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Background: Cognitive‐behavioral therapy for avoidant/restrictive food intake disorder (ARFID; CBT‐AR) theoretically targets three prototypic motivations (sensory sensitivity, lack of interest/low appetite, fear of aversive consequences), aligned with three modularized interventions. As an exploratory investigation, we: (1) evaluated change in candidate mechanisms in relationship to change in ARFID severity, and (2) tested if assignment (vs. not) to a module resulted in larger improvements in the corresponding mechanism. Method: Males and females (N = 42; 10–55 years) participated in an open trial of CBT‐AR. Results: Decreases in scaled scores for each candidate mechanism had medium to large correlations with decreases in ARFID severity—sensory sensitivity: −0.7 decrease (r =.42, p =.01); lack of interest/low appetite: −0.3 decrease (r =.60, p <.0001); and fear of aversive consequences: −1.1 decrease (r =.33, p =.05). Linear mixed models revealed significant weekly improvements for each candidate mechanism across the full sample (ps <.0001). There were significant interactions for the sensory and fear of aversive consequences modules–for each, participants who received the corresponding module had significantly larger decreases in the candidate mechanism than those who did not receive the module. Discussion: Sensory sensitivity and fear of aversive consequences improved more if the CBT‐AR module was received, but lack of interest/low appetite may improve regardless of receipt of the corresponding module. Future research is needed to test target engagement in CBT‐AR with adaptive treatment designs, and to identify valid and sensitive measures of candidate mechanisms. Public Significance: The mechanisms through which components of CBT‐AR work have yet to be elucidated. We conducted an exploratory investigation to test if assignment (vs. not) to a CBT‐AR module resulted in larger improvements in the corresponding prototypic ARFID motivation that the module intended to target. Measures of the sensory sensitivity and the fear of aversive consequences motivations improved more in those who received the corresponding treatment module, whereas the lack of interest/low appetite measure improved regardless of if the corresponding module was received. [ABSTRACT FROM AUTHOR]

Objective: Few studies have focused on brain structure in atypical anorexia nervosa (atypical AN). This study investigates differences in gray matter volume (GMV) between females with anorexia nervosa (AN) and atypical AN, and healthy controls (HC). Method: Structural magnetic resonance imaging data were acquired for 37 AN, 23 atypical AN, and 41 HC female participants. Freesurfer was used to extract GMV, cortical thickness, and surface area for six brain lobes and associated cortical regions of interest (ROI). Primary analyses employed linear mixed‐effects models to compare group differences in lobar GMV, followed by secondary analyses on ROIs within significant lobes. We also explored relationships between cortical gray matter and both body mass index (BMI) and symptom severity. Results: Our primary analyses revealed significant lower GMV in frontal, temporal and parietal areas (FDR <.05) in AN and atypical AN when compared to HC. Lobar GMV comparisons were non‐significant between atypical AN and AN. The parietal lobe exhibited the greatest proportion of affected cortical ROIs in both AN versus HC and atypical AN versus HC. BMI, but not symptom severity, was found to be associated with cortical GMV in the parietal, frontal, temporal, and cingulate lobes. No significant differences were observed in cortical thickness or surface area. Discussion: We observed lower GMV in frontal, temporal, and parietal areas, when compared to HC, but no differences between AN and atypical AN. This indicates potentially overlapping structural phenotypes between these disorders and evidence of brain changes among those who are not below the clinical underweight threshold. Public significance: Despite individuals with atypical anorexia nervosa presenting above the clinical weight threshold, lower cortical gray matter volume was observed in partial, temporal, and frontal cortices, compared to healthy individuals. No significant differences were found in cortical gray matter volume between anorexia nervosa and atypical anorexia nervosa. This underscores the importance of continuing to assess and target weight gain in clinical care, even for those who are presenting above the low‐weight clinical criteria. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. Method: Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21–46 years. Results: Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p <.05). Adjusting for weight, deficits in tibial cortical bone variables persisted (p <.05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high‐resolution peripheral quantitative computed tomography (HR‐pQCT) variables in atypical anorexia nervosa. Discussion: Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR‐pQCT variables are associated with increased fracture risk. Public Significance: Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sleeve gastrectomy (SG) is effective in treating cardiometabolic complications of obesity but is associated with bone loss. Our aim was to determine the effect of SG on the lumbar spine by biomechanical CT analysis in adolescents/young adults with obesity. We hypothesized that SG would lead to a decrease in strength and bone mineral density (BMD) compared with nonsurgical controls. In a 12-month prospective nonrandomized study, adolescents/young adults with obesity underwent SG (n = 29, 18.0 ± 2.1 years, 23 female) or were followed without surgery (controls, n = 30, 17.95 ± 3.0 years, 22 female). At baseline and 12 months, participants underwent quantitative computed tomography (QCT) of L1 and L2 for biomechanical assessment and MRI of the abdomen and midthigh for body composition assessment. Twelve-month changes between groups and within groups were assessed. Analyses were controlled for baseline and 12-month changes in body mass index (BMI) by multivariable analyses. Regression analysis was performed to evaluate the effect of body composition on bone parameters. Our institutional review board (IRB) approved the study, and informed consent/assent was obtained. Participants in the SG group had a higher baseline BMI than controls (p = 0.01) and lost an average of 34.3 ± 13.6 kg 12 months after surgery, whereas weight was unchanged in controls (p < 0.001). There were significant reductions in abdominal adipose tissue and thigh muscle area in the SG group compared with controls (p < 0.001). Bone strength, bending stiffness, and average and trabecular volumetric BMD decreased in the SG group compared with controls (p < 0.001). After controlling for change in BMI, a 12-month reduction in cortical BMD was significant in the SG group compared with controls (p = 0.02). Reductions in strength and trabecular BMD were associated with reductions in BMI, visceral adipose tissue, and muscle (p ≤ 0.03). In conclusion, SG in adolescents decreased strength and volumetric BMD of the lumbar spine compared with nonsurgical controls. These changes were associated with decreases in visceral fat and muscle mass. [ABSTRACT FROM AUTHOR]

Objective: There is a paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID) to aid identification and classification of cases for both clinical and research purposes. To evaluate the factor structure, construct validity, and criterion validity of the Pica ARFID and Rumination Disorder Interview (PARDI; ARFID module), we administered the PARDI to 129 children and adolescents ages 9–23 years (M = 16.1) with ARFID (n = 84), subclinical ARFID (n = 11), and healthy controls (n = 34). Method: We used exploratory factor analysis to examine the factor structure of the PARDI in children, adolescents, and young adults with an ARFID diagnosis, the Kruskal‐Wallis analysis of variance and Spearman correlations to test the construct validity of the measure, and non‐parametric receiver operating characteristic curves to evaluate the criterion validity of the PARDI. Results: Exploratory factor analysis yielded a 3‐factor structure: (1) concern about aversive consequences of eating, (2) low appetite/low interest in food, and (3) sensory sensitivity. Participants with ARFID demonstrated significantly higher levels of sensory sensitivity, low appetite/low‐food interest, and concern about aversive consequences of eating symptoms relative to control participants. The construct validity for each PARDI subscale was supported and clinical cutoffs for the low appetite/low interest in food (1.1) and sensory sensitivity subscales (0.6) were established. Discussion: These data present evidence for the factor structure and validity of the PARDI diagnostic interview for diagnosing ARFID in children, adolescents, and young adults, supporting the use of this tool to facilitate ARFID clinical assessment and research. Public Significance: Due to the paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID), we evaluated the factor structure and validity of the Pica ARFID and Rumination Disorder Interview (ARFID module). Findings suggest that the interview assesses 3 components of ARFID: concern about aversive consequences of eating, low‐appetite, and sensory sensitivity, and that clinical threshold scores on the latter two subscales can be used to advance ARFID assessment. [ABSTRACT FROM AUTHOR]

Objective: Research comparing psychiatric comorbidities between individuals with avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) is limited. ARFID often develops in childhood, whereas AN typically develops in adolescence or young adulthood. Understanding how age may impact differential psychological comorbidity profiles is important to inform etiological conceptualization, differential diagnosis, and treatment planning. We aimed to compare the lifetime frequency of psychiatric comorbidities and suicidality between females with ARFID (n = 51) and AN (n = 40), investigating the role of age as a covariate. Method: We used structured interviews to assess the comparative frequency of psychiatric comorbidities/suicidality. Results: When age was omitted from analyses, females with ARFID had a lower frequency of depressive disorders and suicidality compared to AN. Adjusting for age, only suicidality differed between groups. Discussion: This is the first study to compare comorbidities in a similar number of individuals with ARFID and AN, and a structured clinical interview to confer ARFID and comorbidities, covarying for age, and the first to compare suicidality. Although suicidality is at least three times less common in ARFID than AN, observed differences in other psychiatric comorbidities may reflect ARFID's relatively younger age of presentation compared to AN. Public Significance: Our results highlight that, with the exception of suicidality, which was three times less common in ARFID than AN irrespective of age, observed differences in psychiatric comorbidities in clinical practice may reflect ARFID's younger age at clinical presentation compared to AN. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa (AN) is a serious condition characterized by undernutrition, complicated by endocrine dysregulation, and with few predictors of recovery. Urinary free cortisol (UFC) is a predictor of weight gain, but 24‐h urine samples are challenging to collect. We hypothesized that serum dehydroepiandrosterone sulfate (DHEAS), which like cortisol is regulated by adrenocorticotropic hormone (ACTH), would predict weight gain and increases in fat mass in women with AN. Methods: We prospectively studied 34 women with AN and atypical AN, mean age 27.4 ± 7.7 years (mean ± SD), who received placebo in a 6‐month randomized trial. Baseline DHEAS and 24‐h UFC were measured by liquid chromatography with tandem mass spectrometry. Body composition was assessed at baseline and 6 months by DXA and cross‐sectional abdominal CT at L4. Results: Mean baseline DHEAS level was 173 ± 70 μg/dl (0.7 ± 0.3 times the mean normal range for age) and mean baseline UFC (n = 15) was 20 ± 18 μg/24 h (normal: 0–50 μg/24 h). Higher DHEAS levels predicted weight gain over 6 months (r = 0.61, p <.001). DHEAS levels also predicted increases in fat mass (r = 0.40, p =.03), appendicular lean mass (r = 0.38, p =.04), and abdominal adipose tissue (r = 0.60, p <.001). All associations remained significant after controlling for age, baseline BMI, OCP use, duration of AN, and SSRI/SNRI use. DHEAS levels correlated with UFC (r = 0.61, p =.02). Discussion: In women with AN, higher serum DHEAS predicts weight gain and increases in fat and muscle mass. Additional studies are needed to confirm these findings and further elucidate the association between DHEAS and weight gain. Public Significance: Anorexia nervosa is a severe psychiatric condition, and predictors of weight recovery are needed to improve prognostication and guide therapeutic decision making. While urinary cortisol is a predictor of weight gain, 24‐h urine collections are challenging to obtain. Like cortisol, dehydroepiandrosterone sulfate (DHEAS) is a hormone produced by the adrenal glands. As a readily available blood test, DHEAS holds promise as more practical biomarker of weight gain in anorexia nervosa. [ABSTRACT FROM AUTHOR]

Objective: Data regarding clinical characteristics in males with AN are limited. We aimed to delineate clinical, biochemical, and hematological features in community‐dwelling adolescent and young adult males with AN. Method: A retrospective chart review of electronic medical records from 2000 to 2016 was conducted for 53 males aged 10–23 years old; AN (n = 36) and healthy controls (n = 17) were similar for Tanner stage. Results: Adolescent and young adult males with AN were diagnosed at a mean age of 15.9 ± 3.0 years. The most prevalent strategy for weight loss (following calorie restriction) was over‐exercising. Labs demonstrated polycythemia, leukopenia, and thrombocytopenia, but no electrolyte abnormalities. Compared with healthy controls of similar Tanner stage, males with AN had lower total testosterone levels. A significant proportion of males with AN had traumatic bone fractures. Discussion: Over‐exercising is a common secondary weight loss strategy in males with AN. Testosterone levels are lower than in controls, but electrolyte abnormalities are rare. With enhanced provider awareness, diagnostic delays may be prevented. [ABSTRACT FROM AUTHOR]

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin‐like growth factor 1 (IGF‐1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF‐1 used off‐label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12‐month, randomized, placebo‐controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF‐1 followed by 6 months of risedronate ("rhIGF‐1/Risedronate") (n = 33), 12 months of risedronate ("Risedronate") (n = 33), or double placebo ("Placebo") (n = 16). Outcome measures were lumbar spine (1° endpoint: postero‐anterior [PA] spine), hip, and radius aBMD by dual‐energy X‐ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high‐resolution peripheral quantitative computed tomography (HR‐pCT) (for extremity measurements) and multi‐detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF‐1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF‐1/Risedronate than the Risedronate or Placebo groups (p < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF‐1/Risedronate than Placebo group (p < 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF‐1 was well tolerated. Therefore, sequential therapy with rhIGF‐1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Purpose: Gamma‐aminobutyric acid (GABA) abnormalities have been implicated in a range of neuropsychiatric disorders. Despite substantial interest in probing GABA in vivo, human imaging studies relying on magnetic resonance spectroscopy (MRS) have generally been hindered by technical challenges, including GABA's relatively low concentration and spectral overlap with other metabolites. Although past studies have shown moderate‐to‐strong test‐retest repeatability and reliability of GABA within certain brain regions, many of these studies have been limited by small sample sizes. Methods: GABA+ (macromolecular‐contaminated) test‐retest reliability and repeatability were assessed via a Meshcher‐Garwood point resolved spectroscopy (MEGA‐PRESS) MRS sequence in the rostral anterior cingulate cortex (rACC; n = 21) and dorsolateral prefrontal cortex (dlPFC; n = 20) in healthy young adults. Data were collected on a 3T scanner (Siemens Prisma, Siemens Healthcare, Erlangen, Germany) and GABA+ results were reported in reference to both total creatine (GABA+/tCr) and water (GABA+/water). Results: Results showed strong test‐retest repeatability (mean GABA+/tCr coefficient of variation [CV] = 4.6%; mean GABA+/water CV = 4.0%) and reliability (GABA+/tCr intraclass correlation coefficient [ICC] = 0.77; GABA+/water ICC = 0.87) in the dlPFC. The rACC showed acceptable (but comparatively lower) repeatability (mean GABA+/tCr CV = 8.0%; mean GABA+/water CV = 7.5%), yet low‐moderate reliability (GABA+/tCr ICC = 0.40; GABA+/water ICC = 0.44). Conclusion: The present study found excellent GABA+ MRS repeatability and reliability in the dlPFC. The rACC showed inferior results, possibly because of a combination of shimming impedance and measurement error. These data suggest that MEGA‐PRESS can be utilized to reliably distinguish participants based on dlPFC GABA+ levels, whereas the mixed results in the rACC merit further investigation. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in young adults with obesity. Obesity is associated with relative growth hormone (GH) deficiency, and data from animal studies and from humans with pituitary GH deficiency suggest a role for GH deficiency in the pathogenesis of NAFLD. The effects of GH on NAFLD in those with obesity are unknown, however, prompting this pilot study to assess effects of GH administration on measures of NAFLD in young adults. Methods: Twenty‐four men and women aged 18–29 years with BMI ≥ 30 kg/m2, hepatic fat fraction (HFF) ≥ 5% on proton magnetic resonance spectroscopy (1H‐MRS) and insulin‐like growth factor 1 (IGF‐1) z‐score ≤ 0 were randomized to treatment with recombinant human GH (rhGH) versus no treatment for 24 weeks. The primary endpoint was change in HFF. Results: Compared to no treatment, the effect size of rhGH on absolute HFF over 24 weeks was −3.3% (95% confidence interval: −7.8%, 1.2%; p =.14). At 24 weeks, HFF < 5% was achieved in 5 of 9 individuals receiving rhGH versus 1 of 9 individuals receiving no treatment (p =.04). rhGH did not significantly reduce ALT, AST or GGT. Serum IGF‐1 increased as expected with rhGH treatment, and there were no changes in fasting lipids, C‐reactive protein, fasting glucose or 2‐h glucose following an oral glucose tolerance test. Conclusion: Data from this pilot study suggest that rhGH treatment in young adults with obesity and NAFLD may have benefits to reduce liver fat content, although larger studies are needed to confirm this effect. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the optimal treatment of avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate feasibility, acceptability, and proof‐of‐concept for cognitive‐behavioral therapy for ARFID (CBT‐AR) in children and adolescents. Method: Males and females (ages 10–17 years) were offered 20–30 sessions of CBT‐AR delivered in a family‐based or individual format. Results: Of 25 eligible individuals, 20 initiated treatment, including 17 completers and 3 dropouts. Using intent‐to‐treat analyses, clinicians rated 17 patients (85%) as "much improved" or "very much improved." ARFID severity scores (on the Pica, ARFID, and Rumination Disorder Interview) significantly decreased per both patient and parent report. Patients incorporated a mean of 16.7 (SD = 12.1) new foods from pre‐ to post‐treatment. The underweight subgroup showed a significant weight gain of 11.5 (SD = 6.0) pounds, moving from the 10th to the 20th percentile for body mass index. At post‐treatment, 70% of patients no longer met criteria for ARFID. Discussion: This is the first study of an outpatient manualized psychosocial treatment for ARFID in older adolescents. Findings provide evidence of feasibility, acceptability, and proof‐of‐concept for CBT‐AR. Randomized controlled trials are needed. [ABSTRACT FROM AUTHOR]

Objective: To improve our understanding of medical complications and endocrine alterations in patients with low‐weight avoidant/restrictive food intake disorder (ARFID) and how they may differ from those in anorexia nervosa (AN) and healthy controls (HC). Method: We performed an exploratory cross‐sectional study comparing low‐weight females with ARFID (n = 20) with females with AN (n = 42) and HC (n = 49) with no history of an eating disorder. Results: We found substantial overlap in medical comorbidities and endocrine features in ARFID and AN, but with earlier onset of aberrant eating behaviors in ARFID. We also observed distinct medical and endocrine alterations in ARFID compared to AN, such as a greater prevalence of asthma, a lower number of menses missed in the preceding 9 months, higher total T3 levels, and lower total T4 : total T3 ratio; these differences persisted after adjusting for age and might reflect differences in pathophysiology, acuity of weight fluctuations, and/or nutritional composition of food consumed. Conclusion: These results highlight the need for prompt diagnosis and intensive therapeutic intervention from disease onset in ARFID. [ABSTRACT FROM AUTHOR]

Objective: This study examined the relationship between eating‐disorder behaviors—including restrictive eating, binge eating, and purging—and suicidal ideation. We hypothesized that restrictive eating would significantly predict suicidal ideation, beyond the effects of binge eating/purging. Methods: Participants were 82 adolescents and young adults with low‐weight eating disorders. We conducted a hierarchical logistic regression, with binge eating and purging in Step 1 and restrictive eating in Step 2, to predict suicidal ideation. Results: Step 1 was significant (p =.01) and explained 20% variance in suicidal ideation; neither binge eating nor purging significantly predicted suicidal ideation. Adding restrictive eating in Step 2 significantly improved the model (ΔR2 =.07, p =.009). This final model explained 27% of the variance, and restrictive eating (but not binge eating/purging) significantly predicted suicidal ideation (p =.02). Discussion Restrictive eating is associated with suicidal ideation in youth with low‐weight eating disorders, beyond the effects of other eating‐disorder behaviors. Although healthcare providers may be more likely to screen for suicidality in patients with binge eating and purging, our findings indicate clinicians should regularly assess suicide and self‐injury in patients with restrictive eating. Future research examining how individuals progress from suicidal ideation to suicidal attempts can further enhance our understanding of suicide in eating disorders. [ABSTRACT FROM AUTHOR]

Objective: We aimed to characterize the current and lifetime prevalence of comorbid psychiatric diagnoses and suicidality in treatment‐ and nontreatment‐seeking individuals with full and subthreshold avoidant/restrictive food intake disorder (ARFID). We also sought to examine unique associations between the three DSM‐5 ARFID profiles (i.e., sensory sensitivity, fear of aversive consequences, and lack of interest in food or eating) and specific categories of psychiatric diagnoses and suicidality. Method: We conducted structured clinical interviews with 74 children and adolescents with full or sub threshold ARFID to assess the presence of comorbid psychiatric diagnoses, suicidality, and the severity of each of the three ARFID profiles. Results: Nearly half of the sample (45%) met criteria for a current comorbid psychiatric diagnosis, and over half (53%) met criteria for a lifetime comorbid diagnosis. A total of 8% endorsed current suicidality and 14% endorsed lifetime suicidality. Severity in the sensory sensitivity profile was uniquely associated with greater odds of comorbid disorders in the neurodevelopmental, disruptive, and conduct disorders category; the anxiety, obsessive–compulsive, and trauma‐related disorders category; and the depressive and bipolar‐related disorders category. Severity in the fear of aversive consequences profile was associated with greater odds of disorders in the anxiety, obsessive–compulsive, and trauma‐related disorders category. Discussion: Our findings underscore the severity of psychopathology among individuals with ARFID and related presentations, and also highlight the potential that shared psychopathology between specific ARFID profiles and other psychiatric disorders represent transdiagnostic constructs (e.g., avoidant behavior) that may be relevant treatment targets. [ABSTRACT FROM AUTHOR]

Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual‐energy X‐ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA. Seventy‐five OAs (ages 14 to 25 years) were randomized to (i) a 100‐μg 17β‐estradiol transdermal patch (PATCH) administered continuously with 200 mg cyclic oral micronized progesterone; (ii) a combined 30 μg ethinyl estradiol and 0.15 mg desogestrel pill (PILL); or (iii) no estrogen/progesterone (NONE) and were followed for 12 months. Calcium (≥1200 mg) and vitamin D (800 IU) supplements were provided to all. Bone microarchitecture was assessed using high‐resolution peripheral quantitative CT at the distal tibia and radius at baseline and 1 year. At baseline, randomization groups did not differ by age, body mass index, percent body fat, duration of amenorrhea, vitamin D levels, BMD, or bone microarchitecture measurements. After 1 year of treatment, at the distal tibia there were significantly greater increases in total and trabecular volumetric BMD (vBMD), cortical area and thickness, and trabecular number in the PATCH versus PILL groups. Trabecular area decreased significantly in the PATCH group versus the PILL and NONE groups. Less robust differences between groups were seen at the distal radius, where percent change in cortical area and thickness was significantly greater in the PATCH versus PILL and NONE groups, and changes in cortical vBMD were significantly greater in the PATCH versus PILL groups. In conclusion, in young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β‐estradiol versus ethinyl estradiol–containing pills, particularly at the tibia. © 2019 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Summary: Objective: Few bone mineral density (BMD) data are available in men with anorexia nervosa (AN), and none in those with atypical AN (ATYP) (AN psychological symptoms without low weight) or avoidant/restrictive food intake disorder (ARFID) (restrictive eating without AN psychological symptoms). We investigated the prevalence and determinants of low BMD and estimated hip strength in men with these disorders. Design: Cross‐sectional: two centres. Patients: A total of 103 men, 18‐63 years: AN (n = 26), ARFID (n = 11), ATYP (n = 18), healthy controls (HC) (n = 48). Measurements: Body composition, BMD and estimated hip strength (section modulus and buckling ratio) by DXA (Hologic). Serum 25OH vitamin D was quantified, as was daily calcium intake in a subset of subjects. Results: Mean BMI was lowest in AN and ARFID, higher in ATYP and highest in HC (AN 14.7 ± 1.8, ARFID 15.3 ± 1.5, ATYP 20.6 ± 2.0, HC 23.7 ± 3.3 kg/m2) (P < 0.0005). Mean BMD Z‐scores at spine and hip were lower in AN and ARFID, but not ATYP, than HC (postero‐anterior (PA) spine AN −2.05 ± 1.58, ARFID −1.33 ± 1.21, ATYP −0.59 ± 1.77, HC −0.12 ± 1.17) (P < 0.05). 65% AN, 18% ARFID, 33% ATYP and 6% HC had BMD Z‐scores <−2 at ≥1 site (AN and ATYP vs HC, P < 0.01). Mean section modulus Z‐scores were lower in AN than HC (P < 0.01). Lower BMI, muscle mass and vitamin D levels (R = 0.33‐0.64), as well as longer disease duration (R = −0.51 to −0.58), were associated with lower BMD (P < 0.05). Conclusions: Men with AN, ARFID and ATYP are at risk for low BMD. Men with these eating disorders who are low weight, or who have low muscle mass, long illness duration and/or vitamin D deficiency, may be at particularly high risk. [ABSTRACT FROM AUTHOR]

Objective: The majority of individuals with anorexia nervosa (AN) have a fat‐phobic (FP‐AN) presentation in which they explicitly endorse fear of weight gain, but a minority present as non‐fat‐phobic (NFP‐AN). Diagnostic criteria for avoidant/restrictive food intake disorder (ARFID) specifically exclude fear of weight gain. Differential diagnosis between NFP‐AN and ARFID can be challenging and explicit endorsements do not necessarily match internal beliefs. Method: Ninety‐four adolescent females (39 FP‐AN, 13 NFP‐AN, 10 low‐weight ARFID, 32 healthy controls [HC]) completed implicit association tests (IATs) categorizing statements as pro‐dieting or non‐dieting and true or false (questionnaire‐based IAT), and images of female models as underweight or normal‐weight and words as positive or negative (picture‐based IAT). We used the Eating Disorder Examination to categorize FP‐ versus NFP‐AN presentations. Results: Individuals with FP‐AN and NFP‐AN demonstrated a stronger association between pro‐dieting and true statements, whereas those with ARFID and HCs demonstrated a stronger association between pro‐dieting and false statements. Furthermore, while all groups demonstrated a negative implicit association with underweight models, HC participants had a significantly stronger negative association than individuals with FP‐AN and NFP‐AN. Discussion: Individuals with NFP‐AN exhibited a mixed pattern in which some of their implicit associations were consistent with their explicit endorsements, whereas others were not, possibly reflecting a minimizing response style on explicit measures. In contrast, individuals with ARFID demonstrated implicit associations consistent with explicit endorsements. Replication studies are needed to confirm whether the questionnaire‐based IAT is a promising method of differentiating between restrictive eating disorders that share similar clinical characteristics. [ABSTRACT FROM AUTHOR]

Objective Adolescents and women with anorexia nervosa (AN) are known to severely restrict total calorie and fat intake. However, data are limited regarding specific macronutrient intake associated with weight gain in AN. Objective To prospectively investigate dietary macronutrient composition associated with weight gain in adolescent girls with AN. Method A prospective naturalistic study of 90 girls 12-18 years old; 45 with AN and 45 healthy normal-weight-controls over a 6-12-month period. Participants completed four-day food diaries and underwent body composition assessment using dual energy X-ray absorptiometry. Weight gain was defined as a ≥10% increase in body mass index (BMI) from baseline. Results Baseline clinical characteristics did not differ between girls with AN who did not gain weight (AN-0) versus those who did (AN-1) over the following 6-12 month period except for percentage of calories from proteins ( p = 0.046). At 6-12 month follow-up, AN-1 consumed a lower percentage of total calories from protein ( p = .001), and a higher percentage of total calories from fat ( p = .02) compared to AN-0. AN-1 had a significant increase in the percentage of total calories obtained from and poly-unsaturated-fatty acids (PUFA) ( p = 0.006) compared to AN-0, between baseline and follow-up. Within the AN group, BMI at follow-up was associated positively with percentage of total calories obtained from fat, MUFA, and PUFA ( p < .05) at 6/12 months, and inversely with the percentage of total calories obtained from carbohydrates and proteins ( p = .03). Discussion Consuming a greater proportion of total calories from fat is associated with weight gain in adolescent girls with AN. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective DSM-5 revised the diagnostic criteria for anorexia nervosa (AN) by eliminating the amenorrhea requirement, liberalizing weight and psychological criteria, and adding the formal diagnosis of 'atypical AN' for individuals with AN psychological symptoms without low weight. We sought to determine whether bone density (BMD) is impaired in women diagnosed with AN using the new, more liberal, DSM-5 criteria. Method Cross-sectional study of 168 women, 18 − 45y: (1) AN by DSM-IV ( DSM-IV AN ) ( n = 37), (2) AN by DSM-5 but not DSM-IV criteria ( DSM-5 AN) ( n = 33), (3) atypical AN ( ATYPICAL AN) ( n = 77), (4) healthy comparison group ( HC) ( n = 21). Measurements included dual energy X-ray absorptiometry, Eating Disorder Examination-Questionnaire, Eating Disorder Inventory-2, Hamilton Depression and Anxiety Rating Scales. Results BMD Z-score <−1.0 was present in 78% of DSM-IV, 82% of DSM-5, and 69% of ATYPICAL. Mean Z-scores were comparably low in DSM-IV and DSM-5, intermediate in ATYPICAL, and highest in HC. Lack of prior low weight or amenorrhea was, but history of overweight/obesity was not, protective against bone loss. Mean lean mass and percent fat mass were significantly lower in all AN groups than HC. DSM-IV, DSM-5, and ATYPICAL had comparable psychopathology. Discussion Despite liberalizing diagnostic criteria, many women diagnosed with AN and atypical AN using DSM-5 criteria have low BMD. Presence or history of low weight and/or amenorrhea remain important indications for DXA. Loss of lean mass, in addition to fat mass, is present in all AN groups, and may contribute to low BMD. The deleterious effect of eating disorders on BMD extends beyond those with current low weight and amenorrhea. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:343-351) [ABSTRACT FROM AUTHOR]

Clinicians currently use different low-weight cut-offs both to diagnose anorexia nervosa (AN) and to determine AN severity in adolescent girls. The purpose of this study was to evaluate the clinical utility of existing cut-offs and severity criteria by determining which are most strongly associated with risk for low bone mineral density (BMD). Height adjusted BMD Z scores were calculated for 352 females: 262 with AN and 90 healthy controls (controls) (12-20.5 years), using data from the BMD in Childhood Study, for the lumbar spine, whole body less head, and total hip. For most cut-offs used to define low weight (5th or 10th BMI percentile, BMI of 17.5 or 18.5, and 85 or 90% of median BMI), AN had lower BMD Z scores than controls. AN at >85 or >90% expected body weight for height (EBW-Ht) did not differ in BMD Z scores from controls, but differed significantly from AN at ≤85 or ≤90% EBW-Ht. Among AN, any amenorrhea was associated with lower BMD. AN had lower BMD than controls across DSM-5 and The Society for Adolescent Health and Medicine (SAHM) severity categories. The SAHM moderate severity classification was differentiated from the mildly malnourished classification by lower BMD at hip and spine sites. Amenorrhea and %EBW-Ht ≤ 85 or ≤ 90% are markers of severity of bone loss within AN. Among severity categories, BMI Z scores (SAHM) may have the greatest utility in assessing the degree of malnutrition in adolescent girls that corresponds to lower BMD. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to examine the relative contributions of body mass index ( BMI) and pubertal measures for risk and age of onset of pediatric MS. Methods Case-control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex- and age-stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex-stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity. Results Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls ( OR = 1.60, 95% confidence interval [ CI]: 1.12, 2.27, P = 0.009) and boys ( OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms ( P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS ( P < 0.001). Interpretation Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management. Method Search terms included 'anorexia nervosa' AND 'bone density' for the period 1995-2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995. Results AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN. Discussion To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. [ABSTRACT FROM AUTHOR]

ABSTRACT Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting ( p < 0.0001) but were highest in anorexia nervosa for bending ( p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending ( p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls ( p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass ( R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT ( R = -[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load-to-strength ratio helps explain increased fracture risk in both low-weight and obese women. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Disordered eating may negatively impact bone in athletes. However, it is not known whether this effect is independent of the associated amenorrhea and relative hypercortisolemia. We aimed to compare attitudes, feelings, and cognitions associated with disordered eating using the Three-Factor Eating Questionnaire (TFEQ) and Eating Disorder Inventory-2 (EDI-2) in normal-weight oligomenorrheic athletes (OA), eumenorrheic athletes (EA), and nonathletes, and determine the associations with bone independent of confounders. Method 109 OA, 39 EA, and 36 nonathletes (14-25 years) completed the TFEQ and EDI-2. Dual-energy X-ray absorptiometry was used to assess spine bone mineral density (BMD), and high-resolution pQCT to assess radius microarchitecture. We measured integrated cortisol (q 20′, 11 PM-7 AM), bone formation (procollagen Type 1 N-terminal propeptide, P1NP), and resorption (C-telopeptide, CTX) markers in a subset. Results OA had lower spine BMD Z-scores than EA. Cognitive eating restraint (CER), drive for thinness (DT), ineffectiveness, and interoceptive awareness (IA) were higher in OA than EA ( p < 0.05); CER was higher in OA versus nonathletes ( p = 0.03). Pulsatile cortisol was positively associated with DT, ineffectiveness, and IA (p < 0.03). CER was inversely associated with BMD Z-scores and P1NP, and ineffectiveness with radius cross-sectional area even after controlling for age, BMI, amenorrhea duration, and cortisol (p < 0.03). Discussion Higher CER in athletes independently predicts lower BMD. © 2015 Wiley Periodicals, Inc (Int J Eat Disord 2015; 48:522-526). [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To (i) compare fracture prevalence in adolescent females with anorexia nervosa (AN) versus normal-weight controls and (ii) examine whether reductions in areal bone mineral density (aBMD) predict fracture risk in females with AN. Method Four-hundred eighteen females (310 with active AN and 108 normal-weight controls) 12- to 22-years-old were studied cross-sectionally. Lifetime fracture history was recorded by a physician during participant interviews. Body composition and aBMD measurements of the whole body, whole body less head, lumbar spine, and hip were assessed by dual-energy X-ray absorptiometry, and bone mineral apparent density (BMAD) was calculated for the lumbar spine. Results Participants with AN and normal-weight controls did not differ for chronological age, sexual maturity, or height. The lifetime prevalence of prior fracture was 59.8% higher in those with AN as compared to controls (31.0% vs. 19.4%, p = 0.02), and the fracture incidence rate peaked in our cohort after the diagnosis of AN. Lower aBMD and lumbar BMAD were not associated with a higher prevalence of fracture in the AN or control group on univariate or multivariate analyses. Compared to controls, fracture prevalence was significantly higher in the subgroup of girls with AN who had normal aBMD or only modest reductions of aBMD ( Z-scores > −1 or −1.5). Discussion This is the first study to show that the risk of fracture during childhood and adolescence is significantly higher in patients with AN than in normal-weight controls. Fracture prevalence is increased in this cohort of participants with AN even without significant reductions in aBMD. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:458-466) [ABSTRACT FROM AUTHOR]

Objective Adolescents with anorexia nervosa ( AN) are amenorrheic and have decreased bone mass accrual and low bone mineral density ( BMD). The regulation of mesenchymal stem cell differentiation is an important factor governing bone formation. Preadipocyte factor 1 (Pref-1), an inhibitor of adipocyte and osteoblast differentiation, is elevated in states of oestrogen deficiency. In this study, we aim to (i) investigate effects of transdermal oestradiol on Pref-1 in adolescent girls with AN, and (ii) examine associations of changes in Pref-1 with changes in lumbar BMD and bone turnover markers. Design Adolescent girls with AN and normal-weight controls were studied cross-sectionally. Girls with AN were examined longitudinally in a double-blind study and received transdermal oestradiol (plus cyclic medroxyprogesterone) or placebo for 12 months. Patients Sixty-nine girls (44 with AN, 25 normal-weight controls) 13-18 years were studied at baseline; 22 AN girls were followed prospectively. Measurements Pref-1 levels, bone formation and resorption markers, and BMD. Results Pref-1 levels decreased in girls with AN after treatment with transdermal oestradiol compared with placebo (−0·015 ± 0·016 vs 0·060±0·026 ng/ml, P = 0·01), although at baseline, levels did not differ in AN vs controls (0·246 ± 0·015 vs 0·267 ± 0·022 ng/ml). Changes in Pref-1 over 12 months correlated inversely with changes in lumbar BMD ( r = −0·48, P = 0·02) and positively with changes in CTX ( r = 0·73, P = 0·006). Conclusions For the first time, we show that Pref-1 is negatively regulated by oestradiol in adolescent girls with AN. Inhibition of Pref-1 may mediate the beneficial effects of transdermal oestradiol replacement on BMD in girls with AN. [ABSTRACT FROM AUTHOR]

Objective Hyperinsulinaemia is an important determinant of the polycystic ovarian syndrome ( PCOS). In addition to lifestyle measures, therapeutic strategies include the use of oestrogen-progesterone combination pills ( EP), and insulin sensitizers such as metformin, either alone or in combination. Data are limited regarding the impact of metformin alone vs metformin with EP on cardiometabolic risk in overweight adolescents with PCOS. We hypothesized that metformin alone would lead to an improvement in HbA1C and lipid levels in overweight adolescent girls with PCOS compared with meformin with EP. Study design Retrospective clinic-based therapy. Patients and measurements We examined the effects of therapy with metformin alone ( n = 14) vs metformin with EP ( n = 13) on HbA1C and lipid parameters over 10-14 months in 27 overweight girls, drawn from a clinic population of adolescents with PCOS. Results The groups did not differ for age, body mass index ( BMI), HbA1C or baseline lipids. After at least 10 months, the metformin only group compared with the metformin and EP group had a decrease in total cholesterol (−0·605 ± 0·100 vs 0·170 ± 0·348 m m, P = 0·02, nonparametric test) and triglycerides (−0·342 ± 0·184 vs 0·262 ± 0·133 m m, P = 0·02), despite similar changes in BMI (−1·6 ± 0·7 vs 0·6 ± 2·1 kg/m2, P = 0·25) and HbA1C (0·03 ± 0·06 vs 0·03 ± 0·13%, P = 0·99). Differences between groups remained significant after controlling for baseline parameters and for changes in BMI. Conclusion Metformin alone more effectively improves lipid parameters than metformin with EP in adolescent PCOS, as indicated by a decrease in total cholesterol and triglycerides. This effect is not related to BMI changes. [ABSTRACT FROM AUTHOR]

The objective of this case report is to present a pharmacologic strategy for treatment of adolescents with anorexia nervosa (AN) and low bone mineral density (BMD). We present a 17.5-year-old girl with a 3-year history of AN and longstanding inability to optimize nutrition and gain weight, and a decrease over time in her already low BMD. A year after treatment with the 17-β estradiol patch (100 mcg twice weekly) with cyclic oral progesterone (2.5 mg medroxyprogesterone acetate daily for days 1-10 of every month), her spine and hip BMD Z-scores improved, and a further decrease was prevented. This novel treatment is a consideration for girls with AN at greatest risk for low BMD. Adolescents with AN are at risk for low BMD, and the most effective treatment is weight and menses restoration, which can be difficult to attain and to sustain. Recent studies have shown promising results with pharmacological therapy for low BMD in AN. This article discusses current concepts related to bone loss in AN, and new pharmacologic considerations for adolescents at greatest risk for low BMD. © 2013 by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective Amenorrhoea and low bone density are common in excessive exercisers, yet endocrine factors that differentiate adolescent amenorrhoeic exercisers ( AE) from eumenorrhoeic exercisers ( EE) are unclear. We have previously reported that high ghrelin and low leptin predict lower LH secretion in AE. Leptin and ghrelin impact cortisol secretion, and hypercortisolaemia can inhibit LH pulsatility. We hypothesized that higher cortisol secretion in young endurance weight-bearing AE compared with EE and nonexercisers predicts lower LH secretion, lower levels of a bone formation marker and higher levels of a bone resorption marker. Design Cross-sectional. Subjects We studied 21 AE, 18 EE and 20 nonexercisers aged 14-21 years ( BMI 10th-90th%iles). Measurements Subjects underwent frequent sampling (11 p.m. to 7 a.m.) to assess cortisol, ghrelin, leptin and LH secretory dynamics. Fasting levels of a bone formation ( P1 NP) and bone resorption ( CTX) marker were measured. Results BMI did not differ among groups. Cortisol pulse amplitude, mass, half-life and area under the curve ( AUC) were highest in AE ( P = 0·04, 0·007, 0·04 and 0·003) and were associated inversely with fat mass ( r = −0·29, −0·28 and −0·35, P = 0·03, 0·04 and 0·007). We observed inverse associations between cortisol and LH AUC ( r = −0·36, P = 0·008), which persisted after controlling for fat mass, leptin and ghrelin AUC. Cortisol correlated positively with CTX in EE and inversely with P1 NP in nonexercisers. Conclusions Higher cortisol secretion in AE compared with EE and nonexercisers is associated with lower LH secretion. Effects of leptin and ghrelin on LH secretion may be mediated by increased cortisol. [ABSTRACT FROM AUTHOR]

Objective: Despite a lack of data demonstrating benefit, psychotropic medications are frequently prescribed for patients with anorexia nervosa. Method: We studied 525 women (18-54 years of age) with anorexia nervosa who presented to the Clinical Research Center at the Massachusetts General Hospital between January 1997 and December 2009. For this analysis, participants were a priori divided into two groups based on date of presentation (Group I: participants presenting between 1997 and 2002; Group II: participants presenting between 2003 and 2009). Results: Overall, 53% of participants reported current use of any psychotropic medication; 48.4% reported use of an antidepressant and 13% reported use of an antipsychotic. Twice as many participants in Group II (18.5%) reported using atypical antipsychotics as compared to Group I (8.9%) ( p = 0.002). Discussion: A majority of participants with anorexia nervosa report using psychotropic medications despite lack of data supporting their efficacy. These data are concerning given the known adverse effects of these medications. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012) [ABSTRACT FROM AUTHOR]

Summary Objective Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite-regulating hormones may have opposing effects on mood and stress pathways. Women with anorexia nervosa (AN), hypothalamic amenorrhoea (HA) and obesity are at increased risk of depression and anxiety. It is unknown whether dysregulation of leptin or ghrelin contributes to the development of depression and/or anxiety in these disorders. We investigated the relationship between leptin and ghrelin levels and symptoms of depression, anxiety and perceived stress in women across the weight spectrum. Design Cross-sectional. Patients 64 women: 15 with AN, 12 normal-weight with HA, 17 overweight or obese (OB) and 20 normal-weight in good health (HC). Measurements Fasting serum leptin and plasma ghrelin levels were measured. Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Perceived Stress Scale were administered. Results Leptin levels were inversely associated with HAM-D, HAM-A and Perceived Stress scores. The negative relationships between leptin and severity of symptoms of both depression and anxiety remained significant after controlling for body fat or weight. There was no relationship between ghrelin and symptoms of depression or anxiety. Although ghrelin levels were positively associated with the degree of perceived stress, this relationship was not significant after controlling for body fat or weight. Conclusions Leptin may mediate depressive symptoms across the weight spectrum. Further investigation of the role of leptin in modulating mood will be important. [ABSTRACT FROM AUTHOR]

Summary Objective Strenuous training commonly results in amenorrhoea, which contributes to bone loss in some female collegiate athletes. However, the impact of athletic training on endocrine function and bone mineral density (BMD) in male collegiate athletes is less well understood. The objective of the study was to investigate the specific endocrine determinants of BMD in male collegiate runners and wrestlers, including the potential impact of gonadal steroid levels. Design Cross-sectional study. Patients Twenty-six division I collegiate male athletes (wrestlers, runners and golfers). Measurements Main outcome measures included (i) BMD endpoints measured by dual energy x-ray absorptiometry (DXA); (ii) endocrine end-points: total and free oestradiol, total and free testosterone; (iii) body composition end-points: lean and fat mass, measured by DXA; and (iv) exercise end-points: maximal oxygen uptake (VO2 max), number of miles run weekly and grip strength. Results Free and total oestradiol levels were important positive determinants of BMD. In contrast, total and free testosterone levels were not significant predictors of BMD at any skeletal site (except for free testosterone at the radius). In addition, lean body mass, % ideal body weight, total body weight, body mass index (BMI) and hours per week of resistance training were positive predictors of BMD. VO2 max was a negative predictor of BMD. Mean BMD was higher at all skeletal sites in the wrestlers compared with the runners and a comparison group (golfers). Conclusions Our data suggest that oestradiol levels, BMI, and resistance training are more important determinants of BMD in male collegiate athletes than testosterone. [ABSTRACT FROM AUTHOR]

Summary Background Puberty is characterized by increases in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) and the pubertal growth spurt. Bone formation and resorption also increase, consistent with increased bone metabolism. Objective To determine the relationship between pubertal bone metabolism, GH and IGF-1. We hypothesized that bone turnover peaks at the time of greatest pubertal GH secretion. Design and Subjects Subjects included 86 girls and boys, 9-17 years-old (BMI 10th-90th percentiles). Because higher endogenous GH secretion is associated with a higher nadir following oral glucose, we used the GH nadir following a 2-h OGTT as indicative of GH status. Fasting serum IGF-1, aminoterminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal collagen crosslinks (CTX) were obtained. Subjects were grouped per expected timing of peak growth. Group 1: Tanner 1 girls and Tanner 1-2 boys (period preceding peak growth), Group 2: Tanner 2-3 girls and Tanner 3-4 boys (period of peak growth) and Group 3: Tanner 4-5 girls and Tanner 5 boys (period following peak growth). Results GH peaked at mid-puberty (Group 2) and IGF-1 in late puberty (Group 3). P1NP and CTX were highest in mid-puberty compared with early and late puberty ( P = 0·0009 and 0·006 in girls and P = 0·005 and 0·04 in boys). GH, but not IGF-1, correlated with P1NP ( r = 0·46 in both genders, P ≤ 0·008) and CTX ( r = 0·37 and 0·38, P = 0·04 and 0·02 in girls and boys, respectively). Similarly, on regression modelling, GH (but not IGF-1) predicted both bone turnover markers in both genders. Conclusion GH is strongly associated with pubertal bone metabolism, independent of systemic IGF-1 in girls and boys. [ABSTRACT FROM AUTHOR]

Pseudohypoparathyroid patients have resistance predominantly to parathyroid hormone (PTH), and here we have examined the ability of an alternative Gαs-related protein to inhibit Gαs activity in a hormone-selective manner. We tested whether the GNAS exon A/B-derived NH2-terminally truncated (Tr) αs protein alters stimulation of adenylate cyclase by the PTH receptor (PTHR1), the thyroid-stimulating hormone (TSH) receptor (TSHR), the β2-adrenergic receptor (β2AR), or the AVP receptor (V2R). HEK293 cells cotransfected with receptor and full-length (FL) Gαs ± Tr αs protein expression vectors were stimulated with agonists (PTH [10−7 to 10−9 M], TSH [1 to 100 mU], isoproterenol [10−6 to 10−8 M], or AVP [10−6 to 10−8 M]). Following PTH stimulation, HEK293 cells cotransfected with PTHR1 + FL Gαs + Tr αs had a significantly lower cAMP response than those transfected with only PTHR1 + FL Gαs. Tr αs also exerted an inhibitory effect on the cAMP levels stimulated by TSH via the TSHR but had little or no effect on isoproterenol or AVP acting via β2AR or V2R, respectively. These differences mimic the spectrum of hormone resistance in pseudohypoparathyroidism type 1a (PHP-1a) and type 1b (PHP-1b) patients. In opossum kidney (OK) cells, endogenously expressing the PTHR1 and β2AR, the exogenous expression of Tr αs at a level similar to endogenous FL Gαs resulted in blunting of the cAMP response to PTH, whereas that to isoproterenol was unaltered. A pseudopseudohypoparathyroid patient with Albright hereditary osteodystrophy harbored a de novo paternally inherited M1I Gαs mutation. Similar maternally inherited mutations at the initiation codon have been identified previously in PHP-1a patients. The M1I αs mutant (lacking the first 59 amino acids of Gαs) blunted the increase in cAMP levels stimulated via the PTHR1 in both HEK293 and OK cells similar to the Tr αs protein. Thus NH2-terminally truncated forms of Gαs may contribute to the pathogenesis of pseudohypoparathyroidism by inhibiting the activity of Gαs itself in a GPCR selective manner. © 2011 American Society for Bone and Mineral Research [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low BMD in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiologic estrogen doses that mimic puberty on BMD has not been examined. We enrolled 110 girls with AN and 40 normal-weight controls 12 to 18 years of age of similar maturity. Subjects were studied for 18 months. Mature girls with AN (bone age [BA] ≥15 years, n = 96) were randomized to 100 µg of 17β-estradiol (with cyclic progesterone) or placebo transdermally for 18 months. Immature girls with AN (BA < 15 years, n = 14) were randomized to incremental low-dose oral ethinyl-estradiol (3.75 µg daily from 0 to 6 months, 7.5 µg from 6 to 12 months, 11.25 µg from 12 to 18 months) to mimic pubertal estrogen increases or placebo for 18 months. All BMD measures assessed by dual-energy X-ray absorptiometry (DXA) were lower in girls with AN than in control girls. At baseline, girls with AN randomized to estrogen (AN E + ) did not differ from those randomized to placebo (AN E-) for age, maturity, height, BMI, amenorrhea duration, and BMD parameters. Spine and hip BMD Z-scores increased over time in the AN E+ compared with the AN E- group, even after controlling for baseline age and weight. It is concluded that physiologic estradiol replacement increases spine and hip BMD in girls with AN. © 2011 American Society for Bone and Mineral Research [ABSTRACT FROM AUTHOR]

Accurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitor therapeutic interventions. The purpose of our study was to assess the accuracy of dual-energy X-ray absorptiometry (DXA) for measuring abdominal and thigh fat, and thigh muscle mass in premenopausal women with obesity, AN, and normal weight compared to computed tomography (CT). In addition, we wanted to assess the impact of hydration on DXA-derived measures of body composition by using bioelectrical impedance analysis (BIA). We studied a total of 91 premenopausal women (34 obese, 39 with AN, and 18 lean controls). Our results demonstrate strong correlations between DXA- and CT-derived body composition measurements in AN, obese, and lean controls (r = 0.77-0.95, P < 0.0001). After controlling for total body water (TBW), the correlation coefficients were comparable. DXA trunk fat correlated with CT visceral fat (r = 0.51-0.70, P < 0.0001). DXA underestimated trunk and thigh fat and overestimated thigh muscle mass and this error increased with increasing weight. Our study showed that DXA is a useful method for assessing body composition in premenopausal women within the phenotypic spectrum ranging from obesity to AN. However, it is important to recognize that DXA may not accurately assess body composition in markedly obese women. The level of hydration does not significantly affect most DXA body composition measurements, with the exceptions of thigh fat. [ABSTRACT FROM AUTHOR]

Objectives Radioactive iodine (131I) therapy is increasingly viewed as a safe and effective treatment for paediatric and adolescent hyperthyroidism. Our objective was to estimate treatment response and its predictors and describe current referral practices for 131I therapy. Design Retrospective study. Patients One hundred and thirty-one children 30 days–21 years old with laboratory evidence of hyperthyroidism, seen in an academic paediatric and adolescent endocrinology practice. Measurements Rate of referral, indications for 131I, predictors of poor treatment response. Results Thirty-eight of 102 patients with persistent hyperthyroidism (37%) received 131I (160 μCi/g thyroid tissue/131I uptake), as did an additional 10 patients initially evaluated by adult thyroidologists. Primary indications were intolerance to (29%) or poor control on (19%) antithyroid drugs, patient preference (50%) and unknown (2%). Of 48 patients treated with 131I, 89% and 11% became hypothyroid after one and two 131I doses, respectively. The goal of 131I therapy was attainment of hypothyroidism. ‘Poor treatment response’ (seen in 27%) was defined as requirement for a second 131I dose or failure to achieve hypothyroidism after 6 months. Predictors of poor treatment response included: previous use of antithyroid drugs (37% vs. 0%, P = 0·02), ophthalmopathy (58% vs. 8%, P = 0·002), and an interval of ≥12 months from diagnosis to 131I (50% vs. 10%, P = 0·003). A very elevated free T4 tended to be more prevalent in those with poor response. Conclusions In children and adolescents with hyperthyroidism, high rates of success after 131I are achievable. Use of antithyroid drugs, pre-existing eye disease and prolonged time to 131I may confer relative resistance to 131I. [ABSTRACT FROM AUTHOR]

Orexigenic and anorexigenic pathways mediate food intake and may be affected by meal composition. Our objective was to determine whether changes in levels of active ghrelin and peptide YY (PYY) differ in obese vs. normal-weight adolescent girls following specific macronutrient intake and predict hunger and subsequent food intake. We enrolled 26 subjects: 13 obese and 13 normal-weight girls, 12–18 years old, matched for maturity (as assessed by bone age) and race. Subjects were assigned a high-carbohydrate, high-protein, and high-fat breakfast in random order. Active ghrelin and PYY were assessed for 4 h after breakfast and 1 h after intake of a standardized lunch. Hunger was assessed using a standardized visual analog scale (VAS). No suppression in active ghrelin levels was noted following macronutrient intake in obese or normal-weight girls. Contrary to expectations, active ghrelin increased in obese girls following the high-carbohydrate breakfast, and the percent increase was higher than in controls (P = 0.046). Subsequent food intake at lunch was also higher (P = 0.03). Following the high-fat breakfast, but not other breakfasts, percent increase in PYY was lower (P = 0.01) and subsequent lunch intake higher (P = 0.005) in obese compared with normal-weight girls. In obese adolescents, specific intake of high-carbohydrate and high-fat breakfasts is associated with greater increases in ghrelin, lesser increases in PYY, and higher intake at a subsequent meal than in controls. Changes in anorexigenic and orexigenic hormones in obese vs. normal-weight adolescents following high-carbohydrate and high-fat meals may influence hunger and satiety signals and subsequent food intake. [ABSTRACT FROM AUTHOR]

Objectives Neuroendocrine factors may predict which athletes develop amenorrhea and which athletes remain eugonadal. Specifically, ghrelin and leptin have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that adolescent athletes with amenorrhea (AA) would have higher ghrelin and lower leptin levels than eumenorrheic athletes (EA) and would predict levels of gonadal steroids. Design Cross-sectional Subjects and measurements We enrolled 58 girls, 21 AA, 19 EA and 18 nonathletic controls 12–18 years old. Fasting blood was drawn for active ghrelin, leptin, E2 and testosterone. Athletes were > 85% of ideal body weight for age based on body mass index (BMI). Results AA girls had lower BMI than EA and controls ( P = 0·003). Log ghrelin was higher in AA than in EA and controls ( P < 0·0001), and remained higher after controlling for BMI Z-scores. Leptin was lower in AA than in the other groups ( P < 0·0001), however, the differences did not persist after controlling for BMI Z-scores. Testosterone was lower in AA than in EA and controls ( P = 0·002) and log E2 trended lower in AA ( P = 0·07). We observed inverse associations of log active ghrelin with testosterone ( P = 0·01), and positive associations of leptin with testosterone and log E2 ( P = 0·02 and 0·009). Conclusion Higher ghrelin levels, even after controlling for BMI, and lower leptin in AA compared with EA and controls, and their inverse and positive associations, respectively, with gonadal steroids suggest endocrine perturbations that may explain why hypogonadism occurs in some but not all athletes. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN), an eating disorder characterized by severe undernutrition and associated with hypogonadotropic hypogonadism, causes marked deficits in bone mass accrual when the disorder begins in the teenage years. Although bone mass accrual improves with weight gain and menstrual recovery, residual deficits persist. Women with a history of teenage onset of AN are more likely to be osteopenic than age-matched women without this history, even after many years of weight and menstrual recovery. Non-recovered women with persistent low weight and amenorrhea have continued decreases in bone density, with a high prevalence of both osteopenia and osteoporosis. Unlike anorexia nervosa, normal-weight bulimia is not associated with low bone density, unless there is a past history of low weight or amenorrhea. A second possible skeletal effect of teenage-onset anorexia nervosa is short stature. Duration of illness and time of onset of anorexia nervosa in relation to the pubertal growth spurt are likely important determinants of statural growth. Adolescent boys with anorexia nervosa are more likely than adolescent girls to have short stature, possibly because growth potential persists for two years longer in boys than in girls. Thus, many adolescent girls may have completed growth or be close to growth completion at the time that they develop anorexia nervosa, whereas adolescent boys may still have significant growth potential remaining. This remaining growth potential may be impaired as a consequence of low levels of insulin-like growth factor-I (IGF-I) levels from persistent undernutrition. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition‐related medical conditions. Less is known about the medical comorbidity/complication frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC).In youth with full/subthreshold ARFID (n = 100; 49% female) and HC (n = 58; 78% female), we assessed self‐reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high‐sensitive C‐reactive protein [hs‐CRP]) and nutritional (25[OH] vitamin D, vitamin B12, and folate) markers.Youth with ARFID, compared with HC, were over 10 times as likely to have self‐reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2–112.1) and over two times as likely to have self‐reported immune‐mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1–4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7–10.5) and hs‐CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4–27.0) levels.Self‐reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake. [ABSTRACT FROM AUTHOR]

A correction to the article "Impact of low-weight severity and menstrual status on bone in adolescent girls with anorexia nervosa" that was published in the April 2017 issue is presented.