Bone and fat tissue in children and adolescents: studies with focus on osteocalcin
Abstract
The general AIM was to investigate the possible interplay between bone and
fat tissue through clinical studies of children and adolescents. Osteocalcin
(OC), a bone formation marker, has been proposed to act as a link between
bone and energy metabolism in mice, but human data are inconclusive. The
specific aims of this thesis were: (i) to clarify the role of OC in relation to
weight, with focus on undercarboxylated OC (ucOC) and carboxylated OC
(cOC); (ii) to gain insight on how obesity and underweight affect bone and
fat tissue in children and adolescents and; (iii) to study the effect of whole
body vibration (WBV) on parameters of metabolic syndrome, bone
metabolism and body composition in children with obesity. METHODOLOGY:
Children and adolescents aged 2-24 years were included in the four studies.
Study I and II were cross-sectional (case-control), and study III and IV were
interventional with a 12-week follow-up, of which study IV was a
randomized case-control study. Biochemical parameters were examined in all
four studies. Bone mass and body composition were assessed by dual-energy
X-ray absorptiometry (DXA), peripheral quantitative computed tomography,
heel DXA and laser. Methods of intervention were high-energy diet in
patients with anorexia nervosa (AN) and WBV in patients with obesity.
RESULTS: Total OC and ucOC did not differ between normal-weight and
overweight subjects; however, overweight subjects had lower cOC levels,
and the measured OC forms did not correlate with insulin and glucose.
Overweight children had increased bone mineral content (BMC) and bone
mineral density (BMD) in comparison with normal-weight children, and
there was a positive correlation between BMC, BMD and body mass index
standard deviation score. Adiponectin was inversely correlated with BMC
and BMD, and was an independent determinant of BMC and BMD. Patients
with AN gained in weight and levels of all three forms of OC and BMC
increased. The WBV did not result in any anthropometric changes; however,
a reduction of sclerostin implies that WBV therapy has direct effects on bone
mechanotransduction.
CONCLUSIONS: This thesis could not confirm the hypothesis that OC has a
positive effect on glucose and insulin homeostasis, although cOC was lower
in obese subjects than in normal-weight subjects. The home-based WBV
intervention study in young children with obesity did not result in any effect
on weight, metabolic parameters or calcaneal bone mass.
Parts of work
I. Tubić B, Magnusson P, Swolin-Eide D, Mårild S; IDEFICS Consortium. Relation between bone
mineral density, biological markers and anthropometric measures in 4-year-old children: a pilot study
within the IDEFICS study. International Journal of Obesity (London) 2011; 35(Suppl 1): S119-124. ::PMID:: 21483411 II. Tubić B, Magnusson P, Mårild S, Leu M, Schwetz V, Sioen I, Herrmann D, Obermayer-Pietsch B,
Lissner L, Swolin-Eide D; IDEFICS consortium. Different osteocalcin forms, markers of metabolic
syndrome and anthropometric measures in children within the IDEFICS cohort. Bone 2016; 84: 230-
236. ::PMID:: 26772621 III. Tubić B, Pettersson C, Svedlund A, Bertéus Forslund H, Magnusson P, Swolin-Eide D. Increased
bone mineral content during rapid weight gain therapy in anorexia nervosa. E-published. Hormone
and Metabolic Research. ::doi::10.1055/s-0042-115304 IV. Tubić B, Zeijlon R, Wennergren G, Obermayer-Pietsch B, Mårild S, Dahlgren J, Magnusson P,
Swolin-Eide D. Whole body vibration intervention: a randomized, prospective, controlled study in
children with obesity. Manuscript.
Degree
Doctor of Philosophy (Medicine)
University
University of Gothenburg. Sahlgrenska Academy
Institution
Institute of Clincial Sciences. Department of Pediatrics
Disputation
Fredagen den 7:e oktober 2016, kl. 13.00, Föreläsningssal Tallen, Drottning Silvias barn- och ungdomssjukhus, Göteborg
Date of defence
2016-10-07
bojan.tubic@gu.se
Date
2016-09-15Author
Tubić, Bojan
Keywords
osteocalcin
obesity
adiponectin
carboxylation
anorexia nervosa
paediatric
bone turnover markers
bone mass
whole body vibration
muscle
Publication type
Doctoral thesis
ISBN
978-91-628-9878-6 (printed)
978-91-628-9879-3 (e-pub)
Language
eng