Association between Serum Osteocalcin and Markers of Metabolic Phenotype

Pittas, Anastassios G.; Harris, Susan S.; Eliades, Myrto; Stark, Paul C.; Dawson‐Hughes, Bess

doi:10.1210/jc.2008-1422

Cited by 363 publications

(310 citation statements)

References 33 publications

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Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 65%

“…Posterior crosssectional analysis involving 380 adults aged 65 years or more found a negative correlation between metabolic parameters and osteocalcin levels (26). In this report, 198 patients were followed for three years and those with high basal levels of osteocalcin had lower increase in plasma glucose during the follow -up (26). These results were later corroborated by a large cohort study that evaluated more than 2,760 elderly men and found lower levels of osteocalcin in the presence of metabolic syndrome, as well as worse glycemic and insulin sensitivity indexes (27).…”

Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 94%

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Osteocalcin, energy and glucose metabolism

Zanatta

Boguszewski

Borba

et al. 2014

Arq Bras Endocrinol Metab

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Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome. Arq Bras Endocrinol Metab. 2014;58(5):444-51 Keywords Osteocalcin; undercarboxylated osteocalcin; metabolic syndrome; glucose; energy metabolism; diabetes; obesity; leptin; insulin; adiponectin RESUMO A osteocalcina é uma proteína da matriz óssea que tem sido implicada com várias ações hormonais relacionadas à homeostase de glicose e ao metabolismo energéti-co. Modelos animais e experimentais têm demonstrado que a osteocalcina é liberada do osso para a circulação sanguínea e age nas células betapancreáticas e no tecido adiposo. A osteocalcina decarboxilada é a isoforma hormonalmente ativa e estimula a secreção e sensibilidade à insulina no tecido adiposo e muscular. A insulina e a leptina, por sua vez, atuam no tecido ósseo modulando a secreção da osteocalcina, formando uma alça de retroalimentação tradicional em que o esqueleto torna-se um órgão endócrino. Novos estudos ainda são necessários para elucidar o papel da osteocalcina na regulação glicêmica e no metabolismo energético em humanos, com potenciais implicações terapêuticas no tratamento de diabetes, obesidade e síndrome metabólica. Arq Bras Endocrinol Metab. 2014;58(5):444-51 Descritores

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Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 65%

Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 94%

Osteocalcin, energy and glucose metabolism

Zanatta

Boguszewski

Borba

et al. 2014

Arq Bras Endocrinol Metab

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“…(13) In another study conducted in older healthy men, serum osteocalcin concentrations were inversely associated with blood markers of dysmetabolic phenotype and measures of adiposity. (14) Such studies and others like them (15)(16)(17)(18)(19) suggest that that our proposed endocrine loop comprising insulin, the osteoblast, and osteocalcin represents a conserved regulatory pathway that participates in the global control of glucose metabolism in all bony vertebrates, including humans.…”

Section: From Mice To Humansmentioning

confidence: 76%

The osteoblast: An insulin target cell controlling glucose homeostasis

Clemens

Karsenty

2010

Journal of Bone and Mineral Research

247

179

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The past five years have witnessed the emergence and discovery of unexpected functions played by the skeleton in whole-organism physiology. Among these newly described tasks is the role of bone in the control of energy metabolism, which is achieved through the secretion of osteocalcin, an osteoblasts-derived hormone regulating insulin secretion, insulin sensitivity, and energy expenditure. These initial findings raised several fundamental questions on the nature of insulin action in bone. Discoveries made independently by our two groups have provided answers recently to some of these questions. Through the analysis of mice lacking insulin receptor (InsR) only in osteoblasts, we found that insulin signaling in these cells favors whole-body glucose homeostasis. Importantly, this function of insulin signaling in osteoblasts was achieved through the negative regulation of osteocalcin carboxylation and bioavailability. Our studies also established that insulin signaling in osteoblasts was a positive regulator not only of postnatal bone acquisition but also of bone resorption. Interestingly, it appears that insulin signaling in osteoblasts induced osteocalcin activation by stimulating osteoclast activity. Indeed, the low pH generated during bone resorption is a sufficient means to decarboxylate osteocalcin. Our findings establish that the osteoblast is an important target used by insulin to control whole-body glucose homeostasis and identify bone resorption as the mechanism regulating osteocalcin activation. ß

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“…(17,19) Unfortunately, in this study, uncarboxylated OC, which is specifically reported to have hormonal activity, and blood glucose measurements were unavailable. Polymorphisms may not be able to reflect the status of posttranslational modification (g-carboxylation) that appears to be the mechanism by which OC bioactivity is regulated.…”

Section: Discussionmentioning

confidence: 97%

“…A cross-sectional study in elderly Swedish men reported inverse correlations between total OC and fat mass, (17) whereas a post hoc analysis of elderly male participants in a clinical trial reported similar inverse correlations with blood markers of dysmetabolic phenotype and measures of adiposity. (19) Another study in a Chinese population reported association between serum OC and lipid metabolism. (20) Despite the body of evidence for the role of OC in skeletal biology and energy metabolism, there are at present no studies that have evaluated associations between osteocalcin polymorphisms and measures of adiposity or body composition.…”

Section: Introductionmentioning

confidence: 99%

Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification

McGuigan

Kumar

Ivaska

et al. 2010

Journal of Bone and Mineral Research

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Osteoporosis is a major health problem affecting more than 75 million people throughout Europe, the United States, and Japan. Epidemiologic studies have determined that both genetic and environmental factors contribute to the pathogenesis of osteoporosis. We have investigated the association between polymorphisms at the osteocalcin locus and variables linked to bone health. Osteocalcin provides a link between bone and energy metabolism, hence its potential importance as an osteoporosis candidate gene. In this study, we included a total of 996 women (all aged 75 years) from the Osteoporosis Prospective Risk Assessment (OPRA) cohort. We sequenced the osteocalcin gene along with flanking regions to search for novel coding polymorphisms. We also analyzed four polymorphisms selected from within and flanking regions of the osteocalcin gene to study their association with serum total osteocalcin levels (STotalOC), total-body (TB) bone mineral density (BMD), fracture, TB fat mass, and body mass index (BMI). The promoter polymorphism rs1800247 was significantly associated with S-TotalOC ( p ¼ .012) after controlling for BMI and TB BMD. The polymorphism rs1543297 was significantly associated with prospectively occurring fractures ( p ¼ .008). In a model taking into account rs1543297 and rs1800247, along with TB BMD, BMI, smoking, and S-TotalOC, the polymorphisms together were able to identify an additional 6% of women who sustained a fracture ( p ¼ .02). We found no association between the polymorphisms and TB BMD, BMI, or TB fat mass. In conclusion, polymorphisms in and around the osteocalcin locus are significantly associated with S-TotalOC and fracture. Genotyping at the osteocalcin locus could add valuable information in the identification of women at risk of osteoporosis. ß

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Association between Serum Osteocalcin and Markers of Metabolic Phenotype

Cited by 363 publications

References 33 publications

Osteocalcin, energy and glucose metabolism

Osteocalcin, energy and glucose metabolism

The osteoblast: An insulin target cell controlling glucose homeostasis

Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification

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