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Increases in IGF-1 After Anti-TNF-? Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

ABSTRACT: Context:Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Objective:Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor ? (TNF-?) therapy in pediatric and adolescent CD. Design and Participants:Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. Main Outcome Measures:IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-? therapy. Outcomes were expressed as sex-specific z scores. Results:IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Conclusions:Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-? therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.

SUBMITTER: DeBoer MD

PROVIDER: S-EPMC6276706 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

DeBoer Mark D MD Lee Arthur M AM Herbert Kirabo K Long Jin J Thayu Meena M Griffin Lindsay M LM Baldassano Robert N RN Denson Lee A LA Zemel Babette S BS Denburg Michelle R MR Herskovitz Rita R Leonard Mary B MB

The Journal of clinical endocrinology and metabolism 20180301 3

<h4>Context</h4>Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits.<h4>Objective</h4>Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD.<h4>Design and participants</h4>Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12- ...[more]

PMID: 29329430

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Project description: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 < 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 < 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.

Project description:BackgroundHypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD.MethodsPediatric patients ages 6 to 20 years were enrolled, and their clinical data and anthropometric measurements were obtained. Adipokine levels were measured at 0, 6, and 12 months after CD diagnosis and baseline in control patients (CP). The VAT volumes were measured by magnetic resonance imaging or computed tomography imaging within 3 months of diagnosis.ResultsOne hundred four patients undergoing colonoscopy were prospectively enrolled: 36 diagnosed with CD and 68 CP. The serum adipokine resistin and plasminogen activator inhibitor (PAI)-1 levels were significantly higher in patients with CD at diagnosis than in CP. The VAT volume was similar between CD and CP. Baseline resistin levels at the time of diagnosis in patients with CD who were escalated to biologics was significantly higher than in those not treated using biologic therapy by 12 months (29.8 ng/mL vs 13.8 ng/mL; P = 0.004). A resistin level of ≥29.8 ng/mL at the time of diagnosis predicted escalation to biologic therapy in the first year after diagnosis with a specificity of 95% (sensitivity = 53%; area under the curve = 0.82; P = 0.015 for model with log-scale). There was a significantly greater reduction in resistin (P = 0.002) and PAI-1 (P = 0.010) at the 12-month follow-up in patients on biologics compared with patients who were not treated using biologics.ConclusionsSerum resistin levels at diagnosis of pediatric CD predict the escalation to biologic therapy at 12 months, independent of VAT volumes. Resistin and PAI-1 levels significantly improved in patients with CD after treatment using biologics compared with those not on biologics. These results suggest the utility of resistin as a predictive biomarker in pediatric CD.

Dataset Information

Increases in IGF-1 After Anti-TNF-? Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

Publications

Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

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