Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Morphological determinants of femoral strength in growth hormone-deficient transgenic growth-retarded (Tgr) rats

Evans, Bronwen A. J. ORCID: https://orcid.org/0000-0002-3082-1008, Warner, Justin T., Elford, Carole, Evans, Samuel Lewin ORCID: https://orcid.org/0000-0003-3664-2569, Laib, L., Bains, R. K., Gregory, John Welbourn ORCID: https://orcid.org/0000-0001-5189-3812 and Wells, Tim ORCID: https://orcid.org/0000-0003-3618-0595 2003. Morphological determinants of femoral strength in growth hormone-deficient transgenic growth-retarded (Tgr) rats. Journal of Bone and Mineral Research 18 (7) , pp. 1308-1316. 10.1359/jbmr.2003.18.7.1308

[thumbnail of Morphological_Determinants_of_Femoral_Strength.pdf]
Preview
PDF
Download (251kB) | Preview

Abstract

The extent to which childhood GHD affects adult fracture risk is unclear. We measured femoral strength in adult transgenic growth-retarded rats as a model of GHD. Long-term, moderate GHD was accompanied by endocrine and morphometric changes consistent with a significant reduction in femoral strength. Introduction: Childhood growth hormone deficiency (GHD) is associated with osteopenia, but little is known about its effects on subsequent adult bone strength and fracture risk. Materials and Methods: We have therefore measured femoral strength (failure load measured by three-point bending) in a new model of moderate GHD, the transgenic growth-retarded (Tgr) rat at 15, 22–23, and 52 weeks of age, and have quantified potential morphological and endocrine determinants of bone strength. Results: Skeletal growth retardation in Tgr rats was accompanied by a sustained reduction in the anterior-posterior diameter of the femoral cortex, whereas mid-diaphyseal cortical wall thicknesses were largely unaltered. Total femoral strength was significantly impaired in Tgr rats (p < 0.01), and this impairment was more pronounced in males than females. Compromised bone strength in Tgr rats could not be accounted for by the reduction in mechanical load (body weight) and was not caused by impairment of the material properties of the calcified tissue (ultimate tensile stress), despite marked reductions in femoral mineral density (areal bone mineral density; p < 0.001). Microcomputerized tomographical analysis revealed significant modification of the architecture of trabecular bone in Tgr rats, with reductions in the number and thickness of trabeculae (p < 0.05) and in the degree of anisotropy (p < 0.01). The marked reduction in plasma insulin-like growth factor-1 in Tgr rats was accompanied by the development of high circulating leptin levels (p < 0.01). Conclusion: These results show that the changes in endocrinology and bone morphology associated with long-term moderate GHD in Tgr rats are accompanied by changes consistent with a significant reduction in the threshold for femoral fracture.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Engineering
Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: bone strength; femoral morphology; growth hormone; growth hormone deficiency; leptin; transgenic rats
ISSN: 0884-0431
Last Modified: 09 May 2023 02:03
URI: https://orca.cardiff.ac.uk/id/eprint/2130

Citation Data

Cited 14 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics