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Protein expression profiling supports ‘the biphasic model’ theory of bone mineralization in response to GH treatment in short prepubertal children

Conference paper
Authors Gunnel Hellgren
Björn Andersson
Ralph Decker
Andreas F M Nierop
Ingvar Bosaeus
Kerstin Albertsson-Wikland
Published in Hormone Research Paediatr
Volume 74
Issue Suppl 3
Pages 100-101
Publication year 2010
Published at Institute of Medicine, Department of Clinical Nutrition
Institute of Clinical Sciences, Department of Pediatrics
Pages 100-101
Language en
Keywords Proteomics, bone mineral content, bone mineralization, biomarkers, growth
Subject categories Clinical pharmacology, Clinical physiology

Abstract

According ’the biphasic model’ of GH action in bone it has been suggested that, in the initial phase after the start of treatment, GH increases bone resorption, followed by a phase of increased bone formation. The aim of this study was to use a proteomic approach to identify serum protein markers associated with GH-dependent bone mineralization the first two years of GH treatment. The study group consisted of 128 short GH-treated prepubertal children; 39 GHD and 89 idiopathic short stature (ISS), included in a clinical trial. Serum protein expression profiles were analyzed using SELDI-TOF on 3 different ProteinChip surfaces. Peak data were analyzed using regression methods and random permutation tests with bone mineral content (BMC) as output variable, measured by dual energy x-ray absorptiometry (DEXA). To eliminate height influence of the results BMC was adjusted for height (BMCHA). BMCHA decreased during the 1st yr of treatment in both the GHD and the ISS groups, and then increased to a value higher than at start of treatment during the 2nd yr. Peak data analyses of the GHD group supported the ’the biphasic model’ theory. Different groups of peaks correlated with changes in BMCHA during the 1st yr compared to the 2nd yr. At start of treatment no regression models correlated with 1st yr delta BMCHA, whereas a group of 5 peaks correlated with the 2nd yr delta BMCHA (p=0.036). Changes in protein expression pattern 0 – 1 yr correlated with the 1st (p=0.016) and the 2nd (p=0.006) yr delta BMCHA. There was no overlap of peaks between the regression models correlated with the 1st and the 2nd yr delta BMCHA, respectively. Work is in progress to identify specific proteins of interest. We conclude that these results could be useful to explain the biology behind the different phases of bone metabolism in response to GH treatment. Peaks so far identified, indicate that different forms of monomeric and dimeric apolipoprotein A-2 probably are involved in these processes.

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