Serum Total Osteocalcin Levels Research Articles

Osteocalcin: A Potential Marker of Peripheral Arterial Stiffness in Hypertensive Patients.

Background and Objectives: Brachial-ankle pulse wave velocity (baPWV) is an established independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is recognized to be associated with vascular function. The present study assessed the correlation between serum OC levels and peripheral arterial stiffness (PAS) measured through baPWV in hypertensive patients. Materials and Methods: Fasting blood samples were collected from 120 hypertensive participants. The serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit, whereas the baPWV device was used to detect PAS. The PAS group had left or right baPWV > 18.0 m/s. Results: Among the hypertensive patients, 24 (20.0%) were classified into the PAS group. The PAS group exhibited a significantly older age (p = 0.011), higher prevalence of diabetes (p = 0.010), systolic blood pressure (p = 0.019), levels of serum fasting glucose (p = 0.003), blood urea nitrogen (p = 0.024), creatinine (p = 0.004), C-reactive protein (p = 0.007), OC (p = 0.002), and lower estimated glomerular filtration rate (p = 0.004) than the non-PAS group. Age (odds ratio [OR]: 1.076, 95% CI: 1.004-1.153, p = 0.037) and serum OC level (OR: 1.797, 95% confidence interval (CI): 1.077-3.000, p = 0.025) were independent factors linked to PAS in hypertensive patients in the multivariate logistic regression analysis. Conclusions: Serum OC levels and older age are positively associated with PAS in hypertensive patients.

A CROSS-SECTIONAL STUDY OF SERUM OSTEOCALCIN LEVEL ASSOCIATED WITH PERIPHERAL ARTERIAL STIFFNESS BY BRACHIAL-ANKLE PULSE WAVE VELOCITY IN HYPERTENSIVE PATIENTS

Objective: Brachial-ankle pulse wave velocity (baPWV) is recognized as an independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is associated with vascular function. The aim of this study was to evaluate the relationship between serum OC levels and peripheral arterial stiffness (PAS) in hypertensive patients measuring by baPWV. Design and method: Fasting blood samples were obtained from 120 hypertensive patients. Peripheral arterial stiffness was measured by baPWV device. Serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit. Left or right brachial-ankle pulse wave velocity (baPWV) > 18.0 m/s defined the PAS group. Results: Twenty-four patients (20.0%) were included in the PAS group in hypertensive patients. Hypertensive patients with PAS had a significantly higher percentage of diabetes (P = 0.010), older age (P = 0.011), higher systolic blood pressure (P = 0.019), serum fasting glucose (P = 0.003), blood urea nitrogen (P = 0.024), creatinine (P = 0.004), C-reactive protein (P = 0.007), and OC level (P = 0.002), while lower estimated glomerular filtration rate (P = 0.004) than those without PAS. After multivariable logistic regression analysis, serum OC level (Odds ratio [OR]: 1.797, 95% confidence interval (CI): 1.077–3.000, P = 0.025), and age (OR: 1.076, 95% CI: 1.004–1.153, P = 0.037) are independently associated with PAS in hypertensive patients. Conclusions: Serum OC levels and older age are positively associated with PAS in hypertensive patients.

The Association of Serum Osteocalcin Levels with Metabolic Parameters and Inflammation in Postmenopausal Women with Metabolic Syndrome.

Introduction: Although adipose tissue largely plays a role in the etiopathogenesis of metabolic syndrome (MS), which is an inflammatory process, the skeleton may also contribute to this process through osteocalcin (OC), which is a bone-derived protein. In this study, we aimed to evaluate OC levels in postmenopausal women with MS and to investigate the association of OC levels with the metabolic and inflammatory parameters. Methods: Thirty-five postmenopausal women diagnosed with MS were recruited for the study. Sixteen postmenopausal women without any of the MS criteria formed the control group. Body weight, height, and waist and hip circumference of all of the subjects were measured and body mass indices (BMIs) were calculated. Levels of serum glucose, insulin, C-peptide, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, albumin, creatinine, calcium, phosphorus, total alkaline phosphatase, parathormone, and as inflammatory parameters, erythrocyte sedimentation rate, fibrinogen, and high-sensitive C-reactive protein (hsCRP) were studied from fasting venous blood samples of all the subjects. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Serum total OC levels were studied from all of the subjects. Bone mineral densities were also measured. Results: Serum OC levels of the group with MS median (5.37 ng/mL) were lower than the OC levels of the group without MS (P < 0.01). Serum OC levels significantly and negatively correlated with fasting blood glucose (r = -0.310, P < 0.05), insulin (r = -0.343, P < 0.05), and HOMA-IR (r = -0.384, P < 0.01) values. Serum OC levels showed a significant and negative correlation with body weight (r = -0.293, P < 0.05), BMI (r = -0.333, P < 0.05), and waist-to-hip ratio (r = -0.384, P < 0.05). The inflammatory markers in the patient group were significantly higher than the control group. We found a negative association between serum OC levels and hsCRP levels in all cases (r = -0.283, P < 0.05). Conclusion: In the presence of MS, OC levels are significantly low and display a close association with glucose metabolism and adipose tissue. In addition, OC may play a regulatory role in subclinical systematic inflammatory response.

The Role of Osteocalcin in Placental Function in Gestational Diabetes Mellitus

Evidence for the role of osteocalcin in glucose metabolism is increasing. The aim of this study was to examine the associations between osteocalcin and gestational diabetes mellitus. Thirteen discovery study subjects and 76 reduplication study subjects were recruited from the Maternal and Child Health Hospital Guangxi Zhuang Autonomous Region from May 2018 to August 2018. Total osteocalcin and biochemical indices of maternal serum and umbilical vein serum were analyzed. Placental tissue samples were used for transcriptome sequencing. For the discovery study subjects, the total osteocalcin concentration in umbilical vein serum was significantly higher than that in maternal serum and umbilical artery serum (55.32 ng/mL ± 17.37 vs. 12.06 ng/mL ± 5.42 [P < 0.001] vs. 38.31 ng/mL ± 11.52 [P < 0.01]), suggesting that trophoblasts may synthesize osteocalcin. In a reduplication subject study, the gestational diabetes mellitus group had lower umbilical vein serum total osteocalcin (51.46 ng/mL ± 24.29 vs. 67.00 ng/mL ± 25.33, P = 0.008), lower adiponectin (1099.72 μg/L ± 102.65 vs. 1235.85 μg/L ± 94.63, P < 0.001). Spearman’s correlation analysis showed that umbilical vein serum total osteocalcin levels were closely correlated with leptin (r = -0.456, P = 0.007). A coexpression model of the placental RNA sequence was constructed. Two modules were correlated with osteocalcin, and the Gene ontology pathways of these modules were rich in glucose and lipid metabolism. In conclusion, the placenta may synthesize osteocalcin by itself, and a lower osteocalcin level in umbilical vein serum is associated with gestational diabetes mellitus.

Serum Osteocalcin Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Kidney Transplant Recipients.

Background and Objectives: Osteocalcin is the most abundant noncollagenous protein in bone matrix, which is considered a marker of bone formation. Previous studies indicate that circulating osteocalcin can be expressed by osteoblasts and even by osteoblast-like cells in vessel walls, and it is often associated with arterial stiffness. Our study aims to examine the potential association between osteocalcin levels and endothelial function among kidney transplant (KT) recipients. Materials and Methods: Fasting blood samples were obtained from 68 KT recipients. To measure the endothelial function and vascular reactivity index (VRI), a digital thermal monitoring test (VENDYS) was used. A commercial enzyme-linked immunosorbent assay kit was also utilized to measure serum total osteocalcin levels. In this study, a VRI of less than 1.0 indicated poor vascular reactivity; a VRI of 1.0–2.0 indicated intermediate vascular reactivity; and a VRI of 2.0 or higher indicated good vascular reactivity. Results: Our findings show that 8 KT recipients (11.8%) had poor vascular reactivity (VRI < 1.0), 26 (38.2%) had intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 34 (50%) had good vascular reactivity. Increased serum osteocalcin levels (p < 0.001) were found to be associated with poor vascular reactivity. Advanced age (r = −0.361, p = 0.002), serum alkaline phosphate level (r = −0.254, p = 0.037), and log-transformed osteocalcin levels (r = − 0.432, p < 0.001) were identified to be negatively correlated with VRI in KT recipients. Multivariable forward stepwise linear regression analysis revealed that the serum level of osteocalcin (β = −0.391, adjusted R2 change = 0.174; p < 0.001) and advanced age (β = −0.308, adjusted R2 change = 0.084; p = 0.005) were significantly and independently associated with VRI in KT recipients. Conclusions: Higher serum osteocalcin level was associated with lower VRI and poorer endothelial dysfunction among KT recipients.

Effects of Aqueous Extract of Phyllostachyos Caulis in Taeniam on Longitudinal Bone Growth in Adolescent Rats.

This study examined whether treatment with Phyllostachyos Caulis in Taeniam aqueous extract improves longitudinal bone growth in adolescent male rats. Three-week-old male Sprague-Dawley rats were divided into three groups: a control group, a Phyllostachyos Caulis in Taeniam group (200 mg/kg, p.o.), and a recombinant human growth hormone group (20 µg/kg, s.c.). The total tibial length and the height of each growth plate zone were evaluated by radiography and histomorphometry. The total number of proliferative cells and 5-bromo-2'-deoxyuridine-positive cells were counted after 5-bromo-2'-deoxyuridine staining. Serum total osteocalcin levels were assayed using an enzyme-linked immunosorbent assay. The average total tibial length of the Phyllostachyos Caulis in Taeniam group was significantly longer than that of the control group. The heights of the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group were increased, and the ratio of 5-bromo-2'-deoxyuridine-positive to total cells in the proliferative zone was also increased. The serum osteocalcin, growth hormone, and insulin-like growth factor-1 levels were significantly increased in the Phyllostachyos Caulis in Taeniam group compared to the control group. Insulin-like growth factor-1 and insulin-like growth factor-1 receptor were highly expressed in the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group. The Phyllostachyos Caulis in Taeniam extract increased bone length, promoted cell proliferation, and activated the growth plate zones, which suggested that the extract could play an important role in longitudinal bone growth. Therefore, the Phyllostachyos Caulis in Taeniam extract might be a good alternative medicine to growth hormone therapy.

Association between Serum Total Osteocalcin Level and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Studies on the association between serum total osteocalcin level and type 2 diabetes mellitus (T2DM) had reported controversial results. The aim of this study was to comprehensively assess this association through a meta-analysis. Eligible articles were identified in electronic databases from their inception through May 1, 2015. To assess the relationship between serum total osteocalcin and T2DM, a meta-analysis was performed to determine whether total osteocalcin differed obviously between individuals with and without T2DM, and whether serum total osteocalcin level was associated with the risk of T2DM. The standardized mean difference (SMD) and their 95% confidence intervals (95% CIs) for total osteocalcin between individuals with and without T2DM, and pooled odds ratios (ORs) and their 95% CI for the T2DM risk were calculated by meta-analysis. Twenty-four papers fulfilled the inclusion criteria. From the pooled data, the total osteocalcin level was significantly lower among T2DM patients than controls (SMD: - 2.87; 95% CI-3.76 to - 1.98; p<0.00001), and high total osteocalcin level was significantly and independently associated with decreased risk of T2DM (OR=0.70, 95% CI 0.56-0.88; p=0.002). There was no evidence for publication bias. Serum total osteocalcin level is significantly lower in T2DM patients than controls, and total osteocalcin is inversely associated with the development of T2DM.

A common polymorphism rs1800247 in osteocalcin gene was associated with serum osteocalcin levels, bone mineral density, and fracture: the Shanghai Changfeng Study.

We evaluated the relationship between a common polymorphism rs1800247 in osteocalcin gene and serum osteocalcin levels, bone mineral density and fracture in Chinese. This was a population-based cross-sectional study. We demonstrated that rs1800247 was associated with bone mineral density and fracture in men and serum osteocalcin levels in women. This study aimed to evaluate the relationship between a common polymorphism rs1800247 in osteocalcin gene and serum total osteocalcin levels, bone mineral density (BMD) and fracture in Chinese middle-aged and elderly men and women. This was a population-based cross-sectional study included 5561 individuals aged 45years or older. Information on fractures sustained after age of 45 were collected. BMD at the lumbar spine, femoral neck and total hip were measured using dual-energy X-ray absorptiometry. The genotyping of rs1800247 was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. rs1800247 was associated with lumbar spine BMD and femoral neck BMD in the dominant model adjusted for age, body mass index (BMI), serum total osteocalcin in men (both P = 0.04). Besides, rs1800247 was associated with fracture adjusted for age, BMI, serum total osteocalcin and total hip BMD in the additive and dominant models in men (P = 0.04 and 0.01). In the dominant model, the carriers of CC and TC genotypes was associated with a lower odds of fracture compared with the carriers of TT genotype (OR = 0.60, 95%CI 0.40-0.88, P = 0.01). In men, rs1800247 was not associated with serum total osteocalcin levels in additive, dominant or recessive models. However, rs1800247 was associated with serum total osteocalcin levels in all models adjusted for age, BMI, menopausal status and total hip BMD in women (all p < 0.001), with osteocalcin levels decreasing across TT, TC and CC genotypes. rs1800247 was not associated with BMD or fracture in all models in women. A common polymorphism rs1800247 in osteocalcin gene may affect the risk of osteoporosis and fracture and serum total osteocalcin levels in Chinese, and there may be gender differences underlying these associations.

Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence.

Serum total osteocalcin, a marker of bone formation, may regulate glucose metabolism and influence the risk of developing adverse metabolic outcomes. We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes [e.g., metabolic syndrome (MetS)]. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, and reference lists of relevant studies to May 2015. Mean differences and risk estimates (odds ratios or relative risks) with 95% CIs were aggregated using random-effects models. Fifty-two observational (38 cross-sectional, eight cohort, five case-control, and one both cross-sectional and cohort) studies with data on 46,998 non-overlapping participants were included. Baseline serum total osteocalcin levels were significantly lower in type 2 diabetes compared with non-type 2 diabetes and in MetS compared with non-MetS in pooled analysis of cross-sectional evidence. Pooled risk estimates (95% CIs) for type 2 diabetes in a comparison of extreme fourths of total osteocalcin levels were 0.23 (95% CI 0.12, 0.46) and 0.89 (95% CI 0.78, 1.01) for cross-sectional and cohort studies respectively. The corresponding estimate was 0.39 (0.27, 0.56) for MetS from cross-sectional evidence. In both cross-sectional and cohort studies, a unit increase in serum total osteocalcin levels was associated with a significant mean increase in HOMA-B and mean reduction in HbA1c; with significant mean reductions in fasting plasma glucose levels, HOMA-IR, and body mass index in only cross-sectional studies. Available evidence--mainly from cross-sectional studies, supports inverse associations of serum total osteocalcin with risk of adverse metabolic outcomes. Large-scale prospective studies are needed to establish whether serum total osteocalcin may be useful in the prevention of adverse metabolic outcomes such as type 2 diabetes.

Parameters of bone health and fracture risk in older female fall victims: what do they tell us?

A common and severe osteoporotic type fracture in older women is a hip fracture. It is not clear whether bone turnover parameters measured in blood can be a useful tool to predict fracture risk in older persons. The aim of the current study was to assess the association between serum vitamin D (25OHD) levels, parathyroid hormone (PTH), total osteocalcin, carboxy-terminal collagen crosslinks (CTX) and hip fractures in older fallers. A single centre, prospective cohort study of bone parameters was carried out in 400 female patients aged > 70 years including 200 with a hip fracture and 200 without fractures, admitted after a fall between January 2005 and December 2007. Serum total osteocalcin levels were significantly lower in the fracture group compared to the non-fracture group (20.4ng/ml vs 26.1ng/ml, respectively, p = 0.01). This finding remained significant after exclusion of the patients on bisphosphonates (p = 0.003). There were no significant differences in 25OHD, PTH or CTX levels between the two groups. In the current study there was an association between the presence of a hip fracture and lower total serum osteocalcin concentrations. This could be indicative of low bone turnover osteoporosis in these women. An association for other bone turnover markers was lacking.

Serum total osteocalcin level as a vascular marker in elderly patients with metabolic syndrome

Metabolic syndrome (MetS) is a major public health problem and a clinical challenge worldwide. Several epidemiological studies have confirmed the increased risk for cardiovascular diseases (CVD) in individuals with MetS. Total osteocalcin (TOC) is a bone-derived, noncollagenous protein that was recently recognized as a hormone-regulating energy metabolism factor. Importantly, osteocalcin expression has been described as having a role in calcifying vascular smooth muscle cells. We aimed in the present study to analyze the correlation between serum levels of TOC and vascular calcification in elderly persons with MetS. Seventy-four elderly men aged 65 years or older were included in the present study and divided into two groups. Group I comprised 40 patients who satisfied at least three criteria for MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) definition, and group II comprised 34 age-matched healthy men who served as the control group. BMI was calculated, blood samples were taken for lipid profile analysis, and total osteocalcin (OCN) levels were evaluated using enzyme-linked immunosorbent assay kits. Carotid Doppler B mode ultrasonography was performed for all participants. Patients with MetS exhibited significantly higher BMIs, waist circumference, fasting blood sugar, triglycerides, blood pressure, total cholesterol, and lower high-density lipoprotein-cholesterol compared with controls. Patients with MetS had significantly lower levels of TOC compared with controls. Also, patients with MetS had significantly higher intima-media thickness and a higher number of carotid plaques compared with controls. TOC was significantly negatively correlated with parameters of carotid atherosclerosis. It is also negatively correlated with dyslipidemic parameters. Its correlation with components of MetS did not reach statistical significance. We concluded that serum osteocalcin levels were negatively correlated with carotid atherosclerosis in patients with MetS. This may reflect the role of osteocalcin as a circulating endocrine factor that regulates glucose metabolism and thereby cardiovascular risk in patients with MetS. Prospective studies are needed to assess the time course and relevance of serum osteocalcin in the development of atherosclerosis in patients with MetS.

Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia.

Osteoporosis is a skeletal disorder characterized by impaired bone turnover and compromised bone strength, thereby predisposing to increased risk of fracture. Preclinical research has shown that compounds produced by the olive tree (Olea europaea), may protect from bone loss, by increasing osteoblast activity at the expense of adipocyte formation. The aim of this exploratory study was to obtain a first insight on the effect of intake of an olive extract on bone turnover in postmenopausal women with decreased bone mass (osteopenia). For that, a double blind, placebo-controlled study was performed in which participants were randomly allocated to either treatment or placebo groups. 64 osteopenic patients, with a mean bone mineral density (BMD) T-score between -1.5 and -2.5 in the lumbar spine (L2-L4) were included in the study. PARTICIPANTS received for 12 months daily either 250 mg/day of olive extract and 1000 mg Ca (treatment) or 1000 mg Ca alone (placebo). Primary endpoints consisted of evaluation of bone turnover markers. Secondary endpoints included BMD measurements and blood lipid profiles. After 12 months, the levels of the pro-osteoblastic marker osteocalcin were found to significantly increase in the treatment group as compared to placebo. Simultaneously, BMD decreased in the placebo group, while remaining stable in the treatment group. In addition, improved lipid profiles were observed, with significant decrease in total- and LDL-cholesterol in the treatment group. This exploratory study supports preclinical observations and warrants further research by showing that a specific olive polyphenol extract (Bonolive®) affects serum osteocalcin levels and may stabilize lumbar spine BMD. Moreover, the improved blood lipid profiles suggest additional health benefits associated to the intake of the olive polyphenol extract.

Association between the circulating total osteocalcin level and the development of cardiovascular disease in middle-aged men: a mean 8.7-year longitudinal follow-up study.

Recent studies have suggested that the serum osteocalcin level is associated with various cardiovascular risk factors. The aim of this study was to determine whether the serum total osteocalcin level is associated with the development of cardiovascular disease (CVD). A total of 1,290 men 40-78 years of age were enrolled. The subjects were followed regularly at the Health Promotion Center on an outpatient basis and during hospitalization for a mean of 8.7 years, and the incidence of CVD (coronary heart disease [CHD] and stroke) was determined. At baseline, the body mass index, body fat percentage, fasting glucose, homeostasis model assessment-insulin resistance, triglyceride and non-high density lipoprotein (HDL) cholesterol levels were inversely and the HDL cholesterol levels were positively associated with the serum osteocalcin levels. In addition, the prevalence of diabetes or metabolic syndrome decreased as the osteocalcin tertile increased. However, no differences were observed in the prevalence of hypertension across the osteocalcin tertiles. Incident CVD occurred in 74 (5.7%) of the study subjects (29 patients with CHD and 47 patients with stroke). According to the Cox proportional hazards models, however, there were no statistical differences in the development of stroke, CHD or CVD across the osteocalcin tertiles after adjusting for other risk factors for CVD, including age, body mass index, current smoking, low-density lipoprotein cholesterol, diabetes, hypertension and the serum creatinine level. In conclusion, the serum total osteocalcin level was not associated with the development of CVD after adjusting for other risk factors for CVD in this cohort.

The Association of Osteocalcin and Adiponectin with Glucose Metabolism in Nondiabetic Postmenopausal Women

Background/Aim: This study was designed to determine if osteocalcin is associated with insulin resistance, metabolic risk factors and adiponectin levels in nondiabetic postmenopausal women. Methods: A total of 87 menopausal nondiabetic subjects were enrolled into the study. Levels of fasting plasma glucose (FPG), insulin and serum lipids were determined. To estimate insulin sensitivity, homeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were used. Serum total osteocalcin and adiponectin levels were measured and the features of metabolic syndrome were identified. Results: The mean age of the patients was 54.7 years. Among the participants, 28.7% were obese (body mass index, BMI, ≥30). Insulin resistance was detected by HOMA-IR in 42.5% and by the QUICKI index in 63.2% of the cases. Metabolic syndrome was present in 29.8% of the patients. Neither the baseline characteristics nor the metabolic risk factors were correlated with osteocalcin or adiponectin levels (p > 0.05). When the patients were analyzed regarding BMI, osteocalcin levels were significantly lower in overweight women. Serum adiponectin levels were significantly lower in women with metabolic syndrome. Conclusion: No correlation between total osteocalcin and FPG, fasting insulin and insulin resistance parameters was found in nondiabetic postmenopausal women. Serum levels of adiponectin were associated with metabolic syndrome.

An Independent Positive Relationship Between the Serum Total Osteocalcin Level and Fat-Free Mass in Healthy Premenopausal Women

It is widely reported that osteocalcin is negatively associated with fat mass. However, there are few reports describing its correlation with fat-free mass, particularly in women. The objective of the current study was to investigate the possible relationship between osteocalcin and fat-free mass in healthy, nonobese women. This study was performed in a tertiary university teaching hospital. A total of 504 healthy women aged 20-75 years were enrolled. Body composition was measured using a bioelectronics impedance analyzer. The serum concentrations of total osteocalcin, estradiol, leptin, osteoprotegerin, the receptor activator of nuclear factor-κB ligand, IGF-I, fasting plasma glucose, and urinary N-terminal telopeptide of type I collagen were tested. The bone mineral densities (BMDs) at the lumbar spine and proximal femoral neck were measured by dual-energy X-ray absorptiometry. The serum total osteocalcin level had a significant positive association with fat-free mass (r = 0.168, P = .007) after adjusting for age, fat mass, menopausal status, estradiol, fasting glucose, leptin, osteoprotegerin, receptor activator of nuclear factor-κB ligand, IGF-I, N-terminal telopeptide of type I collagen, BMDs, and waist and hip circumference. Analysis in pre- and postmenopausal women demonstrated that this association was only present in premenopausal women (r = 0.190, P = .005). The multiple stepwise regression analysis revealed that hip circumference, femoral neck-BMD, fat mass, leptin, osteocalcin, and age are the contributors to the changes in fat-free mass in premenopausal women (adjusted R(2) = 0.521, P < .001). The serum level of total osteocalcin was positively associated with fat-free mass independent of age, fat mass, leptin, and other confounders in premenopausal women.

Osteocalcin, glucose metabolism, lipid profile and chronic low‐grade inflammation in middle‐aged and elderly Chinese

To assess the relationship between serum total osteocalcin and measurements of adiposity, glucose tolerance, lipid profile, adipokine and chronic low-grade inflammation in middle-aged and elderly Chinese subjects. We performed a cross-sectional community-based study in central Shanghai. Serum total osteocalcin was measured by radioimmunoassay in 783 men and 946 post-menopausal women. Their associations with measurements of adiposity, glucose tolerance, lipid profile and chronic low-grade inflammation were examined. Serum total osteocalcin levels revealed a sexual dimorphism, with post-menopausal women having significantly higher levels than men (P < 0.001). Serum osteocalcin levels of participants with self-reported cardiovascular disease were significantly lower (P = 0.044) than those without. In men, serum osteocalcin levels of participants with the metabolic syndrome were significantly lower than those without the metabolic syndrome (P = 0.036). Serum osteocalcin correlated negatively with fasting serum insulin, homeostasis model assessment of insulin resistance, alanine aminotransferase, triglycerides and total cholesterol, and positively with homeostasis model assessment of β-cell function in both men and post-menopausal women (all P < 0.05). In men, serum osteocalcin correlated negatively with BMI, diastolic blood pressure, fasting plasma glucose and 2-h oral glucose tolerance test glucose after adjustment for age (all P < 0.05). In post-menopausal women, serum osteocalcin correlated negatively with waist-hip ratio, LDL cholesterol and C-reactive protein, and positively with adiponectin (all P < 0.05). Serum osteocalcin was not associated with CXC chemokine ligand 5 level (P > 0.05). Alanine aminotransferase was an independent predictor of serum osteocalcin in both men and post-menopausal women (both P < 0.001). Adiponectin was an independent predictor of serum osteocalcin in post-menopausal women (P = 0.011). Serum osteocalcin was an independent predictor of homeostasis model assessment of β-cell function in both genders (both P < 0.05). Serum total osteocalcin was closely associated with glucose and lipid metabolism in both Chinese men and post-menopausal women.

Serum Osteocalcin Is Not Associated with Glucose but Is Inversely Associated with Leptin across Generations of Nondiabetic Women

The skeleton is recognized as an important player in energy metabolism through its interactions with other tissues. Whether the association of osteocalcin with glucose metabolism is age dependent has not been fully addressed. The objective of the study was to examine the age-specific association between different forms of osteocalcin and glucose and adipokines. This was a family-based study across three generations. The study was conducted at a university laboratory. Sixty-four daughter-premenopausal mother-maternal grandmother trios participated in the study. Fasting plasma glucose and insulin concentrations, serum total (tOC), carboxylated (cOC), and uncarboxylated (ucOC = tOC - cOC) osteocalcin, leptin, and adiponectin levels, and fat masses were assessed. Generalized estimating equations (GEE) model was used to assess the associations of bone biomarkers with glucose metabolism variables and adipokines. No significant difference in insulin was found between generations, whereas glucose and leptin increased with age. Levels of tOC, cOC, and ucOC were highest in girls and lowest in mothers (P < 0.01). Grandmothers had higher leptin and adiponectin than mothers and girls. Despite the differences in insulin and glucose between the low and high homeostasis model assessment insulin resistance index (HOMA-IR) groups within generations, no significant differences in tOC, cOC, and ucOC were found. Compared with their low HOMA-IR counterparts, the high HOMA-IR group had significantly higher leptin and lower adiponectin in mothers and grandmothers. The tOC, cOC, and ucOC levels did not correlate with HOMA-IR, leptin, or adiponectin when the three generations were evaluated together, but when separated by generation, leptin was inversely correlated with tOC (P = 0.003) and cOC (P = 0.047) in mothers and with ucOC in grandmothers (P = 0.042). Osteocalcin, glucose, and adipokines change with age but in a noncommensurate manner. We infer that the association between osteocalcin and glucose metabolism is minor and age specific in nondiabetic women. Leptin, however, strongly correlated with insulin resistance independently of fat masses, suggesting that obesity, as a metabolic disorder risk factor, affects glucose metabolism, partly through the role of leptin.

A Mediterranean Diet Enriched with Olive Oil Is Associated with Higher Serum Total Osteocalcin Levels in Elderly Men at High Cardiovascular Risk

The intake of olive oil has been related to the prevention of osteoporosis in experimental and in in vitro models. Very few prospective studies have evaluated the effects of olive oil intake on circulating osteocalcin (OC) in humans. The objective of the study was to examine the longitudinal effects of a low-fat control diet (n=34), a Mediterranean diet enriched with nuts (MedDiet+nuts, n=51), or a Mediterranean diet enriched with virgin olive oil (MedDiet+VOO, n=42) on circulating forms of OC and bone formation markers in elderly men at high cardiovascular risk. Longitudinal associations between baseline and follow-up (2 yr) measurements of total OC, undercarboxylated osteocalcin, C-telopeptide of type I collagen, and procollagen I N-terminal propeptide (P1NP) concentrations were examined in 127 elderly men randomized to three healthy dietary interventions. Baseline characteristics (age, body mass index, waist circumference, lipid profile, fasting insulin levels, and bone formation and resorption markers) were similar in all intervention groups. The total osteocalcin concentration increased robustly in the MedDiet+VOO group (P=0.007) in parallel to increased P1NP levels (P=0.01) and homeostasis model assessment-β-cell function (P=0.01) but not in subjects on the MedDiet+nuts (P=0.32) or after the control diet (P=0.74). Interestingly, the consumption of olives was associated positively with both baseline total osteocalcin (r=0.23, P=0.02) and the 2-yr osteocalcin concentrations (r=0.21, P=0.04) in the total cohort. Consumption of a Mediterranean diet enriched with virgin olive oil for 2 years is associated with increased serum osteocalcin and P1NP concentrations, suggesting protective effects on bone.

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

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 (S-TotalOC), 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 = .012) after controlling for BMI and TB BMD. The polymorphism rs1543297 was significantly associated with prospectively occurring fractures (p = .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 = .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.

Anti-fracture efficacy of vitamin K

The objective of the present review of the literature was to evaluate the effect of vitamin K supplementation on the skeleton of postmenopausal women. PubMed was used to search the reliable literature for randomized controlled trials (RCTs) by using the inclusion criteria: >or= approximately 50 subjects per group and study period of >or= 2 years. The results of 7 RCTs that met the inclusion criteria showed that vitamin K (K(1) and K(2)) supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose, but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. Furthermore, a post hoc analysis in a large RCT in Japan showed that high-dose vitamin K(2) supplementation decreased the subsequent incidence of vertebral fractures in osteoporotic postmenopausal women with a history of at least 5 vertebral fractures. The review of the reliable literature showed the effect of high-dose vitamin K supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.