Serum Total Osteocalcin 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.

Reference limits for osteocalcin in infancy and early childhood: A longitudinal birth cohort study.

The longitudinal variations in serum levels of the hormone osteocalcin is largely unknown during infancy and early childhood. Our aim was to establish reference limits for total serum osteocalcin during specific time points from birth until 5 years of age and present those in the context of sex, breastfeeding practices and gestational age (GA). Blood samples from 551 Swedish children were analysed at birth, 4, 12, 36and 60 months of age. Total serum osteocalcin was measured using the IDS-iSYS N-MID Osteocalcin assay technique. Information about the mother, birth, anthropometrics and a food diary were collected. Sex-specific and age-specific reference limits were established for the five time points. The median osteocalcin levels over time were 40.8, 90.0, 67.8, 62.2and 80.9 μg/L for boys and 38.1, 95.5, 78.3, 73.9and 92.6 μg/L for girls. Lower GA was associated to higher osteocalcin at birth, and ongoing breastfeeding was associated to higher osteocalcin levels. Osteocalcin followed a wavelike pattern with low levels in the umbilical cord and a postnatal peak during the first year which then declined and rose again by the age of five. Knowledge of this wavelike pattern and association to factors as sex, breastfeeding and GA may help clinicians to interpret individual osteocalcin levels and guide in future research.

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.

CORRELATION OF SERUM OSTEOCALCIN LEVEL WITH THE INDICES OF OBESITY AND LIPID PROFILE IN TYPE II DIABETIC SUDANESE PATIENTS

Objectives:Osteocalcin, an osteoblast-specific protein, has recently been reported to affect energy metabolism, this study aimed to assess the relationship between serum total osteocalcin and measurements of adiposity and lipid profile in type II diabetic Sudanese patients. Methods: In this cross-sectional study, 115 people with type II diabetes (34 men, 81 women) aged 18 to 94 years were enrolled in the study. Total osteocalcin and insulin were measured using ELISA (enzyme-linked immunosorbent assay) technique. Fasting blood glucose and lipid profile were measured by a spectrophotometer. Results: Mean serum osteocalcin concentration in diabetic patients was significantly lower than those in control subjects (p ≤ 0.001). When the test was done between TOC and lipid profile, there was a moderate negative correlation between TOC and TCHOL. Which was statistically significant (P = 0.003). There was a moderate negative correlation between TOC and TG. Which was statistically non-significant (P = 0.057). There was a strong positive correlation between TOC and HDL. Which was statistically significant (P = 0.000). There was a weak positive correlation between TOC and LDL. That is statistically non-significant P = 0.105. Conclusion:Our findings showed a statistically highly significant negative correlation between TOC and fasting blood glucose concentration. Similarly, the correlation between FBG and ucOC, age, BMI, TCHOL, and HDL showed a negative correlation that was not significant.

Combined vitamin D and magnesium supplementation does not influence markers of bone turnover or glycemic control: A randomized controlled clinical trial

High-dose vitamin D supplementation can increase total osteocalcin concentrations that may reduce insulin resistance in individuals at risk for prediabetes or diabetes mellitus. Magnesium is a cofactor in vitamin D metabolism and activation. The purpose of this study was to determine the combined effect of vitamin D and magnesium supplementation on total osteocalcin concentrations, glycemic indices, and other bone turnover markers after a 12-week intervention in individuals who were overweight and obese, but otherwise healthy. We hypothesized that combined supplementation would improve serum total osteocalcin concentrations and glycemic indices more than vitamin D supplementation alone or a placebo. A total of 78 women and men completed this intervention in 3 groups: a vitamin D and magnesium group (1000 IU vitamin D3 and 360 mg magnesium glycinate), a vitamin D group (1000 IU vitamin D3), and a placebo group. Despite a significant increase in serum 25-hydroxyvitamin D concentrations in the vitamin D and magnesium group compared with the placebo group (difference=5.63; CI, -10.0 to -1.21; P=.001) post-intervention, there were no differences in serum concentrations of total osteocalcin, glucose, insulin, and adiponectin or the homeostatic model assessment of insulin resistance (HOMA-IR) among groups (P > .05 for all). Additionally, total osteocalcin (β=-0.310, P=.081), bone-specific alkaline phosphatase (β=0.004, P=.986), and C-terminal cross-linked telopeptide (β=0.426, P=.057), were not significant predictors of HOMA-IR after the intervention. Combined supplementation was not associated with short-term improvements in glycemic indices or bone turnover markers in participants who were overweight and obese in our study. This trial was registered at clinicaltrials.gov (NCT03134417).

LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome

Abstract Context. Osteocalcin (OCN) is an osteoblast-produced polypeptide, emerging as the core element of the bone-testicular axis toghether with its undercarboxylated form (uOCN), proposed to increase testosterone (Te) levels in healthy men, by binding the Gpcr6a receptor on Leydig cells and modulating the GnRH pulse frequency and amplitude. However little is known with regards to its role in pubertal development and male hypogonadism. Objective and Design We investigated OCN concentrations in 47,XXY men affected by Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism, in a retrospective longitudinal study between 2007 and 2021 at an academic referral center. Patients and Methods 254 KS subjects, divided into the following groups: 1) pre-pubertal (n = 48, from 1 year of age until Tanner stage II), 2) pubertal (n = 46, Tanner stages II through V, <18 years), and 3) adults (n = 160, Tanner stage V, ≥18 years). All (pre-)pubertal patients were Te-naïve. Adult patients were categorized as: 1) eugonadal (total Te > 10.4 nmol/L; n = 47), 2) hypogonadal (Te < 10.4 nmol/L; n = 39), and 3) receiving testosterone replacement therapy (TRT) (n = 74). Data are presented as means ± SD, were tested with Brown-Forsythe and Welch ANOVA tests for unequal variances, corrected for multiple comparisons (Dunnett T3), and with partial correlations, after bootstrapping on 2000 samples. Main outcomes. Total serum OCN, hypothalamic-pituitary-gonadal (HPG) axis hormones (LH, FSH, total Te, 11β-estradiol, SHBG), and derived indexes. Results OCN levels varied throughout the life span, with a mean of 85.9±30.4 ng/mL in pre-pubertal infants, peaking at 130. 0±77.2 ng/mL in pubertal children (p = 0.243 vs pre-pubertal) and then declining to 22.9±9. 0 ng/mL in adults (p < 0. 001 vs pre-pubertal and pubertal). In (pre-)pubertal boys no correlation with HPG axis hormones was found. When comparing adult KS, OCN values were highest in eugonadal (26.5±10.4 ng/mL), slightly lower in hypogonadal (24.5±8.1 ng/mL, p = 0.268 vs eugonadal) and significantly lower in TRT subjects (20.4±8. 0 ng/mL, p = 0. 008 vs. eugonadal and = 0. 013 vs. hypogonadal). In adults, OCN correlated with both LH (r = 0.23, p = 0. 017) and FSH levels (r = 0.28, p = 0. 004). These significancies were maintained after the exclusion of subjects on TRT. Surprisingly, adjusting for age and BMI revealed significant inverse correlations with total Te (r = -0.44, p = 0. 004), calculated free Te (r = -0.37, p = 0. 016), the Te/LH (r = -0.40, p = 0. 010) and the calculated free Te/LH ratios (r = -0.33, p = 0. 031). These results were confirmed on a smaller sample with available uOCN levels. Conclusions In an experimental model of hypergonadotropic hypogonadism, OCN showed no association with gonadal function during normal pre-puberty and pubertal development. In adults, OCN levels were unexpectedly associated with worse testicular function and a higher degree of HPG stimulation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Effect on bone anabolic markers of daily cheese intake with and without vitamin K2: a randomised clinical trial

BackgroundDaily intake of 57 g Jarlsberg cheese has been shown to increase the total serum osteocalcin (tOC). Is this a general cheese effect or specific for Jarlsberg containing vitamin K2...

Low total osteocalcin levels are associated with all-cause and cardiovascular mortality among patients with type 2 diabetes: a real-world study

BackgroundThe association between osteocalcin and mortality has been scantly studied. We aimed to investigate the association between osteocalcin along with its trajectories and mortality based on long-term longitudinal data.MethodsWe performed a retrospective cohort study of 9413 type 2 diabetic patients with at least three measurements of total serum osteocalcin within 3 years since their first inpatient diagnosis of type 2 diabetes. Baseline, mean values of osteocalcin levels and their trajectories were used as exposures. A multivariable-adjusted Cox proportional hazards model was used to estimate the association of osteocalcin levels and their trajectories with mortality.ResultsDuring a mean follow-up of 5.37 years, 1638 patients died, of whom 588 were due to cardiovascular events. Multivariable-adjusted hazard ratios (HRs) across quintiles of baseline osteocalcin levels were 2.88 (95% confidence interval (CI) 2.42–3.42), 1.65 (95% CI 1.37–1.99), 1.17 (95% CI 0.96–1.42), 1.00, and 1.92 (95% CI 1.60–2.30) for all-cause mortality, and 3.52 (95% CI 2.63–4.71), 2.00 (95% CI 1.46–2.73), 1.03 (95% CI 0.72–1.47), 1.00, 1.67 (95% CI 1.21–2.31) for CVD mortality, respectively. When we used the mean values of osteocalcin as the exposure, U-shaped associations were also found. These U-shaped associations were consistent among patients of different baseline characteristics. Patients with a stable or even increasing trajectory of osteocalcin may have a lower risk of both all-cause and CVD mortality.ConclusionsA U-shape association between baseline osteocalcin and mortality was observed among patients with type 2 diabetes. Patients with lower levels of serum osteocalcin during follow-ups had higher risks for all-cause and cardiovascular mortality.

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.

Investigation of the Relationship between the Mid_Thigh Adipose Tissue Distribution Measured by MRI and Serum Osteocalcin-A Sex-Based Approach.

Osteocalcin, in its non-carboxylated form, has a positive effect on glucose metabolism. Additionally, osteocalcin levels are related to body composition, especially muscle mass. The relation to the distribution of different adipose tissue types, such as subcutaneous, intermuscular, and visceral adipose tissue, is unclear. This study aimed to investigate associations between serum osteocalcin and the distribution of subcutaneous and intermuscular adipose tissue of the mid-thigh. Furthermore, the influence of different training methods on osteocalcin levels was investigated. We performed adipose tissue quantification of subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) using MRI measurements of the mid-thigh in 128 volunteers (63 male/65 female). Laboratory analysis included blood lipid panel, serum insulin, adiponectin, and osteocalcin measurements. The main observation was a significant correlation of total serum osteocalcin (TOC) and the distribution of adipose tissue of the mid-thigh (SAT/(SAT + IMAT)) (cc = −0.29/p-value = 0.002), as well as the cross-sectional muscle area (MA), increasing with the weekly resistance training duration in males. Additionally, TOC (p-value = 0.01) and MA (p-value = 0.03) were negatively related to serum insulin. The significant relationship between TOC and SAT/(SAT + IMAT) is a new finding and confirms the negative influence of IMAT on glucose metabolism in a sex-specific approach. We could substantiate this by the negative relation of TOC with serum insulin.

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.

Osteocalcin and Non-Alcoholic Fatty Liver Disease: Lessons From Two Population-Based Cohorts and Animal Models.

Osteocalcin regulates energy metabolism in an active undercarboxylated/uncarboxylated form. However, its role on the development of non-alcoholic fatty liver disease (NAFLD) is still controversial. In the current study, we investigated the causal relationship of circulating osteocalcin with NAFLD in two human cohorts and studied the effect of uncarboxylated osteocalcin on liver lipid metabolism through animal models. We analyzed the correlations of serum total/uncarboxylated osteocalcin with liver steatosis/fibrosis in a liver biopsy cohort of 196 participants, and the causal relationship between serum osteocalcin and the incidence/remission of NAFLD in a prospective community cohort of 2055 subjects from Shanghai Changfeng Study. Serum total osteocalcin was positively correlated with uncarboxylated osteocalcin (r = 0.528, p < .001). Total and uncarboxylated osteocalcin quartiles were inversely associated with liver steatosis, inflammation, ballooning, and fibrosis grades in both male and female participants (all p for trend <.05). After adjustment for confounding glucose, lipid, and bone metabolism parameters, the male and female participants with lowest quartile of osteocalcin still had more severe liver steatosis, with multivariate-adjusted odds ratios (ORs) of 7.25 (1.07-49.30) and 4.44 (1.01-19.41), respectively. In the prospective community cohort, after a median of 4.2-year follow-up, the female but not male participants with lowest quartile of osteocalcin at baseline had higher risk to develop NAFLD (hazard ratio [HR] = 1.90; 95% confidence interval [CI] 1.14-3.16) and lower chance to achieve NAFLD remission (HR = 0.56; 95% CI 0.31-1.00). In wild-type mice fed a Western diet, osteocalcin treatment alleviated hepatic steatosis and reduced hepatic SREBP-1 and its downstream proteins expression. In mice treated with osteocalcin for a short term, hepatic SREBP-1 expression was decreased without changes of glucose level or insulin sensitivity. When SREBP-1c was stably expressed in a human SREBP-1c transgenic rat model, the reduction of lipogenesis induced by osteocalcin treatment was abolished. In conclusion, circulating osteocalcin was inversely associated with NAFLD. Osteocalcin reduces liver lipogenesis via decreasing SREBP-1c expression. © 2020 American Society for Bone and Mineral Research (ASBMR).

Bone Turnover Markers Including Undercarboxylated Osteocalcin Are Associated With Mortality Risk in Older Men

ABSTRACTOsteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all‐cause and cause‐specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all‐cause and cause‐specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N‐propeptide (PINP), and collagen type 1 C‐terminal cross‐linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community‐dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer‐related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all‐cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06–1.18, p < 0.001; PINP HR = 1.06, 95% CI 1.01–1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08–1.19, p < 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow‐up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05–1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04–1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01–1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all‐cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all‐cause and cancer‐related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Serum osteocalcin is inversely associated with lower extremity atherosclerotic disease in Chinese patients with type 2 diabetes mellitus.

Serum osteocalcin (OCN) is closely related to metabolic risk factors, and the relationship between OCN and atherosclerosis has been investigated. However, it is still controversial. Herein, we explored the potential correlation between serum total OCN and lower extremity atherosclerotic disease (LEAD) in 326 hospitalized Chinese patients with type 2 diabetes mellitus (T2DM). Femoral intima-media thickness (F-IMT) and lower limb atherosclerotic plaque were assessed through color Doppler ultrasound. Subjects with LEAD had significantly lower serum OCN levels compared with those without LEAD (14.54 [14.10-14.89] ng/mL versus 16.79 [15.86-18.04] ng/mL, p < 0.001). Spearman's correlation analysis revealed that serum OCN levels were positively associated with high density lipoprotein cholesterol (HDL-C) and negatively associated with fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG), hemoglobin A1c (HbA1c), waist-to-hip ratio (WHR) and F-IMT. Multiple logistic analysis revealed that OCN (OR 0.938, 95% confidence interval (CI 0.933-0.950, p = 0.003) and glomerular filtration rate (GFR) (OR 0.990, 95% CI 0.985-0.996, p = 0.003) were independently and inversely associated with LEAD, while age (OR 1.140, 95% CI 1.127-1.148, p < 0.001), diabetes duration (OR 1.068, 95% CI 1.039-1.080, p < 0.005) and uric acid (UA) (OR 1.005, 95% CI 1.002-1.007, p = 0.032) were independently and positively associated with LEAD. Additionally, multiple linear regression analysis revealed that serum OCN levels were negatively associated with F-IMT (standardized β = -0.180, p = 0.002). In Chinese patients with T2DM, serum OCN levels were independently and inversely correlated with LEAD.

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.

Osteocalcin as a Predictor of Body Composition in Healthy Adults

Abstract Objectives The objectives of this study were to determine if body composition and nutrient status are dependent on serumosteocalcin concentrations in healthy adults. Methods Adults 20 to 70 years of age completed fasting blood sampling to measure serum ionized calcium concentrations, serum ionized magnesium concentrations, and serum total osteocalcin concentrations. Dual Energy X-Ray Absorptiometry was also completed to measure body composition variables including body mass index (BMI), total fat mass, total fat freemass, total lean mass, android fat, gynoid fat, trunk fat, and visceral adipose tissue. Results A sample of 60 women and 78 men with a median age of 33.0 (21.0) years were categorized into two groups accordingto the median osteocalcin concentration measured: low osteocalcin (12.11 ± 2.72 ng/mL), and high osteocalcin (26.80 ± 9.72 ng/mL). Means, standard deviations, medians and interquartile ranges were calculated and independent t-tests, and Mann Whitney U tests were conducted to determine differences between groups in body composition variables. Total fat mass, total fat percentage, android fat, trunk fat, and trunk fat percentage were all significantly higher, and totalfat free mass, fat free mass percentage, total lean mass, lean mass percentage, serum ionized calcium concentrations, and serum ionized magnesium concentrations were all significantly lower (P &amp;lt; 0.05) in the low osteocalcin groupcompared to the high osteocalcin group. There were no differences (P &amp;gt;0.05) between groups in weight, gynoid fat, visceral adiposity tissue, or visceral adiposity tissue percentage. Conclusions The results of this study provide preliminary evidence that serum osteocalcin concentrations can predict bodycomposition. Interventional studies should consider methods to alter osteocalcin concentrations through vitamin ormineral supplementation as a means to improve body composition in adults. Funding Sources American Heart Association; Drexel University.

Association of Serum Total Osteocalcin Concentrations With Endogenous Glucocorticoids and Insulin Sensitivity Markers in 12-Year-Old Children: A Cross-Sectional Study.

Background: Osteocalcin (OC) is an osteoblast-derived marker of bone turnover that has recently been linked to glucose metabolism, glucocorticoid action, and cardiovascular risk.Objective: We determined whether serum total OC (tOC) is associated with cardiometabolic factors, such as insulin sensitivity (IS) markers and endogenous glucocorticoids in 12-year-old children. In addition, we assessed whether low birth weight or exposure to maternal preeclampsia affect tOC concentrations.Methods: In this cross-sectional study, 192 children (109 girls) were studied at 12 years of age. Seventy of them had been born small (SGA), 78 appropriate for gestational age (AGA), and 44 from preeclamptic pregnancies (PRE) as AGA. Blood pressure was measured, and fasting blood samples were collected for markers of glucose metabolism, osteoblast, adipocyte, and adrenocortical function. IS was estimated by Quantitative Insulin Sensitivity Check Index (QUICKI). Free cortisol index (FCI) was calculated as serum cortisol/corticosteroid binding globulin.Results: The highest tOC concentrations were detected in midpubertal children (Tanner B/G stage 3). The children in the highest tOC quartile (n = 48) had lower body mass index (BMI), waist-to-height ratio, diastolic blood pressure, leptin, cortisol/cortisone ratio and FCI, and higher insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and alkaline phosphatase (ALP) than those in the lower tOC quartiles (p < 0.02 for all). QUICKI was similar in these subgroups. In logistic regression analysis, pubertal developmental stages 2 and 3, high ALP, IGF-I, and low FCI and BMI (p < 0.02 for all) were associated independently with higher tOC. The means of serum tOC and IS markers were similar in the SGA, AGA, and PRE subgroups.Conclusions: In both sexes, the highest tOC levels were detected in midpubertal children reflecting the fast pubertal growth phase. Higher tOC levels were associated with lower BMI and FCI, whereas no association was found with IS. Birth weight or exposure to preeclampsia had no effect on tOC concentrations.

The effect of glucocorticoids on Thrombospondin-1, Osteocalcin and the Thrombospondin-1:Osteocalcin ratio in humans.

Thrombospondin-1 (TSP1), a matricellular protein, and Osteocalcin (OCN), a noncollagenous protein secreted by osteoblasts, are known to be up- and down-regulated, respectively, by glucocorticoids. The aim of this study was to determine whether a ratio between TSP1:OCN was altered by changes in glucocorticoid activity in humans. Prospective observational study. Tertiary university hospital in Queensland, Australia. Patients with Cushing's syndrome (CS, n=19), asthma or giant cell arteritis on chronic prednisolone treatment (PRED, n=13), adrenal insufficiency (AI, n=16) and healthy volunteers (HV, n=20). Plasma TSP1 and serum total OCN were measured by immunoassay at 0800h, 1200h and 1600h in patients with CS, patients with AI taking replacement glucocorticoids, HV before and after 4mg dexamethasone and PRED patients predose at 800 and 4hours post-dose at 1200hours. Plasma TSP1 in CS was higher (P<.0001), and serum OCN was lower (P<.0001) than HV. The TSP1:OCN ratio in HV increased significantly after 4mg dexamethasone (P<.0001) and in AI after taking their hydrocortisone replacement therapy (P<.001). PRED patients had a higher TSP1:OCN ratio compared with HV at both 800 and 1200hours (both P<.001), but no significant change occurred from pre- to post-dose. A TSP1:OCN ratio of >73 at 800hours differentiated CS from HV with a sensitivity of 95% and a specificity of 100%. The TSP1:OCN ratio is elevated in patients on prednisolone and in patients with CS compared with healthy volunteers. It may be a useful biomarker of total body glucocorticoid activity in humans.

Changes of bone metabolism markers following additional isokinetic and isotonic training and its subsequent cessation in advanced level adolescent weightlifters

Background: Physically active people present overall accelerated bone turnover. However, less is known about the effects of different types of resistance training on bone metabolism markers among adolescent weightlifters. Objective: The purpose of this study was to investigate the effects of isokinetic training versus isotonic training of rotator cuff muscles and one month of cessation of training on blood bone metabolism markers among adolescent advanced level weightlifters. Methods: Sixteen adolescent male weightlifters (age 14.88 ± 1.31 years) who represented their state in Malaysia were weight-matched and randomly assigned into two training groups: isokinetic training (FIT, n = 7) and isotonic training (TON, n = 9) groups. The experiment was conducted during the preparatory phase of the training cycle for a total of 24 sessions with three sessions per week for eight weeks using dynamometer or dumbbells. Blood samples were collected before the commencement of training, after training and one month following the cessation of training and analyzed for determining blood metabolism markers of serum osteocalcin, serum C-telopeptide of type 1 collagen (CTX-1), and serum total calcium. Results: Total calcium concentrations were not different between groups at any time, as indicated by a non-significant main effect of time (F = 1.89, p = .166) and no condition × time interaction effect (F = 0.64, p = .533). Serum osteocalcin concentrations were not different between groups at any time, as indicated by a non-significant main effect of time (F = 2.10, p = .162) and no condition × time interaction effect (F = 0.024, p = .912). Serum CTX-1 concentrations were not different between groups at any time, as indicated by a non-significant main effect of time (F = 3.12, p = .059) and no condition × time interaction effect (F = 1.59, p = .221). Conclusions: No significant changes were observed in serum total calcium, osteocalcin and CTX-1 following either eight weeks of isokinetic or isotonic additional training among advanced level of adolescent weightlifters.

Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study.

To investigate the relationship of osteocalcin (OC), a marker of bone formation, and C-terminal cross-linked telopeptide of type I collagen (CTX), a marker of bone resorption, with incident diabetes in older women. The analysis included 1,455 female participants from the population-based Cardiovascular Health Study (CHS) (mean [SD] age 74.6 [5.0] years). The cross-sectional association of serum total OC and CTX levels with insulin resistance (HOMA-IR) was examined using multiple linear regression. The longitudinal association of both markers with incident diabetes, defined by follow-up glucose measurements, medications, and ICD-9 codes, was examined using multivariable Cox proportional hazards models. OC and CTX were strongly correlated (r = 0.80). In cross-sectional analyses, significant or near-significant inverse associations with HOMA-IR were observed for continuous levels of OC (β = -0.12 per SD increment; P = 0.004) and CTX (β = -0.08 per SD; P = 0.051) after full adjustment for demographic, lifestyle, and clinical covariates. During a median follow-up of 11.5 years, 196 cases of incident diabetes occurred. After full adjustment, both biomarkers exhibited inverse associations with incident diabetes (OC: hazard ratio 0.85 per SD [95% CI 0.71-1.02; P = 0.075]; CTX: 0.82 per SD [0.69-0.98; P = 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance. In late postmenopausal women, lower OC and CTX levels were associated with similarly increased risks of insulin resistance at baseline and incident diabetes over long-term follow-up. Further research to delineate the mechanisms linking abnormal bone homeostasis and energy metabolism could uncover new approaches for the prevention of these age-related disorders.