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Metabolites Dec 2023Reduced expression of the plasma membrane citrate transporter , also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and...
Reduced expression of the plasma membrane citrate transporter , also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and metabolic diseases. Citrate, a vital component of the tricarboxylic acid cycle, constitutes 1-5% of bone weight, binding to mineral apatite surfaces. Our previous research highlighted osteoblasts' specialized metabolic pathway facilitated by regulating citrate uptake, production, and deposition within bones. Disrupting this pathway impairs bone mineralization in young mice. New Mendelian randomization analysis using UK Biobank data indicated that SNPs linked to reduced function lowered osteoporosis risk. Comparative studies of young (10 weeks) and middle-aged (52 weeks) osteocalcin-cre-driven osteoblast-specific knockout mice () showed a sexual dimorphism: while middle-aged females exhibited improved elasticity, middle-aged males demonstrated enhanced bone strength due to reduced function. These findings suggest reduced function could attenuate age-related bone fragility, advocating for inhibition as a potential osteoporosis treatment.
PubMed: 38132868
DOI: 10.3390/metabo13121186 -
Geriatrics & Gerontology International Apr 2024While insulin sensitivity plays an important role in maintaining glucose metabolic homeostasis and cognitive function, its impact on postoperative delirium (POD) remains...
AIM
While insulin sensitivity plays an important role in maintaining glucose metabolic homeostasis and cognitive function, its impact on postoperative delirium (POD) remains unclear. This study aimed to investigate the association between POD and indicators of insulin sensitivity, including insulin resistance and osteocalcin.
METHODS
A total of 120 elderly patients undergoing joint replacement were recruited and divided into delirium and non-delirium groups. Plasma and cerebrospinal fluid (CSF) samples were collected for the analysis of biomarkers, including insulin, uncarboxylated osteocalcin (ucOC), total osteocalcin (tOC), and glucose. Insulin resistance was assessed through the homeostatic model assessment of insulin resistance (HOMA-IR).
MAIN RESULTS
Out of the total, 28 patients (23.3%) experienced POD within 5 days after surgery. Patients with delirium exhibited higher levels of preoperative HOMA-IR and ucOC in CSF and plasma, and of tOC in CSF (P = 0.028, P < 0.001, P = 0.005, P = 0.019). After adjusting for variables, including age, Mini-Mental State Examination score, surgical site and preoperative fracture, only preoperative ucOC in CSF and HOMA-IR were significantly linked to the incidence of delirium (OR = 5.940, P = 0.008; OR = 1.208, P = 0.046, respectively), both of which also correlated with the severity of delirium (P = 0.007, P < 0.001). Receiver operating curve analysis indicated that preoperative HOMA-IR and ucOC in CSF might partly predict POD (area under the curve [AUC] = 0.697, 95% confidence interval [CI] = 0.501-0.775, AUC = 0.745, 95% CI = 0.659-0.860).
CONCLUSIONS
We observed that preoperative elevated HOMA-IR and ucOC in CSF were associated with the incidence and severity of POD. While these preliminary results need confirmation, they suggest a potential involvement of insulin resistance and osteocalcin in the pathological mechanism of POD. Geriatr Gerontol Int 2024; 24: 421-429.
Topics: Humans; Aged; Insulin Resistance; Osteocalcin; Emergence Delirium; Incidence; Glucose; Arthroplasty, Replacement
PubMed: 38438300
DOI: 10.1111/ggi.14848 -
International Archives of Occupational... Dec 2023The systemic illnesses associated with chronic lead exposure are partially explained by the interaction between lead and calcium metabolism. Lead exposure is posited to... (Observational Study)
Observational Study
OBJECTIVE
The systemic illnesses associated with chronic lead exposure are partially explained by the interaction between lead and calcium metabolism. Lead exposure is posited to alter calcium levels either by altering calcium homeostasis markers or altering bone remodeling. The present study investigated the interaction between blood lead levels and calcium homeostasis markers and bone remodeling markers among lead-smelting plant workers.
METHOD
Adult male workers employed at the lead-smelting plant were clinically investigated as part of their regular occupational health assessment program. Additionally, control participants without occupational lead exposure, employed in administrative and white-collar jobs were invited to participate in the study. Sociodemographic and occupational details were collected by pre-standardized semi-structured questionnaires from all consenting participants, followed by clinical examination and blood collection. Blood lead levels were estimated using microwave-assisted acid digestion and the inductively coupled plasma mass spectrometry technique. Serum calcium and total protein and alkaline phosphatase levels were estimated as per standard biochemical techniques. 25-hydroxy vitamin-D, calcitriol, and osteocalcin were estimated using the enzyme-linked immunosorbent assay. In addition to comparative analysis for comparing the two groups, independent linear regression models were explored to investigate the associations between serum calcium and blood lead and osteocalcin levels.
RESULT
A total of 189 lead-exposed men employed at the lead-smelting plant and 25 male control participants consented to participate. The two groups were similar in age, diet, and body mass index. Occupationally exposed individuals exhibited significantly lower serum calcium and higher bone remodeling markers (osteocalcin and alkaline phosphatase) as compared to controls. However, the serum 25-hydroxy vitamin-D and calcitriol levels were not significantly different between the two groups. Lastly, the serum lead and osteocalcin were weakly but significantly associated with serum calcium levels after controlling for variations in total protein, diet, 25-hydroxy vitamin-D, calcitriol, and alkaline phosphatase in the study participants.
CONCLUSION
Current observations reinforce the adverse role of lead exposure on calcium metabolism. Although lead exposure is posited to affect calcium metabolism by multiple pathways, current study observations favor the bone remodeling pathway. The observations recommend periodic screening for calcium and bone health among lead-exposed adults.
Topics: Adult; Humans; Male; Alkaline Phosphatase; Calcitriol; Calcium; Lead; Osteocalcin; Vitamins
PubMed: 37889332
DOI: 10.1007/s00420-023-02018-y -
BMC Musculoskeletal Disorders Jan 2024Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying...
BACKGROUND
Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying mechanism and bring a potential preventive strategy for postmenopausal osteoporosis in the future.
METHODS
An ovariectomy (OVX)-induced rat osteoporosis model was established for in vivo experiments. Micro-computed tomography and three-point bending test were used to evaluate bone strength. Histological femur slices were processed for immunohistochemistry (IHC). Bone turnover markers and nitric oxide (NO) concentrations in serum were determined with enzyme-linked immunosorbent assay (ELISA). The mouse embryo osteoblast precursor (MC3T3-E1) cells were used for in vitro experiments. The cell viability was analysed with a Cell Counting Kit‑8. We performed Alizarin Red S staining and alkaline phosphatase (ALP) activity assay to observe the differentiation status of osteoblasts. Western blotting was adopted to detect the expression of osteogenesis related proteins and AMP-activated protein kinase/endothelial nitric oxide synthase (AMPK/eNOS) in osteoblasts. DAF-FM diacetate was used for semi-quantitation of intracellular NO.
RESULTS
In OVX rats, alamandine alleviated osteoporosis and maintained bone strength. The IHC showed alamandine increased osteocalcin and collagen type I α1 (COL1A1) expression. The ELISA revealed alamandine decreased bone turnover markers and restored NO level in serum. In MC3T3-E1 cells, alamandine promoted osteogenic differentiation. Western blotting demonstrated that alamandine upregulated the expression of osteopontin, Runt-related transcription factor 2 and COL1A1. The intracellular NO was also raised by alamandine. Additionally, the activation of AMPK/eNOS axis mediated the effects of alamandine on MC3T3-E1 cells and bone tissue. PD123319 and dorsomorphin could repress the regulating effect of alamandine on bone metabolism.
CONCLUSION
Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.
Topics: Mice; Female; Animals; Rats; Osteogenesis; AMP-Activated Protein Kinases; Nitric Oxide Synthase Type III; X-Ray Microtomography; Osteoporosis; Oligopeptides
PubMed: 38200474
DOI: 10.1186/s12891-023-07159-2 -
Clinica Chimica Acta; International... Aug 2023Chronic kidney disease-mineral bone disease (CKD-MBD) is a major complication of CKD. Bone turnover markers (BTMs) are important for clinicians to evaluate and manage...
BACKGROUND
Chronic kidney disease-mineral bone disease (CKD-MBD) is a major complication of CKD. Bone turnover markers (BTMs) are important for clinicians to evaluate and manage patients with CKD-MBD. This study aimed to assess BTMs in patients with CKD and their correlation with parathyroid hormone (PTH) and other clinical characteristics of CKD.
METHODS
A total of 408 subjects were included in this study. The serum BTMs including N-terminal midfragment osteocalcin (N-MID OC), β-isomerized C-terminal telopeptides (β-CTX), and total procollagen type 1 amino-terminal propeptide (tPINP) were measured. Spearman correlation and multiple stepwise regression models were used to investigate the association of N-MID OC, β-CTX, and tPINP with the clinical characteristics of CKD patients.
RESULTS
BTMs was no significant difference between non-CKD and CKD stages 1, 2, and 3. However, N-MID OC, β-CTX were significantly increased in patients with CKD stage 4 compared to non-CKD patients and patients with CKD stages 1, 2, and 3. Compared with non-dialysis dependent (NDD)-CKD stage 5, BTMs were significantly higher in dialysis patients. The estimated glomerular filtration rate was negatively associated with N-MID OC (r = -0.479, P < 0.001), β-CTX (r = -0.474, P < 0.001), and tPINP (r = -0.375, P < 0.001). Multiple analysis showed that N-MID OC (β = 0.67, P < 0.001), β-CTX (β = 0.64, P < 0.001), and tPINP (β = 0.81, P < 0.001) were independently associated with PTH. CKD patients with secondary hyperparathyroidism (SHPT) have higher β-CTX (P < 0.05), and N-MID OC (P < 0.05) than patients with non-SHPT.
CONCLUSIONS
BTMs in advanced CKD stages were significantly higher than in the early disease stages. PTH level was independently and positively associated with the BTM levels in patients with CKD. In the advanced stage of CKD, β-CTX and N-MID OC levels were significantly higher in those with SHPT than those with non-SHPT.
Topics: Humans; Bone Diseases; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Kidney Failure, Chronic; Parathyroid Hormone
PubMed: 37619948
DOI: 10.1016/j.cca.2023.117518 -
Biomarkers in Body Fluids as Indicators of Skeletal Maturity: A Systematic Review and Meta-analysis.Rambam Maimonides Medical Journal Aug 2023This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard... (Review)
Review
OBJECTIVES
This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
MATERIALS AND METHODS
A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
RESULTS
A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
CONCLUSIONS
Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
PubMed: 37669407
DOI: 10.5041/RMMJ.10506 -
Frontiers in Nutrition 2023Vitamin D is a key factor in bone metabolism, yet vitamin D insufficiency and deficiency are prevalent among postmenopausal women, with potential repercussions on bone...
Vitamin D status and its associations with bone mineral density, bone turnover markers, and parathyroid hormone in Chinese postmenopausal women with osteopenia and osteoporosis.
BACKGROUND
Vitamin D is a key factor in bone metabolism, yet vitamin D insufficiency and deficiency are prevalent among postmenopausal women, with potential repercussions on bone mineral density (BMD), bone turnover markers (BTMs), and parathyroid hormone (PTH). Nonetheless, the findings from existing studies exhibit inconsistency, and a notable gap exists in the availability of large-scale investigations.
METHODS
In this real-world study, 8,532 postmenopausal women over 50 years old with a diagnosis of osteopenia (50.9%) and osteoporosis (49.1%) at the first visit were enrolled in this study. Serum 25(OH)D level, PTH, osteocalcin (OC) and Beta-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), were measured. BMD at all sites, including the lumbar spine, femoral neck, and total hip were obtained by dual-energy X-ray absorptiometry (DXA). The associations of serum 25(OH)D level with BMDs and BTMs were investigated using spearman correlation analysis and analysis of general linear model adjusted by age and body mass index.
RESULTS
The serum 25(OH)D level was 22.17 ± 9.75 ng/mL among all patients included in this study. For the osteopenia group, the serum 25(OH)D level was 22.40 ± 9.41 ng/mL, while for the osteoporosis group, it measured 21.93 ± 10.08 ng/mL. In the osteopenia group, the prevalence of vitamin D deficiency, insufficiency and sufficiency was 45.8, 34.6, and 19.6%, respectively, which was close to that of the osteoporosis group (47.4, 34.3, and 18.3%) ( = 0.202). Spearman correlation analysis unveiled negative associations between serum 25(OH)D concentrations and both BTMs and PTH within both the osteopenia and osteoporosis group. In the osteoporosis group, there were positive correlations between 25(OH)D levels and femoral neck BMD ( = 0.040, = 0.010) and total hip BMD ( = 0.053, = 0.001). Furthermore, we found that for the osteopenia group, greater vitamin D levels were associated with greater femoral neck BMD ( = 0.020) and total hip BMD ( = 0.008) and lower β-CTX ( < 0.001), OC ( < 0.001), and PTH ( < 0.001). The same trends were seen in osteoporosis patients ( < 0.05), and with greater lumbar spine BMD with higher levels of 25(OH)D ( = 0.009).
CONCLUSION
This study showed high prevalence of vitamin D deficiency and insufficiency in Chinese postmenopausal women with osteopenia and osteoporosis and the relationships between vitamin D and BMD, BTMs and PTH. The results contribute to a more comprehensive understanding of how vitamin D may impact bone health.
PubMed: 38268673
DOI: 10.3389/fnut.2023.1307896 -
The Journal of Clinical Endocrinology... Sep 2023Hyponatremia is associated with increased risk for osteoporosis. Preclinical studies in untreated hyponatremia suggest osteoclast upregulation, whereas a clinical study... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Hyponatremia is associated with increased risk for osteoporosis. Preclinical studies in untreated hyponatremia suggest osteoclast upregulation, whereas a clinical study showed improved osteoblast function after hyponatremia normalization in hospitalized patients with syndrome of inappropriate antidiuresis (SIAD).
OBJECTIVE
This work aimed to investigate the effect of an increase in sodium on bone turnover, that is, the ratio of the osteoblast marker procollagen type 1 N-terminal propeptide (P1NP) to the osteoclast marker cross-linked C-terminal telopeptide of type 1 collagen (CTX), in outpatients with chronic SIAD.
METHODS
A predefined secondary analysis was conducted of the 2-month double-blind, crossover, placebo-controlled SANDx Trial (NCT03202667) performed from December 2017 to August 2021. Participants included 11 outpatients with chronic SIAD: 6 women, median age 73 years, who received a 4-week treatment with 25-mg empagliflozin or placebo. Main outcome measures included the relationship between the change in bone formation index (BFI), defined as P1NP/CTX, and the change in plasma sodium levels.
RESULTS
Changes in sodium were positively correlated with changes in BFI and P1NP (BFI: ρ=.55; P < .001; P1NP: ρ=.45; P = .004) but not with CTX (P = .184) and osteocalcin (P = .149). A sodium increase of 1 mmol/l was associated with an increase of 5.21 in BFI (95% CI, 1.41-9.00; P = .013) and with an increase of 1.48 µg/l in P1NP (95% CI, .26-2.62; P = .03). The effect of sodium change on bone markers was independent of the study medication empagliflozin.
CONCLUSION
An increase in plasma sodium levels in outpatients with chronic hyponatremia due to SIAD, even when mild, was associated with an increase in bone formation index (P1NP/CTX) triggered by an increase in P1NP, a surrogate marker of osteoblast function.
Topics: Humans; Female; Aged; Hyponatremia; Benzhydryl Compounds; Collagen Type I; Biomarkers; Bone Remodeling; Sodium; Osteoblasts; Procollagen; Peptide Fragments
PubMed: 37098131
DOI: 10.1210/clinem/dgad238 -
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 -
Lipids in Health and Disease Jul 2023Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia...
BACKGROUND AND AIMS
Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia are tightly entangled. The objective of this study was to assess the relations between a broad panel of inflammatory biomarkers and lipoprotein subclass parameters.
METHODS
We utilized data from the population-based Study of Health in Pomerania (SHIP-TREND, n = 403). Plasma concentrations of 37 inflammatory markers were measured by a bead-based assay. Furthermore, we employed nuclear magnetic resonance spectroscopy to measure total cholesterol, total triglycerides, total phospholipids as well as the fractional concentrations of cholesterol, triglycerides, phospholipids, ApoA1, ApoA2 and ApoB in all major lipoprotein subclasses. Associations between inflammatory biomarkers and lipoprotein subclasses were analyzed by adjusted linear regression models.
RESULTS
APRIL, BAFF, TWEAK, sCD30, Pentraxin-3, sTNFR1, sTNFR2, Osteocalcin, Chitinase 3-like 1, IFN-alpha2, IFN-gamma, IL-11, IL-12p40, IL-29, IL-32, IL-35, TSLP, MMP1 and MMP2 were related with lipoprotein subclass components, forming two distinct clusters. APRIL had inverse relations to HDL-C (total and subclasses) and HDL Apo-A1 and Apo-A2 content. MMP-2 was inversely related to VLDL-C (total and subclasses), IDL-C as well as LDL5/6-C and VLDL-TG, IDL-TG, total triglycerides as well as LDL5/5-TG and HDL4-TG. Additionally, we identified a cluster of cytokines linked to the Th1-immune response, which were associated with an atherogenic lipoprotein profile.
CONCLUSION
Our findings expand the existing knowledge of inflammation-lipoprotein interactions, many of which are suggested to be involved in the pathogeneses of chronic non-communicable diseases. The results of our study support the use of immunomodulatory substances for the treatment and possibly prevention of CVD.
Topics: Humans; Inflammation; Cytokines; Apolipoprotein A-II; Apolipoproteins B; Cardiovascular Diseases
PubMed: 37434164
DOI: 10.1186/s12944-023-01856-6