Increases in IGF-1 after Anti–TNF - A therapy are associated with bone and muscle accrual in pediatric Crohn disease

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 a (TNF-a) 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-a therapy. Outcomes were expressed as sex-specific z scores. Results: IGF-1 z scores increased from a median (interquartile range) of 21.0 (21.58 to 20.17) to 20.36 (21.04 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-a therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.