Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2013) 2 P108 | DOI: 10.1530/boneabs.2.P108

ICCBH2013 Poster Presentations (1) (201 abstracts)

Antenatal glucocorticoid injections do not aggravate stress-induced bone loss in young adult mice

Holger Henneicke 1 , Sylvia J Gasparini 1 , Tara C Brennan-Speranza 1 , Hong Zhou 1 & Markus J Seibel 1,

1ANZAC Research Institute Concord Hospital, The University of Sydney, Sydney, New South Wales, Australia; 2Department of Endocrinology and Metabolism, Concord Hospital, The University of Sydney, Sydney, New South Wales, Australia.

Antenatal glucocorticoid (GC) injections are not only used to enhance fetal lung maturation in preterm children but also for the treatment of maternal conditions such as autoimmune diseases or infections. Animal models and clinical studies suggest that the regulation of the hypothalamic–pituitary–adrenal axis is altered in the offspring of GC-treated mothers with increased sensitivity to stress.

Objective: The aim of this study is i) to define the effects of chronic mild stress (CMS) on the skeleton of young adult mice and the molecular pathways involved; and ii) to determine the effect of antenatal exposure to exogenous GCs on CMS-induced bone loss in young adult mice.

Methods: We used a transgenic (tg) mouse model in which the GC-inactivating enzyme, 11β-hydroxysteroid-dehydrogenase type 2, is overexpressed in osteoblasts and osteocytes, resulting in disruption of pre-receptor GC-signaling in these cells. 8-week old tg mice and their wild type (WT) littermates were exposed to CMS for the duration of 4 weeks, followed by euthanasia and analysis of lumbar spine vertebrae by micro-CT. Stressors included: restraint stress, exposure to hot and cold, tilted cages and overnight illuminations. A subset of mice was exposed to elevated levels of GC at the end of the gestational period when their mothers received dexamethasone injections (0.2 mg/kg) on day 14.5 and 15.5 of pregnancy.

Results: Exposure to CMS resulted in spinal bone loss in WT but not tg mice (BV/TV WT: −17%; P=0.10; tg: −0.3%, P=0.97) when compared to their respective non-stressed controls. This was mainly due to a decrease in trabecular number (WT:−17%; P=0.08; tg: −1%; P=0.84) and a corresponding increase in trabecular separation (WT:+14%; P=0.04; tg: +2%; P=0.84) in WT mice only.

At 12 weeks of age the bone phenotype of mice exposed to antenatal dexamethasone did not differ from non-injected, non-stressed mice. Also, antenatal GC exposure did not aggravate stress-induced bone loss in either WT or tg mice (BV/TV WT: −10%, tg: −2%).

Conclusion: i). CMS induces vertebral bone loss in mice via osteoblastic GC signaling. ii). Antenatal exposure to GC does not aggravate stress-induced bone loss in young adult mice.

Volume 2

6th International Conference on Children's Bone Health

Rotterdam, The Netherlands
22 Jun 2013 - 25 Jun 2013


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