ESPE Abstracts (2016) 86 P-P1-143

Impact of Anti-Tumour Necrosis Factor Therapy on the Insulin Like Growth Factor Axis and Bone Development in Childhood Crohn's Disease

M. Altowatia, S. Malika, S. Shepherda, M. McMillana, P. McGroganc, S.F. Ahmeda & S.C. Wonga


aDevelopmental Endocrinology Research Group, Royal Hospital for Children, Glasgow, UK; bDepartment of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, UK; cSidra Medical and Research Centre, Doha, Qatar


Background: There is currently no published study evaluating the role of the IGF axis on bone development following anti-tumour necrosis factor (TNF) therapy in Crohn’s disease (CD).

Method: Prospective, 12-month study in 19CD(12M) who were clinical responders to antiTNF therapy, median age 14.9 years (range 11.2–17.2). IGF1, insulin growth factor binding protein 3(IGFBP3), acid labile subunit (ALS), bone-specific alkaline phosphatase (BALP) and c-telopeptide of collagen cross links (CTX) were adjusted for bone age and gender. Assessment of bone mineral density (BMD) and geometry at tibia were performed using peripheral quantitative tomography (pQCT).

Results: At baseline, IGF1 SDS was +0.1(−3.8,2.1)[P=0.80 vs zero), IGFBP3 SDS +1.4(−2.9,3.0)[P=0.02 vs zero] and ALS SDS −0.9 (−2.2,1.5)[P<0.0001 vs zero]. IGF1 SDS was <−2.0 in 5(26%) at baseline and none at 12 months. At 12 months, IGFBP3 SDS was +0.5(−1.1,2.9) and not different from zero [P=0.09]. ALS SDS was <−2.0 in 1(5%) at baseline and none at 12 months. BALP SDS of −1.7(−3.6,1.0)[P<0.0001 vs zero] and CTX SDS of −1.1(−2.6,0.4)[P=0.01 vs zero] at baseline reflect a low bone turnover state. BALP SDS increased significantly by 6 weeks [P=0.01], whereas CTX remained unchanged, leading to net increase in bone formation. pQCT bone and muscle remained unchanged over 12 months: trabecular BMD −1.6(−3.2,1.1) to −1.3(−2.6,1.2), cortical thickness −0.1(−2.1,1.0) to −0.3 (−2.0,0.7), muscle −2.4(−4.3,−0.3) to −2.0(−4.3,0.2). Mixed model regression analysis showed that ALS SDS (P=0.007) and muscle area (P=0.003) were positively associated with trabecular BMD; muscle area (P<0.0001) and IGFBP3 SDS (P=0.004) were associated with cortical thickness positively and negatively.

Conclusion: Comprehensive assessment of the ternary complex in childhood CD demonstrated disproportionately low ALS for the first time. AntiTNF therapy was associated with improvement in IGF axis for those with low levels. Markers of the IGF-1 axis and muscle mass show independent associations with bone mass and structure. Interventions to improve muscle mass or manipulation of the GH/IGF axis in combination with antiTNF therapy needs further exploration.

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