Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men

Kindblom, Jenny M; Ohlsson, Claes; Ljunggren, Östen; Karlsson, Magnus K.; Tivesten, Åsa; Smith, Ulf; Mellström, Dan

doi:10.1002/jbmr.284

Cited by 102 publications

(155 citation statements)

References 1 publication

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…(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: 73%

The osteoblast: An insulin target cell controlling glucose homeostasis

Clemens

Karsenty

2010

Journal of Bone and Mineral Research

247

179

View full text Add to dashboard Cite

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

show abstract

Section: From Mice To Humansmentioning

confidence: 73%

The osteoblast: An insulin target cell controlling glucose homeostasis

Clemens

Karsenty

2010

Journal of Bone and Mineral Research

247

179

View full text Add to dashboard Cite

show abstract

“…(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: 98%

“…It has been established that mice lacking the osteocalcin gene had a phenotype that was obese, hyperglycemic, insulin-resistant, and glucose-intolerant. (16,17) Another study done in wild-type mice also observed the importance of osteocalcin in the regulation of glucose metabolism and fat mass. (18) At its simplest level, this relationship offers a plausible link between the established inverse relationship between body size, osteoporosis, and fracture risk.…”

Section: Introductionmentioning

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.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

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

McGuigan

Kumar

Ivaska

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

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

show abstract

“…Osteocalcin is produced by osteoblasts and reflects bone formation, but recent studies have demonstrated an association between osteocalcin and metabolic syndrome (24), as well as indications of osteocalcin production and release by the adipose tissue (25). In a group of adult men, osteocalcin was found to be inversely related to fat mass and plasma glucose (26). In our ex-preterm infants with osteocalcin levels above the reference range, a correlation between osteocalcin and current IGF-I levels was present in females, which might indicate that preterm girls with elevated osteocalcin are more sensitive to the effects of IGF-I than are preterm boys.…”

Section: Discussionmentioning

confidence: 99%

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

et al. 2014

View full text Add to dashboard Cite

Background: Children born prematurely may be at risk of developing osteopenia. This study investigated whether insulin-like growth factors (IGFs) in the early postnatal period influence bone mass and body composition in prematurely born children. Methods: A total of 74 control (gestational age >36 wk; n = 37) and preterm (gestational age <32 wk; n = 37) infants were investigated (mean age ± SD: 4.59 ± 0.31 y). Bone mineral density, body composition, and markers of bone and mineral metabolism were investigated in relation to postnatal IGF levels. results: After adjusting for confounders, we found no differences in bone mass, but significantly less lean mass, increased fat mass, and increased osteocalcin levels in ex-preterm infants. Forward stepwise multiple analysis revealed that higher late postnatal IGF-II levels predict lumbar spine bone mineral content (P < 0.05) and lean mass (P < 0.05). When the birth weight standard deviation score was included in the analysis, higher early postnatal IGF-I levels predicted both lumbar spine bone mineral density and bone mineral content (P < 0.05). Higher early postnatal IGF binding protein-3 (P < 0.01) predicted increased fat mass at 4-y follow-up. conclusion: Ex-preterm children have normal bone mass but different body composition compared with full-term controls. Higher early IGF-I and late postnatal IGF-II concentrations are positive predictors of lumbar spine bone mass. c hildren's bone health is an important issue with lifelong importance. Many factors and medical conditions are associated with an increased risk of a bone mineral disorder and future skeletal problems, including genetics, mechanical loading, activity level, longitudinal growth, puberty, hormones, cytokines, and nutritional status. Peak bone mass is achieved during early adulthood and serves as the "bone bank" for the remainder of life. Bone remodeling, the continuous process of bone formation and resorption, can be assessed and monitored by biochemical markers of bone turnover (1). Many studies have found that ex-preterm infants are shorter, lighter, and have lower bone mass (2-5) than their full-term peers, and ex-preterm infants who are small for gestational age at birth seem to have the most risk (6). However, several studies have found that the bone mass in ex-preterm infants is appropriate for their body size (7,8) and one study proposed that bone mineral density (BMD) in very-low-birth-weight infants is normalized at 2 y of age (9). During adolescence, children who were born prematurely do not have different bone mineral content (BMC ) (10) or BMD (11) (adjusted for height and weight) in comparison with normal-weight children born at full term. Supplementation with early diet benefits short-time growth and BMD. Positive outcomes of an early special diet have been shown on body composition and fat mass during the first 2 y of life, but the long-term effects on BMD and other morbidities are not yet known (12).In full-term newborn infants, umbilical cord serum insulinlike growth factor (IGF)-I and ...

show abstract

Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men

Cited by 102 publications

References 1 publication

The osteoblast: An insulin target cell controlling glucose homeostasis

The osteoblast: An insulin target cell controlling glucose homeostasis

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

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

Contact Info

Product

Resources

About