Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study

Iki, Masayuki; Tamaki, Junko; Fujita, Yuki; Kouda, Katsuyasu; Yura, Akiko; Kadowaki, E.; Sato, Yuho; Moon, Jong-Seong; Tomioka, Kimiko; Okamoto, Nobuhiko; Kurumatani, Norio

doi:10.1007/s00198-011-1600-7

Cited by 118 publications

(82 citation statements)

References 43 publications

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“…Metformin is known to enhance the sensitivity for insulin in several tissues showed that undercarboxylated osteocalcin levels were significantly and inversely correlated with fasting plasma glucose, HbA1c and HOMA-IR after adjusting for total osteocalcin, while total osteocalcin was not associated with these parameters after adjusting for undercarboxylated osteocalcin [60]. Thus, these findings suggest that osteocalcin may be involved in glucose metabolism not only in rodents but also in humans.…”

Section: The Association Between Osteocalcin and Glucose Metabolismmentioning

confidence: 71%

Interaction between bone and glucose metabolism [Review]

Kanazawa

2017

Endocr J

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Abstract.Accumulating evidence has shown that bone and glucose metabolism are closely associated with each other. Since the risk of osteoporotic fractures is increased in patients with diabetes mellitus (DM), osteoporosis is recently recognized as one of diabetic complications, called DM-induced bone fragility. Previous studies showed that collagen cross-links of advanced glycation end products (AGEs) and dysfunctions of osteoblast and osteocyte are involved in DMinduced bone fragility. Circulating levels of AGEs and homocysteine are increased in patients with DM, and they directly impair the functions of osteoblast and osteocyte, resulting in decreased bone formation and bone remodeling. On the other hand, bone is recently recognized as an endocrine organ. Previous studies based on in vitro and animal studies showed that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, may regulate glucose homeostasis. Although several clinical studies reported the relationship between osteocalcin and glucose metabolism, further large-scale and intervention studies are necessary to confirm the beneficial effects of osteocalcin on glucose metabolism in human. It has been shown that adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor, is involved in bone metabolism. Adiponectin and metformin stimulate osteocalcin expression and the differentiation of osteoblasts via AMPK activation. Also, AMPK activation protects against oxidative stress-induced apoptosis of osteocytes. These findings suggest that AMPK in osteoblasts and osteocytes may be a therapeutic target for DM-induced bone fragility.

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Section: The Association Between Osteocalcin and Glucose Metabolismmentioning

confidence: 71%

Interaction between bone and glucose metabolism [Review]

Kanazawa

2017

Endocr J

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“…Clinical Study C B Confavreux and others Osteocalcin and metabolic syndrome severity 171:2that blood glucose, HbA1c, and adipokines, as well as elevated BMI or fat mass (13,14,27,28,29), were associated with serum osteocalcin. Moreover, we have previously shown that after surgical resection of osteoid osteoma in young men, serum osteocalcin level decreased, whereas blood glucose increased, thereby providing the first direct evidence of the action of osteocalcin in humans (30).…”

Section: European Journal Of Endocrinologymentioning

confidence: 97%

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

Confavreux¹,

Szulc²,

Casey³

et al. 2014

European Journal of Endocrinology

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Background: Bone has emerged as an endocrine organ regulating energy metabolism through secretion of osteocalcin. In epidemiological studies, presence of metabolic syndrome (MetS) was associated with lower osteocalcin level. Objectives: We evaluated whether osteocalcin level was associated with MetS severity in men and whether it was more strongly associated with MetS compared with N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptide of type I collagen (bCTX). Methods: We included 798 men aged 51-85 years for total osteocalcin measurement. Number of MetS criteria was used to define severity. We used polytomous logistic regression to assess the relationship between MetS severity and osteocalcin level. Results: Thirty percent of men had MetS. In patients with MetS, the higher the number of MetS traits were present, the lower was the average osteocalcin level (0-2 criteria: 551 men: 19.5G6.7 ng/ml, three criteria: 155 men: 19.3G7.4 ng/ml, four criteria: 72 men: 17.3G5.7 ng/ml, and five criteria: 20 men: 15.0G5.1 ng/ml; P for trendZ0.002). In the polytomous logistic regression model, an increase in osteocalcin level of 10 ng/ml was associated with lower prevalence of severe MetS: three criteria (odds ratio (OR)Z0.93 (0.70-1.24)), four criteria (ORZ0.54 (0.34-0.84)), and five criteria (ORZ0.28 (0.10-0.82)) in comparison with no MetS (P for trendZ0.008). After adjustment, using stepwise analysis of the polytomous logistic regression model, we observed that osteocalcin, age, and apparent free testosterone entered in the model but not other bone markers (PINP, bCTX, and BAP). Conclusion: In older Caucasian men, total osteocalcin level was associated with MetS severity. Osteocalcin was more strongly associated with MetS severity than other bone turnover markers.

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“…Body mass index (BMI) was calculated as weight divided by squared height (kg/m 2 ). The assessment of insulin sensitivity was estimated by homeostasis model assessment-insulin resistance (HOMA-IR) based on FPG and insulin measurements as follows: HOMA-IR=[fasting serum insulin (mU/L)×FPG (mmol/L)]/22.5 [14] .…”

Section: Blood Measurementmentioning

confidence: 99%

“…A number of studies have evaluated the complex interactions between the skeleton and glucose and energy homeostasis in humans [7][8][9][10][11][12][13][14][15] . Osteocalcin was found to be inversely associated with fasting plasma glucose (FPG) [7,9,10] , HbA1c [7,12] , body mass index (BMI) [10,13] , fat mass [10] , measures of insulin resistance [8,14] , and measures of lipid metabolism [12,15] .…”

Section: Introductionmentioning

confidence: 99%

“…Osteocalcin was found to be inversely associated with fasting plasma glucose (FPG) [7,9,10] , HbA1c [7,12] , body mass index (BMI) [10,13] , fat mass [10] , measures of insulin resistance [8,14] , and measures of lipid metabolism [12,15] . In these same studies, osteocalcin was positively associated with adiponectin [11] and measures of insulin sensitivity [7,15] .…”

Section: Introductionmentioning

confidence: 99%

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Serum osteocalcin levels are inversely associated with plasma glucose and body mass index in healthy Chinese women

et al. 2014

Acta Pharmacol Sin

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Aim: Osteocalcin, a biochemical marker of bone formation, has been suggested to be involved in the regulation of energy metabolism. The aim of this study was to investigate the possible association between serum osteocalcin and markers of glucose and lipid metabolism in a large sample of healthy Chinese women. Methods: A total of 2032 healthy Chinese women in Shanghai, aged 20-94 (including 1396 discovery-study subjects and 636 postmenopausal women for a reduplication analysis) were recruited. Their serum osteocalcin, calcium and the relevant measurements were analyzed. A Spearman correlation analysis was performed between osteocalcin and the other markers of energy metabolism including triglyceride, total cholesterol, fasting plasma glucose (FPG), serum insulin, body mass index and homeostasis model assessment-insulin resistance. Separate multiple regression analyses were performed with data from the discovery and reduplication subjects to determine whether serum osteocalcin concentration was an independent predictor of the glucose or lipid metabolism markers. Results: For the discovery-study subjects, serum osteocalcin was found to be negatively associated with weight (r=-0.08, P=0.002), BMI (r=-0.13, P<0.001) and FPG (r=-0.13, P=0.001). Similar results were also found in the reduplication subjects P=0.016; P=0.003; P<0.001). In the multiple regression analysis, serum osteocalcin was revealed as a potential independent predictor for FPG (β=-0.07 and -0.210 for discovery and reduplication, respectively, P<0.01) and BMI (β=-0.127 and -0.299 for discovery and reduplication, respectively, P<0.01). Conclusion: Serum osteocalcin is negatively associated with weight BMI and FPG in healthy Chinese women. Therefore, osteocalcin might contribute to obesity and diabetes.

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Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study

Abstract: Levels of ucOC, but not iOC, were inversely associated with glycemic index and insulin resistance in a population of Japanese men. These findings will need to be confirmed with longitudinal studies.

Cited by 118 publications

References 43 publications

Interaction between bone and glucose metabolism [Review]

Interaction between bone and glucose metabolism [Review]

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

Serum osteocalcin levels are inversely associated with plasma glucose and body mass index in healthy Chinese women

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