RESUMO
OBJECTIVE: To evaluate children with Crohn's disease for inverse relationships between systemic inflammatory cytokines and sex hormone regulation in the context of anti-tumor necrosis factor α (TNF-α) therapy. STUDY DESIGN: An observational study design was used to assess sex hormone and gonadotropin levels at the time of initiation of anti-TNF-α therapy and 10 weeks and 12 months later in 72 adolescents (Tanner stage 2-5) with Crohn's disease. Mixed-model linear regression was used to evaluate relationships between hormone levels, systemic inflammation, and dual-energy x-ray absorptiometry whole-body fat mass Z scores over the study interval. RESULTS: Sex hormone Z scores increased significantly during the 10-week induction interval: testosterone Z scores in male patients increased from a median of -0.36 to 0.40 (P < .05) and estradiol Z scores in females increased from -0.35 to -0.02 (P < .01). In mixed model regression, the pediatric Crohn's disease activity index score, cytokine levels, and measures of inflammation were significantly and negatively associated with sex hormone Z scores and with luteinizing hormone and follicle-stimulating hormone levels, adjusted for sex and Tanner stage. Sex hormone and gonadotropin levels were not associated with body mass index or fat mass Z-scores. CONCLUSIONS: Crohn's disease is associated with delayed maturation, and initiation of anti-TNF-α therapy was associated with significant and rapid increases in sex hormone and gonadotropin levels, in association with improvements in disease activity and measures of inflammation. These data are consistent with preclinical studies of the effects of inflammation on sex hormone regulation.
Assuntos
Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Hormônios Esteroides Gonadais/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Absorciometria de Fóton , Adolescente , Anticorpos Monoclonais/uso terapêutico , Criança , Pré-Escolar , Citocinas/metabolismo , Estradiol/sangue , Feminino , Humanos , Inflamação , Infliximab/uso terapêutico , Modelos Lineares , Masculino , Fatores Sexuais , Testosterona/sangue , Adulto JovemRESUMO
OBJECTIVE: To quantify lean mass (LM) and fat mass (FM) in survivors of childhood allogeneic hematopoietic stem-cell transplantation (alloHSCT) compared with healthy reference participants and identify risk factors for body composition abnormalities. STUDY DESIGN: Whole body LM and FM were measured with dual energy x-ray absorptiometry in 54 survivors (ages 5-25 years) and 894 healthy reference participants in a cross-sectional study. Multivariate regression models were used to compare sex- and race-specific Z-scores for LM for height (LM-Ht) and FM for height (FM-Ht) in survivors and reference participants and to identify correlates of LM-Ht and FM-Ht Z-scores in alloHSCT. RESULTS: Height Z-scores were significantly lower in alloHSCT survivors (P < .001) compared with reference participants; body mass index Z-scores did not differ (P = .13). Survivors had significantly lower mean LM-Ht Z-scores (-0.72; 95% CI, -1.02--0.42; P < .001) and greater FM-Ht Z-scores (1.10; 95% CI, 0.84-1.39; P < .001) compared with reference participants. LM-Ht Z-score deficits in alloHSCT survivors were larger (-1.26; 95% CI, -1.53--0.99; P < .001) after adjustment for FM-Ht Z-scores. Endocrinopathies and alloHSCT characteristics were not associated with LM-Ht or FM-Ht Z-scores. CONCLUSION: Survivors of childhood alloHSCT have significant LM deficits and FM excess. Future studies should identify the mechanism and consequences of these abnormalities.
Assuntos
Composição Corporal , Transplante de Células-Tronco Hematopoéticas , Sobreviventes , Tecido Adiposo , Adolescente , Criança , Feminino , Humanos , Masculino , Fatores de Risco , Sobreviventes/estatística & dados numéricosRESUMO
OBJECTIVES: To determine the effects of growth, maturation, and whole body bone mineral content (WB-BMC) accrual on biomarkers of bone formation (bone-specific alkaline phosphatase [BSAP]) and resorption (urine deoxypyridinoline/creatinine [DPD]) in healthy children and children with Crohn's disease. STUDY DESIGN: BSAP and DPD were measured at baseline, with growth and dual energy x-ray absorptiometry (DXA) WB-BMC measured at baseline and 6 months in 202 control subjects and 110 subjects with Crohn's disease, ages 5 to 21 years. Multivariable linear regression identified determinants of biomarkers in control subjects and subjects with Crohn's disease. RESULTS: In control subjects, BSAP and DPD were significantly and independently associated with sex, Tanner stage, WB-BMC, height velocity, and WB-BMC accrual rates; these covariates explained 77% to 80% of the variability in the bone biomarkers, respectively. Subjects with Crohn's disease had lower height-for-age (P < .001) and WB-BMC-for-height (P <.05) than control subjects. Crohn's disease was associated with lower BSAP (P < .001) and greater DPD (P < .001), independent of growth, maturation, baseline WB-BMC, and WB-BMC accrual, compared with control subjects. CONCLUSIONS: These data illustrate the potential confounding effects of growth and WB-BMC on bone metabolism biomarkers in children. After adjustment for these effects, Crohn's disease was associated with lower biomarkers of bone formation and greater bone resorption.