Growth Hormone and Bone

• Published in: Endocrine reviews 1998-02, Vol.19 (1), p.55-79
• Main Authors: Ohlsson, Claes, Bengtsson, Bengt-Åke, Isaksson, Olle G. P., Andreassen, Troels T., Slootweg, Maria C.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Density; Bone Development; Bone Development - physiology; Bone growth; Fracture Healing; Fracture Healing - physiology; Fundamental and applied biological sciences. Psychology; Growth hormones; Human Growth Hormone; Human Growth Hormone - pharmacology; Human Growth Hormone - physiology; Human Growth Hormone - therapeutic use; Humans; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; pharmacology; physiology; Skeleton and joints; therapeutic use; Time Factors; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0163-769X; 1945-7189
• DOI: 10.1210/edrv.19.1.0324

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 i