Higher Osteocalcin Levels Research Articles

The Effects of Acute and Chronic Alcohol Administration and Withdrawal on Bone Microstructure, Mechanical Strength, and Remodeling Protein Expression and Their Relation to an Antioxidant and FGF23 In Vivo.

Alcohol's detrimental effects on bone health are well established, yet some literature suggests moderate consumption may offer benefits. With alcohol use on the rise, we investigate the impact of acute and chronic alcohol administration, along with withdrawal, on male Wistar rat femurs. We observed a transient cortical thickness increase with acute alcohol (AA) compared to chronic exposure (CA) but no significant changes in trabecular parameters or mechanical properties. High osteocalcin and osteopontin expression levels were noted in AA, alongside elevated RANKL expression. Conversely, CA showed low TRAP levels. FGF23 expression significantly increased during alcohol withdrawal (AW), while GPX decreased after chronic exposure but rose during withdrawal. Although mechanical strength changes were insignificant, biochemical shifts suggest alcohol exposure promotes bone resorption, reduces antioxidant protection, and potentially hampers active vitamin D and phosphate reabsorption via FGF23 upregulation.

Selected osteointegration markers in different timeframes after dental implantation: findings and prognostic value.

The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically healthy persons who needed teeth rehabilitation using dental implants. The conical-shaped implants (CI) and hexagonal implants (HI) were used. The content of Osteopontin (OPN), Osteocalcin (OC), Alkaline Phosphatase (ALP), Osteoprotegerin (OPG), and nitric oxide (NO) was determined in patients' gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF), collected 1, 3, and 6months after implantation. During the 3-6months of observation level of OPN increased in patients with CIs (<50years > 50years) and HIs (<50years) (CI: <50years F = 36.457, p < 0.001; >50years F = 30.104, p < 0.001; HI < 50years F = 2.246, p < 0.001), ALP increased in patients with CIs (<50years: F = 19.58, p < 0.001; >50years: F = 12.01; p = 0.001) and HIs (<50years) (F = 18.51, p < 0.001), OC increased in patients <50years (CI: F = 33.72, p < 0.001; HI: F = 55.57, p < 0.001), but in patients >50years - on the 3days month (CI: F = 18.82, p < 0.001; HI: F = 26.26, p < 0.001), but sharply decreased at the end of sixth month. OPG increased during 1-3months of the observation in patients <50years (CI: F = 4.63, p = 0.037; HI: F = 2.8927, p = 0.046), but at the end of the sixth month returned to the initial level; NO content in PISF increased in patients with CI (>50years) during 1-6months of the observation (F = 27.657, p < 0.001). During the post-implantation period, age-related differences in osteointegration were observed. Patients <50years old had relatively high levels of OPN, ALP, OC, and OPG in PISF, resulting in less alveolar bone destruction around dental implants and more intensive osteointegration. These indicators may be used as biological markers for monitoring implant healing. The process of osseointegration was more intense in CIs due to their comparatively high mechanical loading.

Osteocalcin associates with bone mineral density and VDR gene polymorphisms in type 1 and type 2 diabetes.

Bone metabolism is impaired in diabetes mellitus (DM). Our objective is to evaluate the association of bone turnover markers (BTM) and vitamin D receptor (VDR) gene polymorphisms with bone mineral density (BMD) in DM type 1 (T1D) and DM type 2 (T2D). A total of 165 patients (53 T1D and 112 T2D) were enrolled. BMD was measured by dual-energy X-ray absorptiometry (DEXA). Plasma osteocalcin (OC), beta-CrossLaps (β-CTX) and N-amino terminal propeptide of type I collagen (P1NP) and VDR gene polymorphisms were evaluated. Participants were 53 T1D (41 years [31-48]) and 112 T2D (60 years [51-66]). BMD were not statistically different between the groups. OC (p<0.001) and P1NP levels (p<0.001) were higher in patients with T1D. The areas under the curve for the prediction of bone pathology were 0.732 (p=0.038) for OC in T1D and 0.697 (p=0.007) in T2D. A significant association was found between lower lumbar BMD and the A allele of BsmI (p=0.03), the A allele of ApaI (p=0.04) and the allele C of the Taql (p=0.046). Also, a significant correlation was found with higher OC levels and the G allele of BsmI (p=0.044), C allele of ApaI (p=0.011), T allele of Taql (p=0.006) and with C allele of FokI (p=0.004). The high negative predictive value of the cut-off point for OC suggests that could be useful in excluding the risk suffering bone loss, allowing offering a personalized clinical approach to prevent this pathology.

The Relationship Between Bone Metabolism and Peripheral Artery Disease in Patients on Hemodialysis: The Potential Role of Osteocalcin.

To examine the factors associated with PAD, with a specific focus on bone metabolism factors such as osteocalcin. This cross-sectional study examined factors about demographic, clinical, and laboratory parameters including bone metabolism biomarkers in hemodialysis patients. The ankle-brachial index (ABI) was measured in all patients, with PAD diagnosed as an ABI <0.9. Out of the 71 patients, PAD was found in 23 individuals. These patients had an average age of 63.5±13.0 years, with 59.2% being male. Compared to non-PAD patients, those with PAD were older, had a lower proportion of males, and had a higher prevalence of diabetes and coronary artery disease. Among the factors related to bone metabolism, only osteocalcin exhibited a significant increase in the PAD group compared to the non-PAD group. PAD in patients on hemodialysis was independently linked to high levels of osteocalcin in the bloodstream, indicating the presence of bone metabolism disorders.

Relevant Aspects of Titanium Topography for Osteoblastic Adhesion and Inhibition of Bacterial Colonization.

The influence of the surface topography of dental implants has been studied to optimize titanium surfaces in order to improve osseointegration. Different techniques can be used to obtain rough titanium, however, their effect on wettability, surface energy, as well as bacterial and cell adhesion and differentiation has not been studied deeply. Two-hundred disks made of grade 4 titanium were subjected to different treatments: machined titanium (MACH), acid-attacked titanium (AE), titanium sprayed with abrasive alumina particles under pressure (GBLAST), and titanium that has been treated with GBLAST and then subjected to AE (GBLAST + AE). The roughness of the different treatments was determined by confocal microscopy, and the wettability was determined by the sessile drop technique; then, the surface energy of each treatment was calculated. Osteoblast-like cells (SaOs-2) were cultured, and alkaline phosphatase was determined using a colorimetric test. Likewise, bacterial strains S. gordonii, S. oralis, A. viscosus, and E. faecalis were cultured, and proliferation on the different surfaces was determined. It could be observed that the roughness of the GBLAST and GBLAS + AE was higher, at 1.99 and 2.13 μm of Ra, with respect to the AE and MACH samples, which were 0.35 and 0.20 μm, respectively. The abrasive treated surfaces showed lower hydrophilicity but lower surface energy. Significant differences could be seen at 21 days between SaOS-2 osteoblastic cell adhesion for the blasted ones and higher osteocalcin levels. However, no significant differences in terms of bacterial proliferation were observed between the four surfaces studied, demonstrating the insensitivity of bacteria to topography. These results may help in the search for the best topographies for osteoblast behavior and for the inhibition of bacterial colonization.

Three-Dimensional Analysis of the Trapezium Subchondral Bone and its Association with Trapeziometacarpal Joint Osteoarthritis.

Subchondral bone properties are associated with the pathogenesis of osteoarthritis (OA), but this relationship has not been confirmed in the trapeziometacarpal joint (TMCJ). We aimed to evaluate the thickness (SBT) and density (SBD) of three-dimensional (3D) trapezium subchondral bone models derived from computed tomography (CT) images, and their relationships with early-stage TMCJ OA. We reviewed patients with a distal radius fracture who underwent conventional CT scans and such osteoporosis evaluations as bone mineral density (BMD) and bone turnover markers (BTMs). From 3D trapezium subchondral bone models, we measured SBT and SBD according to the OA stage and performed multivariate analyses to evaluate their associations with age, sex, body mass index, BMD, and BTMs. As results, a total of 156 patients (78 men and 78 age-matched women; mean age, 67 ± 10years) were analyzed. There were 30 (19%) with grade 0, 71 (45%) with grade 1, 13 (8%) with grade 2, and 42 (27%) with grade 3 TMCJ OA. SBT was significantly lower in patients with grade 1 OA than those with grade 0 or grade 3 OA, but SBD generally increased according to the OA severity. Low SBT was associated with low BMD, and low SBD with low BMD, high osteocalcin levels, and severe OA grades. In conclusion, patients with early-stage radiographic TMCJ OA have a lower SBT at the trapezium, which may support the potential role of subchondral bone in OA pathogenesis. This study also shows that subchondral bone properties are associated with BMD and osteocalcin levels.

Abstract 13214: Circulating Progenitor Cells Are Associated With Bioprosthetic Aortic Valve Deterioration

Introduction: Mechanisms underlying bioprosthetic valve deterioration (BVD) are multifactorial and incompletely elucidated. Reparative circulating progenitor cells (CPCs), and conversely calcification-associated osteocalcin expressing CPCs (CPC-OCN), have been linked to native aortic valve deterioration. However, their role in BVD remains elusive. This study sought to evaluate the contribution of different subpopulations of CPCs in BVD. Methods: This prospective study enrolled 121 patients who had peripheral blood mononuclear cells (PBMC) isolated prior to bioprosthetic aortic valve replacement (surgical 104, transcatheter 17) and had an echocardiographic follow-up ≥2 years after the procedure. Using flow cytometry, fresh PBMC were analyzed for the surface markers CD34, CD133, and osteocalcin (OCN). BVD was evaluated by hemodynamic valve deterioration (HVD) using echocardiography, which was defined as an elevated mean transprosthetic gradient ≥30mmHg and/or at least moderate intraprosthetic regurgitation. Multivariable models were constructed to evaluate the association of each subpopulation of CPCs and other clinical characteristics with HVD. Results: Sixteen patients (13.2%) developed HVD during follow-up for a median of 5.9 years. Patients with HVD showed significantly lower levels of reparative CD34 + CD133 + cells and higher levels of OCN + cells than those without HVD (CD34 + CD133 + cells: 125 [80, 210] vs 270 [130, 420], P=0.002; OCN + cells: 3060 [523, 5528] vs 670 [180, 1930], P=0.005 respectively). Decreased level of CD34 + CD133 + cells was a significant predictor of HVD. Conclusions: Circulating levels of CD34 + CD133 + cells and OCN + cells were significantly associated with the subsequent occurrence of HVD in patients undergoing bioprosthetic aortic valve replacement. CPCs might play a vital role in the mechanism, risk stratification and a potential therapeutic target for patients with bioprosthetic valve deterioration.

Impact of Vitamin D Elements and Osteoporosis Factors in Postmenopausal Iraqi Women with T2DM

Osteoporosis is a systematic bone disorder characterized by bone mass loss and bone tissue architectural degeneration. The incidence of osteoporosis in women increases with age, reflecting the considerable increase in bone loss rate in postmenopausal women once estrogen loses its protective influence. The purpose of this study was to determine the levels of Osteocalcin, Vitamin D, and other parameters that influence bone quality and increased bone fragility in postmenopausal Iraqi women with type 2 diabetes mellitus (T2DM). The levels of vitamin D receptor and vitamin D binding protein in serum are studied for the first time in our study. The present study included 89 postmenopausal women aged 50-70 years old, 62 T2DM patients, and 27 controls. Ten of the T2DM patients were considered osteoporotic, 28 were considered osteopenia, and 22 were normal; this classification is according to the WHO criterion. After matching for body mass index (BMI) and age for patients and controls, results show a significant difference in serum Osteocalcin, vitamin D, and vitamin D binding protein levels in patients compared to controls. In our study, diabetic patients appear with high levels of Osteocalcin, vit.D, and vitamin D binding protein compared with non-diabetic control. The processes underlying diabetes mellitus-induced skeletal problems are unknown. Anti-diabetic medications might have an adverse or favorable effect on bone metabolism. The study concludes that managing skeletal health in postmenopausal women entails screening fracture risk factors, lowering modifiable risk variables through dietary and lifestyle modifications, and using a pharmacologic treatment for individuals at high risk of osteoporosis or fracture. Women with osteoporosis must be managed for the rest of their lives.

Circulating osteocalcin is associated with time in range and other metrics assessed by continuous glucose monitoring in type 2 diabetes

BackgroundOsteocalcin, a protein secreted mainly by mature osteoblasts, has been shown to be involved in glucose metabolism through various pathways. However, few studies has explored the association between osteocalcin and Time in range (TIR). Continuous glucose monitoring (CGM) -derived metrics, such as TIR and other indexes have been gradually and widely used in clinical practice to assess glucose fluctuations. The main purpose of this study was to investigate the correlation between osteocalcin and indexes from CGM in patients with type 2 diabetes mellitus (T2DM).MethodThe total number of 376 patients with T2D were enrolled, all of them performed three consecutive days of monitoring. They were divided into four groups on account of the quartile of osteocalcin. Time in range, Time below range (TBR), Time above range(TAR) and measures of glycemic variability (GV) were assessed for analysing. After a 100 g standard steamed bread meal, blood glucose (Glu0h Glu0.5 h, Glu1h, Glu2h, GLu3h), C-peptide (Cp0h, Cp0.5 h, Cp1h, Cp2h, Cp3h), serum insulin (INS0h, INS0.5 h, INS1h, INS2h, INS3h) concentrations at different time points were obtained. HOMA-IS, HOMA-βwas calculated to evaluate insulin sensitivity and insulin secreting of the participants.ResultsPatients with higher osteocalcin level had higher TIR (P < 0.05). Spearman correlation analysis showed that osteocalcin was positively correlated with TBR (although the P value for TBR was greater than 0.05) (r = 0.227, P < 0.001 r = 0.068, P = 0.189) and negatively correlated with TAR (− 0.229, P < 0.001). Similarly, there was a negative correlation between osteocalcin and glycemic variability (GV) indicators, including SD, MBG, MODD, ADDR, and MAGE (P value of MAGE > 0.05). Multiple stepwise regression showed that osteocalcin was an independent contributor to TIR, TAR and HOMA-IS.ConclusionCirculating osteocalcin is positively correlated with TIR and negatively correlated with MODD, ADDR, and MAGE. Osteocalcin may have a beneficial impact on glucose homeostasis in T2DM patients.

Chinese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease have lower serum osteocalcin levels compared to individuals with type 2 diabetes mellitus and no liver disease: a single-center cross-sectional study.

Osteocalcin may benefit nonalcoholic fatty liver disease (NAFLD). The present study aimed to explore the levels of serum osteocalcin in NAFLD in patients with type 2 diabetes mellitus (T2DM). In total, 1026 inpatients diagnosed with T2DM were enrolled in the study. NAFLD was defined according to the working definition of the revised guidelines for the management of NAFLD published by the Chinese Liver Disease Association, and confirmed by abdominal ultrasonography. The current study found a NAFLD prevalence of 54% in the T2DM population. Subjects with NAFLD had lower concentrations of osteocalcin (8.28-13.99ng/mL vs. 8.80-16.25ng/mL, P = 0.001) but similar vitamin D, parathyroid hormone, beta-C-terminal telopeptide of type I collagen and procollagen type 1 N-peptide levels. Osteocalcin levels (OR: 0.956; 95% CI 0.926-0.987) were significantly associated with NAFLD. When all significant clinical indicators were analyzed together, increased BMI (OR: 1.120; 95% CI 1.065-1.178), fasting C-peptide (OR: 1.270; 95% CI 1.089-1.481) and triglycerides (OR: 1.661; 95% CI 1.284-2.148) were associated with a greater risk of NAFLD, while older age (OR: 0.967; 95% CI 0.948-0.986) and high osteocalcin levels (OR: 0.935; 95% CI 0.902-0.969) were related with a decreased risk of NAFLD. For every additional unit of osteocalcin, the patients received 7% deduced odds of NAFLD. Low osteocalcin levels were associated with an increased risk for NAFLD in patients with T2DM.

Serum bone metabolism biomarkers in healthy filies and colts from weaning until one year of age

This study aimed to investigate the serum concentration of osteocalcin (OC), parathyroid hormone (PTH), calcitonin (CT), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and acid phosphatase (AP) in healthy-weaned-foals from 8 months of age until the first year of life. Moreover, the correlation of investigated parameters and foals' age, as well as the relationship between the serum values of PTH and the other markers of bone remodeling were assessed. From 20 foals (10 fillies, 10 colts), blood samples were monthly collected (from 8 to 12 months of age, T1-T5) and the concentration of OC, CT, Ca, P, ALP, AP and PTH was assessed. Two-way repeated measures analysis of variance (ANOVA) showed age-related differences on OC concentration in both fillies (P = 0.008) and colts (P = 0.03) with higher OC values at T5 than T1 and T2. Sex-related effect on OC concentration was found with higher OC levels in colts compared to fillies (P = 0.01). A significant positive correlation between the OC, PTH, CT and APL values and foal's age was found in fillies and colts. PTH levels were positively correlated with the values of OC in fillies and colts. Obtained findings confirmed the dynamic bone turnover during growth in foals. The modification of PTH and OC confirmed the potential role of these parameters as indicator of bone growth and metabolism. The sex-related difference observed in OC concentration opens up new insights into the possible involvement of sex hormones in the regulation of bone metabolism in prepubertal foals.

THE RELATIONSHIP BETWEEN THE DISTRIBUTION OF BODY FAT AND THE LEVEL OF OSTEOCALCIN IN CHINESE ADOLESCENTS

Objective: Current studies on body fat distribution and bone metabolism in adolescents are very limited. This study aimed to examine the relationship between the body fat distribution and serum osteocalcin levels in adolescents. Design and method: A total of 1068 subjects (564 boys,52.8%) aged 12–18 years from Ningxia were randomly selected through a stratified cluster sampling. Serum osteocalcin levels were measured by ELISA. An automatic bioelectric impedance analysis (BIA) was used to measure body compositions, which included body fat mass(BFM),trunk fat mass(TFM),limbs fat mass(LFM),visceral fat level(VFL). Results: In the total population, serum osteocalcin levels were negatively correlated with BFM, TFM, LFM, and fat mass percentage (FMP) (r = -0.076, -0.066, -0.094 and -0.117, respectively, all P &lt; 0.05); Serum osteocalcin levels were positively correlated with limb fat mass percentage (LFMP) (r = 0.167, P &lt; 0.001). Logistic regression analysis showed that the odds ratios (ORs) of FMP in the third and second quintiles suggesting high levels of osteocalcin is 0.28 (95% confidence interval [CI],0.13—0.57) and 0.44(95% CI, 0.25—0.76) compared with the lowest quartile level among total population, respectively. Additionally, the corresponding ORs for high levels of osteocalcin were 0.2 (95%CI, 0.05–0.72) in the fourth quantile of FMP,0.21 (95%CI, 0.08–0.55) in the third quantile of FMP and 0.45(95% CI, 0.25–0.82) in the second quantile of FMP in boys, respectively. Compared with the reference subgroup, the fourth quantile level of LFMP could better predict high osteocalcin levels between boys and girls, and the ORs were 7.46 (95%CI, 2.79—19.96) and 2.60(95%CI: 1.36—4.96), respectively. Conclusions: FMP have a negative impact on bone resorption in in Chinese adolescents, especially in boys. However, LFMP has a protective effect on bone metabolism between Chinese boys and girls.

Consistently Low Levels of Osteocalcin From Late Pregnancy to Postpartum Are Related to Postpartum Abnormal Glucose Metabolism in GDM Patients.

ObjectiveIncreasing evidence suggests that osteocalcin (OC), a marker of bone formation, plays an important role in glucose homoeostasis. Few studies have investigated the relationship between OC levels in gestational diabetes mellitus (GDM) patients and their postpartum glucose metabolism. This study evaluated the relationship between OC levels in late pregnancy, their longitudinal changes, and postpartum glucose metabolism among GDM patients.MeasuresSerum OC was measured in late pregnancy and the postpartum period for 721 GDM patients. All patients underwent a 75-g oral glucose tolerance test (OGTT) at 6–8 weeks postpartum. According to postpartum OGTT outcomes, patients were categorized into abnormal glucose metabolism (AGM) (n=255) and normal glucose tolerance (NGT) groups (n=466). Glucose metabolism-related indices were measured and calculated. Logistic regression analysis and linear mixed-effects model were used to assess the association between OC and postpartum AGM.ResultsIn late pregnancy, OC levels were lower in the AGM group than in the NGT group (13.93 ± 6.90 vs 15.33 ± 7.63 ng/ml, P=0.015). After delivery, OC levels increased in both groups. However, OC levels remained lower in the AGM group than in the NGT group (23.48 ± 7.84 vs 25.65 ± 8.37 ng/ml, P=0.001). Higher OC levels in late pregnancy were associated with decreased risk of progressing to postpartum AGM (OR:0.96, 95%CI:0.94–0.99). Linear mixed-effects analysis showed that postpartum AGM patients exhibited consistently lower OC levels than NGT group from late pregnancy to the postpartum period after adjustment for cofactors (β=-1.70, 95% CI: -2.78– -0.62). ConclusionsIn GDM patients, consistently low levels of OC from late pregnancy to postpartum were associated with increased postpartum AGM risk. The increase in serum OC may act as a protective factor to curb the progression of AGM at postpartum for GDM patients.

Osteocalcin and Risks of Incident Diabetes and Diabetic Kidney Disease: A 4.6-Year Prospective Cohort Study.

OBJECTIVEWe aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD).RESEARCH DESIGN AND METHODSWe followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD.RESULTSDuring a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of loge-transformed OC 0.51 [95% CI 0.35–0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44–0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of loge-transformed OC 0.49 [95% CI 0.33–0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38–0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed.CONCLUSIONSLower OC levels were associated with an increased risk of incident diabetes and DKD.

Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment.

ARHGAP21 is a member of the RhoGAP family of proteins involved in cell growth, differentiation, and adhesion. We have previously shown that the heterozygous Arhgap21 knockout mouse model (Arhgap21+/−) presents several alterations in the hematopoietic compartment, including increased frequency of hematopoietic stem and progenitor cells (HSPC) with impaired adhesion in vitro, increased mobilization to peripheral blood, and decreased engraftment after bone marrow transplantation. Although these HSPC functions strongly depend on their interactions with the components of the bone marrow (BM) niche, the role of ARHGAP21 in the marrow microenvironment has not yet been explored. In this study, we investigated the composition and function of the BM microenvironment in Arhgap21+/− mice. The BM of Arhgap21+/− mice presented a significant increase in the frequency of phenotypic osteoblastic lineage cells, with no differences in the frequencies of multipotent stromal cells or endothelial cells when compared to the BM of wild type mice. Arhgap21+/− BM cells had increased capacity of generating osteogenic colony-forming units (CFU-OB) in vitro and higher levels of osteocalcin were detected in the Arhgap21+/− BM supernatant. Increased expression of Col1a1, Ocn and decreased expression of Trap1 were observed after osteogenic differentiation of Arhgap21+/− BM cells. In addition, Arhgap21+/− mice recipients of normal BM cells showed decreased leucocyte numbers during transplantation recovery. Our data suggest participation of ARHGAP21 in the balanced composition of the BM microenvironment through the regulation of osteogenic differentiation.

Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women. Its early diagnosis seems to have a significant impact on the developing fetus, the course of delivery, and the neonatal period. It may also affect the later stages of child development and subsequent complications in the mother. Therefore, the crux of the matter is to find a biopredictor capable of singling out women at risk of developing GDM as early as the very start of pregnancy. Apart from the well-known molecules with a proven and clear-cut role in the pathogenesis of GDM, e.g., adiponectin and leptin, a potential role of newer biomolecules is also emphasized. Less popular and less known factors with different mechanisms of action include: galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, fatty acid-binding protein 4 (FABP4), fibroblast growth factor 21, and lipocalin-2. The aim of this review is to present the potential and significance of these 13 less known biomolecules in the pathogenesis of GDM. It seems that high levels of FABP4, low levels of irisin, and high levels of under-carboxylated osteocalcin in the serum of pregnant women can be used as predictive markers in the diagnosis of GDM. Hopefully, future clinical trials will be able to determine which biomolecules have the most potential to predict GDM.

Остеопонтин та остеокальцин при раку легенів

Актуальність. Рак легенів (РЛ) займає лідуючу позицію в структурі онкологічної захворюваності та є однією з провідних причин смерті від онкозахворювань. Пошук ефективних підходів до оцінки перебігу РЛ з використанням інформативних критеріїв є актуальним завданням сучасної онкології. РЛ зазвичай перебігає з підвищеним рівнем у крові остеопонтину (ОР) та остеокальцину (ОС), що має прогностичну значущість у рамках виживання хворих. Сироватковий вміст цих остеоонкомаркерів прямо асоціюється з наявністю у хворих метастазів і з високими темпами прогресування захворювання, але ці дані вимагають подальшого уточнення. Мета дослідження: оцінити клініко-патогенетичну й прогностичну значущість ОР та ОС у хворих із різними варіантами перебігу РЛ. Матеріали та методи. Обстежено 115 хворих на РЛ віком від 24 до 80 років (у середньому 58 років), серед яких було 78 % чоловіків і 22 % жінок. Жоден пацієнт раніше не був прооперований із приводу РЛ і до обстеження не отримував радіохіміотерапію. Дрібноклітинний гістологічний варіант РЛ встановлений у 17 % від числа хворих, недрібноклітинний — у 83 %. Імуноферментним аналізом вивчали в сироватці крові показники ОР, ОС і судинного ендотеліального фактору росту (VEGF). Результати. У хворих на РЛ збільшуються в сироватці крові показники онкоостеоасоційованих маркерів OP та OC, що спостерігається відповідно в 99 і 98 % випадків. Зміни ОР і ОС пов’язані з формою захворювання, гістологічним його варіантом, ступенем диференціації, інтегральною тяжкістю перебігу РЛ, характером ускладнень первинної пухлини й особливостями метастазування. Високий рівень маркерів у крові мало впливає на трирічне виживання пацієнтів, а прогнознегативними критеріями відносно перебігу РЛ є параметри ОР. Показники ОР і ОС у крові між собою прямо корелюють, а вміст ОР, окрім того, має позитивні співвідношення з таким пухлинним маркером, як VEGF, що належить до стимуляторів неоангіогенезу. Метастатичне ураження скелету й розвиток порушень мозкового кровообігу внаслідок подальшої радіохіміотерапії прямо пов’язані з високою концентрацією в крові ОР, який також є чинником ризику інших ускладнень лікування. Висновки. Підвищені рівні в крові ОР і ОС мають важливе клініко-патогенетичне значення при РЛ, а вивчення показників цих остеоонкомаркерів сприятиме ранній діагностиці окремих ознак перебігу захворювання, підвищенню якості оцінки метастазування в кістково-суглобовий апарат і прогнозуванню можливих ускладнень радіохіміотерапії.

Кальцитонин, остеокальцин и остеопонтин при раке легкого

Актуальность. Маркерами рака легкого являются низкие уровни в крови гормона кальцитонина, а высокие показатели белков остеокальцина и остеопонтина, связанные между собой, отражают процессы костного метастазирования и обладают прогностической значимостью. Цель исследования: оценить уровни в крови кальцитонина, остеокальцина и остеопонтина, факторы, их определяющие, характер взаимосвязей и прогностическую роль в костном метастазировании при разных вариантах течения рака легкого. Материалы и методы. Обследованы 86 больных раком легкого в возрасте от 24 до 80 лет (в среднем 58 лет), среди которых было 84 % мужчин и 16 % женщин. Центральная форма рака имела место в 81 % наблюдений, периферическая — в 19 %. Мелкоклеточный гистологический вариант заболевания установлен у 21 % от числа больных, немелкоклеточный — у 79 %, в том числе аденокарцинома — у 38 %, плоскоклеточная карцинома — у 35 %, крупноклеточная карцинома — у 6 %. IIIA стадия опухолевого процесса отмечена в 12 % случаев, IIIB — в 21 %, IV — в 67 %. Результаты. Рак легкого сопровождается уменьшением в крови у 20 % больных остеоассоциированного гормона кальцитонина на фоне повышения концентраций опухолевых маркеров остеокальцина и остеопонтина (соответственно в 76 и 79 % наблюдений), что тесно связано с морфологическим вариантом (мелко- и немелкоклеточный), стадийностью и тяжестью течения патологического процесса, определяет развитие компрессионного синдрома, прорастание опухоли в грудную стенку, метастазирование в лимфатические узлы и кости, возникновение осложнений химиорадиотерапии в виде лучевого пневмофиброза, легочной гипертензии и миелодепрессии, а показатели остеокальцин- и остеопонтинемии обратно коррелируют с продолжительностью жизни больных. Выводы: кальцитонин, остеокальцин и остеопонтин при раке легкого являются маркерами тяжести течения заболевания, отражают метастазирование опухолевого процесса в скелет и обладают прогностической значимостью.

MO586RISK OF OSTEOPOROSIS IN OBESE PATIENTS WITH TYPE 2 DIABETES: A SYSTEMIC REVIEW AND META-ANALYSIS

Abstract Background and Aims The aim of this study is to evaluate the alterations in bone marrow density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control. Method We searched four electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide (CTX) level and parathyroid hormone (PTH) level. Results Three randomized clinical trials and two observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: -2.90, 95% CI: -2.99∼-2.81, p&amp;lt;0.00001 )and total hip BMD loss (mean difference: -5.81, 95% CI: -9.22∼-2.40, p=0.0008). As to biochemical markers of bone metabolism, we found signifcantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57∼13.75, p&amp;lt;0.00001). However, higher CTX level and PTH level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11∼0.48, p=0.002; mean difference: 1.56, 95% CI: 0.84∼2.27, p&amp;lt;0.0001). Conclusion RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of peri-operative and post-surgical supplementation should be evaluated.

Influence of Age and Phylogenetic Background on Blood Parameters Associated With Bone Metabolism in Laying Hens

The high laying performance of today’s laying hens places enormous demands on their mineral metabolism. While up-to-date data are rare, the present study aimed to describe blood parameters associated with egg laying and bone metabolism during the pre-laying period, in the course of the laying period and the daily egg laying cycle. Ten to 15 laying hens of two high-performing, phylogenetically divergent lines (BLA: brown-egg layer; WLA: white-egg layer), kept in single cages were blood sampled at 17, 25, 29, 49, and 69 weeks of age. Sampling was made at 6 a.m., 10 a.m., 2 p.m. and, with the exception of week 17, 6 p.m. Blood samples were analyzed for concentrations of total and ionized calcium, inorganic phosphate (PO4), markers of bone formation (osteocalcin) and resorption [carboxyterminal crosslinked telopeptide of type I collagen (CTX-I)], 25-hydroxycholecalciferol (25(OH)D3) and estradiol-17β. In the pre-laying period (17 week), the estradiol-17β level calculated for WLA was more than twice as high as the level calculated for BLA, while no significant difference could be observed in the laying period (25 to 69 weeks). BLA hens had significantly higher total calcium concentrations at 49 weeks of age as well as up to twice as high levels of osteocalcin and 25(OH)D3 than WLA at any time of the day from 25 to 69 weeks of age. While osteocalcin, CTX-I and 25(OH)D3 concentrations were significantly higher before the onset of lay, total calcium and estradiol-17β levels significantly increased from 17 to 69 weeks of age. In contrast, PO4 values varied only slightly during the experimental period and ionized calcium was highest at 17 and 49 weeks of age and lowest around peak production (29 week). In the course of the daily egg laying cycle blood concentrations clearly reflected the stage of egg formation. Our results provide up-to-date data of bone- and egg laying-associated blood parameters of two contemporary purebred layer lines over the course of the pre- and egg-laying period and the daily egg laying cycle. Differences between brown- and white-egg layers raise questions, whether phylogenetic background determines their efficiency to cope with high calcium demands relating to egg production.