kcal/d), and Mifflin (1707±242 kcal/d). The Institute of Medicine of the National Academies (2437±386 kcal/d) had the largest discrepancy with measured RMR. Predicted RMR determined with 8 of 9 equations was between 9% and 18% greater than measured RMR. Appendicular lean mass (r=0.64, P<.001), total lean mass (r=0.64, P<.001), and V̇o2peak (r=0.41, P<.001) were associated with measured RMR. ConclusionsRMR predictive equations established in adults without stroke are not appropriate for the population with stroke population, indicating the need to measure RMR until a more accurate predictive equation is developed. This could support modifications to nutritional intake guidelines in patients with conditions of muscle atrophy. If measurement of RMR is not feasible, the Katch-McArdle equation should be used to estimate RMR in a patient with stroke because on average it provides the lowest percentage overestimate compared with other equations.

Effect of high dose vitamin D supplementation on indices of sarcopenia and obesity assessed by DXA among older adults: A randomized controlled trial.

Hypovitaminosis D is associated with Sarcopenic Obesity (SO), but evidence from randomized Vitamin D 3 (VD3) trials is scarce. Compare the effect of VD3 supplementation, at two doses, on SO indices at 12 months. Overweight older adults (>65 years) with baseline 25-hydroxyvitamin D (25OHD) of 10-30 ng/mL were recruited in this double-blind, randomized, controlled multicenter trial (clinicaltrial.gov identifier: NCT01315366). All subjects received 1000 mg calcium citrate/day and underwent total body Dual-energy X-ray Absorptiometry for body composition assessment. Low Dose Group (LDG) and High Dose Group (HDG) received 600 IU -Institute of Medicine (IOM) Recommended Dietary Allowance (RDA)- and 3750 IU VD3/day, respectively. Mean age was 71 ± 4.6 years, 55% females, BMI: 30.2 ± 4.5 Kg/m2, and 43% had metabolic syndrome. There were no differences in baseline characteristics between groups. At 12 months, 248 participants had body composition data, 122 in LDG and 126 in HDG. Proportions of patients with diminished muscle mass, muscle strength, and visceral adiposity did not differ between the 2 groups at baseline or 12 months. Similarly, no significant differences were noted in the proportion of patients with SO at study entry (1.8% in LDG vs 1.6% HDG; p = 0.99) and at 12 months (3.7% in LDG vs. 0.9% HDG; p = 0.18) across arms. Weekly VD3, at the daily equivalent of 3750 IU/day, did not improve indices of sarcopenia nor adiposity compared to the IOM RDA dose in adults.

Automated Measurement of Size of Spinal Curve in Population-Based Cohorts: Validation of a Method Based on Total Body Dual Energy X-Ray Absorptiometry Scans

Automated Measurement of Size of Spinal Curve in Population-Based Cohorts: Validation of a Method Based on Total Body Dual Energy X-Ray Absorptiometry Scans

Prediction of Distal Femur and Proximal Tibia Bone Mineral Density From Total Body Dual Energy X-Ray Absorptiometry Scans in Persons with Spinal Cord Injury

Bone density decreases rapidly after spinal cord injury (SCI), increasing fracture risk. The most common fracture sites are at the knee (i.e., distal femur or proximal tibia). Despite this high fracture incidence, knee-specific scans for bone density using dual x-ray absorptiometry (DXA) were not available until 2014 and are still not routinely used in clinical practice today. This has made it difficult to determine the rehabilitation efficacy and hindered understanding of the long-term changes in knee areal bone density. The purpose of this investigation was to compare areal bone mineral density values for the knee from both total-body and knee-specific DXA scans in persons with SCI. A total of 20 participants (16 males) >1 yr-post spinal cord injury received two DXA scans; a total-body scan and a knee-specific scan. Standardized methods were used to create regions of interest to determine bone density of four regions – the epiphysis and metaphysis of the distal femur and proximal tibia – from the total-body scan. Linear regressions and Bland-Altman analyses were conducted to determine the correlation (r2) and agreement (mean bias ± 95% level of agreement) respectively between the two scan types for each region. Linear regression analyses showed strong significant (p < 0.001) relationships between the two scan types for the distal femur epiphysis (r2 = 0.88) and metaphysis (r2 = 0.98) and the proximal tibia epiphysis (r2 = 0.88) and metaphysis (r2 = 0.99). The mean bias ± 95% level of agreement were distal femur epiphysis (0.05 ± 0.1 g/cm2) and metaphysis (0.02 ± 0.04 g/cm2); proximal tibia epiphysis (-0.02 ± 0.1 g/cm2) and metaphysis (0.02 ± 0.03 g/cm2). Results suggest knee-specific bone density can be assessed using a total-body DXA scan. This may allow for more comprehensive use of DXA scans which would reduce the burden of multiple site-specific scans for persons with SCI and enable more widespread adoption of knee bone density assessment in this population.

DXA-Derived Adiposity and Lean Indices for Management of Cardiometabolic and Musculoskeletal Frailty: Data Interpretation Tricks and Reporting Tips.

The proper assessment and follow-up of obesity and sarcopenia are relevant for the proper management of the complications of cardiometabolic and musculoskeletal frailty. A total body dual-energy X-ray absorptiometry (DXA) scan should be systematically incorporated in the rehabilitative routine management of patients with obesity and sarcopenia. In the former patients, the total body DXA can be used to assess the fat tissue amount and distribution, while in the latter patients, it can be used to quantify the reduction of appendicular lean mass and to investigate the inter-limb lean mass asymmetry. This tutorial article provides an overview of different DXA-derived fat and lean indices and describes a step-by-step procedure on how to produce a complete DXA report. We suggest that the systematic incorporation of these indices into routine examinations of the patients with obesity and sarcopenia can be useful for identifying the patients at risk for cardiometabolic and neuromuscular impairment-related comorbidities and for evaluating the effectiveness of pharmacological and rehabilitative interventions.