GH is an important anabolic hormone involved in the regulation of longitudinal bone growth. However, acromegaly patients have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that overexpression of GH has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyse the effects of high serum GH levels on bone architecture and mechanical strength. Five month-old hemizygous male bGH mice were compared with age- and sex-matched wild type (WT) controls (n=7 in each group). Tibia and lumbar vertebrae were harvested from these mice and BMD and bone architecture analysed using micro-computed tomography. Femora were tested to failure using three-point-bending. As expected, bGH transgenic mice displayed significant increases in body weight and lengths of tibiae and vertebrae. Both cortical and trabecular bone compartments were altered in bGH tibia compared to WT ones. bGH mice showed decreases in trabecular bone volume fraction (BV/TV) (−49%) and trabecular number (−48%), while trabecular pattern factor (+797%) and structure model index (+68.9%) were significantly increased indicating deterioration in trabecular bone structure and connectivity. Although cortical tissue perimeter was drastically increased in transgenic mice (+53.2%), cortical thickness was reduced by 25%. bGH mice showed similar trabecular BMD in lumbar vertebra (L4) relative to controls, while cortical BMD was significantly reduced in bGH vertebra compared to controls. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared to WT, including ultimate stress (−27.6%) and Youngs modulus (−54.1%). Preliminary histomorphometry results also indicate that bone resorption is increased in bGH tibia compared to controls. These data collectively suggest that high serum GH levels negatively affects bone architecture and quality and that bGH transgenic mice are a useful model to understand the mechanisms involved in the skeletal changes observed in acromegaly patients.
Declaration of funding: Yes.
Details: This work was supported by the Society For Endocrinology.