title: The endocrine role of the skeleton: background and clinical evidence.
abstract: Based on the observation that diabetes, obesity, and hypogonadism influence bone metabolism, the existence of a feedback loop and a common regulation was postulated and an endocrine role ascribed to the skeleton. In the first part of this review, two pathways are described whereby adipose tissue acts on bone mass. In the first, leptin activates the sympathetic nervous system via serotonin and diminishes bone mass accrual. The second pathway functions via the activation of CART (CARTPT) and inhibits bone resorption. The first pathway leads to a decrease in bioactivity of the osteoblast-produced hormone osteocalcin (OC) (part 2). In its undercarboxylated form, OC acts on the three targets pancreas, adipose tissue, and gonads (part 3) and thereby causes an increase in insulin secretion and sensitivity, β-cell proliferation, and male fertility. Insulin (part 4) is part of a recently discovered regulatory feedback loop between pancreas and osteoblasts. It is a strong counterplayer of leptin as it causes a decrease in OPG expression and enhances bone resorption and OC decarboxylation. Numerous clinical studies (part 5) have shown associations of total and undercarboxylated OC and markers of energy metabolism. Interventional studies, to date only performed in murine models, have shown positive effects of OC administration on energy metabolism. Whether bone tissue has an even further-reaching endocrine role remains to be elucidated.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Schwetz
authors.forename: Thomas
authors.initials: T
authors.lastname: Pieber
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D049109:Cell Proliferation; D003653:Decarboxylation; D004703:Endocrine System / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D025461:Feedback, Physiological; D006066:Gonads / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000502:physiology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D015675:Osteocalcin; D012701:Serotonin