Ginsenoside Rc alleviates osteoporosis by the TGF-ß/Smad signaling pathway.

Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. µ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-ß/Smad pathway by increasing TGF-ß as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-ß/Smad pathway.

Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison's disease.

PURPOSE: Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison's disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement. METHODS: Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN). RESULTS: Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10-6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient's age (p = 1.038 × 10-5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD. CONCLUSION: Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.

Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 µg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

To investigate the association of serum osteocalcin with cognitive functional status in patients with type 2 diabetes: A systematic review with meta-analysis.

BACKGROUND: To systematically evaluate the correlation between serum osteocalcin levels and cognitive function status in type 2 diabetes mellitus (T2D) patients. METHODS: This review was conducted according to the PRISMA guidelines, and was developed and submitted to PROSPERO (CRD42022339295). We comprehensively searched PubMed, EMBASE, Web of Science, Scopus, ProQuest, and Chinese Databases (China National Knowledge Infrastructure, Wan Fang, Chinese Science and Technology Periodical Database, and China Biology Medicine) up to 1 June 2023. 3 investigators performed independent literature screening and data extraction of the included literature, and 2 investigators performed an independent quality assessment of case-control studies using the Newcastle-Ottawa-Scale tool. Data analysis was performed using Review Manager 5.4 software. For continuous various outcomes, mean difference (MD) or standardized MD with 95% confidence intervals (CIs) was applied for assessment by fixed-effect or random-effect model analysis. The heterogeneity test was performed by the Q statistic and quantified using I2, and publication bias was evaluated using a funnel plot. RESULTS: 9 studies with T2D were included (a total of 1310 subjects). Meta-analysis results indicated that cognitive function was more impaired in patients with lower serum osteocalcin levels [MD = 9.91, 95% CI (8.93, -10.89), I2 = 0%]. Serum osteocalcin levels were also significantly different between the 2 groups of T2D patients based on the degree of cognitive impairment [MD = -0.93, 95% CI (-1.09, -0.78), I2 = 41%]. It summarized the statistical correlation between serum osteocalcin and cognitive function scores in patients with T2D at r = 0.43 [summary Fisher's Z = 0.46, 95% CI (0.39, -0.50), I2 = 41%). After sensitivity analysis, the heterogeneity I2 decreased to 0%, indicating that the results of the meta-analysis are more reliable. CONCLUSION SUBSECTIONS: Based on a meta-analysis of included studies, we concluded that there is a moderately strong positive correlation between serum osteocalcin levels and patients' cognitive function in T2D. An intervention to increase serum osteocalcin levels can contribute to delaying and improving cognitive decline in patients with T2D.

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

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

Objective: Osteoblasts 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). Methods: A 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. Results: OI 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). Conclusions: Obesity, 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.

Effects of Whole-Body Vibration on Breast Cancer Bone Metastasis and Vascularization in Mice.

We evaluated whether whole-body vibration (WBV) prevented bone loss induced by breast cancer (BC) metastasis and the involvement of bone marrow vasculature. One day after orthotopic transplantation of mammary 4T1 tumor cells, 8-week-old BALB/c mice were subjected to 0.3 g/90 Hz vertical vibration for 20 min/day for 5 days/week (BC-WBV) or sham-handled (BC-Sham) over 3 weeks. Age-matched intact mice (Intact) were also sham-handled. Both tibiae were harvested from BC-WBV (n = 7), BC-Sham (n = 9), and Intact (n = 5) mice for bone structure imaging by synchrotron radiation-based computed tomography (SRCT) and hematoxylin and eosin staining, whereas right tibiae were harvested from other BC-WBV and BC-Sham (n = 6 each) mice for vascular imaging by SRCT. Tumor cells were similarly widespread in the marrow in BC-WBV and BC-Sham mice. In BC-Sham mice, cortical bone volume, trabecular volume fraction, trabecular thickness, trabecular number density, and bone mineral density were smaller, and marrow volume and trabecular separation were larger than in Intact mice. However, although trabecular thickness was smaller in BC-WBV than Intact mice, the others did not differ between the two groups. Serum osteocalcin tended to be higher in BC-WBV than BC-Sham mice. Compared with BC-Sham mice, BC-WBV mice had a smaller vessel diameter, a trend of a larger vessel number density, and smaller vessel diameter heterogeneity. In conclusion, WBV mitigates bone loss in BC bone metastasis, which may be partly due to increased bone anabolism. The alteration of marrow vasculature appears to be favorable for anti-tumor drug delivery. Further studies are needed to clarify the multiple actions of WBV on bone, tumor, and marrow vasculature and how they contribute to bone protection in BC metastasis.

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

BACKGROUND: The 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. METHODS: We 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. RESULTS: During 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. CONCLUSIONS: A 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.

Epidural Steroid Injections Acutely Suppress Bone Formation Markers in Postmenopausal Women.

CONTEXT: Over 9 million epidural steroid injections (ESIs) are performed annually in the United States. Although these injections effectively treat lumbar radicular pain, they may have adverse consequences, including bone loss. OBJECTIVE: To investigate acute changes in bone turnover following ESI. We focused on postmenopausal women, who may be at greatest risk for adverse skeletal consequences due to the combined effects of ESIs with aging and estrogen deficiency. METHODS: Single-center prospective observational study. Postmenopausal women undergoing lumbar ESIs and controls with no steroid exposure were included. Outcomes were serum cortisol, markers of bone formation, osteocalcin, and procollagen type-1 N-terminal propeptide (P1NP), and bone resorption by C-telopeptide (CTX) measured at baseline, 1, 4, 12, 26, and 52 weeks after ESIs. RESULTS: Among ESI-treated women, serum cortisol declined by ~50% 1 week after injection. Bone formation markers significantly decreased 1 week following ESIs: osteocalcin by 21% and P1NP by 22%. Both markers remained suppressed at 4 and 12 weeks, but returned to baseline levels by 26 weeks. There was no significant change in bone resorption measured by CTX. Among controls, there were no significant changes in cortisol or bone turnover markers. CONCLUSION: These results provide evidence of an early and substantial reduction in bone formation markers following ESIs. This effect persisted for over 12 weeks, suggesting that ESIs may have lasting skeletal consequences. Given the large population of older adults who receive ESIs, further investigation into the long-term skeletal sequelae of these injections is warranted.

Serum osteocalcin concentration as an independent biomarker of osteoporosis in patients with chronic kidney disease.

OBJECTIVES: Osteocalcin, an osteoblast-derived hormone, is associated with the development of osteoporosis and arteriosclerosis in the general population. However, its role on the pathogenesis of osteoporosis and vascular calcification in patients with chronic kidney disease (CKD) is unclear. Here, we investigated the connection between osteocalcin, bone mineral density (BMD), and abdominal aortic calcification (AAC) in CKD patients. MATERIALS AND METHODS: In total, 95 patients with stage 2 to stage 5 CKD were enrolled. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay. BMD was determined by dual-energy X-ray absorptiometry, and AAC scores were generated from lateral lumbar radiograph findings. RESULTS: 95 patients were assigned into normal bone density (30.5%, n = 29), osteopenia (45.3%, n = 43), and osteoporosis (24.2%, n = 23) groups. The osteoporosis group was characterized by older age, higher female-to-male ratio, phosphorous levels, calcification scores, osteocalcin levels, and intact parathyroid hormone (PTH) levels, while with lower hemoglobin levels as compared to normal and osteopenia groups. Multivariate multinominal regression analysis showed age, female sex, intact PTH, and serum osteocalcin level were independent determinants of osteoporosis severity in CKD patients. Furthermore, serum osteocalcin level is positively correlated to intact PTH in multivariate linear regression model, indicating that osteocalcin might be a bone turnover marker in patients with CKD. Multivariate stepwise linear regression analysis revealed that age, diabetes mellitus, poorer renal function, rather than osteocalcin, have independent associations with AAC score. CONCLUSION: Elevated serum osteocalcin levels could be considered as a marker of osteoporosis rather than that of vascular calcification in patients with CKD.

RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function.

PURPOSE: Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate testosterone (T) production by Leydig cells in rodents, in parallel with the hypothalamus-pituitary-gonadal axis (HPG) mediated by luteinizing hormone (LH). The aim of this cross-sectional study was to evaluate the association among serum ucOCN, rs2247911 polymorphism of GPRC6A gene and the endocrine/semen pattern in a cohort of infertile males, possibly identifying an involvement of the ucOCN-GPRC6A axis on testis function. METHODS: 190 males, including 74 oligozoospermic subjects, 58 azoosperminc patients and 58 normozoospermic controls, were prospectively recruited at the Orient Hospital for Infertility, Assisted Reproduction and Genetics in Syria (Study N. 18FP), from July 2018 to June 2020. Outpatient evaluation included the clinical history, anthropometrics and a fasting blood sampling for hormonals, serum OCN (both carboxylated and undercarboxylated), glycemic and lipid profile and screening for rs2247911 GPRC6A gene polymorphism. RESULTS: Higher serum ucOCN associated with higher T and HDL-cholesterol (respectively: r = 0.309, P < 0.001 and r = 0.248, P = 0.001), and with lower FSH (r = - 0.327, P < 0.001) and LDL-cholesterol (r = - 0.171; P = 0.018). Patients bearing the GG genotype of rs2247911 had higher sperm count compared to GA genotype (P = 0.043) and, compared to both AG and AA genotypes, had higher serum T (P = 0.004, P = 0.001) and lower triglycerides levels (P = 0.002, P < 0.001). Upon normalization for LH levels and body mass index, rs2274911 and ucOCN were significantly associated with higher serum T at linear stepwise regression analysis (P = 0.013, P = 0.007). CONCLUSIONS: Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis, subsidiary to HPG.

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.

Decreased Serum Wnt Antagonist Levels in Patients With Active Acromegaly.

OBJECTIVE: The Wnt signaling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients. METHODS: We recruited 77 patients recently diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. At baseline and posttreatment, Wnt antagonists (sclerostin [SOST], dickkopf-related protein 1 [DKK-1], and Wnt inhibitory factor 1 [WIF-1]), bone turnover markers (osteocalcin, procollagen type 1 N-terminal propeptide [P1NP], and C-terminal telopeptide of type 1 collagen [CTX]) and the bone remodeling index were investigated. RESULTS: Acromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodeling index than controls (P < .01). Serum SOST, DKK-1, and WIF-1 levels were significantly decreased in patients compared to controls (all P < .01). Serum SOST and WIF-1 levels were negatively correlated with growth hormone levels; SOST levels were positively correlated with WIF-1. After treatment, serum bone turnover markers and the bone remodeling index decreased, while SOST and WIF-1 significantly increased (P < .05). DKK-1 levels did not change compared to baseline (P > .05). In biochemically controlled patients, SOST and WIF-1 levels and bone turnover markers were restored and did not differ from those of the control participants (all P > .05). CONCLUSION: Patients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists is a compensatory mechanism to counteract increased bone fragility in active acromegaly.

The Short-Term Effect of Prunes in Improving Bone in Men.

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between -0.1 and -2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.

Osteocalcin-expressing endothelial progenitor cells and serum osteocalcin forms are independent biomarkers of coronary atherosclerotic disease severity in male and female patients.

PURPOSE: Osteocalcin (OC), an osteoblast-derived regulator of metabolic processes, and circulating early endothelial progenitor cells (EPC, CD34 - /CD133 + /KDR +) expressing OC (OC +) are potential candidates linking bone metabolism and the vasculature and might be involved in vascular atherosclerotic calcification. This study aimed at assessing the association of circulating levels of different OC forms and of EPCs count with disease severity in patients with documented coronary atherosclerosis (CAD). METHODS: Patients (n = 59) undergoing coronary angiography were divided, according to stenosis severity, into (1) early coronary atherosclerosis (ECA) (n = 22), and (2) late coronary atherosclerosis (LCA) (n = 37). Total OC (TOC), carboxylated OC (cOC), undercarboxylated OC (unOC) were quantified by ELISA. EPC OC + count was assessed by flow cytometry. RESULTS: EPC OC + counts showed significant differences between ECA and LCA groups. unOC and unOC/TOC ratio were inversely correlated with EPC OC + count. A significant decrease in TOC and unOC plasma levels was associated with higher cardiovascular risk factors (CVRFs) number. EPC OC + count was correlated with LDL-C, total cholesterol, and triglycerides, with a greater significance in the LCA group. No association between the different forms of circulating OC (TOC, ucOC, cOC) and severity of CAD was found. CONCLUSION: This study showed a significant association between EPCs (CD34 - /CD133 + /KDR + /OC +), CAD severity and CVRFs, suggesting an active role for EPC OC + in the development of CAD. An inverse correlation between TOC, ucOC, and number of CVRFs was observed, suggesting that OC, regardless of its carboxylation status, may be developed as a further cardiovascular risk biomarker.

Sclerostin and bone turnover markers response to cycling and running at the same moderate-to-vigorous exercise intensity in healthy men.

BACKGROUND: Recreational cycling is a popular activity which stimulates and improves cardiovascular fitness. The corresponding benefits for bone are unclear. PURPOSE: This study examined the effect of running (high-impact) vs. cycling (low-impact), at the same moderate-to-vigorous exercise intensity, on markers of bone formation (N-terminal propeptide of type I collagen, PINP) and bone resorption (C-telopeptide of type I collagen, CTX-1), a non-collagenous bone remodeling marker (osteocalcin), as well as bone-modulating factors, including parathyroid hormone (PTH), irisin (myokine) and sclerostin (osteokine). METHODS: Thirteen healthy men (23.7 ± 1.0 y) performed two progressive exercise tests to exhaustion (peak VO2) on a cycle ergometer (CE) and on a treadmill (TM). On subsequent separate days, in randomized order, participants performed 30-min continuous running or cycling at 70% heart rate reserve (HRR). Blood was drawn before, immediately post- and 1 h into recovery. RESULTS: PTH transiently increased (CE, 51.7%; TM, 50.6%) immediately after exercise in both exercise modes. Sclerostin levels increased following running only (27.7%). Irisin increased following both running and cycling. In both exercise modes, CTX-1 decreased immediately after exercise, with no significant change in PINP and osteocalcin. CONCLUSION: At the same moderate-to-vigorous exercise intensity, running appears to result in a greater transient sclerostin response compared with cycling, while the responses of bone markers, PTH and irisin are similar. The longer-term implications of this differential bone response need to be further examined.

BONE FORMATION MARKERS (N-TERMINAL PROPEPTIDE TYPE I PROCOLLAGEN, OSTEOCALCIN AND VITAMIN D) AS EARLY PREDICTORS OF OSTEOPOROSIS IN PATIENTS SUFFERING FROM CHRONIC OBSTRUCTIVE LUNG DISEASE.

The aim of the work was to find out whether markers of bone formation can be early predictors of osteoporosis in patients with COPD. The study involved 66 patients with COPD with disease duration from 10 to 30 years, age 53.59±12.83 years. 37 (66.06%) patients smoked, the pack / year index was (29.08±16.62). According to the results of CAT testing, all patients were divided into 4 clinical groups: GOLD I-IV. The content of serum markers of bone formation was determined: N-terminal procollagen type I propeptide (PINP), osteocalcin and vitamin D depending on the age and severity of COPD. A decrease in all markers of bone formation was found with the age of patients and the severity of COPD. Thus, in patients under 45 years, the P1NP level was 48.75% higher than in patients aged 75 and older (p<0.001). A significant relationship was established between the age of patients and the P1NP level (r= -0.46; p=<0.05). With GOLD I, a decrease in the P1NP content was observed in 40.0% of patients, with GOLD II - 48.0%, GOLD III - in 45.0%, and with GOLD IV, such a decrease was in 66.67% of patients. The level of osteocalcin decreased in patients with COPD of old age compared with the control by 2.72 times and in young people - by 1.88 times. With GOLD I, a decrease in osteocalcin content was observed in 66.67%, with GOLD II - 89.0%, GOLD III - in 85.0%, and with GOLD IV, a decrease was observed in all (100%) patients. The concentration of vitamin D was reduced in all patients with COPD, and severe vitamin D deficiency was diagnosed in 23.08% of patients under 45 years, in 70.59% of elderly patients, in 100% of elderly people. Among the representatives of GOLD IV, the level of vitamin D decreased by 1.75 times as compared with patients with GOLD I. A severe form of vitamin D deficiency was diagnosed in 46.67% of patients with GOLD I, 40.0% in GOLD II, 65.0% in GOLD III, and in 100% of patients with GOLD IV. The data obtained indicate that with increasing age and increasing severity of COPD, the formation of markers of bone tissue formation is inhibited. These processes occur against the background of vitamin D deficiency. As a result of this imbalance, favorable conditions are created for the development of osteoporosis. Considering that the first signs of these disorders, in particular a decrease in the levels of vitamin D and osteocalcin, are diagnosed already with GOLD I, it can be argued that COPD is the leading factor.

Effect of Fermented Soymilk-Honey from Different Probiotics on Osteocalcin Level in Menopausal Women.

Osteoporosis has been discovered to be a risk factor for menopausal women. Although synbiotics (probiotics and prebiotics) are found in fermented soymilk-honey made using local probiotics, their effect on osteocalcin levels is still unknown. Therefore, this study's objective was to determine the influence of fermented soymilk-honey from different probiotics on osteocalcin levels. A 90-day pre-post quasi-experimental study with a control design was conducted on 54 postmenopausal women divided into three intervention groups namely, the soymilk (SM) group, the soymilk-honey fermented with Lactobacillus casei subsp. casei R-68 (SMH Lc) group, and the soymilk-honey fermented with Lactobacillus plantarum 1 R 1.3.2 (SMH Lp) group. Participants consumed 100 mL of soymilk (SM) or fermented soymilk with honey (SMH Lc or SMH Lp) for 90 days. At the beginning and end of the study, the blood serum osteocalcin level was measured and subjects' health status was assessed, such as cholesterol total, random blood glucose, and uric acid levels. Our results presented that in the SMH Lp group, 90 days supplementation of soy-honey milk fermented with Lactobacillus plantarum 1 R 1.3.2 significantly reduced the level of blood serum osteocalcin. Based on these results it is justified to perform more detailed studies on the effect of fermented soy-honey milk on bone health.

Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

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.