<p><strong>OBJECTIVES: </strong>Anemia is the most common systemic complication of inflammatory bowel disease, is more common in affected children than in adults, and is mediated in large part by chronic inflammation. Inflammation increases levels of the iron-regulatory protein hepcidin, which have been elevated in adults with Crohn disease.</p>

<p><strong>METHODS: </strong>We measured serum hepcidin-25 and hemoglobin (Hgb) in 40 children and adolescents with Crohn disease at baseline and 10 weeks after initiation of anti-tumor necrosis factor (TNF)-α therapy. Measures of disease activity, inflammatory markers, and cytokines were obtained in all subjects. Anemia was defined by World Health Organization criteria.</p>

<p><strong>RESULTS: </strong>At baseline hepcidin and C-reactive protein levels were correlated, and 95% of subjects were anemic. After anti-TNF-α therapy, median (interquartile range) hepcidin concentrations decreased significantly and the distribution narrowed (27.9 [16.2, 52.9] vs 23.2 [11.1, 37.7] ng/mL, P = 0.01). Mean (standard deviation) Hgb also increased significantly (10.6 ± 1.2 to 10.9 ± 1.1 g/dL, P = 0.02), and the increase was sustained at 12 months, although 90% of participants continued to meet anemia criteria at 10 weeks. Disease activity and markers of inflammation also decreased and albumin levels increased. In generalized estimating equation analyses, higher TNF-α, interleukin 6, erythrocyte sedimentation rate, and C-reactive protein were associated with higher hepcidin concentrations (P = 0.04, P = 0.03, P = 0.003, and P &lt; 0.001, respectively), and increased levels of disease activity were associated with higher hepcidin.</p>

<p><strong>CONCLUSIONS: </strong>In children with Crohn disease, anti-TNF-α therapy is associated with decreased levels of hepcidin and increased Hgb 10 weeks after induction. Improvement in anemia may be a secondary benefit for children who receive this therapy.</p>

<p>Annual gains in BMC and areal bone mineral density (aBMD) in children vary with age, pubertal status, height-velocity, and lean body mass accrual (LBM velocity). Evaluating bone accrual in children with bone health-threatening conditions requires consideration of these determinants. The objective of this study was to develop prediction equations for calculating BMC/aBMD velocity SD scores (velocity-Z) and to evaluate bone accrual in youth with health conditions. Bone and body compositions via DXA were obtained for up to six annual intervals in healthy youth (n = 2014) enrolled in the Bone Mineral Density in Childhood Study (BMDCS) . Longitudinal statistical methods were used to develop sex- and pubertal-status-specific reference equations for calculating velocity-Z for total body less head-BMC and lumbar spine (LS), total hip (TotHip), femoral neck, and 1/3-radius aBMD. Equations accounted for (1) height velocity, (2) height velocity and weight velocity, or (3) height velocity and LBM velocity. These equations were then applied to observational, single-center, 12-month longitudinal data from youth with cystic fibrosis (CF; n = 65), acute lymphoblastic leukemia (ALL) survivors (n = 45), or Crohn disease (CD) initiating infliximab (n = 72). Associations between BMC/aBMD-Z change (conventional pediatric bone health monitoring method) and BMC/aBMD velocity-Z were assessed. The BMC/aBMD velocity-Z for CF, ALL, and CD was compared with BMDCS. Annual changes in the BMC/aBMD-Z and the BMC/aBMD velocity-Z were strongly correlated, but not equivalent; LS aBMD-Z = 1 equated with LS aBMD velocity-Z = -3. In CF, BMC/aBMD velocity-Z was normal. In posttherapy ALL, BMC/aBMD velocity-Z was increased, particularly at TotHip (1.01 [-.047; 1.7], p &lt; 0.0001). In CD, BMC/aBMD velocity-Z was increased at all skeletal sites. LBM-velocity adjustment attenuated these increases (eg, TotHip aBMD velocity-Z: 1.13 [0.004; 2.34] versus 1.52 [0.3; 2.85], p &lt; 0.0001). Methods for quantifying the BMC/aBMD velocity that account for maturation and body composition changes provide a framework for evaluating childhood bone accretion and may provide insight into mechanisms contributing to altered accrual in chronic childhood conditions. © 2018 American Society for Bone and Mineral Research.</p>

<p>Though previous studies have demonstrated an increased fracture risk in females with anorexia nervosa (AN), fracture risk in males is not well characterized. The objective of this study was to examine sex differences in fracture risk and site-specific fracture incidence in AN. We performed a population-based retrospective cohort study using The Health Improvement Network (THIN; a large database of anonymized electronic medical records collected at primary care clinics throughout the United Kingdom). The median calendar year for the start of the observation period was 2004-2005. We identified 9239 females and 556 males &lt;60 years of age with AN, and 97,889 randomly selected sex-, age-, and practice-matched participants without eating disorders (92,329 females and 5560 males). Multivariable Cox regression was used to estimate the hazard ratio (HR) for incident fracture. Median age at start of observation was 29.8 years in females and 30.2 years in males. The HR for fracture associated with AN differed by sex and age (interaction p = 0.002). Females with AN had an increased fracture risk at all ages (HR, 1.59; 95% confidence interval [CI], 1.45 to 1.75). AN was associated with a higher risk of fracture among males &gt;40 years of age (HR, 2.54; 95% CI, 1.32 to 4.90; p = 0.005) but not among males ≤40 years. Females with AN had a higher risk of fracture at nearly all anatomic sites. The greatest excess fracture risk was noted at the hip/femur (HR, 5.59; 95% CI, 3.44 to 9.09) and pelvis (HR, 4.54; 95% CI, 2.42 to 8.50) in females and at the vertebrae (HR, 7.25; 95% CI, 1.21 to 43.45) for males with AN. AN was associated with higher incident fracture risk in females across all age groups and in males &gt;40 years old. Sites of highest fracture risk include the hip/femur and pelvis in females and vertebrae in males with AN. © 2016 American Society for Bone and Mineral Research.</p>

<p>This population-based retrospective cohort study sought to determine if anorexia nervosa (AN) is associated with a higher risk of urolithiasis. Nine thousand three hundred two females with AN were compared to 92 959 randomly selected age-matched and practice-matched females. Cox regression was used to estimate the hazard ratio (HR) for urolithiasis and evaluate effect modification by age. Twenty-three participants with AN (0.25%) developed urolithiasis compared with 154 unexposed participants (0.17%) over a median of 4&nbsp;years of observation. The risk of urolithiasis varied significantly with age (interaction p = 0.02). AN was associated with a more than threefold higher risk of urolithiasis in females ≤25&nbsp;years of age (HR 3.49, 95% CI: 1.56-7.81; p = 0.002), but not in females over 25&nbsp;years (HR 1.18, 95% CI: 0.69-2.02; p = 0.54). The distribution of diagnosis codes for urolithiasis differed between groups (p = 0.04), with a higher proportion of codes for uric acid urolithiasis in the AN (16.2%) versus unexposed group (5.0%). Copyright © 2017 John Wiley &amp; Sons, Ltd and Eating Disorders Association.</p>

<p><strong>BACKGROUND: </strong>Variability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making.</p>

<p><strong>METHODS: </strong>We conducted a prospective single-center study of children (3.6-17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study.</p>

<p><strong>RESULTS: </strong>The median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1-6.5% for calcium, 9.5-14.9% for phosphate and 32.7-33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33-56%, 19-28%, and 30-33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant's values within clinical target ranges was 55% (26-86%) for calcium, 58% (0-96%) for phosphate, and 21% (0-64%) for PTH.</p>

<p><strong>CONCLUSIONS: </strong>There is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20-30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements.</p>

<p>We previously reported significant gains in pQCT measures of tibia trabecular bone mineral density (BMD) and cortical structure following completion of therapy in children and adolescents with acute lymphoblastic leukemia (ALL). The objective of this study was to examine changes in DXA measures used in clinical practice and expressed as Z-scores using robust national reference data. Children and adolescents, ages 5 to 18 years were enrolled within 2 (median 0.8) years of completing ALL therapy. DXA total-body less-head bone mineral content (TBLH-BMC), and spine, total hip, femoral neck, and 1/3rd radius areal BMD (aBMD) were assessed in 45 participants at enrollment and 12-months later. Linear regression models examined correlates of changes in DXA Z-scores. Changes in DXA outcomes were compared to changes in tibia pQCT trabecular and cortical volumetric BMD (vBMD) and cortical area. At enrollment, DXA TBLH-BMC, spine and radius aBMD Z-scores were not significantly reduced in ALL survivors; however, total hip [median -0.74 (IQ range -1.51 to -0.04)] and femoral neck [-0.51 (-1.24 to 0.14)] aBMD Z-scores were lower (both p &lt; 0.01) compared to reference data. DXA Z-scores at all skeletal sites increased over 12 months. Despite improvement, total hip Z-score remained lower at -0.55 (-1.05 to 0.18). The increases in TBLH-BMC, total hip and femoral neck aBMD Z-scores were more pronounced in those enrolled within 6 months of completing ALL therapy, compared to those enrolled at &gt;6 months. Gains in TBLH-BMC, total hip, femoral neck and radius aBMD Z-scores were significantly associated with gains in tibia cortical area Z-scores (R = 0.56 to 0.67, p ≤ 0.001). Changes in TBLH and proximal femur sites were associated with gains in trabecular vBMD Z-scores (R = 0.37 to 0.40; p ≤ 0.01); these associations were not significant when adjusted for gains in cortical area. In summary, gains in DXA measures were most pronounced in total hip and femoral neck following ALL therapy. The gains in all DXA measures, with the exception of lumbar spine, reflected gains in cortical area. Overall, ALL survivors demonstrate skeletal recovery following completion of therapy; a small sub-group continue to demonstrate deficits and benefit from continued observation to ensure improvement over time.</p>

<p><strong>PURPOSE: </strong>Rheumatoid arthritis (RA) is associated with adverse body composition profiles, and low muscle density due to accumulation of intramuscular fat. This study assessed associations between muscle density, body composition, muscle strength, and physical functioning in patients with RA and a reference group.</p>

<p><strong>METHODS: </strong>Patients with RA, ages 18-70 years, and healthy control participants completed whole-body DXA and peripheral quantitative CT (pQCT) to quantify appendicular lean mass (ALMI, kg/m) and fat mass indices (FMI, kg/m), visceral fat area, and muscle density. Dynamometry was used to measure hand-grip strength and muscle strength at the knee and lower leg (ft-lbs). Disability and physical functioning were measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Linear regression analyses assessed differences related to RA and associations between muscle density, strength, and function.</p>

<p><strong>RESULTS: </strong>The study consisted of 103 RA patients (51 men) and 428 healthy participants. Low muscle density was associated with greater disease activity, CRP, and Interleukin-6, greater total and visceral fat, lower ALMI Z-Scores, physical inactivity, and long-term use of glucocorticoids (&gt;1yr). Patients with low ALMI Z-Scores had lower muscle density Z-Score compared to reference participants with similarly low ALMI. Low muscle density was independently associated with lower muscle strength, higher HAQ, and lower SPPB after adjusting for ALMI and FMI Z-Scores.</p>

<p><strong>CONCLUSIONS: </strong>Low muscle density observed among patients with RA is observed in association with low muscle mass, excess adiposity, poor strength, and greater disability. Interventions to address poor muscle quality could potentially affect important functional outcomes. This article is protected by copyright. All rights reserved.</p>

<p>The impact of glucocorticoids (GC) on skeletal development has not been established. The objective of this study was to examine changes in volumetric bone mineral density (vBMD) and cortical structure over 1 year in childhood nephrotic syndrome (NS) and to identify associations with concurrent GC exposure and growth. Fifty-six NS participants, aged 5 to 21 years, were enrolled a median of 4.3 (0.5 to 8.1) years after diagnosis. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained at enrollment and 6 and 12 months later. Sex, race, and age-specific Z-scores were generated for trabecular vBMD (TrabBMD-Z), cortical vBMD (CortBMD-Z), and cortical area (CortArea-Z) based on &gt;650 reference participants. CortArea-Z was further adjusted for tibia length-for-age Z-score. Quasi-least squares regression was used to identify determinants of changes in pQCT Z-scores. At enrollment, mean TrabBMD-Z (-0.54 ± 1.32) was significantly lower (p = 0.0001) and CortBMD-Z (0.73 ± 1.16, p &lt; 0.0001) and CortArea-Z (0.27 ± 0.91, p = 0.03) significantly greater in NS versus reference participants, as previously described. Forty-eight (86%) participants were treated with GC over the study interval (median dose 0.29 mg/kg/day). On average, TrabBMD-Z and CortBMD-Z did not change significantly over the study interval; however, CortArea-Z decreased (p = 0.003). Greater GC dose (p &lt; 0.001), lesser increases in tibia length (p &lt; 0.001), and lesser increases in CortArea-Z (p = 0.003) were independently associated with greater increases in CortBMD-Z. Greater increases in tibia length were associated with greater declines in CortArea-Z (p &lt; 0.01); this association was absent in reference participants (interaction p &lt; 0.02). In conclusion, GC therapy was associated with increases in CortBMD-Z, potentially related to suppressed bone formation and greater secondary mineralization. Conversely, greater growth and expansion of CortArea-Z (ie, new bone formation) were associated with declines in CortBMD-Z. Greater linear growth was associated with impaired expansion of cortical area in NS. Studies are needed to determine the fracture implications of these findings.</p>

<p><strong>BACKGROUND: </strong>Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH.</p>

<p><strong>PROCEDURE: </strong>Retrospective cohort study (1980-2010) of 119 survivors treated with rhGH for irradiation-induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD.</p>

<p><strong>RESULTS: </strong>Median survivor follow-up since rhGH initiation was 4.8 (range 0.2-18.3) years. SCFE was diagnosed in 10 subjects post-TBI and none after CI (P &lt; 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211-fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency.</p>

<p><strong>CONCLUSIONS: </strong>The markedly greater SCFE incidence rate in childhood cancer survivors with TBI-associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE.</p>

<p><strong>OBJECTIVE: </strong>Rheumatoid arthritis (RA) is associated with low muscle mass and density. The objective of our study was to evaluate associations between 2 serum biomarkers [insulin-like growth factor 1 (IGF-1) and adiponectin] and skeletal muscle in RA.</p>

<p><strong>METHODS: </strong>Whole-body dual energy X-ray absorptiometry measures of the appendicular lean mass index (ALMI; kg/m(2)) and total fat mass index (kg/m(2)), as well as the peripheral quantitative computed tomography measures of the lower leg muscle and fat cross-sectional area (CSA; cm(2)) and muscle density (an index of fat infiltration) were obtained from 50 participants with RA, ages 18-70 years. Multivariable linear regression analyses evaluated associations between body composition and levels of adiponectin and IGF-1, adjusted for age, sex, and adiposity.</p>

<p><strong>RESULTS: </strong>Greater age was associated with higher adiponectin (p = 0.06) and lower IGF-1 (p = 0.004). Eight subjects had IGF-1 levels below the reference range for their age and sex. These subjects had significantly lower ALMI and muscle CSA in multivariable models. Lower IGF-1 levels were associated with greater clinical disease activity and severity, as well as low ALMI, muscle CSA, and muscle density (defined as 1 SD below normative mean). After adjusting for age and sex, greater adiponectin levels were associated with lower BMI (p = 0.02) as well as lower ALMI, and lower muscle CSA, independent of adiposity (p &lt; 0.05). Only greater Health Assessment Questionnaire scores were significantly associated with lower adiponectin levels.</p>

<p><strong>CONCLUSION: </strong>Low IGF-1 and greater adiponectin levels are associated with lower muscle mass in RA. Lower IGF-1 levels were seen in subjects with greater disease activity and severity.</p>