Abstract
Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are important regulators of bone remodelling and metabolism and have an essential role in the achievement and maintenance of bone mass throughout life. Evidence from animal models and human diseases shows that both GH deficiency (GHD) and excess are associated with changes in bone remodelling and cause profound alterations in bone microstructure. The consequence is an increased risk of fractures in individuals with GHD or acromegaly, a condition of GH excess. In addition, functional perturbations of the GH–IGF1 axis, encountered in individuals with anorexia nervosa and during ageing, result in skeletal fragility and osteoporosis. The effect of interventions used to treat GHD and acromegaly on the skeleton is variable and dependent on the duration of the disease, the pre-existing skeletal state, coexistent hormone alterations (such as those occurring in hypogonadism) and length of therapy. This variability could also reflect the irreversibility of the skeletal structural defect occurring during alterations of the GH–IGF1 axis. Moreover, the effects of the treatment of GHD and acromegaly on locally produced IGF1 and IGF binding proteins are uncertain and in need of further study. This Review highlights the pathophysiological, clinical and therapeutic aspects of skeletal fragility associated with perturbations in the GH–IGF1 axis.
Key points
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Most of the actions of the growth hormone (GH)–insulin-like growth factor 1 (IGF1) axis on the skeleton are mediated by IGF1, either synthesized by the liver or locally produced by skeletal cells.
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In GH deficiency (GHD) caused by pituitary disease, osteoblastogenesis is impaired and bone strength is decreased, with a consequent increase in the risk of vertebral and non-vertebral fractures.
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In patients with GHD, replacement therapy with recombinant GH decreases the risk of fractures prior to the onset of changes in bone mineral density.
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In individuals with uncontrolled acromegaly, a deterioration of bone architecture and increase in the risk of vertebral fractures occurs due to long-term exposure to excess GH and IGF1.
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Biochemical control of GH hypersecretion in acromegaly does not necessarily restore normal bone architecture and the risk of fractures can persist.
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Specific scenarios associated with dysregulation of the GH–IGF1 axis (for example, anorexia nervosa and ageing) are associated with skeletal fragility and increased risk of fracture.
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The authors thank G. R. Hargis and C. Bonin, at UConn Health, for help with the first versions of the figures.
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Mazziotti, G., Lania, A.G. & Canalis, E. Skeletal disorders associated with the growth hormone–insulin-like growth factor 1 axis. Nat Rev Endocrinol 18, 353–365 (2022). https://doi.org/10.1038/s41574-022-00649-8
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DOI: https://doi.org/10.1038/s41574-022-00649-8
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