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Background: Adolescents and women with anorexia nervosa have increased bone marrow fat and decreased bone formation, at least in part due to hormonal changes leading to preferential stem cell differentiation to adipocytes over osteoblasts., Objective: The purpose of this study was to evaluate marrow fat content and correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R) and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa., Materials and Methods: We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE. Metaphyses were scored visually on the T1-W images for red marrow. Visual T1 score, T1 relaxometry values, MRS lipid indices and fat fractions were analyzed by regression on age, body mass index (BMI) and bone mineral density (BMD) as disease severity markers. MRS measures included unsaturated fat index, T2 water, unsaturated and saturated fat fractions., Results: All red marrow measures declined significantly with age. T1-R values were associated negatively with BMI and BMD for girls ≤16 years (P=0.03 and P=0.002, respectively) and positively for those≥17 years (P=0.05 and P=0.003, respectively). MRS identified a strong inverse association between T2 water and saturated fat fraction from 60 ms TE data (r=-0.85, P<0.0001). There was no association between unsaturated fat index and BMI or BMD., Conclusions: The association between T1 and BMI and BMD among older girls suggests more marrow fat in those with severe anorexia nervosa. In contrast, the physiological association between marrow fat content and age remained dominant in younger patients. The strong association between T2 water and saturated fat may relate to the restricted mobility of water with increasing marrow fat.

This article reviews the effects of restrictive eating disorders on bone health. The relationship between eating disorders and amenorrhea is discussed in detail. The pathologic impact of malnutrition on bone is explored by examining the results of studies using various available imaging techniques. The multiple hormonal alterations seen in adolescents and young women with anorexia nervosa are reviewed, as well as how these alterations may influence bone turnover, density, structure, and strength. The diagnostic clinical evaluation for adolescents and young women with these disorders is also outlined. Available treatment options, including those that hold promise for efficacy, as well as those we deemed to be ineffective, are considered from both the clinical and mechanistic standpoints. Finally, future research opportunities are offered, including intriguing work in the area of fat and bone interactions.

Cosponsoring Associations: The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society., Objective: To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA)., Participants: The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer., Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies., Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline., Conclusions: FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation., (Copyright © 2017 Endocrine Society)

Study Objective: Use of gonadotropin-releasing hormone agonists (GnRHa) to treat endometriosis can cause mood and vasomotor side effects. "Add-back therapy," the combination of low-dose hormones, limits side effects but research is limited to adults. We sought to characterize quality of life (QOL) before treatment and to compare an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects of GnRHa therapy in female adolescents with endometriosis., Design: Twelve-month double-blind, placebo-controlled trial., Setting: Pediatric Gynecology clinic in Boston, Massachusetts., Participants: Fifty female adolescents (aged 15-22 years) with surgically confirmed endometriosis initiating treatment with GnRHa., Interventions: Subjects were randomized to: NA (5 mg/d) with CEE (0.625 mg/d) or NA (5 mg/d) with placebo. All subjects received leuprolide acetate depot every 3 months., Main Outcome Measures: The Short Form-36 v2 Health Survey, Beck Depression Inventory II, and Menopause Rating Scale were completed at repeated intervals., Results: At baseline, subjects reported impaired physical health-related QOL compared with national norms (all P < .0001). Over 12 months, these Short Form-36 v2 scores improved (all P < .05). Subjects receiving NA with CEE showed greater improvements in the pain, vitality, and physical health subscales (P between groups < .05) than those receiving NA alone, as well as better physical functioning (P < .05). There were no changes in depression or menopause-like symptoms in either group., Conclusion: Female adolescents with endometriosis initiating GnRHa therapy have impaired QOL. Treatment with GnRHa combined with add-back therapy led to improved QOL, with no worsening of mood or menopausal side effects. NA with CEE was superior to NA alone for improving physical health-related QOL., (Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

We sought to determine whether low-magnitude mechanical stimulation (LMMS) normalizes bone turnover among adolescents hospitalized for anorexia nervosa (AN). Brief, daily LMMS prevents the decline in bone turnover typically seen during bed rest in AN. LMMS may have application for patients with AN in the inpatient setting to protect bone health., Introduction: Malnourished adolescents with AN requiring medical hospitalization are at high risk for rapid reduction in skeletal quality. Even short-term bed rest can suppress normal patterns of bone turnover. We sought to determine whether LMMS normalizes bone turnover among adolescents hospitalized for complications of AN., Methods: In this randomized, double-blind trial, we prospectively enrolled adolescent females (n = 41) with AN, age 16.3 ± 1.9 years (mean ± SD) and BMI 15.6 ± 1.7 kg/m 2 . Participants were randomized to stand on a platform delivering LMMS (0.3 g at 32-37 Hz) or placebo platform for 10 min/day for 5 days. Serum markers of bone formation [bone-specific alkaline phosphatase (BSAP)], turnover [osteocalcin (OC)], and bone resorption [serum C-telopeptides (CTx)] were measured. From a random coefficients model, we constructed estimates and confidence intervals for all outcomes., Results: BSAP decreased by 2.8% per day in the placebo arm (p = 0.03) but remained stable in the LMMS group (p = 0.51, p diff  = 0.04). CTx did not change with placebo (p = 0.56) but increased in the LMMS arm (+6.2% per day, p = 0.04; p diff  = 0.01). Serum OC did not change in either group (p > 0.70)., Conclusions: Bed rest during hospitalization for patients with AN is associated with a suppression of bone turnover, which may contribute to diminished bone quality. Brief, daily LMMS prevents a decline in bone turnover during bed rest in AN. Protocols prescribing strict bed rest may not be appropriate for protecting bone health for these patients. LMMS may have application for these patients in the inpatient setting.

Purpose: We examined the relationships between malnutrition, lifestyle factors, and bone health in anorexia nervosa (AN) via dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT)., Methods: Seventy adolescent girls with AN and 132 normal-weighted controls underwent pQCT tibial measures including trabecular volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness. Participants with AN underwent DXA measures of the axial skeleton. We assessed the association of DXA and pQCT measures with clinical and lifestyle variables., Results: Body mass index Z-score and ideal body weight percentage were positively correlated with trabecular vBMD, cortical CSA, and section modulus (p < .04). Exercise was associated with all pQCT measures but only with hip BMD by DXA. In AN, the use of antidepressants was associated with lower pQCT measures (p < .03)., Conclusions: Antidepressants may negatively, and exercise positively, influence BMD in adolescents with eating disorders. These findings offer a provocative look at two longstanding questions., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity., Methods: In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)-uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)-vitamin D-fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups., Results: There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (-1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = -0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables., Conclusions: These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group., Clinical Trials Registration: NCT01769469., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Individuals with restrictive eating disorders present with co-morbid psychiatric disorders and many attempt to control symptoms using strenuous exercises that increase caloric expenditure. Yoga offers a safe avenue for the engagement in physical activity while providing an outlet for disease-associated symptoms. This study sought to examine use of yoga practice in an outpatient setting and its impact on anxiety, depression and body image disturbance in adolescents with eating disorders., Methods: Twenty adolescent girls were recruited from an urban eating disorders clinic who participated in weekly yoga classes at a local studio, in addition to standard multidisciplinary care. Yoga instructors underwent training regarding this patient population. Participants completed questionnaires focused on anxiety, depression and body image disturbance prior to the first class, and following completion of 6 and 12 classes., Results: In participants who completed the study, a statistically significant decrease in anxiety, depression, and body image disturbance was seen, including: Spielberger State anxiety mean scores decreased after the completion of 7-12 yoga classes [47 (95%CI 42-52) to 42 (95%CI 37-47), adj. p  = 0.0316]; as did the anorexia nervosa scale [10 (95% CI 7-12) vs. 6 (95%CI 4-8), adj. p  = .0004], scores on Beck depression scales [18 (95%CI 15-22) to 10 (95%CI 6-14), adj. p  = .0001], and weight and shape concern scores [16 (95%CI 12-20) to 12 (95%CI 8-16), adj. p  =0.0120] and [31 (95%CI 25-37) to 20 (95%CI 13-27), adj. p  = 0.0034], respectively. No significant changes in body mass index were seen throughout the trial., Conclusions: Yoga practice combined with outpatient eating disorder treatment were shown to decrease anxiety, depression, and body image disturbance without negatively impacting weight. These preliminary results suggest yoga to be a promising adjunct treatment strategy, along with standard multidisciplinary care. However, whether yoga should be endorsed as a standard component of outpatient eating disorder treatment merits further study.

Background: Vertebral fracture is the most common type of osteoporotic fracture. While thiazide diuretics, which are commonly prescribed for the treatment of hypertension, decrease calciuria, they may also induce hyponatremia, which has been associated with increased vertebral fracture risk. Loop diuretics increase calciuria, which would reduce bone mineral density and increase vertebral fracture risk, but they rarely cause hyponatremia. Recent studies on diuretics and fractures did not include or specifically examine vertebral fracture. The few studies of diuretics and vertebral fracture have been limited by cases defined by self-report or administrative data, relatively small number of cases, study design that was not prospective, and lack of long-term follow-up with updated information on diuretic use., Methods: We conducted a prospective cohort study of thiazide diuretic use, loop diuretic use, and risk of incident clinical vertebral fracture in 55,780 women, 55-82 years of age, participating in the Nurses' Health Study, without a prior history of any fracture. Diuretic use was assessed by questionnaire every 4 years. Self-reported vertebral fracture was confirmed by medical record review. Cox proportional-hazards models were used to simultaneously adjust for potential confounders., Results: Our analysis included 420 incident vertebral fracture cases documented between 2002 and 2012. The multivariate-adjusted relative risk of clinical vertebral fracture for women taking thiazides compared with women not taking thiazides was 1.47 (95% confidence interval, 1.18-1.85). The multivariate adjusted relative risk of vertebral fracture for women taking loop diuretics compared with women not taking loop diuretics was 1.59 (95% confidence interval, 1.12-2.25)., Conclusion: Thiazide diuretics and loop diuretics are each independently associated with increased risk of vertebral fracture in women., Competing Interests: Disclosures: Julie M. Paik, Harold N. Rosen, Catherine M. Gordon, and Gary C. Curhan declare that they have no conflicts of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We conducted the first comparison of dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) outcomes in adolescent girls with anorexia nervosa. We observed deficits in bone density by both tools. pQCT assessments were associated with many of the same clinical parameters as have been previously established for DXA., Introduction: Adolescents with anorexia nervosa (AN) commonly exhibit bone loss, but effects on bone geometry are less clear. We compared measures obtained by DXA and pQCT in girls with AN., Methods: Seventy females (age 15.5 ± 1.9 years ) with AN and 132 normal-weighted controls underwent tibial measures by pQCT including trabecular volumetric bone mineral density (vBMD) at the 3 % site, cortical vBMD and dimensions at the 38 % site, and muscle cross-sectional area (CSA) at the 66 % site. Participants with AN also underwent standard DXA measures. Independent t tests compared the pQCT results, while Pearson coefficient assessed correlations among DXA and pQCT measures., Results: Trabecular vBMD Z-scores were lower in AN compared to controls (AN -0.31 ± 1.42 vs +0.11 ± 1.01, p = 0.01) and cortical vBMD Z-scores were higher (AN +0.18 ± 0.92 vs -0.50 ± 0.88, p < 0.001). Trabecular vBMD and cortical CSA Z-scores positively correlated with DXA BMD Z-scores (r range 0.57-0.82, p < 0.001). Markers of nutritional status positively correlated with Z-scores for trabecular vBMD, cortical CSA, section modulus, and muscle CSA (p < 0.04 for all)., Conclusions: This study is the first to compare DXA and pQCT measurements in adolescent girls with AN. We observed deficits in BMD by both DXA and pQCT. pQCT assessments correlated well with DXA bone and body composition measures and were associated with many of the same clinical parameters and disease severity markers as have been previously established for DXA. The differences in cortical vBMD merit further study.

Concerns about bone health and potential fragility in children and adolescents have led to a high interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve expected gains in bone size, mass, and strength, leaving them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less clear. This clinical report summarizes current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and risks and costs. The report emphasizes updated consensus statements generated at the 2013 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, whereas others reflect expert opinion, because data are sparse on many topics. The statements from this and other expert panels provide general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. The interpretation of bone densitometry results in children differs from that in older adults. The terms "osteopenia" and "osteoporosis" based on bone densitometry findings alone should not be used in younger patients; instead, bone mineral content or density that falls >2 SDs below expected is labeled "low for age." Pediatric osteoporosis is defined by the Pediatric Position Development Conference by using 1 of the following criteria: ≥1 vertebral fractures occurring in the absence of local disease or high-energy trauma (without or with densitometry measurements) or low bone density for age and a significant fracture history (defined as ≥2 long bone fractures before 10 years of age or ≥3 long bone fractures before 19 years of age). Ongoing research will help define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk. The Pediatric Endocrine Society affirms the educational value of this publication., (Copyright © 2016 by the American Academy of Pediatrics.)

Unlabelled: Young adults with cystic fibrosis have compromised plate-like trabecular microstructure, altered axial alignment of trabeculae, and reduced connectivity between trabeculae that may contribute to the reduced bone strength and increased fracture risk observed in this patient population., Introduction: The risk of fracture is increased in patients with cystic fibrosis (CF). Individual trabecular segmentation (ITS)-based morphological analysis of high-resolution peripheral quantitative computed tomography (HR-pQCT) images segments trabecular bone into individual plates and rods of different alignment and connectivity, which are important determinants of trabecular bone strength. We sought to determine whether alterations in ITS variables are present in patients with CF and may help explain their increased fracture risk., Methods: Thirty patients with CF ages 18-40 years underwent DXA scans of the hip and spine and HR-pQCT scans of the radius and tibia with further assessment of trabecular microstructure by ITS. These CF patients were compared with 60 healthy controls matched for age (±2 years), race, and gender., Results: Plate volume fraction, thickness, and density as well as plate-plate and plate-rod connectivity were reduced, and axial alignment of trabeculae was lower in subjects with CF at both the radius and the tibia (p < 0.05 for all). At the radius, adjustment for BMI eliminated most of these differences. At the tibia, however, reductions in plate volume fraction and number, axially aligned trabeculae, and plate-plate connectivity remained significant after adjustment for BMI alone and for BMI and aBMD (p < 0.05 for all)., Conclusions: Young adults with CF have compromised plate-like and axially aligned trabecular morphology and reduced connectivity between trabeculae. ITS analysis provides unique information about bone integrity, and these trabecular deficits may help explain the increased fracture risk in adults with CF not accounted for by BMD and/or traditional bone microarchitecture measurements.

Background: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation., Methods: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial., Results: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial., Conclusions: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747., (© 2016 American Heart Association, Inc.)

Background: This study comprehensively evaluated a myofascial triggerpoint release (MTR) technique for shoulder pain., Methods: Twenty-three (from an initial sample of 25) patients experiencing shoulder pain received MTR, in four 10-min sessions over a period of 2 weeks, applied exclusively on the more painful shoulder, with assessments being recorded both before and after treatment (and for pain at 1 and 13 months). Measures of stiffness and elasticity were collected to monitor the process of therapy, while subjective measures of pain and objective measures of pressure pain thresholds tracked primary outcomes. Secondary outcomes focused on suffering, stress, and quality of life., Results: A statistically significant decrease in stiffness and increase in elasticity was observed post intervention for the treated side only, while pressure pain thresholds improved on the untreated side as well. Reports of pain significantly decreased after treatment, with gains being maintained at 1 and 13 months following treatment. Levels of suffering, stress, and quality of life revealed statistically significant improvement as well., Conclusions: MTR resulted in clinically significant improvements in the primary measures of pain, objective mechanical tissue properties, and secondary measures in patients with chronic shoulder pain., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Evidence is lacking to recommend one diet over another when treating polycystic ovary syndrome (PCOS)., Objectives: To obtain preliminary data, comparing the impact of a low-glycaemic load (LGL) vs. low-fat (LF) diet on biochemical hyperandrogenism in overweight and obese adolescents with PCOS. To ascertain feasibility of recruiting study participants, in partnership with an adolescent clinic, and implementing dietary interventions., Methods: Randomized controlled trial of 19 overweight and obese adolescents with PCOS and not using hormonal contraceptives (HCs). Interventions comprised nutrition education, dietary counselling and cooking workshops to foster adherence to a LGL (45% carbohydrate, 35% fat, 20% protein) or LF (55% carbohydrate, 25% fat, 20% protein) diet over 6 months. Serum bioavailable testosterone was the primary outcome., Results: Sixteen (LGL, n = 7; LF, n = 9) participants completed the study. Body fat percentage decreased (P < 0.05) in response to the interventions, with no difference between the LGL and LF groups (-1.2% vs. -2.2%; P = 0.16). Bioavailable testosterone did not change for either group (-0.4 vs. -1.8 ng dL(-1) ; P = 0.35). Regarding feasibility, recruiting adolescents posed a challenge, and use of HCs was a main reason for ineligibility. Participants attended 5.9 of 6 in-person visits and 2.6 of 3 cooking workshops, completed 4.9 of 6 telephone counselling calls, and reported high satisfaction with the diets and cooking workshops (≥8 on a 10-cm scale)., Conclusions: Dietary interventions were beneficial for weight control but did not attenuate biochemical hyperandrogenism. Innovative strategies are needed to recruit adolescents for studies aimed at assessing independent effects of diet on features of PCOS., (© 2015 World Obesity.)

Dual-energy X-ray absorptiometry (DXA) is a technology that is widely used to diagnose osteoporosis, assess fracture risk, and monitor changes in bone mineral density (BMD). The clinical utility of DXA is highly dependent on the quality of the scan acquisition, analysis, and interpretation. Clinicians are best equipped to manage patients when BMD measurements are correct and interpretation follows well-established standards. Poor-quality acquisition, analysis, or interpretation of DXA data may mislead referring clinicians, resulting in unnecessary diagnostic evaluations, failure to evaluate when needed, inappropriate treatment, or failure to provide medical treatment, with potentially ineffective, harmful, or costly consequences. Misallocation of limited healthcare resources and poor treatment decisions can be minimized, and patient care optimized, through meticulous attention to DXA instrument calibration, data acquisition and analysis, interpretation, and reporting. This document from the International Society for Clinical Densitometry describes quality standards for BMD testing at DXA facilities worldwide to provide guidance for DXA supervisors, technologists, interpreters, and clinicians. High-quality DXA testing is necessary for correct diagnostic classification and optimal fracture risk assessment, and is essential for BMD monitoring., (Copyright © 2016 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. [Table: see text] Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years-a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one's genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.

Background: UVB light from the sun increases serum 25-hydroxyvitamin D [25(OH)D] concentration, but this relation may depend on skin pigmentation among different racial/ethnic groups., Objective: We used quantitative measures of exposed (facultative) and unexposed (constitutive) skin color to examine relations between serum 25(OH)D concentration, tanning, race/ethnicity, and constitutive skin color over the summer, following winter vitamin D supplementation., Methods: The subjects (n= 426, mean age 11.7 ± 1.4 y, 51% female) were racially/ethnically diverse schoolchildren (57% non-white/Caucasian) enrolled in a 6-mo vitamin D supplementation trial (October-December to April-June). In this secondary analysis, measures of serum 25(OH)D concentration and skin color, with the use of reflectance colorimetry, were taken over a 6-mo period after supplementation, from pre-summer (April-June) to post-summer (September-December). Multiple linear regression was used to evaluate longitudinal relations., Results: Following supplementation, mean serum 25(OH)D concentration was 29.3 ± 9.5 ng/mL but fell to 25.6 ± 7.9 ng/mL (P< 0.0001) by the end of summer. The decrease in white/Caucasian children was less than in black/African American children (P< 0.01) and tended to be less than in Hispanic/Latino, Asian, and multiracial/other children (P= 0.19-0.50) despite similar changes in sun-exposed skin color among all groups. Tanning was significantly associated with post-summer serum 25(OH)D concentration (β = -0.15,P< 0.0001), as was race/ethnicity (P= 0.0002), but the later association disappeared after adjusting for constitutive skin color., Conclusions: Tanning significantly contributed to serum 25(OH)D concentration over the summer, independent of race/ethnicity, but was not sufficient to maintain serum 25(OH)D concentration attained with supplementation. Much of the variation in serum 25(OH)D concentration between racial/ethnic groups may be explained by skin color. This trial was registered atclinicaltrials.govasNCT01537809., (© 2016 American Society for Nutrition.)

Background: Vitamin D insufficiency is common in children with cystic fibrosis (CF), yet data are sparse regarding the most effective form of vitamin D supplementation. The aim of this study was to compare two different vitamin D replacement regimens., Methods: We conducted a randomized controlled trial comparing 50,000 IU of ergocalciferol (vitamin D2) twice weekly for 8 weeks versus 50,000 IU of cholecalciferol (vitamin D3) weekly in patients with CF, pancreatic insufficiency, age 6-21 years and a 25(OH)D<30 ng/mL. The primary outcome was change in serum 25(OH)D concentration. For secondary analyses, we examined changes in IgG, IgE and CRP in patients who normalized their vitamin D levels., Results: A total of 47 patients completed the trial. The mean pre-treatment 25(OH)D concentration was 23.1 (SD 4.7) ng/mL. The overall mean increase in 25(OH)D was 11.1 (11.9) ng/mL and 31/47 (66%) achieved a 25(OH)D concentration ≥ 30 ng/mL; of the 26 participants who received D2, 18 (69%) achieved sufficiency while 13/21 (62%) participants treated with D3 achieved sufficiency. There was no difference between groups in change of 25(OH)D (p=0.65). Similarly, there was no difference in the number of patients to achieve vitamin D sufficiency between treatments (p=0.6)., Conclusions: Ergocalciferol administered as 50,000 IU twice weekly is as effective as cholecalciferol 50,000 IU weekly for 8 weeks in pediatric patients with CF and vitamin D insufficiency. Only 66% of the patients studied achieved the desired 25(OH)D concentration., (Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Objective: Fractures occurring in hospitalized children may be an underrecognized preventable harm with implications for current and future bone health, but few data exist regarding the clinical characteristics of these pediatric patients. We describe the clinical characteristics of patients who sustained fractures during hospitalization over a 4.5-year period at a single tertiary care center., Methods: We retrospectively identified subjects who experienced inpatient fractures using a voluntary safety event reporting system and computer-assisted keyword search of the electronic medical record. We used the medical record to collect clinical characteristics, laboratory data, and survival status., Results: The safety event reporting system and keyword search identified 57% and 43% of subjects, respectively. Fifty-six subjects sustained 128 fractures while hospitalized, most frequently at the femur (33 fractures) and humerus (30 fractures). Twenty-seven subjects sustained multiple fractures. Common clinical characteristics included age ≤1 year (64%); preterm birth (53%); admission to an ICU (90%); immobilization (88%); and weight-for-age z score less than or equal to -2.0 (52%). Sixteen (29%) subjects died, and the mortality rate varied by primary diagnosis., Conclusions: Critically ill, immobilized infants under 1 year of age and who were often born preterm sustained the majority of fractures occurring during hospitalization. A voluntary reporting system was insufficient to identify all inpatient fractures. Future studies should explore optimal fracture screening strategies and the relationship among fractures, severity of illness and mortality in hospitalized children., (Copyright © 2016 by the American Academy of Pediatrics.)

Objective: Critically ill children with congenital heart disease (CHD) are at risk for metabolic bone disease (MBD) and bone fractures. Our objective was to characterize a cohort of CHD patients with fractures and describe a Fragile Bone Protocol (FBP) developed to reduce fractures., Design/setting: Patients who developed fractures in the Cardiac Intensive Care Unit (CICU) of Boston Children's Hospital from 3/2008 to 6/2014 were identified via quality improvement and radiology databases. The FBP (initiated July 2011) systematically identifies patients at risk for MBD and prescribes special handling precautions., Results: Twenty-three fractures were identified in 15 children. Median age at fracture identification was 6.2 months, with a median duration of hospitalization before fracture diagnosis of 2.7 months. Six patients (40%) had single ventricle CHD. Hyperparathyroidism and low 25-OH vitamin D levels were present in 77% and 40% of those tested, respectively. Compared with patients not diagnosed with fractures, fracture patients had increased exposure to possible risk factors for MBD and had elevated parathyroid and decreased calcitriol levels.Six patients (40%) did not survive to hospital discharge, compared with an overall CICU mortality rate of 2.6% (P < .01). The fracture case rate before implementation of the FBP was 2.6 cases/1000 admissions and was 0.7/1000 after implementation of the FBP (P = .04)., Conclusions: Critically ill CHD patients are at risk for fractures. They represent a complex group who frequently has hyperparathyroidism and decreased calcitriol levels, and each may predispose to fractures. FBPs consisting of identification and careful patient handling should be considered in at-risk patients., (© 2015 Wiley Periodicals, Inc.)

This narrative review summarizes the role that nutrition plays in the development and maintenance of a healthy skeleton throughout the life-course. Nutrition has a significant influence on bone health throughout the life cycle. This narrative review summarizes current knowledge and guidance pertaining to the development and maintenance of a healthy skeleton. The primary objectives proposed for good bone health at the various stages of life are the following: Children and adolescents: achieve genetic potential for peak bone mass Adults: avoid premature bone loss and maintain a healthy skeleton Seniors: prevention and treatment of osteoporosis Findings from cohort studies, randomized controlled trials, systematic reviews and meta-analyses, in addition to current dietary guidelines, are summarized with the intention of providing clear nutritional guidance for these populations and pregnant women.

Health-related behaviors are among the most significant determinants of health and quality of life. Improving health behavior is an effective way to enhance health outcomes and mitigate the escalating challenges arising from an increasingly aging population and the proliferation of chronic diseases. Although it has been difficult to obtain lasting improvements in health behaviors on a wide scale, advances at the intersection of technology and behavioral science may provide the tools to address this challenge. In this paper, we describe a vision and an approach to improve health behavior interventions using the tools of behavioral informatics, an emerging transdisciplinary research domain based on system-theoretic principles in combination with behavioral science and information technology. The field of behavioral informatics has the potential to optimize interventions through monitoring, assessing, and modeling behavior in support of providing tailored and timely interventions. We describe the components of a closed-loop system for health interventions. These components range from fine grain sensor characterizations to individual-based models of behavior change. We provide an example of a research health coaching platform that incorporates a closed-loop intervention based on these multiscale models. Using this early prototype, we illustrate how the optimized and personalized methodology and technology can support self-management and remote care. We note that despite the existing examples of research projects and our platform, significant future research is required to convert this vision to full-scale implementations.

Background: Intake of sugar-sweetened beverages (SSBs) is linked to greater cardiometabolic risk in adults. Although longitudinal evidence is sparse among children, SSB intake reduction is targeted to reduce cardiometabolic risk factors in this group., Objective: We investigated characteristics associated with consumption of SSBs in a multi-ethnic sample of children/adolescents and measured cross-sectional and longitudinal associations between SSB intake and plasma HDL cholesterol and triglycerides (TGs) over 12 mo., Methods: In a diverse cohort of children aged 8-15 y, cross-sectional associations (n = 613) between baseline SSB intake and blood lipid concentrations and longitudinal associations (n = 380) between mean SSB intake, changes in SSB intake, and lipid changes over 12 mo were assessed with multivariable linear regression., Results: Greater SSB intake was associated with lower socioeconomic status, higher total energy intake, lower fruit/vegetable intake, and more sedentary time. In cross-sectional analysis, greater SSB intake was associated with higher plasma TG concentrations among consumers (62.4, 65.3, and 71.6 mg/dL in children who consumed >0 but <2, ≥2 but <7, and ≥7 servings/wk, respectively; P-trend: 0.03); plasma HDL cholesterol showed no cross-sectional association. In the longitudinal analysis, mean SSB intake over 12 mo was not associated with lipid changes; however, the 12-mo increase in plasma HDL-cholesterol concentration was greater among children who decreased their intake by ≥1 serving/wk (4.6 ± 0.8 mg/dL) compared with children whose intake stayed the same (2.0 ± 0.8 mg/dL) or increased (1.5 ± 0.8 mg/dL; P = 0.02)., Conclusions: In a multi-ethnic sample of children, intake of SSBs was positively associated with TG concentrations among consumers, and changes in SSB intake were inversely associated with HDL cholesterol concentration changes over 12 mo. Further research in large diverse samples of children is needed to study the public health implications of reducing SSB intake among children of different racial/ethnic groups. The Daily D Health Study was registered at clinicaltrials.gov as NCT01537809., (© 2015 American Society for Nutrition.)

Context: Trabecular bone score (TBS) is a bone assessment tool that offers information beyond that afforded by dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) measurements. Adolescents with anorexia nervosa (AN) are known to exhibit compromised bone density and skeletal strength., Objectives: This study aimed to determine TBS among adolescents with AN and evaluate the correlation with anthropometric, clinical and densitometric variables., Design: Areal BMD spinal measures were analyzed for TBS. Findings were compared with clinical (height, weight, body mass index [BMI], age, pubertal development, 25-hydroxyvitamin D) and self-reported data (illness duration, amenorrhea, exercise, fracture, family history of osteoporosis, and antidepressant use), and BMD measures by DXA and peripheral quantitative computed tomography (pQCT)., Setting and Participants: This was an urban adolescent program consisting of 57 females with AN, age 11-18 y., Interventions: Interventions included DXA (absolute BMD and Z-score), pQCT (volumetric BMD [vBMD] and stress-strain index [SSI]), laboratory evaluation, and questionnaire administration., Main Outcome Measures: Main outcome measures included TBS, areal and vBMD, SSI, fracture history, disease duration., Results: The TBS of six participants (11%) showed degraded and 19 (33%) partially degraded microarchitecture. Spinal TBS was correlated (P < .05) with age, height, weight, BMI, pubertal stage, BMD, and body composition by DXA, and BMD and SSI by pQCT. TBS was not correlated with disease duration, fracture, vitamin D status, race, or ethnicity, and self-reported health data., Conclusions: TBS showed evidence of degraded microarchitecture in over 40% of this study sample, and strongly correlated with anthropometric data and measures of BMD and skeletal strength. TBS is a novel tool that captures another dimension of bone health in adolescents with AN.

Objective: To assess whether add-back therapy with norethindrone acetate or norethindrone acetate plus conjugated equine estrogens is superior to maintain bone health in adolescents and young women using gonadotropin-releasing hormone agonists for endometriosis. Gonadotropin-releasing hormone agonists are associated with deleterious effects on bone. Hormonal add-back may mitigate these effects., Methods: Adolescents and young women (n=51) received a random, double-blind assignment to add-back with norethindrone acetate (5 mg/day) plus conjugated equine estrogens (0.625 mg/day) or norethindrone acetate plus placebo for 12 months. Body composition, bone mineral content, and bone mineral density (BMD) were obtained by dual-energy X-ray absorptiometry every 6 months. Quality-of-life measures were collected every 3 months. Intention-to-treat comparison of outcomes was conducted by repeated-measures analysis of variance., Results: Thirty-four adolescents and young women completed the trial; dropouts did not differ from those who completed the trial. Bone mineral density was normal at baseline. At 12 months, total body bone mineral content and BMD had increased in the norethindrone acetate plus conjugated equine estrogens group (bone mineral content +37 g, P<.001 and BMD +0.012 g/cm, P=.05), but not in those receiving norethindrone acetate plus placebo (bone mineral content P=.19 and BMD P=.95). Lean mass increased only in those receiving conjugated equine estrogens (+1.4 kg, P=.001). Improvements in physical functioning domains of quality-of-life assessments were greater with norethindrone acetate plus conjugated equine estrogens (P=.005). No differences were seen at the hip or lumbar spine by dual-energy X-ray absorptiometry. No significant adverse events occurred., Conclusion: Hormonal add-back successfully preserved bone health and improved quality of life for adolescents and young women with endometriosis during 12 months of gonadotropin-releasing hormone agonist therapy. Combination norethindrone acetate plus conjugated equine estrogens add-back appears to be more effective for increasing total body bone mineral content, areal BMD, and lean mass than norethindrone acetate monotherapy., Clinical Trial Registration: ClinicalTrials.gov; www.clinicaltrials.gov, NCT00474851., Level of Evidence: I.

Anorexia nervosa (AN) is a psychiatric illness with profound medical consequences. Among the many adverse physical sequelae of AN, bone health is impacted by starvation and can be permanently impaired over the course of the illness. In this review of skeletal complications associated with eating disorders, we discuss the epidemiology, neuroendocrine changes, adolescent vs. adult skeletal considerations, orthopedic concerns, assessment of bone health, and treatment options for individuals with AN. The focus of the review is the skeletal sequelae associated with anorexia nervosa, but we also briefly consider other eating disorders that may afflict adolescents and young adults. The review presents updates to the field of bone health in AN, and also suggests knowledge gaps and areas for future investigation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose of Review: We provide an overview of new insights into the genetic causes of primary ovarian insufficiency (POI) and address the challenges faced by clinicians who care for adolescents with this condition., Recent Findings: In most cases, the cause of POI remains a mystery after appropriate clinical testing has been completed. Large-scale genomic sequencing approaches are uncovering new mechanisms underlying the disorder. Gene variants that affect the normal processes of primordial germ-cell proliferation and migration, oocyte meiosis, and ovarian follicle formation/activation are plausible mechanisms. Whole exome sequencing has been used to associate many of these variants with human POI. POI is a serious chronic condition with no cure. It qualifies as a rare disease and as such presents special challenges to patients, parents, and clinicians. Although the diagnosis of POI is often delayed because of the assumption that irregular menses are common among adolescents, early detection is critical for the maintenance of bone and cardiovascular health. Treatment options have focused on hormonal therapy and fertility preservation. However, many studies prove the increasing need to incorporate mental health support and a family systems approach into the management plan., Summary: Large-scale genomic sequencing has recently identified new mechanisms of POI. However, at present this testing is not clinically indicated as routine. Practice will change as genomic medicine is integrated into standard care. Adolescents with POI are best served by an integrated personal care approach centered on the patient and provided by a primary care clinician who has support from a multidisciplinary team.

Background: Improvements in clinical care have led to increased life expectancy in patients with cystic fibrosis (CF) over the past several decades. Whether these improvements have had significant effects on bone health in patients with CF is unclear., Methods: This is a cross-sectional study comparing clinical characteristics and bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in adults with CF evaluated in 1995-1999 to age-, race-, and gender-matched patients with CF evaluated in 2011-2013 at the same center on calibrated DXA machines., Results: The cohorts were similar in terms of age, BMI, pancreatic insufficiency, presence of F508del mutation, and reproductive history. In the most recent cohort, pulmonary function was superior, and fewer patients had vitamin D deficiency or secondary hyperparathyroidism. Areal BMD measures of the PA spine, lateral spine, and distal radius were similarly low in the two cohorts., Conclusions: Although pulmonary function and vitamin D status were better in patients in the present-day cohort, areal BMD of the spine was reduced in a significant number of patients and was no different in patients with CF today than in the late 1990s. Further attention to optimizing bone health may be necessary to prevent CF-related bone disease., (Copyright © 2015 European Cystic Fibrosis Society. All rights reserved.)

In summary, addressing the challenges of the HIV care continuum is critical so that the goals of the NHAS can be achieved. CDC is working closely with federal partners, public health departments, and communities throughout the United States on multiple surveillance, programmatic, and research initiatives to inform and improve outcomes along the HIV care continuum. Currently, a large number of research projects are being conducted to describe the care continuum in various populations, assess and model the impact of interventions, and monitor the quality of care. To contribute to this knowledge base, NIH is working with its academic partners to support research that will inform the optimization of HIV treatment and prevention programs. As part of this focus, the CFAR/APC HIV Continuum of Care Working Group was formed to encourage communication between academic investigators and their local DOHs and to support joint research initiatives that are both timely and relevant to their own cities and environments. Finally, the results presented in this supplement may have implications for jurisdictions beyond those in which the studies were conducted.

We report an MR imaging phenomenon that can lead to misinterpretation. The unique appearance of the soft tissues and bone marrow in a 19-year-old severely malnourished woman with anorexia nervosa raised concerns about technical failure or systemic pathology. Due to extreme fat depletion, the T1-weighted images appeared to be fat-suppressed and the fat-suppressed fluid-sensitive images appeared to be non-fat-suppressed ("flip-flopped"). Failure to recognize the influence of a patient's overall nutritional status on MR images may cause confusion and misdiagnosis.

Background: While rarely used for supplementation trials in the United States, schools present a practical alternative to a clinical setting., Purpose: We describe the successful recruitment and retention of urban schoolchildren into a 6-month randomized, double-blind vitamin D3 supplementation trial., Methods: Boston-area urban schoolchildren, aged 8-15 years, were recruited in 2011-2012 through classroom and auditorium presentations. Informed consent forms in five languages were sent home to parents. Retention methods included regular telephone calls and gift cards for completed study visits., Results: In total, 691 schoolchildren enrolled. Their mean (standard deviation) age was 11.7 (1.4) years; 59% were racial/ethnic minorities and 68% qualified for free or reduced-price school meals. Multi-level, culturally sensitive, creative approaches contributed to success in recruitment and retention. Of 691 participants, 81% completed the 6-month intervention period. Reasons for attrition included missed appointments and fear of a blood draw. More children from households with higher incomes were retained than those from households with lower incomes (85% vs 79%, respectively, P = 0.04)., Limitations: The need for three fasting blood draws over the 6-month supplementation period was a limiting factor in the recruitment and retention of children in this study., Conclusion: Recruitment of urban children into a school-based randomized controlled trial represents a feasible approach for a supplementation study. Particular attention to children of lower socioeconomic status may enhance participation and retention when conducting intervention studies among diverse populations., (© The Author(s) 2014.)

Skeletal health is modulated by a variety of factors, including genetic makeup, hormonal axes, and environment. Across all ages, extremes of body weight may exert a deleterious effect on bone accretion and increase fracture risk. The incidence of both anorexia nervosa and obesity, each involving extreme alterations in body composition, is rising among youth, and secondary osteoporosis is increasingly being diagnosed among affected children and adolescents. Compared with the elderly, the definition of osteoporosis that stems from any underlying condition differs for the pediatric population and special precautions are required with regard to treatment of young patients. Early recognition and management of both underweight and overweight youth and the accompanying consequences on bone and mineral metabolism are essential for preservation of skeletal health, although prevention of bone loss and optimization of bone mineral accrual remain the most important protective measures.

Context: Young adults with cystic fibrosis (CF) are at risk for low bone density and fractures, but the underlying alterations in bone microarchitecture that may contribute to their increased fracture risk are currently unknown., Objective: The main goal of this study was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) to characterize the bone microarchitecture, volumetric bone mineral density (vBMD), and estimated strength of the radius and tibia in young adults with CF compared with healthy volunteers., Design and Setting: This was a cross-sectional study at an outpatient clinical research center within a tertiary academic medical center., Participants: Thirty young adults with CF, 18 to 40 years of age, were evaluated and compared with 60 healthy volunteers matched by age (±2 years), gender, and race., Main Outcome Measures: The primary outcomes were HR-pQCT-derived cortical and trabecular vBMD, bone microarchitecture, and estimates of bone strength., Results: At the radius and tibia, young adults with CF had smaller bone cross-sectional area and lower vBMD. Cortical and trabecular microarchitecture were compromised at both sites, most notably involving the trabecular bone of the tibia. These differences translated into lower estimated bone strength both at the radius and tibia. After accounting for body mass index differences, young adults with CF had lower bone area and estimated bone strength at the radius and had compromised trabecular microarchitecture and lower total and trabecular vBMD and estimated bone strength at the tibia. Alterations in trabecular bone density and microarchitecture and estimated strength measures of the tibia were also greater than expected based on dual-energy x-ray absorptiometry-derived areal BMD differences., Conclusions: Young adults with CF have compromised bone microarchitecture and lower estimated bone strength at both the radius and tibia, even after accounting for their smaller body size. These skeletal deficits likely explain the higher fracture risk observed in young adults with CF.

Context: Vitamin D promotes bone health and regulates the immune system, both important actions for pediatric patients with inflammatory bowel disease (IBD). The supplementation dose that would maintain optimal serum 25-hydroxyvitamin D concentration (25OHD ≥ 32 ng/mL) is unknown., Objective: The objective of the study was to compare two supplementation regimens' efficacy and safety in maintaining optimal 25OHD in children with IBD., Design: This was a randomized, not blinded, controlled trial., Setting: The trial was conducted in the Boston Children's Hospital Clinical and Translational Study Unit., Participants: Sixty-three patients, aged 8-18 years with IBD and baseline 25OHD greater than 20 ng/mL were enrolled; 48 completed the study, and one withdrew for adverse events., Intervention: Arm A received 400 IU of oral vitamin D2 daily (n = 32). Arm B received 1000 IU daily in the summer/fall and 2000 IU in the winter/spring (n = 31)., Main Outcome: The main outcome was the probability of maintaining 25OHD of 32 ng/mL or greater in all trimonthly visits for 12 months., Results: Three participants in arm A (9.4%) and three in arm B (9.7%) achieved the primary outcome (P = .97). The incidence of adverse events, all minor, did not differ. More participants in arm A developed C-reactive protein level of 1 mg/dL or greater (31% vs 10%, P = .04) and IL-6 greater than 3 pg/mL (54% vs 27%, P = .05)., Conclusions: Daily oral vitamin D2 doses up to 2000 IU were inadequate to maintain optimal 25OHD but were well tolerated. The finding of lower incidence of elevated inflammatory markers and cytokines among participants receiving higher vitamin D2 doses merits further study.

The evidence continues to mount for the important role of vitamin D as a hormone that provides protective benefits to the immune system. Guidelines have been developed recommending routine vitamin D supplementation in order to optimize bone health, including aiming for a goal 25(OH)D concentration greater than 30 ng/mL among select patient groups who are at risk for skeletal deficits or vitamin D deficiency itself. Whether this level is the optimal one that confers the extraskeletal benefits of vitamin D remains unknown. Whether healthy children and adolescents may benefit from maintenance of 25(OH)D levels at higher thresholds also is unknown and under study. Adolescence is a critical time for the accrual of peak bone mass, and optimizing vitamin D during this important developmental period and throughout the life cycle may be beneficial for and beyond the skeleton. Although routine screening of 25(OH)D levels is not currently recommended, those individuals at higher risk for insufficiency/deficiency should be screened and appropriately supplemented.

Objectives: We sought to determine whether serum citrulline (CIT), an amino acid produced by small bowel enterocytes, was associated with clinical and biochemical markers of gastrointestinal function in children undergoing hematopoietic cell transplantation (HCT)., Methods: We conducted a multicenter, prospective cohort study of 26 children to define time-related changes in serum CIT during the course of HCT. Markers of gastrointestinal function including oral energy intake, emesis, stool volume, presence of graft-versus-host disease (GVHD), oral mucositis severity, and cytokine and neurohormone levels were measured. Weekly serum CIT concentrations were obtained from 10 days prior until 30 days after HCT., Results: Mean baseline CIT concentration was 22.7 μmol/L (95% confidence interval [CI] 17.7-27.6) on day -10, which decreased to a nadir of 7.5 μmol/L (95% CI 3.1-18.0, P = 0.017) on day 8 following HCT before returning to baseline by day 30. After adjustment for IL-6 level (1.0% lower CIT per 10% increase in interleukin-6, P = 0.004), presence of acute GVHD (27% lower CIT, P = 0.025), and oral energy intake (2.1% lower CIT per 10% decrease in energy intake, P = 0.018), the nadir shifted to day 10, when mean CIT concentration was lower in patients with severe oral mucositis (6.7 μmol/L, 95% CI 3.4-13.1) than in those without severe mucositis (11.9 μmol/L, 95% CI 5.8-24.4, P = 0.003). Change in CIT was not correlated with stool volume, C-reactive protein, tumor necrosis factor-α, leptin, or ghrelin., Conclusions: In children undergoing HCT, serum CIT correlates with measures of gastrointestinal function (oral mucositis severity, dietary intake, acute GVHD) and may reflect mucosal injury to the gastrointestinal tract.

Purpose: To evaluate mediators of resumption of menses (ROM) in adolescents with anorexia nervosa (AN)., Methods: Anthropometrics, body composition by dual-energy X-ray absorptiometry, hormonal studies, and responses to mental health screens were obtained at 6-month intervals for 18 months in 37 adolescents with AN randomized to the placebo arm of a double-blind treatment trial. Outcomes were compared between subjects with menstrual recovery and those without., Results: Twenty-four subjects (65%) had ROM. Higher percentage body fat was associated with ROM (odds ratio, 1.19; 95% confidence interval, 1.06, 1.33; p < .01), as was body mass index and percent median body weight. Estradiol ≥30 ng/mL alone did not predict menses (p = .08) but was associated with ROM when coupled with percent mean body weight (odds ratio, 2.49; 95% confidence interval, 1.09, 5.65; p = .03). Changes in leptin, cortisol, and mental health were not associated with return of menses., Conclusions: Percentage body fat may be an additional, useful clinical assessment to follow in caring for adolescents with AN., (Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The International Society for Clinical Densitometry Official Revised Positions on reporting of densitometry results in children represent current expert recommendations to assist health care providers determine which skeletal sites should be measured, which, if any, adjustments should be made, reference databases to be used, and the elements to include in a dual-energy X-ray absorptiometry report. The recommended scanning sites remain the total body less head and the posterior-anterior spine. Other sites such as the proximal femur, lateral distal femur, lateral vertebral assessment, and forearm are discussed but are only recommended for specific pediatric populations. Different methods of interpreting bone density scans in children with short stature or growth delay are presented. The use of bone mineral apparent density and height-adjusted Z-scores are recommended as suitable size adjustment techniques. The validity of appropriate reference databases and technical considerations to consider when upgrading software and hardware remain unchanged. Updated reference data sets for all contemporary bone densitometers are listed. The inclusion of relevant demographic and health information, technical details of the scan, Z-scores, and the wording "low bone mass or bone density" for Z-scores less than or equal to -2.0 standard deviation are still recommended for clinical practice. The rationale and evidence for the development of the Official Positions are provided. Changes in the grading of quality of evidence, strength of recommendation, and worldwide applicability represent a change in current evidence and/or differences in opinion of the expert panelists used to validate the position statements for the 2013 Position Development Conference., (Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

The International Society for Clinical Densitometry (ISCD) convened its second Pediatric Position Development Conference (PDC) on October 2-3, 2013 in Baltimore, MD. The conference was co-sponsored by the American Society for Bone and Mineral Research (ASBMR) and was held immediately before their annual meeting. The aim of a PDC is to make recommendations for standards in the field of bone densitometry. The recommendations address issues such as quality control, data acquisition and analysis, and the interpretation and reporting of bone densitometric results. In 2007, ISCD convened its first Pediatric PDC to address issues specific to skeletal health assessments in children and adolescents. The 2013 Pediatric PDC focused on advances in the field since that initial conference that would lead to revisions of the original positions. Topics for consideration were developed by the ISCD and its Scientific Advisory Committee. Clinically relevant questions related to each topic were assigned to task forces for a comprehensive review of the medical literature and subsequent presentation of reports to an international panel of experts. Expert panelists included representatives from both the ISCD and ASBMR. The recommendations of the PDC Expert Panel were subsequently reviewed by the ISCD Board of Directors and positions accepted by majority vote. The approved recommendations became the Official Positions of the ISCD. The positions are to be submitted to the ASBMR for its consideration for endorsement. Topics considered at the Pediatric PDC included fracture prediction and definition of osteoporosis, dual-energy X-ray absorptiometry assessment in chronic diseases that may affect the skeleton, dual-energy X-ray absorptiometry interpretation and reporting, quantitative computed tomography measurements, and densitometry in infants and young children. We discuss potential implications of the new recommendations and factors leading to a change in the wording of these positions, considering the science that has evolved over the past 6yr., (Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: Abnormal β-amyloid (Aβ) is associated with deleterious changes in central acetylcholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist. We aimed to establish an optimal "microdose" of scopolamine for the development of a "cognitive stress test.", Methods: Healthy older adults (n = 26, aged 55-75 years) with two risk factors for AD, but with low cortical Aβ burden, completed the Groton Maze Learning Test (GMLT) at baseline and then received scopolamine (0.20 mg subcutaneously). Participants were reassessed at 1, 3, 5, 7, and 8 hours postinjection., Results: There were significant differences, of a moderate magnitude, in performance between baseline and 3 hours postinjection for total errors, rule break errors, and the GMLT composite (d ≈ 0.50) that were all unrelated to body mass., Conclusions: A very low dose of scopolamine leads to reliable cognitive impairment at 3 hours postdose (Tmax) and full cognitive recovery within 5 hours, supporting its use as a prognostic test paradigm to identify individuals with potential preclinical AD. This paradigm is being implemented in a larger cohort of healthy adults, with high or low Aβ, to identify pharmacodynamic differences between groups., (Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)