Assessment of fracture risk in women with eating disorders: The utility of dual-energy x-ray absorptiometry (DXA)-Clinical cohort study.

OBJECTIVE: Eating disorders (EDs) are associated with decreased bone mineral density (BMD) and increased fracture risk. The association between BMD and fracture risk in EDs is not well elucidated. We aimed to assess BMD in an ED cohort of patients with active disease and patients in remission, and to assess the predictive value of BMD on incidence of fractures. METHOD: We included 344 female patients (median age 19, IQR 16; 24) referred to ED treatment. Later, patients were invited to follow-up including assessment of remission status and a dual-energy x-ray absorptiometry (DXA)-scan. Information on fractures was obtained through the Danish National Registry of Patients. RESULTS: Patients with current anorexia nervosa (AN) had significantly lower BMD compared to controls at lumbar spine (16% lower, p < .0001), femoral neck (18% lower, p < .0001), and total hip (23% lower, p < .0001). Recovered AN patients had higher BMD compared to those with current disease (p < .0001 for all measures), but lower BMD compared to controls at lumbar spine (p < .01) and hip (p < .001). BMD did not differ between BN patients and controls. In patients with active eating disorders not otherwise specified, BMD was lower only at the total hip (p < .005). We found no association between BMD and fracture risk. CONCLUSION: We confirm that AN is associated with low BMD, whereas BN is not. Remission is associated with higher BMD compared to patients with active AN, but a deficit remains. We found no significant association between BMD and fracture risk, challenging the benefit of the widespread use of DXA scans in young women with ED. CLINICAL TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov, number NCT00267228.

Fractures in women with eating disorders-Incidence, predictive factors, and the impact of disease remission: Cohort study with background population controls.

OBJECTIVE: Malnutrition and low weight in eating disorders (EDs) are associated with increased fracture risk compared to the general population. In a cohort study, we aimed to determine fracture rates compared to age and gender matched controls (ratio 5:1), assess the impact of disease remission on fracture risk, and establish predictive factors for fractures. METHOD: Of note, 803 ED patients referred to specialized ED treatment between 1994 and 2004 were included. In 2016, data on fractures were obtained through the Danish National Registry of Patients. RESULTS: Fracture risk was increased in anorexia nervosa (AN; IRR 2.2 [CI 99%: 1.6-3.0]) but not in bulimia nervosa (BN; IRR 1.3, ns) or other specified feeding or eating disorders (OSFED; IRR 1.8, ns). IRR in the AN group were increased for vertebral fractures (IRR 3.8 [CI 99%: 1.4-10.3]), upper arm (IRR 3.0 (CI 99% 1.6-5.5) and hip (IRR 6.6 [CI 99%: 2.6-18.0]). Disease remission in AN is associated to lower fracture risk compared to active disease, but higher fracture risk compared to controls (IRR 1.7 [CI 99%: 1.1-2.7]). In regression analysis, age at debut of disease, nadir BMI and duration of disease before referral to treatment, independently predicted fracture. DISCUSSION: We confirm increased fracture risk in AN, and show significant differences in fracture risk between patients in disease remission and patients with active disease. Furthermore, we show that age at debut of disease and duration of disease before referral to treatment is positively correlated to fracture risk, whereas nadir BMI is negatively correlated to fracture risk.

Hunger and satiety perception in patients with severe anorexia nervosa.

OBJECTIVES: Appetite is a subjective essential sense. In patients with severe anorexia nervosa (AN), controversy remains whether this sensation is altered. The objectives were to clarify, in patients with severe AN: (1) Whether the appetite changes during partial weight restoration, (2) Whether potential changes in appetite are related to (i) diagnostic subtype of AN, (ii) psychopharmacological treatment, (iii) disease duration, (iv) duration of hospitalization, and (v) baseline body mass index (BMI). METHODS: The study consisted of 39 patients, with a mean age of 23.7 ± 8 and an admission mean BMI of 13.1 ± 2.0 kg/m2. The patients were consecutively admitted to a specialized somatic nutrition unit between 2015 and 2016. They were asked to rate their hunger and satiety on a numeric visual analog scale (VAS), before and after a lunch meal at admission and at discharge in the same standardized environment. The patients could participate more than once if readmitted, resulting in a total of 119 observed meals. Data were analyzed in a regression model for repeated measures. RESULTS: At admission, changes in hunger and satiety perception were weak. After weight gain of 10.4% ± 8.5% within a median of 26 (IQR: 25) days, there was a slight increase in hunger perception, p = 0.049. However, there was no detectable change in satiety perception. There was no noticeable correlation between appetite change and psychopharmacological treatment, diagnostic subtype, BMI, duration of hospitalization, and disease duration. CONCLUSION: Hospitalized patients with severe AN exhibit strikingly weak changes in hunger and satiety perception during standardized and supervised meals. LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time series analysis.

The Role of Body Weight on Bone in Anorexia Nervosa: A HR-pQCT Study.

Anorexia nervosa (AN) is associated with decreased bone mineral density and increased risk of fracture. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), trabecular microarchitecture and estimated failure load in weight-bearing vs. non-weight-bearing bones in AN. We included twenty-five females with AN, and twenty-five female controls matched on age and height. Bone geometry, vBMD and trabecular microarchitecture were assessed using high-resolution peripheral quantitative computed tomography of the distal radius and tibia. At both sites, cortical perimeter and total bone area were similar in patients and controls. Total vBMD was lower in the AN group in the tibia (p < 0.0005) but not in the radius. In the tibia, cortical thickness was approximately 25% lower (p < 0.0005) in the AN group, whereas there was no significant difference in the radius. In terms of trabecular microarchitecture, all indices [bone volume/tissue volume (BV/TV); trabecular thickness (Tb.Th.), trabecular number (Tb.N) and trabecular spacing (Tb.Sp.)] were impaired in AN in the tibia (p values range < 0.01-0.0001). In the radius, BV/TV and Tb.N were lower (p < 0.05 and p < 0.001, respectively); Tb.Sp. was higher (p < 0.001), whereas Tb.Th. did not differ, compared to controls. Estimated failure load was lower in patients in both the radius and the tibia (p < 0.0005 and p < 0.0001, respectively), most pronounced in the tibia. In conclusion, the impairment of cortical thickness and estimated failure load were significantly more pronounced in the weight-bearing tibia, compared to the non-weight-bearing radius, implying a direct effect of low body weight on bone loss in AN.

Body composition and menstrual status in adults with a history of anorexia nervosa-at what fat percentage is the menstrual cycle restored?

OBJECTIVE: To study the association between body composition measures and menstrual status in a large sample of adult patients with a history of anorexia nervosa and to calculate the predicted probability of resumption of menstrual function. Furthermore, to establish whether fat percentage is superior to body mass index in predicting the resumption of menses. METHOD: One hundred and thirteen adult women with a history of anorexia nervosa underwent a dual energy X-ray absorptiometry (DXA) scan and completed questionnaires regarding medication prescription and menstrual function. RESULTS: Fifty percent of patients were expected to resume their menstrual function at a body mass index of 19 kg m-2 or a fat percentage of 23%. Twenty-five percent of patients were expected to resume their menstrual function at body mass index 14 kg m-2 or fat percentage 11%. Fat percentage and body mass index were equally capable of predicting the resumption of menses. DISCUSSION: Fat percentage and body mass index were positive predictors of the resumption of menses, however, body composition measured by dual energy X-ray absorptiometry was not superior to body mass index in predicting menstrual recovery, which is of great clinical relevance as body mass index is easier and cheaper to obtain. Body composition measures only account for one of numerous factors involved in the resumption of menses. Regression models based on our data had a R2 value of 0.14, indicating that only 14% of the variation in menstrual recovery could be explained by the variables included. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:370-377).

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Long-Term Selenium-Yeast Supplementation Does Not Affect Bone Turnover Markers: A Randomized Placebo-Controlled Trial.

Higher selenium status has been associated with lower bone turnover markers (BTM) in epidemiological studies. However, the long-term impact of selenium supplementation on BTMs has not been studied. We investigated the effects of selenium supplementation on BTMs including osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), collagen type I cross-linked C-telopeptide (CTX), and bone alkaline phosphatase (BALP) in the short (6 months) and long term (5 years). A total of 481 Danish men and women (60-74 years) were randomized to receive placebo-yeast versus 100, 200, or 300 µg selenium as selenium-enriched yeast daily for 5 years. Plasma selenium concentration was measured using inductively coupled plasma mass spectrometry, and BTMs were measured in nonfasted samples at baseline, 6 months, and 5 years. Data were analyzed by ANCOVA to investigate the shape of the dose-response relationships. Covariates included age, body mass index, baseline selenium status, baseline BTM, smoking, alcohol, supplement use, and medication. Plasma selenium concentration (mean 86.5 µg/d at baseline) increased significantly with increasing selenium supplementation to 152.6, 209.1, and 253.7 µg/L after 6 months and remained elevated at 5 years (158.4, 222.4, and 275.9 µg/L for 100, 200, and 300 µg supplemental selenium/d, respectively (p < 0.001)). There was no change in plasma selenium concentration in the placebo-treated group. There was no significant effect of selenium supplementation on OC (6 months p = 0.37; 5 years p = 0.63), PINP (6 months p = 0.37; 5 years p = 0.79), CTX (6 months p = 0.91; 5 years p = 0.58) or BALP (6 months p = 0.17; 5 years p = 0.53). The relatively replete baseline selenium status in the study participants may explain this lack of effect. Testing in more deficient populations may provide further insights into the impact of selenium supplementation on bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism.

The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.

Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment.

OBJECTIVES: Mental illness is often accompanied by poor physical health and shorter life expectancy. Second-generation antipsychotics (SGAs) are suspected of increasing cardiovascular risk, possibly through development of metabolic syndrome (MetS), and the risk of adverse outcome is even higher if obesity or metabolic aberration starts in childhood or adolescence. METHODS: Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were determined through regular follow-ups. RESULTS: The sample included 35 SGA-naive patients aged 7-19 (mean: 15.5) with a diagnosis of psychosis. Over 12 months, the overall rate of MetS changed significantly (from 0% to 20% [p < 0.016]). There was a significant increase in BMI (18.4% [p < 0.001]), WC (14.3% [p < 0.001]), TG (25.2% [p = 0.039]), and FBG (3.6% [p = 0.038]), whereas there was a significant decrease in HDL (-11.5% [p < 0.001]). No significant change was found for BP. Compared with the 2014 Danish references BMI-for-age charts, after 12 months the participants' BMI had increased from 0.5 to 1.57 standard deviation (SD) above the 50th percentile for age and gender (p = 0.0001). CONCLUSION: To our knowledge, this is the first study to include all the aspects of MetS in a sample of drug-naive adolescents followed over the first 12 months after starting SGA treatment. A significant shift in all parameters (except BP) toward MetS was found, presumably due to SGA use. Therefore, these adolescents will need proper follow-up, consisting of not only monitoring but also preventive measures to diminish these effects of SGA use.

Patient- and clinician- reported outcome in eating disorders.

Patient-reported outcome is increasingly applied in health sciences. Patients with eating disorders (EDs) characteristically have a different opinion of their needs to that of the health professionals, which can lead to ambivalence towards treatment and immense compliance difficulties. This cross-sectional study compared data assessed by the clinician to patient-reported measures in patients with a history of EDs. We included data from a cohort of patients with EDs (n=544) referred to a specialized ED unit in Denmark. Patient-reported measures included the Eating Disorder Inventory-2 (EDI-2) and the Short Form 36 (SF-36), and clinical data included remission status and body mass index (BMI). We found a positive association between BMI and EDI-2 scores for anorexia nervosa (AN) and eating disorder not otherwise specified (EDNOS), reflecting increasing ED symptomatology with increasing BMI. This association was not observed in bulimia nervosa (BN). We did not find a correlation between SF-36 scores and BMI in any of the diagnostic groups.

To the limit of extreme malnutrition.

Extreme malnutrition with body mass index (BMI) as low as 10 kg/m(2) is not uncommon in anorexia nervosa, with survival enabled through complex metabolic adaptations. In contrast, outcomes from hunger strikes and famines are usually fatal after weight loss to about 40% below expected body weight, corresponding to BMI 12 to 13 kg/m(2) in adults. Thus, many years of adaptation in adolescent-onset anorexia nervosa, supported by supplements of vitamins and treatment of intercurrent diseases, may allow survival at a much lower BMI. However, in the literature only a few cases of survival in patients with BMI <9 kg/m(2) have been described. We report on the case of a 29-y-old woman who was successfully treated in a specialized unit. She had a BMI of 7.8 kg/m(2). To our knowledge, this level of extreme malnutrition has not previously been reported. The present case emphasizes the importance of adherence to guidelines to decrease refeeding complications.

Kwashiorkor: an unexpected complication to anorexia nervosa.

We present the case of a woman aged 48 years, diagnosed with anorexia nervosa (AN) at the age of 12. She was admitted to a highly specialised eating disorder facility with distended abdomen, muscular atrophy, ulcerative dermatitis, electrolyte derangements and low serum albumin. Her weight was 53.1 kg, corresponding to a body mass index (BMI) of 17.9 kg/m2 After initial stabilisation, a therapeutic ascites puncture relieved the patient from 6500 mL of ascites. After 6 weeks of nutritional and diuretic treatment, the patient was discharged with a weight of 46.8 kg (BMI 15.7 kg/m2), without ascites and with healed ulcerations. The condition was consistent with kwashiorkor, a complication to malnutrition rarely seen in AN.