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Endocrinology. 2015 Apr;156(4):1362-71. doi: 10.1210/en.2014-1572. Epub 2015 Feb 3.

Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength.

Author information

1
Department of Comparative and Biomedical Sciences (S.V.L., M.H., M.P., B.J., C.C.), Royal Veterinary College, London NW1 0TU, United Kingdom; Imperial College (M.M.), London SW7 2AZ, United Kingdom; Edison Biotechnology Institute (E.O.L., J.J.K.), Ohio University, Ohio 45701; INSERM Unité Mixte de Recherche 1033 and Université de Lyon (J.P.R., P.C.), 69372 Lyon Cedex 08, France; and Department of Endocrinology (M.K.), Barts and the London School of Medicine, Queen Mary University of London, London EC1A 6BQ, United Kingdom.

Abstract

Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites.

PMID:
25646711
PMCID:
PMC4399323
DOI:
10.1210/en.2014-1572
[Indexed for MEDLINE]
Free PMC Article

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