ucOC Levels Research Articles

Serum 25(OH)D and vitamin K1 levels in patients with severe motor and intellectual disability: A Japanese single-center experience

PurposeTo investigate whether patients with severe motor and intellectual disability (SMID) have nutritional vitamin D and K insufficiencies and clarify the required vitamin supplementation. MethodsThis prospective observational study enrolled Japanese adults with SMID receiving institutionalized care who underwent blood sampling between February 2020 and February 2022 during annual medical checkups. Serum vitamin K1 and 25-hydroxy vitamin D (25(OH)D) levels were measured to determine their relationship with serum uncarboxylated osteocalcin (ucOC) levels. Vitamin D and K intake was compared among tube-fed and oral-intake patients with SMID and control participants using corresponding serum levels. ResultsThe study included 124 patients with SMID (56 men and 68 women; mean age: 53.0 years) and 20 control participants. Serum 25(OH)D levels were significantly higher in the SMID group than in the control group and the oral intake SMID group than in the tube-fed SMID group. In the tube-fed SMID group, vitamin D intake was lower than the daily recommended intake and correlated with serum 25(OH)D levels. Daily vitamin K intake in the tube-fed group was lower than recommended but not correlated with serum vitamin K levels. Serum ucOC levels were significantly higher in the SMID group than in the control group. Tube feeding was significantly and positively correlated with serum 25(OH)D levels. Serum 25(OH)D levels were not correlated with serum vitamin K1 levels. ConclusionsThe SMID group had higher ucOC levels than the control group, possibly owing to daily vitamin K and D deficiencies. Vitamin D supplementation is recommended to decrease ucOC levels.

Insulin resistance and osteocalcin associate with the incidence and severity of postoperative delirium in elderly patients undergoing joint replacement.

While insulin sensitivity plays an important role in maintaining glucose metabolic homeostasis and cognitive function, its impact on postoperative delirium (POD) remains unclear. This study aimed to investigate the association between POD and indicators of insulin sensitivity, including insulin resistance and osteocalcin. A total of 120 elderly patients undergoing joint replacement were recruited and divided into delirium and non-delirium groups. Plasma and cerebrospinal fluid (CSF) samples were collected for the analysis of biomarkers, including insulin, uncarboxylated osteocalcin (ucOC), total osteocalcin (tOC), and glucose. Insulin resistance was assessed through the homeostatic model assessment of insulin resistance (HOMA-IR). Out of the total, 28 patients (23.3%) experienced POD within 5 days after surgery. Patients with delirium exhibited higher levels of preoperative HOMA-IR and ucOC in CSF and plasma, and of tOC in CSF (P = 0.028, P < 0.001, P = 0.005, P = 0.019). After adjusting for variables, including age, Mini-Mental State Examination score, surgical site and preoperative fracture, only preoperative ucOC in CSF and HOMA-IR were significantly linked to the incidence of delirium (OR = 5.940, P = 0.008; OR = 1.208, P = 0.046, respectively), both of which also correlated with the severity of delirium (P = 0.007, P < 0.001). Receiver operating curve analysis indicated that preoperative HOMA-IR and ucOC in CSF might partly predict POD (area under the curve [AUC] = 0.697, 95% confidence interval [CI] = 0.501-0.775, AUC = 0.745, 95% CI = 0.659-0.860). We observed that preoperative elevated HOMA-IR and ucOC in CSF were associated with the incidence and severity of POD. While these preliminary results need confirmation, they suggest a potential involvement of insulin resistance and osteocalcin in the pathological mechanism of POD. Geriatr Gerontol Int 2024; 24: 421-429.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum β-isomer of C-terminal telopeptides of type I collagen (β-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

The Effect of Vitamin K2 Supplementation on PIVKA-II Levels in Patients with Severe Motor and Intellectual Disabilities Undergoing Long-Term Tube Feeding.

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

#5184 THE RELATIONSHIP OF BONE MINERAL DENSITY AND VITAMIN K IN RENAL TRANSPLANT PATIENTS

Abstract Background and Aims Kidney transplantation is the best treatment for end-stage renal disease (ESRD). Osteoporosis is a common health problem in kidney transplant recipients. It is known that the risk of bone fracture increases by 30% in the first 3 years after transplantation in kidney transplant recipients. Vitamin K is a cofactor involved in the activation of osteocalcin. This protein plays a role in bone mineralization. Currently, vitamin K cannot be measured directly from blood samples, and markers such as proteins induced in the absence of vitamin K (PIVKA-II) and undecarboxylated osteocalcin (ucOC) are used for indirect measurement of vitamin K. In our study, we aimed to investigate the relationship between vitamin K and osteoporosis by measuring serum PIVKA-II, ucOC and BMD in kidney transplant recipients. Method It was a cross-sectional observational study. Patients were selected from kidney transplant patients over 18 years old. A control group was formed from dialysis patients over the age of 18. For vitamin K levels, PIVKA-II and ucOC levels were measured in serum samples taken from patients. The relationship between vitamin K markers, bone mineral densitometry and the risk of major osteoporotic fracture calculated by FRAX in kidney transplant patients was evaluated. Results 68 kidney transplant patients and 20 dialysis patients followed in our clinic were included in this study. As results, it was observed the increased risk of osteoporosis in postmenopausal women patients related with decreased serum vitamin K level (r = −0.520, p = 0.047). Of the transplant group, PIVKA-II and Lumbar I-IV BMD values were statistically significant (p = 0.034, r = -0.258). PIVKA-II was found to be a risk factor for low BMD by multiple linear regression analysis in the transplant group (beta coefficient = −0.195, p = 0.037). Conclusion In our study, it has been proven that as the vitamin K level decreases in kidney transplant patients, the vertebral bone mineral density decreases while the risk of osteoporosis increases. This result shows that vitamin K replacement may have positive effects on bone metabolism.

Study on Undercarboxylated Osteocalcin in Improving Cognitive Function of Rats with Type 2 Diabetes Mellitus by Regulating PI3K-AKT-GSK/3β Signaling Pathwaythrough medical images

ABSTRACT This paper aims to clarify the effect of Undercarboxylated osteocalcin (ucOC) on cognitive function in rats with type 2 diabetes mellitus (T2DM). This research reviewed the cognitive function of 35 diabetic patients, 33 non-diabetic patients and the serum levels of Undercarboxylated osteocalcin (ucOC) in patients. What’s more, we analyzed the correlation between serum ucOC levels and cognitive function. Diabetic rats were treated with high (30 μg·kg−1·d−1) and low (10 μg·kg−1·d−1) doses of ucOC to investigate its effects in regulating ucOC on blood lipid, blood glucose and cognitive function. We systematically detected the phosphorylation levels of cognitive level-related proteins (PI3K, AKT, and GSK/3β) in the hippocampus by Western Blot. Finally, PI3K-Akt pathway involved in regulating cognitive function in diabetic rats by ucOC was verified with AKT pathway inhibitor LY294002. MoCA score and serum ucOC levels were significantly reduced in patients with diabetes mellitus. ucOC could concentration-dose-dependently decrease the blood glucose and lipid levels, and improve glucose metabolism and weaken insulin resistance in diabetic rats (P < 0.001). In addition, escape latency in diabetic rats was significantly higher than that of normal rats in the Morris maze test, and ucOC dose-dependently shortened the escape latency in diabetic rats (all with P < 0.05). After using AKT pathway inhibitor, ucOC failed to shorten the escape latency in diabetic rats. In conclusion, this study explored the relevant mechanisms in inducing cognitive dysfunction of T2DM, suggesting the potential value of ucOC as a drug to improve cognitive dysfunction in patients with T2DM in clinical.

Assessment of Uncarboxylated Osteocalcin Levels in Type 2 Diabetes Mellitus.

Osteocalcin is one of the main organic components of the bone matrix and consists of 49 amino acids excreted from osteoblastic cells in carboxylated and uncarboxylated forms. Carboxylated Osteocalcin belongs to the bone matrix, whereas uncarboxylated osteocalcin (ucOC) is an important enzyme of osteocalcin in the circulatory system. It is an essential protein for balancing the minerals in bones, binding with calcium, and regulating body glucose levels. In this review, we point out the assessment of ucOC levels in type 2 diabetes mellitus. The experimental results that show ucOC controls glucose metabolism are significant because they relate to the current obesity, diabetes, and cardiovascular disease. To confirm that, low serum levels of ucOC were a risk factor for poor glucose metabolism, and further clinical studies are required.

Impact of serum vitamin D level on selected bone-related markers in obese- type 2 diabetes patients

Background: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for skeletal fractures. The causes are probably a mix of factors, including poor glycemic control, a higher risk of falling due to hypoglycemia, osteopenia, bone quality deterioration, and drug side effects related to bone fragility. Undercarboxylated osteocalcin (ucOC) is a protein generated by osteoblasts that affects insulin secretion and sensitivity. Methods: A total number of 47 obese (BMI ˃ 30) patients with confirmed type 2 diabetes were selected depending on the American Diabetes Association ADA criteria. The control participants were similar to the patients in age and gender, with a total number of 43 obese (BMI ˃ 30) and healthy subjects chosen from the general population. The selected subjects were grouped according to their serum vitamin D levels. Their blood specimen was used for assaying ucOC, parathyroid hormone (PTH), and vitamin D3 levels by specific ELISA kits, and to estimate calcium (Ca2+) levels and inorganic phosphate (PO43−) via enzymatic colorimetric methods. Results: Serum parathyroid hormone and inorganic phosphate median (IQR) values were markedly increased in patients with T2DM when compared to healthy controls, whereas serum calcium and ucOC levels were lowered significantly in diabetic patients when compared to healthy controls. This was irrespective of serum vitamin D levels. Conclusions: Elevated serum levels of PTH and PO43− values in obese type 2 diabetic patients compared to obese non-diabetic controls were accompanied by a significant decrease in ucOC and Ca2+ levels, irrespective of serum vitamin D levels. Hence, serum vitamin D3 levels had no significant impact on levels of ucOC, PTH, Ca2+, and PO43− in obese patients with type 2 diabetes.

Functional tooth number in the posterior region associated serum ucOC levels

PurposeThe purpose of this study was to investigate serum undercarboxylated osteocalcin (ucOC) levels in partially edentulous patients scheduled to receive implant treatment and determine the association between ucOC levels, vegetable intake, vitamin K, dietary fiber intake, and functional tooth number in the posterior region (p-FTN).MethodsA total of 46 patients (20 male and 26 female, 61.9 ± 12.7 years old) were included. The association among serum ucOC levels, vegetable intake, vitamin K and dietary fiber intake was assessed using Spearman’s rank correlation coefficient and binary logistic regression analysis.ResultsIn total, 35% of patients (16/46 subjects) showed an abnormally high ucOC level (≧ 4.5 ng/mL). p-FTN showed a weak positive correlation with vegetable intake, vitamin K and dietary fiber intake (r = 0.28, 0.21, and 0.14, respectively) and a significant negative correlation with ucOC levels (r = − 0.51). Multivariate analysis demonstrated that p-FTN as well as vitamin K intake showed a significant negative association with serum ucOC levels.ConclusionsMore than one-third of patients showed abnormally high ucOC levels. p-FTN showed a negative association with serum ucOC levels, which indicated the possibility that oral status affected bone quality.

Association between serum uncarboxylated osteocalcin levels and nutritional intake in Japanese female athletes.

The current study aimed to determine the association between serum uncarboxylated osteocalcin (ucOC) levels and dietary vitamin K intake in female Japanese athletes. The nutritional profile and food group intake of 52 Japanese female athletes were investigated using a digital photographic method with data obtained from 3-day dietary records. The food groups were categorized into 18 groups in line with the standard tables of food composition in Japan. Fasting blood samples were collected for serum ucOC levels, and dual-energy X-ray absorptiometry (DXA) evaluated body composition and bone parameters. The results showed that dietary vitamin K intake level was 235 ± 148 µg/day, and approximately 70% (n = 36) of participants consumed more than the adequate intake (AI) level, based on the Dietary Reference Intakes for Japanese females aged 18-29. Serum ucOC levels were negatively associated with daily vitamin K intake (r = -0.388, P = 0.004) and calcium (r = -0.596, P = 0.004) after adjusting for energy intake. Our study revealed that serum ucOC levels were negatively associated with dietary vitamin K intake in female Japanese athletes. Serum ucOC levels reflected dietary vitamin K intake in female athletes. In summary, female athletes consume more vitamin K than the general population to maintain bone health. Furthermore, our results indicated that serum ucOC levels might be linked to dietary calcium intake.

Serum Carboxylated and Undercarboxylated Osteocalcin association with Coronary Atherosclerosis Disease and Cardiovascular Risk Markers in: Analysis of a Syrian Male Cohort

Background: New assumption concerning association of osteocalcin and Vascular calcification has emerged in reaction to observations that the mechanism of vascular calcification resembles that of bone mineralization, thus linking bone and the vasculature. However, studies reported contrasting results about the association between osteocalcin and atherosclerosis. This study was designed to evaluate capacity relationships among different forms of circulating osteocalcin and cardiovascular risk markers in male with coronary atherosclerosis. Methods: A cross-sectional study was conducted on 58 male patients, divided into two groups according to the severity of coronary artery disease (CAD), as determined by coronary angiography assessment: Early coronary atherosclerosis (ECA), n=20, patients with mild CAD (&lt;50% stenosis in any major epicardial arteries), and late coronary atherosclerosis (LCA), n=38, patients with severe, multivessel CAD (&gt;50% stenosis in at least one or more major epicardial arteries). The healthy control (HC) group included 26 healthy male subjects. Carboxylated (cOC) and ucOC were measured using ELISA technique. Results: We observed significantly lower ucOC levels in both stages of cardiovascular disease (CVD) (ECA and LCA) compared to the HC group (2.34±2.23 and 2.48±1.60 vs 6.65±1.78ng/mL, P&lt;0.01). ucOC was inversely correlated with an increasing number of cardiovascular risk factors (CVRFs). Moreover, ucOC levels were markedly reduced in high-fasting plasma glucose (FPG) groups (IFG and T2DM-threshold level), compared to the normal FPG group (NG). cOC levels were higher in the IFG group, compared to the normal FPG group (8.50±4.76 vs 7.13±3.13ng/mL, p=0.008) possibly predicting such condition. Conclusions: In the present study, patients with coronary atherosclerosis, regardless of the onset of stenosis, showed lower ucOC levels which were inversely correlated with an increasing number of CVRFs. Moreover, ucOC levels were markedly reduced in high-FPG groups. Serum ucOC may be considered as a potential biomarker for coronary atherosclerosis disease and therefore its measurement may help to establish preventive and therapeutic approaches. Moreover, cOC may be associated with a high alert for diabetes at the IFG stage, but not when the disease progresses to diabetes.

Interleukin-6, undercarboxylated osteocalcin, and brain-derived neurotrophic factor responses to single and repeated sessions of high-intensity interval exercise

ObjectivesThe purpose of this study was to compare the effects of a single session of high-intensity interval exercise (HIIE) with 2 consecutive HIIEs, separated by 3 h of recovery, on plasma interleukin-6 (IL-6), undercarboxylated osteocalcin (ucOC), and brain-derived neurotrophic factor (BDNF) responses. MethodsTwenty male recreational endurance athletes completed two HIIE trials in a randomized crossover design: a single session of HIIE on the single exercise day (HIIE-S) and two sessions of HIIE 3 h apart on the double exercise day (HIIE-D). The HIIE protocol consisted of 10 × 1 min cycling at 100 % of peak oxygen uptake, with 75 s of low-intensity cycling at 60 W. Blood samples were collected to analyze IL-6, ucOC, and BDNF levels before and immediately after HIIE on the HIIE-S and before and immediately after the second HIIE on the HIIE-D. ResultsBoth HIIE interventions significantly increased (p < 0.001) plasma IL-6 (HIIE-S 33.90 % vs HIIE-D 31.04 %; p = 0.64), ucOC (HIIE-S 37.18 % vs HIIE-D 39.54 %; p = 0.85), and BDNF levels (HIIE-S 236.01 % vs HIIE-D 216.68 %; p = 0.69), with no group effect. ConclusionsOur results demonstrate that performing two consecutive HIIEs on the same day with a 3-h rest results in similar changes in plasma levels of IL-6, BDNF, and ucOC compared with a single session of HIIE.

Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials.

IntroductionVitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women.MethodsWe searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria.ResultsSixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (P = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 (P = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, P = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, P = 0.76).ConclusionsThe results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.

The role of osteocalcin in regulation of glycolipid metabolism and muscle function in children with osteogenesis imperfecta.

ObjectiveOsteoblasts are discovered to secrete hormones with endocrine effects on metabolism, and osteocalcin (OC) is the most abundant non-collagenous protein in bone. We investigate the relationship between serum OC levels and glycolipid metabolism and muscle function in children with osteogenesis imperfecta (OI).MethodsA total of 225 children with OI and 80 healthy controls matched in age and gender were included in this single center study. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated analyzers. Serum levels of fasting insulin (FINS) were measured using an automated electrochemiluminescence system. Serum levels of OC and undercarboxylated osteocalcin (ucOC) were measured by enzyme-linked immunosorbent assay. Grip strength and timed-up-and-go (TUG) test were measured. Bone mineral density (BMD) and body composition were measured using dual-energy X-ray absorptiometry.ResultsOI patients had significantly higher body mass index (BMI), FBG, and HOMA-IR, but lower HDL-C levels, lower grip strength and longer TUG than control group (all P<0.05). Serum OC, ucOC levels, and ucOC/OC in OI type III patients were significantly lower than those in OI patients with type I and IV. Serum levels of OC, ucOC, and ucOC/OC were negatively correlated to BMI, FBG, insulin levels, and HOMA-IR (all P<0.05). The ratio of ucOC/OC was positively correlated to grip strength (r=0.512, P=0.036), lean mass percentage (%LM) of the total body and limbs, and negatively correlated to fat mass percentage (%FM) of the total body, %FM and fat mass index (FMI) of the trunk (all P<0.05).ConclusionsObesity, glucolipid metabolic abnormalities, and reduced grip strength were common in children with OI. Circulating osteocalcin and ucOC may play an important role in the regulation of glucose metabolism, as well as the muscle function of children with OI.

Undercarboxylated Osteocalcin: A Promising Target for Early Diagnosis of Cardiovascular and Glycemic Disorders in Patients with Metabolic Syndrome: A Pilot Study.

Lifestyle changes are causing an exponential increase in the prevalence of obesity and metabolic syndrome (MetS) worldwide. The most frequent complications of these are the development of diabetes (T2D) and cardiovascular disease (CVD). Accurate tools are needed to classify the cardiovascular risk (CVR) in the MetS population. In recent years, numerous biomarkers of bone metabolism have been associated with CVR. The aim of this study was to determine the levels of undercarboxylated osteocalcin (ucOC) in a cohort of patients with MetS and to analyse its association with MetS parameters and CVR as well as with T2D prevalence. A longitudinal study was conducted in which a MetS population was followed for one year. Weight change, adherence to the Mediterranean diet (MedDiet), ucOC levels, MetS parameters and CVR were analysed and CVR was calculated using different scores. Our results showed a decrease of CVR associated with a better adherence to the MetDiet resulting in higher HDL-C and ucOC levels though the improvement of MetS risk factors. This bone protein appeared as a potential biomarker to classify CVR in the MetS population, especially for MetS patients without prevalent T2D. Furthermore, ucOC serum levels could be good predictors of T2D prevalence.

Undercarboxylated Osteocalcin and Its Associations With Bone Mineral Density, Bone Turnover Markers, and Prevalence of Osteopenia and Osteoporosis in Chinese Population: A Cross-Sectional Study.

ObjectiveUndercarboxylated osteocalcin (ucOC) is one form of osteocalcin lacking full carboxylation, which plays an important role in bone homeostasis, glucose homeostasis, and energy metabolism. Our aim is to obtain the profile of serum ucOC level according to gender and age and explore its associations with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteopenia and osteoporosis in the Chinese population.MethodsThis is a cross-sectional study with 900 subjects, composed of 431 men and 469 women. Clinical information was collected, and BMD values of the lumbar spine (L1–4), left femoral neck, and total hip were scanned. Biochemical markers including hepatic and renal function, serum calcium, serum phosphorus, procollagen type 1 N-propeptide (P1NP) β-CrossLaps of type I collagen-containing cross-linked C-telopeptide (β-CTX) intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ucOC were measured.ResultsWe found that the median ucOC level was higher in men than women [men, 2.6 ng/ml; women, 1.6 ng/ml; p < 0.001]. The profile according to age showed that ucOC levels were the lowest at the age of 40–49 years in both men [2.55 ng/ml (95% CI = 1.96–3.13 ng/ml)] and women [1.57 ng/ml (95% CI = 1.12–2.03 ng/ml)]; in patients younger than 49 years, they decreased with age; then over 50 years, they quickly increased. Furthermore, we found that a higher ucOC level was correlated with lower BMD values at the lumbar spine (men, r = −0.128, p = 0.013; women, r = −0.321, p < 0.001), femoral neck (men, r = −0.095, p = 0.062; women, r = −0.260, p < 0.001), and total hip (men, r = −0.123, p = 0.015; women, r = −0.209, p < 0.001) and higher P1NP (men, r = 0.307, p < 0.001; women, r = 0.239, p < 0.001) and β-CTX (men, r = 0.169, p = 0.001; women, r = 0.354, p < 0.001) levels in both men and women. Furthermore, we also showed that a 1 − SD increase in ucOC was associated with an odds ratio (OR) of 1.63 and 1.70 for having osteopenia or osteoporosis in men and women, respectively (men, 95% CI = 1.25–2.13, p = 0.004; women, 95% CI = 1.19–2.42, p = 0.004).ConclusionsWe first revealed the profile of serum ucOC levels according to gender and age in the Chinese population and demonstrated the associations of ucOC with BMD and BTMs and the risk of prevalent osteopenia or osteoporosis. Our findings provide a clue to elucidate the function of ucOC in bone metabolism.

The impact of vitamin K2 and native vitamin D supplementation on vascular calcification in pediatric patients on regular hemodialysis. A randomized controlled trial.

Vascular calcification is one of the most prevalent disorders in pediatric hemodialysis patients that eventually lead to cardiovascular morbidity. Vitamin K2 was investigated in adults in previous studies and showed favorable effects on calcification markers. Our aim in this study was to evaluate the efficacy and safety of vitamin K2 and cholecalciferol on the calcification regulators in pediatric patients. A prospective, randomized and controlled trial was conducted on sixty hemodialysis pediatric patients who were divided to four groups; Group 1: administered 100 µg of vitamin K2 (MK-7); Group 2: administered 10 µg of native vitamin D; Group 3: administered 100 µg of vitamin K2 (MK-7) in addition 10 µg of native vitamin D, and Group 4: administered the standard therapy only. The duration of supplementation was 4 months. In addition to a group of healthy normal control of age and sex-matched. At the end of the study period, serum levels of FGF23, dp-uc-MGP, and uc-OC were measured. It was found that serum levels of dp-uc-MGP, uc-OC, and FGF23 were significantly higher (p < 0.05) in the hemodialysis patients as compared to the healthy normal control. After 4 months, group 3 revealed the most significant decrease in dp-uc-MGP, uc-OC as compared to the other groups. However, there was no change in FGF23. Vitamin K2 and native vitamin D showed a beneficial effect on calcification regulators in pediatric hemodialysis patients. clinical trial.gov (NCT04145492).

Serum undercarboxylated osteocalcin levels are related to bone disease in hemodialysis and peritoneal dialysis patients

Objectives: In our study, we investigated whether the undercarboxylated osteocalcin (ucOC) is an indicator of bone turnover for patients treated with hemodialysis (HD) or peritoneal dialysis (PD). Furthermore, we have examined the relationships between ucOC levels and other bone inidicators such as osteocalcin (OC), bone specific alkaline phosphatase (B-ALP), calcitonin, vitamin D, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), magnesium (Mg) and bone mineral density (BMD). Methods: Study group was consisted of 24 HD, 30 PD patients and 30 control subjects. ucOC measurements were based on precipitation of carboxylated OC with barium sulfate. After precipitation, ucOC was measured in supernatant by ELISA. Results: In chronic kidney disease (CKD), increased ucOC levels were present both in HD and PD groups. The ucOC levels in HD group were higher than those of PD group. ucOC levels in samples after HD were lower than in samples before HD. But there is no difference between groups for ucOC% levels. We observed that ucOC levels for CRF were higher compared to that of control group and statistically significant. ucOC levels were positively correlated with OC, B-ALP, ALP, iPTH, P and Mg levels. There were negative and significant correlations between ucOC levels and BMD values. ucOC has a good discrimination power for both high and low turnover ROD groups. Conclusions: ucOC is a useful marker to evaluation of bone metabolism in patients undergone hemodialysis or peritoneal dialysis in end-stage renal disease.

Uncovering the Bone-Muscle Interaction and Its Implications for the Health and Function of Older Adults (the Wellderly Project): Protocol for a Randomized Controlled Crossover Trial.

BackgroundBone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism.ObjectiveThe proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality.MethodsA total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press; one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function.ResultsThe trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019.ConclusionsThis study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions.Trial RegistrationAustralia New Zealand Clinical Trials Registry ACTRN12618001756213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925.International Registered Report Identifier (IRRID)DERR1-10.2196/18777

Circulating osteocalcin levels were not significantly associated with the risk of incident type 2 diabetes mellitus in elderly Japanese men: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

Cross-sectional studies have shown that patients with type 2 diabetes mellitus (T2DM) have low circulating levels of osteocalcin (OC) and undercarboxylated OC (ucOC). This longitudinal study aimed to examine whether low OC or ucOC levels at baseline are associated with the risk of incident T2DM. We examined 1700 community-dwelling Japanese men (≥65years) after excluding those with history of diseases (other than T2DM) or medications that affect bone and glucose metabolism. T2DM was defined as fasting plasma glucose (FPG) ≥126mg/dl or glycated hemoglobin A1c (HbA1c) ≥6.5%. Participants without prevalent T2DM at baseline were invited to follow-up surveys 5 and 10years after baseline. Among the participants, 309 with prevalent T2DM showed significantly lower serum OC and ucOC levels at baseline than those without. After excluding these participants, 46 and 57 participants with incident T2DM were identified in the first and second follow-up surveys, respectively. These participants did not show significantly different OC and ucOC levels at baseline relative to those without T2DM, although their FPG and HbA1c levels at baseline were significantly higher compared to those without incident T2DM. Increase in glycemic indices preceded decrease in OC and ucOC levels. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM identified in the follow-up surveys. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM. Our results do not support the findings of animal studies that ucOC is a hormone regulating glucose metabolism.