Lower Osteocalcin Research Articles

Low serum osteocalcin levels are associated with the presence of diabetes mellitus in glucocorticoid treated patients

Low serum osteocalcin levels are associated with the presence of diabetes mellitus in glucocorticoid treated patients

Are there sex differences in the reaction of undercarboxylated osteocalcin to hypoglycemia?

There has been increasing evidence in recent years for the hypothesis of bones as endocrine organs. Osteocalcin, long considered just a marker of new bone formation, is now seen as the first hormone produced by bones, and seems to be associated with regulating glucose metabolism and reproduction. The aim of this work was to monitor changes of osteocalcin in reaction to hypoglycemia, and determine if there are differences in such reactions between the sexes. The study included 61 healthy probands with physiological calciophosphate metabolism (30 men and 31 women). We applied to each of them an insulin tolerance test, and then monitored levels of undercarboxylated osteocalcin and reactions to hypoglycemia at regular time intervals. We found differences in the reaction to hypoglycemia between the sexes. In men there was a significant decline in undercarboxylated osteocalcin between the 30 and 40 min (p<0.0015), which reflects a reaction to a glycemic decline between 25-30 min, followed by reversal. Low undercarboxylated osteocalcin in men lasted up to 90 min, after which they returned to levels before the test. In women we did not find any significant changes in undercarboxylated osteocalcin levels. Changes in undercarboxylated osteocalcin induced by hypoglycemia indicate a relationship between bones and glucose metabolism. There was an interesting difference between the sexes. However, a definitive conclusion about the role of osteocalcin in human metabolism will require numerous future studies.

Показники кісткового ремоделювання у хворих на цукровий діабет 2-го типу з різним конституційно-метаболічним фенотипом

SummaryIntroduction. According to the latest data, osteocalcin – hormonally active productof bone tissue – plays an active role in the humoral control of homeostatic processes. Inparticular, osteocalcin was shown to regulate sensitivity of peripheral tissues to insulin,carbohydrate metabolism, transport and deposition of lipids.An inverse correlations were found between the level of osteocalcin and the degreeof insulin resistance, levels of glucose, insulin and adipokines, manifestation of themetabolic syndrome, visceral obesity, type 2 diabetes, cardiovascular risk. Osteocalcinmay be a significant factor of regulation of energy processes and formation of certainconstitutional and metabolic phenotypic characteristics of the organism, in particular interms of regional distribution and metabolic activity of adipose tissue.Purpose of the study was to study the relationship between the level of osteocalcinand constitutionally-metabolic phenotypic traits.Materials and methods. 44 patients with type 2 diabetes over 50 years old wereallocated into 3 groups by the serum osteocalcin level. Anthropometric measurements(height, weight, waist circumference), determining of insulin resistance degree (HOMAIR), lipid spectrum were carried out. Visceral adiposity index (VAI) was calculated byempirical formulas for men and women, which includes body mass index, waistcircumference, blood level of triglycerides, and high density lipoprotein. The controlgroup included 23 people of the same age without diabetes.Results. In the groups 1–3 of men osteocalcin levels were: <2.0 ng/ml;(2.75±0.21) ng/ml; (5.3±0.39) ng/ml, respectively. In the groups 1–3 of women:<2.0 ng/ml; (2.91±0,15) ng/ml; (6.01±0,56) ng/ml. In all groups of diabetic patientsmean osteocalcin levels were significantly lower than in control subjects withoutdiabetes (in men (10.78±1.08) ng/ml; in women (8.12±1.03) ng/ml; p<0.05).Reducing of osteocalcin level in subjects with type 2 diabetes was associated with asignificant increase in the degree of insulin resistance. Especially high values ofHOMA-IR were observed in patients of group 1 with low osteocalcin levels (HOMA-IRin men (7.25±1.04); in women (8.25±1.45)), comparing with high osteocalcin group 3(in men (4.23±0.87); in women (2.78±0.34); p<0.05).It was found that the decrease of osteocalcin in groups of men with type 2 diabetes wasaccompanied by a significant increase in VAI (in men groups 1–3: (4.21±1.09); (3.05±0.38);(1.43±0.27); p<0.05; in women groups 1–3: (4.86±1.17); (3.15±0.58); (2.75±0.53)).Increase of VAI characterizes the worsening of morphological and functional characteristicsof adipose tissue. In women, such changes were not significant.Our results show the relationship between slowing of osteosynthesis andconstitutional manifestations and metabolic disorders, which in turn are associated withphenotypic changes in patients with type 2 diabetes.Conclusions. Reduction of serum osteocalcin in patients with type 2 diabetesoccurred in parallel with the strengthening of insulin resistance, visceral obesity, anddyslipidemia. The visceral obesity index, which includes both humoral andanthropometric parameters, was more precise and standardized parameter for revealingof constitutional and metabolic phenotypic changes as compared with the waistcircumference.

Bone Metabolism in Patients Treated for Depression.

Background: Depression and osteoporosis are severe public health problems. There are conflicting findings regarding the influence of depression on bone metabolism. The aim of the presented study was to compare bone turnover markers and vitamin D levels between patients treated for depression and healthy controls. Patients and Methods: We determined a concentration of osteocalcin, carboxy-terminal telopeptide of type I collagen (β-CTX), 25-hydroxyvitamin D (25OHD) and 1,25(OH)2D3 in 99 patients, aged 46.9 ± 11 years, treated for depression, as well as in 45 healthy subjects. Depressive status was determined with the Hamilton Depression Scale (HDRS). Results: In patients treated for depression, we demonstrated significantly lower osteocalcin concentrations (p < 0.03) and higher concentration of β-CTX (result on the border of significance; p = 0.08). Those relationship were stronger in women. The level of 25OHD and 1,25(OH)2D3 did not differ significantly between the examined groups. We observed a negative correlation between the 25OHD and HDRS score after treatment in all patients treated for depression and in subgroups of women and subjects with recurrent depression. Conclusions: Our results indicate that depression is related to disturbances in bone metabolism, especially in women and patients with recurrent depression, suggesting its role in context of osteoporosis development.

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.

Evaluation of Osteocalcin Levels in Saliva of Periodontitis Patients and Their Correlation with the Disease Severity: A Cross-Sectional Study.

Objectives The present study aimed to investigate osteocalcin levels in saliva of healthy and periodontitis patients and correlate these levels with periodontitis severity. Materials and Methods This cross-sectional study was conducted in a hospital setup. A total of 95 individuals participated in the study with 46 subjects in group I (healthy individuals) and 49 subjects in group II (mild, moderate, and severe chronic periodontitis patients). A detailed assessment of clinical periodontal parameters and alveolar bone loss was made. Unstimulated saliva samples were collected from all study subjects and osteocalcin levels were quantitatively analyzed by sandwich enzyme-linked immunosorbent essay technique. Statistical Analysis One-way analysis of variance, Spearman’s correlation test, and Pearson’s chi-squared test were applied at a significance level of 95%. p -Values less than 0.05 were considered statistically significant. Results The results showed a significant association of qualification with group II ( p < 0.02). Bone loss scores were also significantly associated with periodontitis severity ( p < 0.01). However, no statistically significant difference was observed between group I and group II in terms of mean salivary osteocalcin levels ( p = 0.68). Also, an insignificant correlation was also observed between osteocalcin levels and periodontitis severity ( p = 0.13). Conclusion The overall study results showed that there was no significant difference between saliva osteocalcin levels of healthy and periodontitis patients. Also, there was a nonsignificant correlation between osteocalcin levels and periodontitis severity. The findings of the present study support the hypothesis that low osteocalcin levels in saliva might be considered as a poor indicator of periodontal disease progression and severity.

Dietary Calcium and Phosphorus Amounts Affect Development and Tissue-Specific Stem Cell Characteristics in Neonatal Pigs

Dietary calcium and phosphorus are required for bone and muscle development. Deficiencies of these macrominerals reduce bone mineral and muscle accretion potentially via alterations of mesenchymal stem cell (MSC) and satellite cell (SC) activities. With increasing interest in the role of early-life events on lifetime health outcomes, we aimed to elucidate the impact of dietary calcium and phosphorus, from deficiency through excess, on MSC and SC characteristics during neonatal development. Neonatal pigs [30 females, 1-d-old, 1.46±0.04kg body weight (BW)] were fed milk replacers for 16 d that were isonitrogenous and isocaloric with a consistent ratio of calcium to phosphorus, but either 25% deficient (calcium: 0.78%; phosphorus: 0.60%; CaPD), adequate (calcium: 1.08%; phosphorus: 0.84%; CaPA), or 25% in excess (calcium: 1.38%; phosphorus: 1.08%; CaPE) of calcium and phosphorus requirements based on sow-milk composition and extrapolation from NRC requirements for older pigs. BW and feed intake were recorded daily. Blood was collected for serum phosphorus, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) determination. Humeri were collected for MSC isolation and radii/ulnae bone were collected for analysis. Longissimus dorsi muscle was collected for SC isolation and analysis. There was 4.6% increase in bone ash percentage in CaPE- versus CaPD-fed pigs (P<0.05). In vivo proliferation indicated a 41.3% increase in MSCs in CaPA compared with CaPD and a 19% increase in SCs in CaPA compared with both CaPE and CaPD. MSCs from CaPD had 2- to 5-fold greater expression of peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), and lipoprotein lipase (LPL) but lower osteocalcin (BGLAP) and fibronectin (FN1) expression than CaPA (P<0.05). SCs from CaPD-fed pigs had 19% lower in vivo proliferation than in CaPA-fed pigs. These findings demonstrated that feeding a diet marginally deficient in calcium and phosphorus to neonatal pigs had a great impact on bone development, MSC, and SC characteristics. These dietary deficiencies may program future bone health and muscle development by altering MSC and SC activities.

Effects of Glycated Hemoglobin Level on Bone Metabolism Biomarkers in Patients with Type 2 Diabetes Mellitus.

PurposeWe aimed to determine the relationship between the levels of glycated hemoglobin (HbA1c) and biomarkers of bone metabolism in patients with type 2 diabetes mellitus (T2DM), and whether HbA1c independently influences any of these biomarkers.Patients and MethodsA cohort study of 240 patients with T2DM was performed. Serum was obtained and used to measure HbA1c, total cholesterol (TC), triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total protein, albumin, blood urea nitrogen (BUN), creatinine, serum 25-hydroxyvitamin D (25OHD), osteocalcin (OC), β-C-terminal cross-linked telopeptide of type I collagen (β-CTX), procollagen type 1 N-terminal propeptide (P1NP), or parathyroid hormone (PTH) concentrations. The participants were divided into three study groups according to HbA1c level: <7%, 7–9% and ≥9%. Chi-square testing and one-way analysis of variance were used to compare groups. The relationships between HbA1c and bone metabolism biomarker values were analyzed using linear correlation analysis and multiple linear regression analysis.ResultsAge, duration of T2DM, and the concentrations of TC, LDL-C, apolipoprotein B, albumin, and BUN showed significant difference among the <7%, 7–9% and ≥9% HbA1c groups. Of the bone metabolism biomarkers, there were significant differences in serum 25-hydroxyvitamin D (25OHD) and osteocalcin (OC) among the groups. The correlation coefficients (r) for the relationships of HbA1c with 25OHD and OC were −0.200 and −0.183, respectively (P <0.05). Regardless of adjustment for none, some, or all of the confounding factors (age, sex, and duration of T2DM), the 25OHD and OC concentrations were significantly lower in the HbA1c ≥9% group than in the HbA1c <7% group. HbA1c showed no relationship with β-CTX, PINP, or PTH.ConclusionT2DM patients with poorer glycemic control had lower concentrations of serum 25OHD and OC, suggesting that HbA1c is an independent risk factor for low 25OHD and OC.

Associations between circulating bone-derived hormones lipocalin 2, osteocalcin, and glucose metabolism in acromegaly.

The aim was to examine changes in the bone-derived hormone lipocalin 2 (LCN2) levels in patients with active acromegaly and to investigate the potential roles of LCN2 and osteocalcin in glucose metabolism. We recruited 50 consecutive acromegalic patients. Of those, 39 patients with complete postoperative follow-up data were included. Thirty sex-, age-, and BMI-matched healthy individuals were recruited as normal controls. The pre- and postoperative serum LCN2 and osteocalcin levels were compared. The homeostasis model assessment insulin resistance (HOMA-IR) index and secretion [β-cell function (HOMA-β)] were calculated. Compared with controls, acromegalic subjects had lower LCN2 levels (34.15 ± 9.95 vs 57.50 ± 29.75ng/mL, P < 0.01) and higher osteocalcin levels (55.45 ± 34.02 vs 19.46 ± 6.69ng/mL, P < 0.01). Acromegalic patients also had elevated HOMA-IR levels, and the HOMA-β and the area under the curve for insulin (AUC INS) levels were slightly but nonsignificantly increased. The serum levels of LCN2 significantly increased after surgery (37.03 ± 9.73 vs 45.15 ± 15.33ng/mL, P < 0.05), and those of osteocalcin significantly decreased [43.51 (26.73-65.66) vs 24.79 (18.39-32.59) ng/mL, P < 0.01]. Total lean mass was the only positive predictor of LCN2, and elevated serum IGF-I was a positive predictor of osteocalcin. Low LCN2 and elevated serum osteocalcin levels were predictors of the AUC INS, and osteocalcin was a positive predictor of HOMA-β. The bone-derived hormones, osteocalcin and LCN2 changed significantly in active acromegaly, were altered after treatment and served as predictors of β-cell function in acromegaly. This study shows that the bone could be involved in regulating glucose metabolism in acromegaly.

Serum osteocalcin levels in saudi females with type 2 diabetes mellitus in Al Madinah Al Munawarah

Background: Osteocalcin (OC), a bone-derived protein hormone, regulates glucose and fat metabolism. In Saudi population, the relationship between serum OC levels and Type 2 diabetes mellitus (DM) is limited. The association of OC with cardiovascular disease (CVD) is also not clear. Objectives: We performed a case–control study to explore the relationship between OC and Type 2 DM and CVD among Saudi females in Almadinah. Materials and Methods: A case–control study was conducted between January 2017 and January 2019 for 50 female patients with Type 2 DM attending Prince Abdelaziz Ben Maged Ben Abdelaziz Diabetic Center in Almadinah enrolled as research subjects. Fifty Type 2 DM female patients, aged about 30–55 years, and 50 age-matched healthy female control subjects were enrolled in our study. After overnight fasting, total OC, glucose, glycated hemoglobin (HbA1c), and lipid profile were analyzed to determine association of OC with glucose intolerance and lipid profile. Data processing was performed using GraphPad Prism 7 (GraphPad Software, CA, USA). Results: There was a significant elevation in the frequency of low OC levels in Type 2 DM patients compared with controls (P < 0.001). Fasting serum glucose varied inversely with the OC tertials (P = 0.049). However, no statistically significant difference was noted in HbA1c or lipid levels with the OC tertials. The Atherogenic Index of Plasma (AIP = Log10 [TG/HDL]) was 36% among Type 2 DM patients, indicating higher cardiovascular risk, while 26% had intermediate risk, with increased frequency of low OC levels in patients with high and intermediate cardiovascular risk compared to low-risk patients group (P = 0.047). Conclusions: Low serum OC level was associated with impaired glucose metabolism and increased cardiovascular risk in Type 2 diabetes.

Short-term stall housing of horses results in changes of markers of bone metabolism

In previous research, stall-housing growing horses resulted in decreased bone mineral content (BMC) of the third metacarpal (MCIII) compared to pasture-housing. To determine whether stall confinement negatively impacts bone, regardless of age, and whether the effects could be reversed upon return to pasture, 12 mature horses (5-15 years) and 12 yearlings were pair-matched by age and gender and randomly assigned to one of two treatment groups: pasture (PT) or stall (ST). Horses on PT remained there for the 84-d study, while horses on ST spent the first 28 d in stalls and the remaining 56 d on pasture. Radiographs and blood samples were taken on d 0 for baseline determinants. Radiographs and blood were taken every 7 d for radiographic photodensitometry estimates of BMC and analysis of osteocalcin (OC) and C-telopeptide (CTX-1)-markers of bone formation and degradation. There were no differences in BMC between treatments at the medial cortex of MCIII in mature horses. There were treatment (P=0.05) and day (P&lt;0.01) differences in BMC at the lateral cortex of MCIII. In yearling horses, the BMC of the medial cortex of MCIII had a day difference with the lowest overall average at d 21 and highest at d 70 (P=0.04). There were day by treatment differences (P&lt;0.05) for both OC and CTX-1 with the mature and yearling horses on ST having lower OC on d 14 than PT horses (P&lt;0.05) indicative of reduced bone formation. In mature and yearling ST horses, CTX-1 was greater on d 14 and 28 compared to horses on PT (P≤0.05) suggesting greater bone resorption. Results from serum markers of bone formation and deformation confirm that stalling negatively impacts bone formation in horses regardless of age.

Osteocalcin and epicardial adipose tissue in obesity: new hints for epicardial adipose tissue–bone crosstalk

Objectives: Osteocalcin (OC) appears to be involved in the regulation of glucose and fat metabolism. We aimed to determine the association between OC and epicardial adipose tissue (EAT) in premenopausal obese women. Design: The study included 73 premenopausal obese women and 55 non-obese women. Echocardiographic examination was performed to measure EAT. Serum OC levels were measured by chemiluminescence immunoassay. Results: OC levels were significantly lower in obese women than controls (18.26 ± 5.27 vs. 22.53 ± 6.84 ng/ml, p < .001). EAT thickness was higher in obese women than controls (5.19 ± 0.73 vs. 3.25 ± 1.35 mm, p < .001). In obese women, OC was positively correlated with EAT thickness (p = .043; r = 0.326). There was no correlation in controls. Conclusions: Premenopausal obese women had lower OC levels and thicker EAT than controls. There was a weak positive correlation between OC and EAT in premenopausal obese women. This potential cross talk between bone metabolism and EAT could play a role in the development of atherosclerosis in obesity.

2444-PUB: Bone Mineral Density and Bone Biomarkers in Women with Type 2 Diabetes Mellitus of Buryat Ethnic Group

There is a difference of bone tissue state of women belonging to various ethnic groups. We have conducted a study of bone tissue state among postmenopausal women of Buryat origin. Buryats are a main northern group of Mongolians, they are a core population of Siberia with a compact residence close to Lake Baikal. We have examined the associations between bone mineral density (BMD), trabecular bone score (TBS) and bone biomarkers in 17 postmenopausal women with T2D (59 years, diabetes duration 5.2 years, A1c &amp;lt;8.0%) and 21 postmenopausal women without diabetes (56 years). Collagen type 1 cross-linked C-telopeptide (CTX), 25-hydroxyvitamin D, ionized calcium (iCa), femoral neck BMD were similar between two groups. T2D postmenopausal women had lower osteocalcin (OC), procollagen type 1 N propeptide (P1NP), TBS and higher BMD total hip, BMD lumbar spine 1-4 (L1-L4) compared to the controls (Table). Total hip BMD in women with T2D was associated with body mass index (BMI). TBS was positively correlated with iCa. Twenty-five-hydroxyvitamin D was associated with lower OC, P1NP and CTX. Total hip BMD and BMD L1-L4 were positively correlated with BMI in women without diabetes. Femoral neck BMD was positively correlated with P1NP and inversely correlated with women’s age. T2D in Buryat women is associated with low levels of osteosynthesis markers, TBS and higher BMD. TBS was positively correlated only with iCa. Disclosure T. Bardymova: None. M. Mistiakov: None. M. Berezina: None. S. Tsyretorova: None. V. Velm: None.

Risk Factor Analysis of Severe Cerebral White Matter Hyperintensities in Type 2 Diabetes Patients: A Retrospective Single-Center Observational Study

Background: Bone is recently confirmed to be an endocrine organ, and may influence the neuron, leading to the cognitive decline and emotional disorder. However, the interaction between bone and cerebral white matter hyperintensities (WMH) is still unclarified in type 2 diabetes patients. Methods: WMH was quantified on magnetic resonance imaging (MRI) using the Fazekas and Schmidt's scoring protocol. Patients with scores ranging from 0 to 1 were defined as none or mild WMH (Group 1), and patients with scores ranging from 2 to 3 as severe WMH (Group 2). Logistic regression analysis was done to determine the association between WMH severity and selected clinical factors. Findings: Of the 194 subjects who were included in the study, there were significant differences among the two groups with respect to age and osteocalcin. After adjustment for possible confounders, age (odds ratio (OR): 1.07; 95% confidence interval (CI): 1.04-1.12; P < 0.001) and low density lipoprotein (OR: 1.51; 95% CI: 1.09-2.08; P =0.012) were associated with severe WMH, while osteocalcin could decrease the severity of WMH (OR: 0.96; 95% CI: 0.84-0.98; P =0.014). Interpretation: Our data indicate that aging, lower osteocalcin and higher LDL are associated with severe WMH in type 2 diabetes patients. The mechanism of the relationship between osteocalcin and WMH needs further research. Funding Statement: This work was supported by General Scientific Research Project of Zhejiang Education Department (Y201838964), Project of medicine and health technology program in Zhejiang province (2019314900). Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: Ethics approval was obtained from the Ethics Board of Shanghai Tenth People’s Hospital.

Lower serum osteocalcin concentrations in patients with type 2 diabetes and relationships with vascular risk factors among patients with coronary artery disease

BackgroundLower serum concentrations of the osteoblast-derived protein, osteocalcin, have been associated with poorer glycemic control, insulin resistance and atherosclerosis, and with the development of type 2 diabetes (T2DM). MethodsThis study compares concentrations of two physiological forms of osteocalcin, carboxylated (cOCN) and uncarboxylated (unOCN), between participants with T2DM (n = 20) and age-, gender- and body mass index (BMI)-matched participants without T2DM (n = 40) among patients with coronary artery disease (CAD), and it explores relationships between osteocalcin concentrations and cardiovascular risk factors. ResultsConcentrations of unOCN (2.71 ± 1.86 vs. 4.70 ± 2.03 ng/mL; t = −3.635, p = 0.001) and cOCN (8.70 ± 2.27 vs. 10.77 ± 3.69 ng/mL; t = −2.30, p = 0.025) were lower in participants with T2DM. In participants without T2DM, concentrations of cOCN were associated with fitness (VO2Peak rho = 0.317, p = 0.047) and lower body fat (rho = −0.324, p = 0.041). In participants with T2DM, lower unOCN was associated with HbA1c (rho = −0.516, p = 0.020). Higher body mass was associated with higher unOCN (rho = 0.423, p = 0.009) in participants without T2DM, but with lower concentrations of both unOCN (rho = −0.590, p = 0.006) and cOCN (rho = −0.632, p = 0.003) in participants with T2DM. ConclusionIn patients with CAD, lower osteocalcin concentrations were related to type 2 diabetes, and to adverse fitness, metabolic and obesity profiles.

Relation between osteocalcin and the energy metabolism in obesity

Background/Aim. Numerous findings have indicated the potential relation between the osteocalcin, the traditional parameter of bone turnover and the regulation of energy metabolism. The aim of this study was to identify the relationship between osteocalcin and calculated indexes, which evaluate insulin sensitivity, insulin resistance and/or secretory capacity of the pancreas, in non-diabetic, obese subjects. Methods. The study included 57 (11 men and 46 women) euglycemic, obese patients (the body mass index ? BMI : 41.03 ? 6.61 kg/m?) and 48 healthy individuals, age and sex matched (BMI : 23.15 ? 2.04 kg/m?). Plasma glucose and the insulin levels during the two-hour oral glucose tolerance test (OGTT) were determined in order to calculate the Homeostatic Model Assessment (HOMA) indexes (HOMA-IR, HOMA-B%), EISI (estimated insulin sensitivity index), EFP (estimated first phase) and ESP (estimated second phase). Osteocalcin was measured by using the Electro-chemiluminescence (ECLIA) methodology. Results. Statistically lower osteocalcin was found in the obese subjects (24.72 ? 9.80 vs 33.31 ? 10.89 ng/mL; p &lt; 0.01). ?here was a statistically significant positive correlation between osteocalcin and EISI (r = 0.340; p &lt; 0.01). The inverse correlations were found between the osteocalcin and HOMA-IR (r = -0.276; p &lt; 0.01), HOMA-B% (r = -0.337; p &lt; 0.01), EFP (r = -0.332; p &lt; 0.01) and ESP (r = -0.266; p &lt; 0.01). Multiple regression showed that the BMI and osteocalcin have a significant inverse prediction with the EISI and HOMA-IR, but the level of prediction of the BMI was substantially higher. Conclusion. The effect of osteocalcin in the glycoregulation is evident, but its contribution is significantly smaller in relation to other obesity associated factors. Therefore, when assessing its position and the role in glycemic control it is always necessary to bear in mind that osteocalcin represents only one of the many contributing factors, some of which exhibit dominant influence than osteocalcin itself.

Acute Myeloid Leukemia Induced Remodelling of the Human Bone Marrow Niche Predicts Clinical Outcome

The hematopoietic stem cell (HSC) niche consists of different cellular and non-cellular constituents which regulate HSC maintenance and retention in the bone marrow. It has been shown in a number of murine models of myeloid neoplasia how leukemia infiltration alters the HSC niche to reinforce malignancy. Acute myeloid leukemia (AML) is characterized in human by a high relapse rate indicating that leukemia initiating cells are protected by its niche. However, despite our knowledge in murine models little is known about the bone marrow architecture in human and the impact of the leukemic niche on clinical outcome.In this study, we combined immunohistochemical stainings (IHC) with protein and global gene expression analyses together with clinical data to dissect the human bone marrow architecture in AML and assess its clinical impact. Human bone marrow was collected from AML patients at first diagnosis and matching non-leukemic donors. To evaluate the bone marrow architecture CD271+ mesenchymal stem and progenitor cells (MSPCs) were automatically quantified on bone marrow sections. In fact, AML patients showed 1.5-fold increase in bone marrow MSPCs compared to non-leukemic donors (Median (IQR), AML: 5.5% (2.8-9.5), n=36; control: 3.7% (2.1-5.7), n=58; p < 0.01). MSPCs proved to produce reticular fibers, an extracellular matrix protein frequently associated with different malignancies. In AML bone marrow these fibers were also found to be more abundantly expressed (Median (IQR), AML: 3.4% (1.8-4.5), n=37; control: 1.6% (1.1-3.3), n=19; p < 0.05).Next, to globally assess the gene expression profile of MSPCs in AML bone marrow we performed microarray analyses (ClariomTM S Human Assay) of freshly isolated uncultured lineage- CD146+ CD271+ MSPCs. Strikingly, HSC-regulating genes in particular CXCL12, ANGPT1 and VCAM1 showed lower expression in AML MSPCs which correlated with the degree of hematopoietic failure in AML patients. Along with the increased number of MSPCs, geneset enrichment analysis (GSEA) revealed higher proliferation of MSPCs in AML. In murine models loss of quiescence of MSPCs was previously found to be due to bone marrow sympathetic neuropathy. We therefore measured catecholamines and neurotrophic factor in the bone marrow extracellular fluid of AML patients and non-leukemic donors at first diagnosis. In fact, noradrenalin and brain-derived neurotrophic factor (BDNF) showed a 2-fold (p=0.26) resp. 4-fold (p<0.0001) lower expression in AML bone marrow. Importantly, BDNF is proved to be essential for sympathetic neuron proliferation and differentiation.In order to get an overview of alterations of canonical pathways in bone marrow MSPCs upon AML infiltration, we applied QIAGEN's Ingenuity® Pathway Analysis software. Several of the major differently regulated pathways proved to involve differentiation and mineralization of MSPCs. We therefore assessed bone metabolism in AML patients at first diagnosis and quantified serum osteocalcin levels. Notably, AML patients showed 30% lower osteocalcin levels than non-leukemic donors (Median (IQR), AML, 12.15ng/ml (7.53-16.28) n=58; control, 17.2ng/ml (12.5-23.45) n=31; p < 0.05). To evaluate if the deficiency in osteoblast mineralization is specifically due to AML infiltration we performed in vitro co-culture assays. Both MSPCs and an osteoblast-like cell line (SaOS2) showed significant impaired mineralization in presence of certain AML cell lines as well as primary human AML cells, while healthy mononuclear cells did not affect mineralization. Strikingly, this AML-induced defect in osteoblast mineralization proved to be of clinical significance. Patients with low osteocalcin levels (<11ng/ml) showed inferior overall survival with 1-year survival rate of 38.7% while patients with high osteocalcin levels reached 66.8% (n=58; median duration of follow-up 9.7 months).In summary, we globally characterized the bone marrow architecture in AML patients in comparison to non-leukemic donors and assessed its clinical significance. This increasing understanding of the human AML bone marrow microenvironment might open the window for new niche-targeted therapies to eradicate leukemic stem cells and eventually decrease the high relapse rate in AML. DisclosuresDuehrsen:Amgen: Research Funding; Roche: Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Janssen: Honoraria.

Testosterone level in aging male with different glucose tolerance state and its association with osteocalcin

Objective: To investigate the relationship of testosterone and different glucose tolerance state, and its association with osteocalcin.Methods: A cross-sectional study was conducted of 1176 males aged 60–97 years who were arranged for an annual regular checkup from March to May 2012 in Chinese PLA general hospital in Beijing.Results: Individuals categorized as having prediabetes or diabetes were more likely to have lower osteocalcin, testosterone, and SHBG levels compared to those with normal glucose tolerance (p < .05 in males). In aging males, after adjusting for age, the negative association between osteocalcin and BMI, waist circumference, FPG, 2hPBG, or TG were significant. And serum TT was negatively associated with BMI, waist circumference, FPG, 2hPBG, or TG independent of age, ALP, Ca, P, VitD, and PTH.Conclusions: It showed that serum osteocalcin and TT were closely related with BMI, blood glucose, and TG, which supported the hypothesis that regulation of bone remodeling, energy metabolism, and reproduction are linked.

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.

Low serum osteocalcin levels are correlated with left ventricular systolic dysfunction and cardiac death in Chinese men.

Osteocalcin is a newly identified type of cytokine secreted by osteoblasts, which has an endocrine function, mediates energy and glycol-lipid metabolism, and is closely related to cardiovascular diseases. In this study, we investigated the value of serum osteocalcin levels in predicting left ventricular systolic dysfunction and cardiac death. A total of 258 patients in the Department of Cardiology were included. Two-dimensional echocardiography was performed in all the subjects. The cardiac death of subjects occurring with a median follow-up of 4.6 years was informed via phone calls or the electronic medical records. The serum osteocalcin levels were measured using electrochemiluminescent immunoassay. We found that the median left ventricular ejection fractions (LVEFs) were 62% in men and 63% in women. In the men with a LVEF > 62%, the serum osteocalcin levels were significantly higher than in those with LVEF ≤ 62% (P = 0.042), whereas this difference was absent in the women. Both the serum osteocalcin (β = 0.095, P = 0.028) and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP; β = -0.003, P < 0.01) levels remained independently significantly correlated with LVEF in the men but not in the women. Receiver operating characteristic (ROC) analyses of the men revealed that the serum osteocalcin (P = 0.007), serum NT-pro-BNP (P = 0.018) and serum osteocalcin + NT-pro-BNP (P < 0.01) levels were all significant in identifying left ventricular systolic dysfunction at baseline, but the pairwise comparisons of the three areas under the curves (AUCs) were all non-significant. The men in the lower osteocalcin level group at baseline suffered a greater risk of future cardiac death than those in the higher osteocalcin level group, whereas the result for NT-pro-BNP exhibited the opposite pattern. In conclusion, lower serum osteocalcin levels in the men could identify left ventricular systolic dysfunction and cardiac death in a manner that was not inferior to high serum NT-pro-BNP levels.