Growth Hormone and Bone*

Abstract

It is well known that GH is important in the regulation of longitudinal bone growth. Its role in the regulation of bone metabolism in man has not been understood until recently. Several in vivo and in vitro studies have demonstrated that GH is important in the regulation of both bone formation and bone resorption. In Figure 9 a simplified model for the cellular effects of GH in the regulation of bone remodeling is presented (Fig. 9). GH increases bone formation in two ways: via a direct interaction with GHRs on osteoblasts and via an induction of endocrine and autocrine/paracrine IGF-I. It is difficult to say how much of the GH effect is mediated by IGFs and how much is IGF-independent. GH treatment also results in increased bone resorption. It is still unknown whether osteoclasts express functional GHRs, but recent in vitro studies indicate that GH regulates osteoclast formation in bone marrow cultures. Possible modulations of the GH/IGF axis by glucocorticoids and estrogens are also included in Fig. 9. GH deficiency results in a decreased bone mass in both man and experimental animals. Long-term treatment (> 18 months) of GHD patients with GH results in an increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with a normal GH secretion. Recent clinical studies demonstrate that GH treatment of patients with normal GH secretion increases biochemical markers for both bone formation and bone resorption. Because of the short duration of GH treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. Interestingly, GH treatment to GHD adults initially results in increased bone resorption with an increased number of bone-remodeling units and more newly produced unmineralized bone, resulting in an apparent low or unchanged bone mass. However, GH treatment for more than 18 months gives increased bone formation and bone mineralization of newly produced bone and a concomitant increase in bone mass as determined with DEXA. Thus, the action of GH on bone metabolism in GHD adults is 2-fold: it stimulates both bone resorption and bone formation. We therefore propose "the biphasic model" of GH action in bone remodeling (Fig. 10). According to this model, GH initially increases bone resorption with a concomitant bone loss that is followed by a phase of increased bone formation. After the moment when bone formation is stimulated more than bone resorption (transition point), bone mass is increased. However, a net gain of bone mass caused by GH may take some time as the initial decrease in bone mass must first be replaced (Fig. 10). When all clinical studies of GH treatment of GHD adults are taken into account, it appears that the "transition point" occurs after approximately 6 months and that a net increase of bone mass will be seen after 12-18 months of GH treatment. It should be emphasized that the biphasic model of GH action in bone remodeling is based on findings in GHD adults. It remains to be clarified whether or not it is valid for subject...

Neutral sphingomyelinase 2 ( smpd3 ) in the control of postnatal growth and development

“…The function of IGF1 in the regulation of skeletal growth and development is well known (28,31). Reduced pituitary GH synthesis and IGF1 serum concentration in smpd3 Ϫ/Ϫ mice explain the retardation of chondrocyte proliferation, differentiation in the epiphyseal growth plate and secondary ossification centers, and of the calcification in metaphyseal long bone.…”

Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice

“…This finding and the decreased longitudinal as well as radial skeletal growth seen in ERKO and DERKO males led us to seek other explanations to the skeletal phenotype in these mice. Overall size and cortical radial growth are parameters that are highly sensitive to changes in the GH͞IGF-I axis (43). Because these parameters were altered in ERKO and DERKO males, serum IGF-I was measured to investigate whether the GH͞IGF-I axis was affected in ERKO and DERKO males.…”

Impairment of Bone Healing by Insulin Receptor Substrate-1 Deficiency

“…Impairment of IRS-1 Ϫ/Ϫ fracture healing might partly be caused by systemic hormones, of which actions are mediated by IGF-I. Growth hormone is a well known stimulus of IGF-I production in a variety of tissues, including bone, and exerts its effects on bone mainly through IGF-I mediation (39). Parathyroid hormone also increases IGF-I production, and decreases of IGF-I signaling can block selective anabolic actions of parathyroid hormone on bone (40,41).…”