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PloS One 2015To investigate whether total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC) and percentage of uncarboxylated osteocalcin (%ucOC) are associated with the risk of...
OBJECTIVE
To investigate whether total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC) and percentage of uncarboxylated osteocalcin (%ucOC) are associated with the risk of type 2 diabetes.
METHODS
This nested case control study included 1,635 participants, 833 incident diabetes cases and 802 non-diabetic control participants, aged 21-70 years from the EPIC-NL cohort. Baseline concentrations of tOC, ucOC and %ucOC were assessed. During 10 years of follow-up, diabetes cases were self-reported and verified against information from general practitioners or pharmacists. The association between the different forms of osteocalcin and diabetes risk was assessed with logistic regression adjusted for diabetes risk factors (waist circumference, age, sex, cohort, smoking status, family history of diabetes, hypertension, alcohol intake, physical activity and education) and dietary factors (total energy intake and energy adjusted intake of fat, fiber, protein and calcium).
RESULTS
TOC concentration was not associated with diabetes risk, with an odds ratio (OR) of 0.97 (0.91-1.03) for each ng/ml increment after adjustment for diabetes risk factors and dietary factors. No association between ucOC and %ucOC and the risk of diabetes was observed either. In sex stratified analyses (P interaction = 0.07), higher %ucOC tended to be associated with an increased risk of type 2 diabetes in a multivariable model in women (OR 1.05 for each increment of 5% ucOC (1.00-1.11), Ptrend = 0.08), but not in men (OR 0.96 for each increment of 5% ucOC (0.88-1.04)). When waist circumference was replaced by body mass index, none of the osteocalcin forms were associated with the risk of type 2 diabetes in the final model among both women and men.
CONCLUSIONS
Available evidence suggests that tOC, ucOC and %ucOC are each not associated with the risk of type 2 diabetes. However, more large-scale cohort studies are needed to clarify the presence of any association between the different forms of osteocalcin and the risk of type 2 diabetes.
Topics: Adult; Aged; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Osteocalcin; Prospective Studies; Risk Factors; Surveys and Questionnaires; Young Adult
PubMed: 26418005
DOI: 10.1371/journal.pone.0138693 -
Journal of Biomechanics Oct 2018Non-collagenous proteins are a vital component of bone matrix. Amongst them, osteocalcin (OC) and osteopontin (OPN) hold special significance due to their intimate...
Non-collagenous proteins are a vital component of bone matrix. Amongst them, osteocalcin (OC) and osteopontin (OPN) hold special significance due to their intimate interaction with the mineral and collagenous matrix in bone. Both proteins have been associated with microdamage and fracture, but their structural role in energy dissipation is unclear. This study used bone tissue from genetic deficient mice lacking OC and/or OPN and subjected them to a series of creep-fatigue-creep tests. To this end, whole tibiae were loaded in four-point bending to 70% stiffness loss which captured the three characteristic phases of fatigue associated with initiation, propagation, and coalescence of microdamage. Fatigue loading preceded and followed creep tests to determine creep and dampening parameters. Microdamage in the form of linear microcracks and diffuse damage were analyzed by histology. It was shown that OC and OPN were 'activated' following stiffness loss associated with fatigue damage where they facilitated creep and dampening parameters (i.e. increased energy dissipation). More specifically, post-fatigue creep rate and dampening were significantly greater in wild-types (WTs) than genetic deficient mice (p < 0.05). These results were supported by microdamage analysis which showed significant increase in creep-associated diffuse damage formation in WTs compared to genetic deficient groups (p < 0.05). Based on these findings, we propose that during local yield events, OC and OPN rely on ionic interactions of their charged side chains and on hydrogen bonding to dissipate energy in bone.
Topics: Animals; Bone and Bones; Fractures, Bone; Genotype; Hindlimb; Hydrogen Bonding; Male; Materials Testing; Mice; Mice, Inbred C57BL; Mice, Knockout; Minerals; Osteocalcin; Osteopontin; Tibia
PubMed: 30205977
DOI: 10.1016/j.jbiomech.2018.08.014 -
Journal of Medicine and Life Jun 2013Lately, the in vitro and in vivo studies on serotonin metabolism pointed their influence in bone health. In addition, there are no particular recommendations in...
INTRODUCTION
Lately, the in vitro and in vivo studies on serotonin metabolism pointed their influence in bone health. In addition, there are no particular recommendations in performing the serum serotonin assessment in order to evaluate the skeletal status. Aim. We aimed to correlate the bone turnover markers and lumbar bone mineral density (BMD) with serotonin.
MATERIAL AND METHODS
There is a cross-sectional study in Caucasian postmenopausal women. They were not diagnosed with carcinoid syndrome, or bone anomalies, and received no treatment (including antiresorptives). We performed the bone formation markers: serum alkaline phosphatase (AP), serum osteocalcin (OC), and the bone resorption marker: serum CrossLaps (CL). Serum serotonin (high-pressure liquid chromatography), as well as central DXA (GE Prodigy) were assessed.
RESULTS
191 women of 57.1 years mean age were grouped according to DXA (WHO criteria). The linear regression analysis between serum serotonin and CL was not statistically significant (SS), between serotonin and OC was SS in the newly diagnosed osteoporosis group (N=40, r=0.4, p=0.03), between serotonin and AP we found SS in osteopenia group (N=88, r=0.24, p=0.03), with no changes when adjusting for age and BMI. The partial correlation between serotonin and BMD was not SS.
DISCUSSION
The study raises the question of serotonin as a bone metabolism marker seeing that the results were not consistent. The main limit of our study is that we did not analyze the possible use of antidepressants by these women. Overall, this is a pilot study in clinical practice in which few reports have been published yet, but still necessary because the use of serum serotonin in current skeletal evaluation is still unclear.
Topics: Absorptiometry, Photon; Adult; Aged; Alkaline Phosphatase; Bone Density; Cross-Sectional Studies; Female; Humans; Middle Aged; Osteocalcin; Serotonin
PubMed: 23904874
DOI: No ID Found -
BioMed Research International 2017Osteocalcin (Ocn) and testosterone play important roles in male skeleton. However, the concentrations of serum osteocalcin and testosterone have never been... (Meta-Analysis)
Meta-Analysis
Osteocalcin (Ocn) and testosterone play important roles in male skeleton. However, the concentrations of serum osteocalcin and testosterone have never been systematically compared between populations with and without primary male osteoporosis, a common skeletal disorder in adult males. We searched the PubMed, Embase, and Cochrane Library for relevant studies. A meta-analysis was performed to compare the serum osteocalcin and testosterone concentrations between primary osteoporotic males and age-matched nonosteoporotic (non-OP) males. Five case-control studies with 300 adult males were included. We found no significant difference between cases and controls in serum total osteocalcin (TOcn) [95% confidence interval (CI): -1.25, 1.31; = 0.96] and total testosterone (TT) concentrations [95% CI: -0.88, 4.22; = 0.20]. The level of evidence of this carefully performed meta-analysis is 3a according to Oxford (UK) CEBM Levels of Evidence. Future well-designed studies with larger sample size and better standardization of Ocn assay are awaited to confirm and update our current findings.
Topics: Adult; Aged; Case-Control Studies; Humans; Male; Middle Aged; Osteocalcin; Osteoporosis; Testosterone
PubMed: 28831400
DOI: 10.1155/2017/9892048 -
Medicine Oct 2023To systematically evaluate the correlation between serum osteocalcin levels and cognitive function status in type 2 diabetes mellitus (T2D) patients. (Meta-Analysis)
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.
Topics: Humans; Case-Control Studies; Cognition; Diabetes Mellitus, Type 2; Functional Status; Osteocalcin
PubMed: 37832077
DOI: 10.1097/MD.0000000000034440 -
Scientific Reports Dec 2018Stress fractures are a limitation for athletes not only in sports performance but in activities of daily living. Thus, preventing them is crucial. In female athletes, a...
Elevated Creatine Kinase and Lactic Acid Dehydrogenase and Decreased Osteocalcin and Uncarboxylated Osteocalcin are Associated with Bone Stress Injuries in Young Female Athletes.
Stress fractures are a limitation for athletes not only in sports performance but in activities of daily living. Thus, preventing them is crucial. In female athletes, a triad of symptoms including low energy availability, functional hypothalamic amenorrhea and osteoporosis are considered risk factors for stress injuries, but biomarkers predictive of these outcomes are not available. Here, we evaluated 56 female university athletes and found that 13 had a history of stress bone injuries. Logistic regression analysis demonstrated that dysmenorrhea including amenorrhea, but not reduced food intake or body weight loss, was significantly associated with stress injuries. When we subdivided subjects into stress fracture and non-fracture groups, we found that serum levels of creatine kinase (CK) and lactic acid dehydrogenase (LDH) were significantly higher in the fracture group, while osteocalcin and uncarboxylated osteocalcin (ucOC), which are bone forming parameters, significantly decreased. Low vitamin D levels are associated with stress fractures, but serum vitamin D levels were higher in fracture compared to non-fracture subjects. We followed up 32 subjects for one year, and three exhibited new stress injuries during that period. A history of stress fracture history is significantly associated with experiencing a new stress fracture. We also found that subjects with new fracture performed significantly greater exercise activity than did non-fracture subjects. Taken together, our data indicate that increased serum CK and LDH and decreased serum osteocalcin and ucOC are biomarkers of stress injuries, and evaluating these markers along with dysmenorrhea, stress fracture history or high sports activity could predict future stress fractures in female athletes.
Topics: Adolescent; Adult; Athletes; Athletic Injuries; Biomarkers; Carbon Dioxide; Case-Control Studies; Creatine Kinase; Female; Fractures, Bone; Fractures, Stress; Humans; Isoenzymes; L-Lactate Dehydrogenase; Lactic Acid; Osteocalcin; Retrospective Studies; Young Adult
PubMed: 30575777
DOI: 10.1038/s41598-018-36982-0 -
Genes & Genomics Jun 2022Cleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification...
BACKGROUND
Cleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in runt-related transcription factor 2 (RUNX2) gene.
OBJECTIVE
Identification and functional characterization of RUNX2 mutation associated with CCD.
METHODS
We performed genetic testing of a patient with CCD using whole exome sequencing and found a novel RUNX2 frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type RUNX2 through immunofluorescence microscopy and osteocalcin promoter luciferase assay.
RESULTS
We found a novel RUNX2 frameshift mutation, c.1550delT (p.Trp518Glyfs*60). Both mutant RUNX2 and wild-type RUNX2 protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of RUNX2 on osteocalcin promoter.
CONCLUSIONS
We explored a novel RUNX2 deletion/frameshift mutation in a sporadic CCD patient. This finding suggests that the VWRPY domain may play a key role in RUNX2 transactivation ability.
Topics: Cleidocranial Dysplasia; Core Binding Factor Alpha 1 Subunit; Frameshift Mutation; Humans; Mutation; Osteocalcin
PubMed: 35235174
DOI: 10.1007/s13258-022-01229-w -
International Journal of Environmental... Aug 2022Oral dysfunction is related to long-term cares including activities of daily living. The objective of this study was to determine the association between oral function...
BACKGROUND
Oral dysfunction is related to long-term cares including activities of daily living. The objective of this study was to determine the association between oral function and the bone-related physiological substances osteocalcin (OC) and insulin-like growth factor-1 (IGF-1).
METHODS
The study participants were 139 community-dwelling older people in Japan. Evaluation of oral dysfunction was based on subjective judgment by each participant. Blood analysis included OC, IGF-1, and albumin.
RESULTS
Univariate and multiple logistic analyses showed that IGF-1 was significantly associated with a "decline in masticatory function" ( = 0.0074 and = 0.0308, respectively). Receiver operating characteristic curve analysis of IGF-1 levels revealed a threshold score of 108 ng/mL ( < 0.01) for discriminating a "decline in masticatory function". Logistic regression analysis revealed that participants with an IGF-1 level ≤108 ng/mL had an odds ratio of 4.31 ( < 0.05) for a "decline in masticatory function". No significant association was found between the OC level and oral dysfunction.
CONCLUSIONS
These results suggest a possible relationship between lower serum IGF-1 levels and a decline in masticatory dysfunction in community-dwelling older people.
Topics: Activities of Daily Living; Aged; Cross-Sectional Studies; Humans; Independent Living; Insulin-Like Growth Factor I; Japan; Mastication; Oral Health; Osteocalcin
PubMed: 36078393
DOI: 10.3390/ijerph191710677 -
Medical Science Monitor : International... Mar 2020BACKGROUND Osteoblast differentiation is a critical process to maintain the stability of the bone homeostasis. Zingerone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (ZG),...
BACKGROUND Osteoblast differentiation is a critical process to maintain the stability of the bone homeostasis. Zingerone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (ZG), isolated from ginger, performs a wide range of biological functions in human diseases. The objective of this paper was to clarify the role of ZG in human bone mesenchymal stem cells (hBMSCs) and associated mechanisms of ZG promoting osteoblast differentiation. MATERIAL AND METHODS The cytotoxicity of ZG was detected by MTT assay. The expression levels of miR-200c-3p, smad7, and osteoblast differentiation markers (alkaline phosphatase [ALP], osteocalcin [OC], osterix [OSX] and runt-related transcription factor 2 [RUNX2]) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of smad7, ALP, OC, OSX, and RUNX2 were quantified by western blot analysis. The target mRNAs were predicted by bioinformatics tools TargetScan. The interaction between miR-200c-3p and smad7 was verified by luciferase reporter assay and RIP assay. RESULTS ZG was nontoxic to hBMSCs, and it accelerated osteoblast differentiation by inducing the expression of ALP, OC, OSX, and RUNX2. MiR-200c-3p was upregulated, but smad7 was downregulated in hBMSCs treated with ZG at different concentrations at different periods. Besides, miR-200c-3p positively regulated the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs. Moreover, miR-200c-3p targeted smad7 and strengthened the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs by downregulating smad7. CONCLUSIONS ZG contributed to osteoblast differentiation via miR-200c-3p/smad7 regulatory axis by promoting the expression of ALP, OC, OSX, and RUNX2 in hBMSCs.
Topics: Alkaline Phosphatase; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Guaiacol; Humans; Mesenchymal Stem Cells; MicroRNAs; Osteoblasts; Osteocalcin; Osteogenesis; Smad7 Protein; Sp7 Transcription Factor
PubMed: 32146478
DOI: 10.12659/MSM.919309 -
Journal of Bone and Mineral Research :... Aug 2022Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether...
Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP), and collagen type 1 C-terminal cross-linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community-dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06-1.18, p < 0.001; PINP HR = 1.06, 95% CI 1.01-1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08-1.19, p < 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05-1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04-1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01-1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Aged; Biomarkers; Bone Remodeling; Cardiovascular Diseases; Collagen Type I; Humans; Male; Osteocalcin; Prospective Studies
PubMed: 35689459
DOI: 10.1002/jbmr.4631