Hyperadiponectinemia During Infliximab Induction Therapy in Pediatric Crohn Disease.

OBJECTIVES: The inflammatory process in Crohn disease (CD) involves the visceral fat, characterized by adipocyte hyperplasia and altered adipose tissue and serum concentrations of tumor necrosis factor (TNF), leptin, adiponectin and resistin. We investigated the effect of anti-TNF therapy with infliximab (IFX) on serum adipokine levels in pediatric CD. METHODS: Serum concentrations of resistin (ng/mL), leptin (ng/mL), and total adiponectin (µg/mL) were assessed by enzyme-linked immunosorbent assays (ELISA) in 18 pediatric CD patients (mean age 15.0 ±â€Š1.5 years) before first, second, and fourth IFX infusion (weeks 0, 2, and 14) and compared with baseline values from sex- and BMI-matched healthy controls (HC, mean age 13.4 ±â€Š1.6 years). RESULTS: At baseline, CD patients (mean age 15.0 ±â€Š1.5 years, 10 of 18 boys) compared with HC (13.4 ±â€Š1.6 years, 7 of 15 boys) had higher resistin levels (median 14.7 ng/mL, range 5.1-50.5 vs 7.3 ng/mL, 0.5-14.5); P = 0.0002). At weeks 2 and 14, resistin decreased to 6.9 ng/mL (2.9-16.8) (P < 0.0001) and 9.2 ng/mL (4.1-20.6; P = 0.0011), respectively. Leptin and adiponectin were comparable between patients and HC at baseline. Leptin increased in girls from 9.5 ng/mL (4.0-30.1) to 16.0 ng/mL (7.9-35.2; P = 0.0156) and 17.2 ng/mL (10.8- 26.8; P = 0.1953) at weeks 0, 2, and 14 respectively; with a trend in boys from 2 (0.6-12.9) to 2.8 (1.7-8.6; P = 0.0840) and 3.3 (1.3-4.6; P = 0.1309). Adiponectin peaked initially from 7.8 µg/mL (4.6-11.9) at week 0 to 9.2 µg/mL (4.1-20.7; P = 0.0005) at week 2 and thereafter fell to 6.5 µg/mL (3.0-12.7; P = 0.0182) at week 14. CONCLUSIONS: TNF blockade is associated with changes in circulating adipokines. The marked early increase of the potent anti-inflammatory adiponectin may contribute to the rapid response to IFX in CD.

Lean body mass, physical activity and quality of life in paediatric patients with inflammatory bowel disease and in healthy controls.

BACKGROUND AND AIMS: Physical activity is important for muscle and bone strength in the growing child and may be impaired in paediatric patients with inflammatory bowel disease (IBD) even during quiescent disease. The SenseWearPro(2) armband allows to measure physical activity under everyday life conditions. METHODS: Thirty-nine IBD patients (27 Crohn's disease, 12 ulcerative colitis, 24 boys) in remission (n=26) or with only mild disease activity (n=13) were compared to 39 healthy age and sex-matched controls. Body weight, height, body mass index (BMI), lean body mass as phase angle α (determined by bioelectrical impedance analysis), and dynamometric grip force were expressed as age- and sex-related Z-scores. SenseWearPro(2) armbands were applied for three consecutive days to record number of steps, duration of physical activity and sleeping time. Quality of life was assessed with the German KINDL and IMPACT III questionnaires, energy intake with prospective food protocols. Differences between patients and pair-matched controls were analysed by paired t-test. RESULTS: Patients showed lower Z-scores for phase angle α (difference -0.72; 95% CI [-1.10; -0.34]) and lower grip strength (-1.02 [-1.58; -0.47]) than controls. They tended towards lesser number of steps per day (-1339 [-2760; 83]) and shorter duration of physical activity (-0.44 h [-0.94; 0.06]), particularly in females and patients with mild disease. Quality of life and energy intake did not differ between patients and controls. CONCLUSION: In spite of quiescent disease lean body mass and physical activity were reduced. Interventions to encourage physical activity may be beneficial in this lifelong disease.

Long-term development of bone geometry and muscle in pediatric inflammatory bowel disease.

OBJECTIVES: The muscle-bone unit is crucial for normal bone development. As muscle mass is frequently reduced in pediatric patients with inflammatory bowel disease (pIBD), we investigated the impact of muscles on the bone development over time. METHODS: Bone and muscle parameters were measured repeatedly in 102 pIBD patients (67 boys; 82 Crohn's disease; 30 newly diagnosed) by peripheral quantitative computed tomography (pQCT) at the forearm. The first and last measurements were included in the evaluation. Results were expressed as sex- and age-specific and partly height-corrected Z-scores for a healthy reference population. RESULTS: At baseline, patients showed reduced Z-scores for height (median -0.7; range -3.7 to 1.6), trabecular bone mineral density (TrbBMD; -0.6; 3.0-2.8), and for height-corrected cortical cross-sectional area (CSA(height); -0.4; -3.0 to 2.2), cortical thickness (CrtTh(height); -0.7; -3.0 to 1.2), and MuscleCSA(height) (-1.0; -4.9 to 2.0; all P<0.01). Cortical bone mineral density (CrtBMD) and height-corrected TotalCSA(height) Z-scores were elevated (0.57; -4.55 to 2.8, both P<0.01). Over time, TotalCSA(height) (+0.36; -1.5 to 4.5) further increased, CorticalCSA(height) (+0.21; -2.1 to 3.0) and MuscleCSA(height) (+0.64; -2.0 to 3.9, all P<0.01) improved, whereas CrtBMD decreased toward normalization (-0.36; -5.1 to 3.6, P<0.05). The change in MuscleCSA(height) significantly correlated with the changes in TrbBMD (r=0.42), TotalCSA(height) (r=0.35), CorticalCSA(height) (r=0.38), and CrtTh(height) (r=0.24; all P<0.02). The relations became even stronger after adjustment for several confounders. CONCLUSIONS: Bone metabolism and geometry are altered in pIBD patients expressed by low trabecular mineral density, low cortical thickness, and high cortical mineral density. The increased height-corrected cortical CSA might reflect a compensatory effect. In our cohort, treatment increased height-corrected muscle CSA and its changes were closely associated with bone parameters. Therefore, physical activity to enhance muscle mass and bone health should be promoted in pIBD patients.