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


BACKGROUND
Childhood growth hormone deficiency (GHD) is associated with osteopenia, but little is known about its effects on subsequent adult bone strength and fracture risk.


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).


CONCLUSIONS
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.
Evans
B A J
BA
Department of Child Health, University of Wales College of Medicine, Cardiff, United Kingdom.
Warner
J T
JT
Elford
C
C
Evans
S L
SL
Laib
A
A
Bains
R K
RK
Gregory
J W
JW
Wells
T
T
D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D001696:Biomechanical Phenomena; D015519:Bone Density; D001846:Bone Development; D002113:Calcification, Physiologic; D019245:Compressive Strength; D004392:Dwarfism / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005269:Femur / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood; D008297:Male; D051381:Rats; D012727:Sex Characteristics; D015430:Weight Gain
D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone