The role of osteocalcin in human glucose metabolism: marker or mediator?

Abstract

Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent γ-carboxylated form. In circulation, the concentration of osteocalcin is a measure of bone formation. The undercarboxylated form of osteocalcin is reported to be active in glucose metabolism in mice. Total serum osteocalcin concentrations in humans are inversely associated with measures of glucose metabolism; however, human data are inconclusive with regard to the role of uncarboxylated osteocalcin in glucose metabolism because most studies do not account for the influence of vitamin K on the proportion of undercarboxylated osteocalcin or differentiate between the total and uncarboxylated forms of osteocalcin. Furthermore, most human studies do not concomitantly measure other bone turnover markers to isolate the role of osteocalcin as a measure of bone formation from its effect on glucose metabolism. Carefully designed studies are required to define the role of osteocalcin and its carboxylated or undercarboxylated forms in the regulation of glucose metabolism in humans.

Undercarboxylated osteocalcin may be an attractive marker of teriparatide treatment in RA patients: response to Mokuda

“…Under carboxylated osteocalcin (ucOC) is a bone matrix protein released from both osteoblasts and resorped bone extracellular matrix by osteoclasts (which peripheral acid environment decarboxylates intact osteocalcin), then γ-carboxylated by vitamin K in blood circulation [3]. We agree that serum ucOC levels and oral glucocorticoid dose are inversely correlated in rheumatoid arthritis (RA) patients [4], which may represent suppressed total bone turnover by glucocorticoid.…”

Endogenous Glucocorticoids and Bone

“…Interestingly, the expression of osteocalcin, a gene down-regulated by glucocorticoids, is higher in OG2-11βHSD2 transgenic mice when compare to age and gender matched wild-type animals (63). There is now mounting evidence that osteocalcin is involved in the regulation of normal fuel metabolism (70)(71)(72)(73)(74)(75)(76) and recent research suggests that the peptide plays a central role in the pathogenesis of glucocorticoid-induced dysmetabolism (77). Up to date, it is not known whether the age-related changes in body composition and fuel metabolism involve the action of endogenous glucocorticoid on osteoblast function, specifically via osteocalcin.…”

Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness

“…These cases include studies involving brain serotonin metabolism, [28][29][30] bone phenotypes in mice with disrupted leptin signaling, 10,[31][32][33][34] bone phenotypes in mice with KOs of b-adrenergic receptors [35][36][37] and actions of osteocalcin on glucose metabolism and diabetes. [38][39][40] Potential explanations for observations of distinct phenotypes in similar mouse models include, but are not limited to, environmental conditions, age, genetic backgrounds and diets. To help understand mechanisms behind these observed differences, Lexicon's Tph1 (TF4141) and Tph2 (TF2875) KO mice are available from Taconic Biosciences.…”