The Role of Growth Hormone in the Development of Bone Microarchitecture, Craniofacial Shape and Bone Strength

Growth hormone (GH) is essential for growth of the body. A GH deficiency (GHD) in childhood causes a short stature, immature facial appearance and a diminished areal bone mineral density (aBMD) that is suspected to cause poor bone quality later in life. Daily injections of GH administered during development have been successful in recovering bone mass and aBMD, although it can induce an altered facial shape. However, the effects of GHD on many aspects of bone quality are still unknown. Therefore, the aim of this thesis was to elucidate the effects of GH on bone using high-resolution imaging and determine if pre-pubertal GH treatment can recover bone deficits caused by GH deficiency to a better degree than post-pubertal treatment.;It was shown that GHD leads to significant reductions in bone size and a deterioration in microstructure, leading to substantially diminished bone mechanical properties. Both pre-pubertal and post-pubertal GH treatments partially restored bone size, although the earlier treatment led to greater recovery of microstructure, resulting in improved bone mechanical properties compared to the late treatment animals. Full 3D shape analysis, using a novel high-throughput method developed as part of this work, revealed that GHD mice have an immature craniofacial shape and that although GH treatment stimulated growth of the facial skeleton, there was limited growth of the braincase and skull base. Thus, GHD led to significant alterations in skull shape, and both pre-pubertal and post-pubertal GH treatments were unable to restore a normal craniofacial size and shape.;In conclusion, GHD causes significantly compromised bone quality, however pre-pubertal GH treatment was successful at restoring some aspects such as trabecular microarchitecture and strength. However, the partial recovery of some aspects of bone quality indicate that GH treatment may need to commence at even an earlier age to realize the best potential for a full rescue of bone quality.;GHD mice were treated with GH at pre-pubertal or post-pubertal time points, and high-resolution micro-computed tomography images measured longitudinally were obtained to assess bone size, microstructure, strength and shape as compared to GH sufficient control mice.