Abstract
Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS) controls (P < 0.001). GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV) and trabecular thickness (Tb.Th), respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp.) than the GHS controls (P < 0.001). Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls) and the whole bone mechanical properties (24 to 43% larger than GHD animals) although there remained a sustained 27–52% net deficit compared to normal mice (P < 0.05). Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD.
Highlights
Growth hormone (GH) plays an important role in the growth of bone, and a lack of GH during development results in a delayed bone age and reduced bone mineral density [1]
There were no significant differences between the GH-deficient and saline injection control mice for any parameter, supporting the assumption that any stress due to daily injections did not have a detectable effect on bone size, microarchitecture, or mechanical properties
All of these morphological parameters remained smaller in both treatment groups compared to the GH-sufficient mice (15% to 32% smaller than GHS, P < 0.001), and GH treatment only resulted in the partial rescue of bone macrostructure
Summary
Growth hormone (GH) plays an important role in the growth of bone, and a lack of GH during development results in a delayed bone age and reduced bone mineral density [1]. A GH deficiency in childhood is believed to cause an increased fracture risk and risk of osteoporosis later in life with GH treatment potentially mitigating this risk [2, 3]. A high prevalence of fractures has been observed in adults with hypopituitarism including GH deficiency with onset in childhood or adulthood [5,6,7], and these increased fracture rates have been mainly attributed to a lack of GH [5, 6]. Adolescents, and adults with childhoodonset isolated GH deficiency had an increased fracture risk [6, 8], while a separate study found a low prevalence of fractures in this same population [7]. GH treatment has been shown to have a protective effect by reducing fracture frequency the mechanisms behind this are not clear [8, 9]
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