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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]

Background: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity. Methods: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm²], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6. Results: Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [-1036 to 1428]; visceral fat: 3.1 cm² [-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups. Conclusions: In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.) [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]

Context: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency.Objective: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes.Design: Double-blind, randomized, placebo-controlled 12-month longitudinal study.Participants: Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study.Intervention: Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range.Main Outcome Measures: Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates.Results: Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups.Conclusions: We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN. [ABSTRACT FROM AUTHOR]

Context: Sleeve gastrectomy (SG), the most common metabolic and bariatric surgery in adolescents, is associated with bone loss. Marrow adipose tissue (MAT) is a dynamic endocrine organ that responds to changes in nutrition and might serve as a novel biomarker for bone health. Two types of MAT have been described, which differ in anatomic location-proximal regulated MAT vs distal constitutive MAT.Objective: To determine the effects of SG on volumetric bone mineral density (vBMD) and MAT in adolescents with obesity. We hypothesized that SG would lead to a decrease in vBMD and differential changes in MAT.Design: 12-month prospective study in 52 adolescents with moderate-to-severe obesity (38 female; mean age:17.5 ± 2.2 years; mean BMI 45.2 ± 7.0 kg/m2), comprising 26 subjects before and after SG and 26 nonsurgical controls.Main Outcome Measures: Lumbar vBMD by quantitative computed tomography; MAT of the lumbar spine, femur and tibia by proton magnetic resonance spectroscopy; abdominal fat and thigh muscle by magnetic resonance imaging.Results: Adolescents lost 34.1 ± 13.1 kg after SG vs 0.3 ± 8.4 kg in the control group (P < 0.001). Lumbar vBMD decreased in the SG group (P = 0.04) and this change was associated with a reduction in weight and muscle area (P < 0.05) and an increase in lumbar MAT (P = 0.0002). MAT of the femur and tibia decreased after SG vs controls (P < 0.05); however, the differences were no longer significant after controlling for change in weight.Conclusion: SG in adolescents decreased lumbar vBMD associated with an increase in lumbar MAT and decrease in extremity MAT. This demonstrates differential changes of regulated MAT in the lumbar spine and constitutive MAT in the distal skeleton in adolescents in response to SG. [ABSTRACT FROM AUTHOR]

Purpose Of Review: DSM-5 defined avoidant/restrictive food intake disorder (ARFID) as a failure to meet nutritional needs leading to low weight, nutritional deficiency, dependence on supplemental feedings, and/or psychosocial impairment. We summarize what is known about ARFID and introduce a three-dimensional model to inform research.Recent Findings: Because ARFID prevalence, risk factors, and maintaining mechanisms are not known, prevailing treatment approaches are based on clinical experience rather than data. Furthermore, most ARFID research has focused on children, rather than adolescents or adults. We hypothesize a three-dimensional model wherein neurobiological abnormalities in sensory perception, homeostatic appetite, and negative valence systems underlie the three primary ARFID presentations of sensory sensitivity, lack of interest in eating, and fear of aversive consequences, respectively. Now that ARFID has been defined, studies investigating risk factors, prevalence, and pathophysiology are needed. Our model suggests testable hypotheses about etiology and highlights cognitive-behavioral therapy as one possible treatment. [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 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]

Peripubertal boys with autism spectrum disorder (ASD) have lower bone mineral density (BMD) than typically developing controls. However, it is not clear whether lower BMD in ASD results in an increased fracture rate. This study examined the rate of fractures in children and adults with and without ASD using a national database of emergency room visits (Nationwide Emergency Department Sample). A higher odds ratio for hip fractures in children and young adults (3-22 years) as well as older adults (23-50 years) with ASD than those without ASD, and a higher odds ratio for forearm and spine fractures in women ages 23-50 with ASD were found. Further studies are necessary to better understand the decreased bone density in ASD and its implications for fracture development. [ABSTRACT FROM AUTHOR]

Aims: Low-weight hypogonadal conditions such as anorexia nervosa are associated with marked changes in body composition, hemodynamic and hematological parameters, and liver enzymes. The impact of athletic activity in normal-weight adolescents with/without amenorrhea on these parameters has not been assessed. Our aim was to examine these parameters in normal-weight athletes and nonathletes and determine any associations with body composition, oligo-amenorrhea, and exercise intensity. Methods: We assessed vital signs, complete blood counts, liver enzymes, and regional body composition in 43 oligo-amenorrheic athletes (OAA), 24 eumenorrheic athletes (EA), and 23 nonathletes aged 14-21 years. Results: The BMI was lower in OAA than in EA. Systolic and pulse pressure and temperature were lowest in OAA. Blood counts did not differ among groups. Aspartate aminotransferase (AST) was higher in both groups of athletes, while alanine aminotransferase (ALT) was higher in OAA than in EA and nonathletes. Total and regional fat were lower in OAA than in other groups, and these factors were associated positively with heart rate and inversely with liver enzymes. Conclusions: Athletic activity is associated with higher AST levels, whereas menstrual dysfunction is associated with lower total and regional fat and higher ALT levels. Higher liver enzymes are associated with reductions in total and regional fat. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article focuses on the consensus statement of International Olympic Committee (IOC) on the term Relative Energy Deficiency in Sport (RED-S). This term describes the physiological and pathophysiological effects of energy deficiency in both male and female athletes. According to the authors, this term more accurately describes the clinical syndrome Female Athlete Triad.

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]

We determined whether bone mineral density (BMD) is lower in boys with autism spectrum disorders (ASD) than controls, and also assessed variables that may affect BMD in ASD. BMD was measured using dual energy X-ray absorptiometry (DXA) in 18 boys with ASD and 19 controls 8-14 years old. Boys with ASD had lower BMD Z-scores at the spine, hip and femoral neck, and differences at the hip and femoral neck persisted after controlling for maturity and BMI. Vitamin D intake from food and in serum were lower in ASD subjects, as was exercise activity. We conclude that BMD is lower in peripubertal boys with ASD and may be associated with impaired vitamin D status and lower exercise activity. [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]

Although Eating Disorders (ED) are known to affect bone health and development, little is known about the longitudinal effect of ED and ED behaviours on bone health in community dwelling adult women. Women (n = 3507) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) participated in a two-phase prevalence study to assess lifetime ED and ED behaviours (fasting, restrictive eating, vomiting and misuse of medication). Crude and adjusted linear regression methods investigated the association between ED diagnoses and behaviours, and total body, hip, leg and arm bone mineral density (BMD) DXA scans at mean ages of 48 and 52 years. Lifetime occurrence of Anorexia Nervosa (AN) was associated with lower BMD Z-scores for the whole body (mean difference (MD) = -0.28; 95% CI: -0.49, -0.05), hip (MD = -0.45; 95% CI -0.74, -0.16), leg (MD = -0.28; 95% CI -0.52, -0.03) and arm (MD = -0.44; 95% CI -0.68, -0.19) compared to no ED. This effect was mostly accounted for by lowest ever BMI. In post-hoc analyses, Restrictive AN, but not Binge-Purge AN was associated with a lower total body BMD Z-scores (MD = -0.37; 95% CI -0.62, -0.12). Lifetime Fasting and Restrictive Eating were associated with low BMD of the total body, hip, arm and leg in adjusted analyses, all p < 0.05. Both lifetime ED diagnoses and ED behaviours in a large community sample were predictive of low BMD in mid-life. This study confirms that the effects of AN, fasting and restrictive eating, and low BMI on bone health seen in clinical samples also occur in community samples. [ABSTRACT FROM AUTHOR]

Introduction: This study was aimed to compare fracture prevalence in oligoamenorrheic athletes (AA), eumenorrheic athletes (EA), and nonathletes (NA) and determine relationships with bone density, structure, and strength estimates. Methods: One hundred seventy-five females (100 AA, 35 EA, and 40 NA) 14-25 yr old were studied. Lifetime fracture history was obtained through participant interviews. Areal bone mineral density (BMD) was assessed by DXA at the spine, hip, and whole body (WB). Bone structure was assessed by HRpQCT at the radius and tibia, and strength by finite element analysis. Results: AA, EA, and NA did not differ in age, sexual maturity, or height. AA had lower BMI, and older menarchal age than EA and NA (P ≤ 0.001). Bone mineral density Z-scores were lower in AA versus EA at the total hip, femoral neck, spine, and whole body (P ≤ 0.001). Lifetime fracture risk was higher in AA than EA and NA (47%, 25.7%. 12.5%; P ≤ 0.001), largely driven by stress fractures in AA versus EA and NA (32% vs 5.9% vs 0%). In AA, those who fractured had lower lumbar and WB BMD Z-scores, volumetric BMD (vBMD) of outer trabecular region in radius and tibia, and trabecular thickness of the radius (P ≤ 0.05). In AA, those who had two or more stress fractures had lower lumbar and WB BMD Z-scores, total cross-sectional area, trabecular vBMD, stiffness, and failure load at radius; and lower stiffness and failure load at tibia versus those with fewer than two stress fractures (P ≤ 0.05). Conclusion: Weight-bearing athletic activity increases BMD but may increase stress fracture risk in those with menstrual dysfunction. Bone microarchitecture and strength differences are more pronounced in AA with multiple stress fractures. This is the first study to examine fractures in relation to bone structure in adolescent female athletes. [ABSTRACT FROM AUTHOR]

Context: Anorexia nervosa is complicated by severe bone loss and clinical fractures. Mechanisms underlying bone loss in adults with anorexia nervosa include increased bone resorption and decreased formation. Estrogen administration has not been shown to prevent bone loss in this population, and to date, there are no approved, effective therapies for this comorbidity.Objective: To determine whether antiresorptive therapy with a bisphosphonate alone or in combination with low-dose transdermal testosterone replacement would increase bone mineral density (BMD) in women with anorexia nervosa.Design and Setting: We conducted a12-month, randomized, placebo-controlled study at a clinical research center.Study Participants: Participants included 77 ambulatory women with anorexia nervosa.Intervention: Subjects were randomized to risedronate 35 mg weekly, low-dose transdermal testosterone replacement therapy, combination therapy or double placebo.Main Outcome Measures: BMD at the spine (primary endpoint), hip, and radius and body composition were measured by dual-energy x-ray absorptiometry.Results: Risedronate increased posteroanterior spine BMD 3%, lateral spine BMD 4%, and hip BMD 2% in women with anorexia nervosa compared with placebo in a 12-month clinical trial. Testosterone administration did not improve BMD but increased lean body mass. There were few side effects associated with either therapy.Conclusions: Risedronate administration for 1 yr increased spinal BMD, the primary site of bone loss in women with anorexia nervosa. Low-dose testosterone did not change BMD but increased lean body mass. [ABSTRACT FROM AUTHOR]