CLINICAL STUDY The decrease of IGF-I, IGF-binding protein-3 and bone alkaline phosphatase isoforms during gluten challenge correlates with small intestinal inflammation in children with coeliac disease

Objective: In children with coeliac disease, the ingestion of gluten causes small intestinal inflammation and a clinical picture of malabsorption, weight reduction and short stature. Decreased alkaline phosphatase (ALP) during gluten challenge was found in a previous study. ALP is a marker of bone formation and ALP activities are correlated with growth velocity. The aim of this study was to characterise the previously observed decrease of total ALP by investigating three specific bone ALP isoforms (bone/intestinal, B1 and B2) and three specific liver ALP isoforms (L1, L2 and L3) and, moreover, to correlate these ALP isoforms with other growth factors and growth markers. In addition, we also studied the association with possible weight changes, small intestinal mucosa inflammation, sex, age and gluten dose during gluten challenge. Materials and methods: Bone and liver ALP isoforms, IGF-I, IGF-binding protein (IGFBP)-3 and serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were measured together with change in weight and small intestinal mucosa histopathology in 54 children with earlier enteropathy who participated in a 4-week gluten challenge. Results: We observed a decreased total ALP activity after 4 weeks of gluten challenge, 7:8 ^ 1:8 to 6:5 ^ 1:7mkat=l …means ^ S.D.), which was mainly due to a reduction of the bone ALP isoforms. The sum of all three bone ALP isoforms decreased from 6:3 ^ 1:7 to 5:1 ^ 1:6mkat=l: The decreased activities of the bone ALP isoforms correlated with the observed reductions of IGF-I …r ˆ 0:74; P , 0:001†; IGFBP-3 …r ˆ 0:51; P , 0:001† and ICTP …r ˆ 0:57; P , 0:001†: The decrease of the growth factors and growth markers correlated with weight reduction, but when influences from the change in weight were adjusted for, the partial correlation of the small intestinal mucosa inflammation was significant for IGF-I …r ˆ 20:56; P , 0:001† and IGFBP-3 …r ˆ 20:55; P , 0:001†: Conclusion: The decrease of total ALP was due to a reduction of bone ALP. The decrease of IGF-I and IGFBP-3 was independently correlated with weight change and small intestinal inflammation. European Journal of Endocrinology 144 417±423