N-terminal Propeptide Of Type Research Articles

Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures

AimsBone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.MethodsA total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months.ResultsCTX and P1NP concentrations peaked at six weeks in all groups. Elevated six-week CTX and P1NP were associated with radiological healing at 12 weeks post-injury (odds ratio (OR) 10.5; 95% confidence interval 2.71 to 53.5, p = 0.002). We found no association between CTX or P1NP and functional healing. Baseline serum 25(OH)D showed a weak inverse relationship with P1NP (p = 0.036) and CTX (p = 0.221) at 12 weeks, but we observed no association between vitamin D supplementation and either BTM.ConclusionGiven the association between six-week BTM concentrations and three-month radiological fracture healing, CTX and P1NP appear to be potential surrogate markers of fracture healing.Cite this article: Bone Joint Res 2022;11(4):239–250.

Bone metabolism parameters and their relation to cytogenetics in multiple myeloma.

Our aim was to correlate serum levels of selected markers of bone metabolism and bone marrow microenvironment to cytogenetic changes in patients with multiple myeloma (MM). We assed cytogenetic changes in 308 patients and correlated them with the following levels of bone marrow metabolism: thymidine kinase (TK), β2-microglobulin (b-2-m), Dickkopf-1 protein (DKK-1), C-terminal telopeptide collagen-I (ICTP), N-terminal propeptide of type I procollagen (PINP), receptor for interleukin 6 (rIL-6), vascular cell adhesive molecule-1 (VCAM), soluble intercellular adhesion molecule-1, osteoprotegerin (OPG), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), syndecan-1 (SYN-1) and Fas antigen. Individuals with delRB1 had lower levels of OPG (M=7.39 vs. 5.46pmol/L, p=.025) and VEGF (M=304 vs. 196pg/ml; p=.036). t(14;16) was associated with higher β2m levels (M=7.59 vs. 4.13mg/L; p=.022) and lower DKK-1 levels (M=4465ng/L vs. 12,593). The presence of 1q21 gain was associated with higher levels of TK (M=100.0 vs. 11.0IU/L, p=.026) and lower levels of PINP (M=49.3 vs. 67.4mg/L, p=.030). Our analysis has shown, some cytogenetic changes, especially delRB1, t(14;16) and 1q21gain, which affect the components of the cytokine network in multiple myeloma.

Relationships between Bone Turnover Markers and Factors Associated with Metabolic Syndrome in Prepubertal Girls and Boys

The associations between individual components of metabolic syndrome (MetS) and bone health in children are complex, and data on this topic are sparse and inconsistent. We assessed the relationship between bone turnover markers and markers of the processes underlying MetS (insulin resistance and inflammation) in a group of presumably healthy children aged 9–11 years: 89 (51 girls, 38 boys) presenting without any features of MetS and 26 (10 girls, 16 boys) with central obesity and two features of MetS. Concentrations of glucose, triglycerides (TG), HDL cholesterol (HDL-C), C-reactive protein (CRP), HbA1c, total 25-hydroxyvitamin D (25(OH)D), intact-P1NP (N-terminal propeptide of type I procollagen), CTX-1 (C-terminal telopeptide of type I collagen) were assayed and insulin resistance was assessed (HOMA-IR). BMI centile, waist circumference (WC) and blood pressure were measured. The presence of MetS in girls resulted in significantly lower concentrations of CTX-1 and a trend to lower CTX-1 in boys. The concentrations of bone formation marker i-P1NP were not affected. Among the features associated with MetS, HOMA-IR appeared as the best positive predictor of MetS in girls, whereas CRP was the best positive predictor in boys. A significant influence of HOMA-IR on the decrease in CTX-1 in girls was independent of BMI centile and WC, and the OR of having CTX-1 below the median was 2.8-fold higher/1SD increased in HOMA-IR (p = 0.003). A weak relationship between CTX-1 and CRP was demonstrated in girls (r = −0.233; p = 0.070). Although TG, as a MetS component, was the best significant predictor of MetS in both sexes, there were no correlations between bone markers and TG. We suggest that dyslipidemia is not associated with the levels of bone markers in prepubertal children whereas CRP is weakly related to bone resorption in girls. In prepubertal girls, insulin resistance exerts a dominant negative impact on bone resorption, independent of BMI centile and waist circumference.

Fluctuations in Metabolites and Bone Markers Across the Menstrual Cycle in Eumenorrheic Women and Oral Contraceptive Users.

Little is known about changes in circulating metabolites during the menstrual cycle and how use of oral contraceptives (OCs) affects these changes. To study fluctuations in circulating metabolite and bone marker levels during the menstrual/pill cycle in eumenorrheic women and OC users. Plasma samples were collected from 28 eumenorrheic women and 10 OC users at 7 to 9 time points across a menstrual/pill cycle. Longitudinal and cross-sectional analyses were performed to examine the cycle- and OC-induced variations in the plasma metabolite and bone turnover marker levels. In eumenorrheic women, plasma levels of alanine, glutamine, threonine, and tyrosine varied significantly across the menstrual cycle, and all dropped to the lowest level around day 21 of the menstrual cycle. These amino acid concentrations were negatively correlated with fluctuations in progesterone and/or estrogen levels. A between-group analysis showed that plasma levels of alanine, glutamine, glycine, proline, and tyrosine were lower in OC users than in nonusers. Concomitantly, plasma C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (PINP) levels were lower in OC users. Intriguingly, when all data were pooled, variations in CTX and PINP levels were positively correlated with fluctuations in proline and glycine concentrations (r > 0.5 or 0.3 < r < 0.5, P < 0.05). The menstrual cycle and the use of OCs alter plasma levels of metabolites and bone turnover markers in young women. While the impact of these findings remains to be established, the lower glycine level among OC users and the accompanying lower CTX level supports that the use of OCs lowers collagen turnover in young women and may thereby have long-term implications for bone health among OC users.

Night shift work and osteoporosis - bone turnover markers among female blue-collar workers in Poland

ABSTRACT Osteoporosis is an important public health problem worldwide. Although many factors relating to bone structure have been described so far, the current knowledge on the occupational factors that may affect bone tissue metabolism is strongly limited. Literature data suggest that night shift work, via circadian rhythm disruption, may be considered a potential risk factor. To this date, only five epidemiological studies addressing this problem have been conducted worldwide. The outcomes of three studies confirmed such relationship, namely, a higher fracture risk was found among nurses with a long lifetime duration of night shift work in one study; and a lower bone mineral density was associated with occupational activity during night-time in two studies. In adults, the bone undergoes constant remodelling through bone resorption followed by bone formation. The various molecules released into the circulatory system during these processes are called bone turnover markers. We investigated the possible associations between night shift work and selected bone turnover markers: N-terminal propeptide of type I procollagen (P1NP), C-terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin, osteopontin, fibroblast growth factor 23 (FGF-23) and osteoprotegerin, measured in plasma of 189 female blue-collar workers. A significantly higher bone turnover rate was noted among the women working night shifts than among those working only during the day. This may potentially lead to a future development of osteoporosis in this population even if the macroscopic changes in the bone structure are not detectable. Night shift work is a prevailing occupational characteristics nowadays. It has been estimated that about 15–20% of the working population in Europe and the USA perform work under this system. Thus, the problem of osteoporosis can affect a large part of the working-age population.

Development of a Chemiluminescence Assay for Total N-Terminal Propeptide of Type I Collagen and Its Evaluation in Lung Transplantation.

Serum P1NP, one of the important biomarkers for bone turnover, is commonly used for the prediction of bone fracture and the prognosis of osteoporosis after therapy. We developed a P1NP chemiluminescence assay and evaluated changes in bone metabolism markers in lung transplant patients. The screened 2 P1NP antibodies with constructed antigens and α-1 chain antigens expressed by the Corynebacterium glutamate expression system were applied into assay development. The assay performance was evaluated to examine the reliability. A normal Q-Q plot was used to establish male reference interval. Changes of bone metabolism markers before and after lung transplantation in 19 patients were evaluated. The linear factor R of P1NP reagent was greater than 0.99. The limit of detection was 3.32 ng/ml. The precision of the three batches of P1NP reagents was lower than 8%. Method comparison with Roche P1NP reagent showed that the correlation coefficient R2 was 0.91. In the monitoring of bone mass in a short time, bone metabolism markers can better indicate the change of bone mass, while the traditional bone mineral density detection is lagging behind the bone metabolism markers. P1NP and β-CrossLap to bone mass change in patients after lung transplantation, and P1NP and β-CrossLap are very good clinical markers for bone mass monitoring.

Ethnic characteristics of bone remodeling in female patients with type 2 diabetes mellitus

Background: Structural and metabolic disorders of bone tissue in women with T2DM have no clinical manifestations, but they are accompanied by the risk of fractures.Aim: To study the parameters of bone metabolism, BMD and microarchitectonics in female patients with T2DM in the Buryat population.Materials and methods: The observational single-center one-stage controlled study included 73 women with T2DM, which were divided into 2 groups depending on the functional state of the ovaries (reproductive and postmenopausal periods). In each group, subgroups of the Buryat and Russian populations were identified. The first group included 34 patients with T2DM of the reproductive period: 16 from the Buryat population and 18 from the Russian population. The second group consisted of 39 postmenopausal patients with T2DM: 17 from the Buryat population and 22 from the Russian population. The study of BMD in the lumbar spine (L1-L4), femoral neck (Neck), in the proximal femur (Total hip), trabecular bone score (TBS), serum osteocalcin (OC), N-terminal propeptide type 1 procollagen was carried out (P1NP), vitamin D 25 (OH), blood plasma type I collagen C-terminal telopeptide (β-Cross laps) and ionized calcium (iCa).Results: In female patients with T2DM of the reproductive age of the Buryat population, an increase in both markers of osteosynthesis P1NP (p=0.035), OC (p=0.047), and bone resorption β-Cross laps (p=0.040) was found relative to the similar group of the Russian population. In women with T2DM in the postmenopausal period of the Buryat population, there was also an increase in P1NP (p = 0.016), OC (p = 0.048), β-Cross laps (p = 0.020) compared with the group of postmenopausal women in the Russian population. Structural disorders, characterized by a decrease in TBS, were detected only in the postmenopausal period in female patients of the Buryat population compared to women in the Russian population (p = 0.029).Comparative analysis among women with T2DM of the Buryat population, depending on the functional state of the ovaries, showed that activation of bone remodeling with an increase in P1NP (p = 0.019), OC (p = 0.004) and β-Cross laps (p = 0.004) is characteristic of postmenopausal women accompanied by a decrease in BMD Neck (p = 0.006), BMD Total hip (p = 0.003), BMD L1-L4 (p = 0.049) and TBS (p = 0.020) relative to female patients with T2DM in the reproductive period.Conclusion: In women with T2DM in the Buryat population, both in the reproductive and postmenopausal periods, an increase in bone remodeling markers and BMD stability was found when compared with the corresponding groups of patients in the Russian population. The postmenopausal period was characterized by an additional decrease in TBS in patients with T2DM in the Buryat population relative to women in the Russian population.

КЛИНИКО-ФУНКЦИОНАЛЬНАЯ, КЛЕТОЧНО-МОЛЕКУЛЯРНАЯ ХАРАКТЕРИСТИКА ПРОФЕССИОНАЛЬНОЙ ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНИ ЛЕГКИХ В ЗАВИСИМОСТИ ОТ СОСТАВА НЕНАМЕРЕННЫХ НАНОЧАСТИЦ

Introduction. Occupational chronic obstructive pulmonary disease (OCOPD) is characterized by steadily progressive persistent bronchial obstruction and emphysema, which leads to disability and reduced life expectancy of patients. Industrial aerosols are one of the main occupational health risks. According to Federal State Statistics Service, 4.5% of all workers are exposed to aerosols of predominantly fibrogenic action, 7.7% – to a chemical factor. At present, the determination of the physicochemical properties of nanoparticles and the study of their effect on the phenotype of occupational bronchopulmonary pathology are still insufficiently studied. Aim of the research. To identify clinical, functional, cellular and molecular features of the phenotype of occupational chronic obstructive pulmonary disease under exposure to aerosols with unintentional nanoparticles of various compositions. Materials and methods. A single-center cohort study was performed. Patients with OCOPD (GOLD 2011-2021 criteria) who worked under conditions of exposure to aerosols containing unintentional nanoparticles were included (n = 70). Comparison group – COPD due to tobacco smoking (n = 70), control – conditionally healthy (n = 70). The groups are comparable in terms of demographic indicators, duration of the disease. Nanoparticles in the air of the working area were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) and scanning electron microscopy. At the workplaces, in 36 persons, the mass concentration of metal nanoparticles was the highest, in 34 persons – that of silica nanoparticles. Spirography, body plethysmography, assessment of the diffusing capacity of the lungs (DLco/Va) for carbon monoxide (DLco/Va), cytological examination of induced sputum were performed. Markers of cellular inflammation and fibrosis were studied: interleukin-1β (IL1-β), interleukin-5 (IL-5), C-reactive protein (CRP), fibroblast growth factor-2 (FGF-2), transforming growth factor-β1 (TGF-β1), procollagen type 3 N-terminal propeptide (PIIINP), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9), soluble vascular cell adhesion molecule-1 (sVCAM 1) and distribution subpopulations of blood monocytes by flow cytometry. Correlations were determined by the method of linear regression. Results. The clinical and functional peculiar characteristics of COPD when exposed to aerosols with metal nanoparticles are: the greatest severity of dyspnea according to mMRC scale 2.35 ± 0.120 points, dry cough with paroxysms 75.0%, low quality of life 70.8 ± 5.68 points, ventilation function of the lungs with the greatest severity of bronchial obstruction (Raw 0.66 kPa s/l, FEV1 36%) and static pulmonary hyperinflation (functional residual capacity (FRC) 192%, residual volume of the lungs (PRV) 187%), maximum pulmonary hypertension (37 mm Hg), the lowest values of DLco 36%. The cellular and molecular composition in OCOPD from exposure to metal nanoparticles is characterized by: eosinophilic type of inflammation 47.2%, the highest level of classical monocytes 95.4%, high expression of CCR5 21.56%, elevated serum concentrations of PIIINP 156.7 ± 15.23 ng/mL, IL-5 2.1 ± 0.42 pg/mL and MMP-9 346.2 ± 31.74 pg/mL. In COPD due to expose to industrial aerosols containing silica nanoparticles, the disease is characterized by the least severity of dyspnea mMRC 1.64 ± 0.118 points, the presence of a pronounced dry cough 61.7%, a significant decrease in DLco/Va (47%) with the least severity of bronchial obstruction (Raw 0.51 kPa s/l, FEV1 56%) and pulmonary hyperinflation. The cellular and molecular features of COPD from exposure to silica nanoparticles include: paucigranulocytic type of inflammation 44.1%, the lar¬gest proportion of non-classical CD14DimCD16+ monocytes – 21.1%, a significant level of CCR2 expression 11.10%, elevated serum concentrations of PIIINP 92, 1 ± 9.32ng/mL, FGF-2 16.1 ± 3.51pg/mL and sVCAM-1 46.1 ± 9.15 pg/mL. Reliable correlations between the mass concentrations of metal nanoparticles and classical monocytes (B = 1.6), silicon nanoparticles and nonclassical monocytes (B = 1.2) were determined. At the same time, classic monocytes were significant predictors of DLco (B = –1.7), functional residual lung capacity (B = 1.3), mean pulmonary artery pressure (B = –1.6), inflammation with eosinophilia (B = 1.2), non-classical monocytes – DLco (B = –1.4), paucigranulocytic inflammation (B = 1.3), p &lt; 0.015. In the linear regression model, the mass concentration of metal nanoparticles is associated with the N-terminal propeptide of type 3 procollagen, interleukin-5, and matrix metalloproteinase-9. Serum PIIINP concentrations were associated with carbon monoxide diffusing capacity (DLco), IL-5 – with eosinophilic airway inflammation, and MMP-9 – with residual volume of lungs/total lung capacity (RV/TLC) ratio. The mass concentration of silica nanoparticles was associated with PIIINP, FGF-2 and sVCAM-1. In turn, the N-terminal propeptide of procollagen type 3 was associated with DLco, mean pulmonary artery pressure (MPAP); fibroblast growth factor-2 – with DLco, and sVCAM-1 – with MPAP (p &lt; 0.01). Conclusion. Under conditions of exposure to industrial aerosol, various phenotypes of chronic obstructive pulmonary disease are formed depending on the composition of unintentional nanoparticles.

Among simple non-invasive scores, Pro-C3 and ADAPT best exclude advanced fibrosis in Asian patients with MAFLD

BackgroundWith metabolic dysfunction-associated fatty liver disease (MAFLD) incidence and prevalence increasing, it is necessary to identify patients with advanced fibrosis (F3-F4 stages). We evaluated the performance of new biomarkers and algorithms for diagnosing advanced fibrosis in an Asian population. MethodsData from two Asian cohorts (including 851 biopsy-proven MAFLD [578 from Wenzhou, 273 from Hong Kong]) were studied. The association between N-terminal propeptide of type 3 collagen (PRO-C3) and the histologic stage of liver fibrosis was analyzed by multivariable linear regression. The area under the receiver operating characteristic curve (AUROC) was used to test the diagnostic performance of serum PRO-C3 and the ADAPT score for advanced fibrosis and compared them to other established non-invasive tests. ResultsSerum PRO-C3 levels increased progressively across liver fibrosis stages and correlated with advanced fibrosis (P < 0.001). The ADAPT score had an AUROC of 0.865 (95% confidence interval 0.829–0.901) for advanced fibrosis; the accuracy, sensitivity and negative predictive values were 81.4%, 82.2% and 96.1%, respectively. This result was better compared to that of PRO-C3 alone or other non-invasive fibrosis biomarkers (aspartate aminotransferase-to-platelet ratio index, Fibrosis-4, BARD, and NAFLD fibrosis score). In subgroup analyses (including sex, age, diabetes, NAFLD activity score, body mass index or serum alanine aminotransferase levels), the ADAPT score had good diagnostic performance. ConclusionPRO-C3 and the ADAPT score reliably exclude advanced fibrosis in MAFLD patients and reduce the need for liver biopsy.

Bone turnover markers in gingival crevicular fluid and blood serum of patients with fixed orthodontic appliances.

Bone remodelling can be followed through the bone turnover markers (BTMs). Aim of the present study was to record the fluctuation of an osteoclastic and an osteoblastic BTM [C-terminal telopeptide of type I collagen (CTX) and N-terminal pro-peptide of type I pro-collagen (PINP), respectively] in both the gingival crevicular fluid (GCF) and the serum of orthodontic patients before and after the initial application of orthodontic forces. Twenty-one Caucasian patients were prospectively evaluated. GCF and blood samples were collected in order to measure the selected biomarkers by ELISA at three time-points: exactly before, 5 days, and 14 days after bonding of the appliances. Standardized sample handling and patient preparation procedures were adopted in order to reduce pre-analytical variability. GCF and serum CTX levels were found to be independent of age, although higher in the serum of female subjects. PINP levels were found higher in the serum of patients ≥25 years old, as well as in the GCF of males. A positive correlation between serum and GCF baseline PINP levels was observed. The effect of orthodontic treatment on bone remodelling might not be absolutely representative of the local bone microenvironment as the levels of the specific BTMs where measured within the GCF of the lower front teeth. This is the first time PINP and CTX have been evaluated in the GCF and serum of orthodontic patients with fixed appliances. No statistically significant alterations of CTX and PINP levels in the GCF and the serum of patients were recorded over time during the initial stages of orthodontic treatment.

Correlation between genotypes with metabolic markers and microstructure of bones in children with Gitelman syndrome

To explore the correlation between the genotypes and metabolic markers and microstructure of bones in children with Gitelman syndrome (GS). For 15 children with GS and 10 healthy individuals, baseline data and bone metabolic markers including parathyroid hormone, alkaline phosphatase, osteocalcin, N-terminal propeptide of type I procollagen, beta isomer of the C-terminal telopeptide of type I collagen and 25-hydroxyvitamin D, high-resolution peripheral quantitative computed tomography indicators (volumetric bone mineral density, bone microstructure indicators) were collected. Genetic testing was carried out to determine their genotypes. The volumetric bone mineral density, bone geometry and bone microstructure parameters of the GS group were better than those of the healthy controls (P<0.05). Variants of the SLC12A3 gene were identified in 9 of the 15 patients but none of the 10 healthy controls. The phenotype of GS children is influenced by the interaction of genetic variants, though the phenotype associated with high frequency mutations showed no specificity. There is also a correlation between their genotype and the bone microstructure.

The prognostic value of hypoxia biomarkers in older patients with chronic heart failure

Abstract Chronic kidney disease (CKD) worsens the prognosis of chronic heart failure (CHF). Hypoxia is the leading link in pathogenesis, especially in older patients with comorbidity. The aim of this study was to investigate the prognostic value of biomarkers of myocardial, renal dysfunction and hypoxia in older patients with CHF. Materials and methods 80 older hypertensive patients with CHF (48 females, mean age 70.7±8.7 years) were examined. CHF was defined according to ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, 2016. CKD was diagnosed and classified according to the KDIGO guidelines (2012). Serum levels of hypoxia-inducible factor 1-alpha (HIF-1α), endogenous erythropoietin (eEPO), N-terminal propeptide of type B natriuretic hormone (NT-proBNP), cystatin C were assessed. The follow-up period was 12 months; the primary endpoint was total mortality. Results CKD was diagnosed in 49 (61.3%) older patients with CHF. The HIF-1α level was significantly higher in the group of deceased patients than in the survivors (0.08 (IQR 0.06; 0.11) and 0.05 (IQR 0.04; 0.07) ng/ml, p=0.02), as well as the level of NT-proBNP (1126.3 (IQR 551.8; 2750.0) and 164.4 (IQR 135.5; 1100.9) pg/ml, p&amp;lt;0.0001), eEPO (16.92 (ICR 5.43; 64.57) and 5.36 (IQR 1.65; 8.85) mIU/ml, p&amp;lt;0.0001), cystatin C (1.49 (ICR 0.86; 2.13) and 0.99 (IQR 0.82; 1.32) Mg/l, p=0.0005). Cox regression analysis adjusted for sex, age and comorbidity (χ2=36.8, p&amp;lt;0.0001) showed that endogenous erythropoietin, independently of other factors and biomarkers, determined the prognosis of annual mortality in patients with chronic heart failure (HR 3.27 (95% CI 1.08–9.91, p=0.03); χ2=30.7, p=0.0002). When constructing classification trees, in older patients with CHF in the presence of eEPO less than 16.19 mIU/ml NT-proBNP more than 232.5 pg/ml is an unfavorable factor (in patients with NT-proBNP &amp;lt;232.5 pg/ml the risk decreased to 0) (for model: sensitivity – 57.1%; specificity – 92.3% (AUC=0.87); p=0.0015). Conclusions The level of eEPO in older patients with CHF has an independent and closer relationship with the annual mortality of patients than the NT-proBNP – currently accepted biomarker of the severity and prognosis of CHF. Funding Acknowledgement Type of funding sources: None.

Effect of fasting hyperglycemia and insulin resistance on bone turnover markers in children aged 9-11years.

Impaired regulation of glucose metabolism in childhood adversely affects bone health. We assessed the effect of fasting hyperglycemia and insulin resistance on bone turnover markers in prepubertal children with normal glycemia (<100mg/dL) and fasting hyperglycemia (100-125mg/dL). Glucose, hemoglobin A1c, IGF-I (insulin-like growth factor I), iP1NP (N-terminal propeptide of type I procollagen), CTX-1 (C-terminal telopeptide of type I collagen) and insulin were measured. Bone turnover index (BTI) and HOMA-IR (homeostasis model assessment) were calculated. Bone resorption marker (CTX) levels were decreased by 26.5% in boys with hyperglycemia, though only 7% in girls. Hyperglycemia had no effect on the bone formation marker iP1NP. IGF-1, the best predictor of bone marker variance accounted for 25% of iP1NP and 5% of CTX variance. Girls presented significantly higher BTI indicating the predominance of bone formation over resorption. Insulin resistance significantly decreased CTX. In girls, HOMA-IR and IGF-1 predicted 15% of CTX variance. Fasting hyperglycemia and insulin resistance in children impact bone turnover suppressing bone resorption. Hyperglycemia decreased resorption, particularly in boys, while suppression of resorption by insulin resistance was more pronounced in girls. We suggest that the progression of disturbances accompanying prediabetes, may interfere with bone modelling and be deleterious to bone quality in later life.

Postoperative zoledronic acid for osteoporosis in primary hyperparathyroidism: a randomized placebo-controlled study.

In primary hyperparathyroidism (PHPT) with osteoporosis, bone mineral density (BMD) improves after parathyroidectomy. It is unclear whether combining surgery with postoperative bisphosphonate treatment can further improve bone health. This randomized, placebo-controlled study compared the effects of surgery alone and surgery combined with zoledronic acid on bone metabolism in PHPT with osteoporosis. Fifty-six patients (f/m 47/9, mean age 68.4 years) with PHPT and osteoporosis were randomized 1-3 months after parathyroidectomy to receive a 2-year treatment of zoledronic acid or placebo. Dual-energy X-ray absorptiometry (DXA) and bone turnover markers (N-terminal propeptide of type 1 procollagen, C-terminal telopeptide of type 1 collagen, and alkaline phosphatase) were measured annually during the 2-year follow-up. Two years after parathyroidectomy, BMD was significantly higher in the zoledronic acid (ZOL) group compared with the placebo (PBO) group at the femoral neck (P = 0.045 for Z-score) and lumbar spine (P = 0.039 and 0.017 for T- and Z-scores, respectively). Bone turnover markers were significantly lower in the ZOL group (P < 0.001 for all markers). Of the 18 patients who had received bisphosphonates for >1 year before surgery, BMD improved significantly in the ZOL group both in the femoral neck and lumbar spine (n = 10; all P < 0.001-0.01), but in the PBO group, only in the lumbar spine (n = 8, P = 0.03), (P = 0.08-0.95 for between-group changes). BMD increases after parathyroidectomy both with and without zoledronic acid but the increase is significantly higher with postoperative zoledronic acid.

Уровень N-терминального пропептида проколлагена І типа в сыворотке крови у людей разного возраста и пола

Целью исследования является определение уровня N-терминального пропептида проколлагена І типа (PINP) в сыворотке крови у здоровых мужчин и женщин всех возрастов. Материалы и методы. В исследование были включены 1568 человек (1422 лица женского и 146 — мужского пола) в возрасте 20–89 лет (средний возраст — 60,36 ± 13,68 года). Всех пациентов разделили на 7 групп, в соответствии с десятилетиями и геронтологической классификацией возраста: молодой возраст — 20–44 года, средний — 45–59 лет, пожилой — 60–74 года и старческий возраст — 75–89 лет. Во время исследования изучали влияние демографических характеристик (возраста и пола) на уровень PINP в сыворотке крови методом электрохемилюминесцентного иммуноанализа ECLIA на анализаторе cobas e 411. Результаты. В результате исследования у женщин не выявлено достоверного влияния возраста на вариабельность PINP в сыворотке крови (F = 1,453, р = 0,19). Выявлено достоверное снижение уровня PINP в возрастных группах: 40–49 лет (47,74 ± 21,31, р = 0,02), 60–69 лет (49,76 ± 25,75, р = 0,03), 70–79 лет (50,49 ± 26,71, р = 0,04), по сравнению с возрастной группой 20–29 лет (58,67 ± 27,46). По результатам регрессионного анализа выявлено достоверное снижение уровня PINP с возрастом у молодых женщин и мужчин (20–44 лет). При сравнении уровня PINP в сыворотке крови у представителей старшей возрастной группы (80–89 лет) обнаружено его повышение у женщин (55,20 ± 28,38 нг/мл) по сравнению с группой 70–79 лет (50,49 ± 26,71 нг/мл) и снижение у мужчин (54,87 ± 28,24 нг/мл и 39,16 ± 12,46 нг/мл соответственно). У мужчин обнаружено вероятное влияние возраста на вариабельность PINP в сыворотке крови (F = 3,08, р = 0,007). Выводы. По результатам регрессионного анализа установлено достоверное снижение уровня PINP с возрастом у мужчин и женщин 20–44 лет. Доказано вероятное влияние возраста на вариабельность PINP в сыворотке крови у мужчин. При сравнении уровня PINP в сыворотке крови у представителей старшей возрастной группы (80–89 лет) выявлено его повышение у женщин по сравнению с группой 70–79 лет и снижение у мужчин. Полученные нами результаты могут быть использованы как референтные данные уровня PINP в сыворотке крови у представителей украинской популяции разного возраста и пола.

Low Serum 25-hydroxyvitamin D Level Does Not Adversely Affect Bone Turnover in Prepubertal Children.

Both vitamin D and insulin-like growth factor 1 (IGF-1) play essential roles in bone metabolism and may interact during prepubertal bone accrual. We investigated the association of low serum 25-hydroxyvitamin D (25(OH)D) (<20 ng/mL) with the circulating bone turnover markers, when compared to their interaction with IGF-1. Subjects and Methods: Serum 25(OH)D, IGF-I, P1NP (N-terminal propeptide of type I procollagen), and CTX-1 (C-terminal telopeptide of type I collagen) were measured, and the bone turnover index (BTI) was calculated in 128 healthy children, aged 9–11 years. Results: Mean 25(OH)D concentration was 21.9 ± 4.9 ng/mL, but in 30.5% of participants it was <20 ng/mL (<50 nmol/L). We observed a trend for higher P1NP (p < 0.05) and IGF-1 (p = 0.08), towards lower 25(OH)D in tertiles. Levels of P1NP in the lowest 25(OH)D tertile (<20 ng/mL) were the highest, while CTX and BTI remained unchanged. Additionally, 25(OH)D negatively correlated with IGF-1, while the correlation with P1NP was not significant. A strong positive correlation of IGF-1 with P1NP and BTI but weak with CTX was observed. Low 25(OH)D (<20 ng/mL) explained 15% of the IGF-1 variance and 6% of the P1NP variance. Conclusions: Low levels of 25(OH)D do not unfavorably alter bone turnover. It seems that serum 25(OH)D level may not be an adequate predictor of bone turnover in children.

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

Recreational cycling is a popular activity which stimulates and improves cardiovascular fitness. The corresponding benefits for bone are unclear. 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). 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. 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. 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 Metabolism and RANKL/OPG Ratio in Rheumatoid Arthritis Women Treated with TNF-α Inhibitors.

The aim of this study was to evaluate the effect of anti-tumor necrosis factor α (anti-TNF-α) therapy in combination with methotrexate on bone remodeling and osteoclastogenesis in female patients with RA. Serum levels of bone turnover markers (i.e., C- and N-terminal propeptides of type I procollagen (PICP and PINP), C- and N-terminal cross-linking telopeptides of type I collagen (CTX-I and NTX-I), and soluble receptor activator of nuclear factor κB ligand (sRANKL) and osteoprotegerin (OPG)) were determined by immunoassay at baseline and 15 months after initiation of treatment. Bone mineral density was measured by dual-energy x-ray absorptiometry. We found a significant decrease in serum PINP levels, a biomarker of bone formation, and higher levels of CTX-I and sRANKL indicative of increased bone resorption in RA patients prior to TNFαI treatment compared to the controls. Anti-TNF-α therapy was effective in improving bone metabolism in RA patients as reflected in a decrease in CTX-I (at least partially due to the RANKL/OPG reduction) and a concomitant increase in PINP levels. The bone metabolism changes were independent of the type of TNFαI used. PINP and CTX-I were found to be useful markers of bone metabolism, which may prove the effectiveness of TNF-α therapy earlier than the bone density assessment.

Bone remodeling markers and their role in oncology

Bone metastases are a common complication of cancer. Patients with bone metastases may have experienced skeletal-related events, such as hypercalcemia, pathological fractures, pain syndrome of varying intensity, spinal cord compression with negative effects on the quality of life. Current diagnostic tools have some limitations, such as high cost and limited availability in the distant areas, as well as falls negative and falls positive results. In this aspect, non-invasive sensitive markers of bone metabolism might give additional valuable information. Bone remodeling markers (N-terminal propeptide of type 1 collagen, osteocalcin, C-terminal telopeptide of type 1 collagen, etc.) have been used for a long time to predict the effectiveness of osteoporosis treatment; as additional risk factors for treatment initiation in patients with osteoporosis, in diagnostic search for secondary forms of osteoporosis; and as predictors of fracture in population studies. This review summarizes the clinically relevant biochemical markers of bone remodeling and the available evidence for their use in the metastatic bone disease in particularly in the diagnosis and prognosis of bone metastases risk and skeletal complications, predicting clinical outcomes, bone disease progression and overall survival. It has been shown that a sufficient suppression of bone remodeling biochemical markers while on treatment with bisphosphonates is associated with an improvement in survival and a decrease in the risk of skeletal complications in patients with bone metastases. New data may become a rational basis for wider use of bone metabolism markers in oncological practice. However, it is necessary to standardize and validate the determination of bone markers and verification of cut-off diagnostic values for their introduction into the routine clinical practice of patients with malignancy.

Nomogram for predicting advanced liver fibrosis and cirrhosis in patients with chronic liver disease

BackgroundWe aimed to formulate a novel predictive nomogram to discriminate liver fibrosis stage in patients with chronic liver disease.MethodsNomograms were established based on the results of multivariate analysis. The predictive accuracy of the nomograms was assessed by ROC analysis and calibration. Decision curve analysis (DCA) was used to determine the clinical benefit of the nomograms.ResultsINR, platelets, and N-terminal propeptide type III collagen (PIIINP) were independent predictors for advanced liver fibrosis (≥ S3) and cirrhosis (S4) in patients with chronic liver disease in the training cohort. In the training set, the areas under the ROCs (AUROCs) of nomogram S3S4, APRI, FIB-4, and GPR for stage ≥ S3 were 0.83, 0.71, 0.68, and 0.74, respectively; the AUROCs of nomogram S4, APRI, FIB-4, and GPR for stage S4 were 0.88, 0.74, 0.78, and 0.79, respectively. The calibrations showed optimal agreement between the prediction by the established nomograms and actual observation. In the validation set, the AUROCs of nomogram S3S4, APRI, FIB-4, and GPR for stage ≥ S3 were 0.86, 0.79, 0.78, and 0.81, respectively; the AUROCs of nomogram S4, APRI, FIB-4, and GPR for stage S4 were 0.88, 0.77, 0.81, and 0.83, respectively. Furthermore, the decision curve analysis suggested that the nomograms represent better clinical benefits in both independent cohorts than APRI, FIB-4, and GPR.ConclusionThe constructed nomograms could be a superior tool for discriminating advanced fibrosis and cirrhosis in chronic liver disease.