ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 S7.3

Ghrelin and bone

Patric Delhanty

Erasmus MC, Rotterdam, The Netherlands.

Gastrectomy causes rapid development of osteopenia that, in animal models at least, is independent of nutritional effects. Ghrelin is produced primarily in the stomach, suggesting a link between the loss of ghrelin and gastrectomy induced osteopenia. Ghrelin stimulates growth hormone (GH) secretion and could positively affect bone metabolism via the GH-IGF axis, although ghrelin receptor (GHS-R) deleted mice have unaltered BMD and BMC, despite having suppressed IGF-I serum levels. However, there is evidence that the GHS-R and ghrelin are expressed in bone cells in vitro as well as in vivo, and that osteoblasts respond to ghrelin through altered growth rate and pattern of differentiation, pointing to possible subtle effects on structural characteristics of bone. Moreover, in GH-deficient rats BMD is increased by infusion of ghrelin, demonstrating a GH-independent effect. Unacylated ghrelin (UAG), which activates the GHS-R only at supraphysiological concentrations, also appears to alter parameters of osteoblast growth, presumably via an alternate receptor. In partial corroboration of these findings, overexpression of UAG in mice leads to development of a small phenotype, contributed partly by reduced skeletal length. The clinical utility of ghrelin or activation of the GHS-R in bone disease is less clear, perhaps because of the paucity of studies. MK-677, a GHS-R agonist, has been demonstrated to synergise with bisphosphonate treatment in improving femoral head BMD, but not at other sites. Additionally, in a study of an older population, ghrelin shows an inverse association with NTx, a marker of bone turnover, in men but not women. In conclusion, recent evidence suggests that ghrelin and its unacylated isoform modulate bone growth in rodents independently of GH, and alter growth and differentiation of bone cells in vitro. Although clinical studies are limited, there is some evidence that ghrelin, or GHS-R agonists, can affect bone health in humans.

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