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Annals of Clinical Biochemistry Jul 2017Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common...
Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16-25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27-131 µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers' relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.
Topics: Adolescent; Adult; Age Factors; Biomarkers; Bone Remodeling; Bone and Bones; Collagen Type II; Contraceptives, Oral, Hormonal; Cross-Sectional Studies; Female; Humans; Internet; Peptide Fragments; Procollagen; Reference Values; Sex Factors; Surveys and Questionnaires
PubMed: 27496795
DOI: 10.1177/0004563216665123 -
Yonsei Medical Journal Dec 2019Bone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone...
PURPOSE
Bone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone turnover, children and adolescents have higher bone marker levels than adults. Thus, a valid age- and sex-specific reference should be established for pediatric populations living in similar environments. We aimed to assess the associations of procollagen type I N-terminal propeptide (P1NP) and osteocalcin with age and sex in a group of healthy Korean children and adolescents.
MATERIALS AND METHODS
The participants (290 boys and 290 girls, age range 0-18 years) were Korean outpatients. Serum P1NP and osteocalcin levels were measured in control materials and patient samples by electrochemiluminescence immunoassay using an automated Cobas e411 analyzer.
RESULTS
Significant age-dependent variations in bone marker levels were observed in both sexes (<0.001). The highest P1NP levels were observed during the first year of life; thereafter, levels decreased until puberty. There was no postnatal peak for osteocalcin; however, its levels remained higher than the adult reference range throughout childhood. Significant differences were observed between boys and girls (<0.05), especially between the ages of 12 and 17 years. Cobas e411 results for P1NP showed satisfactory precision and linearity.
CONCLUSION
We established reference data for P1NP and osteocalcin levels in healthy Korean children and adolescents, as the first and only study of these parameters in pre-adulthood in Korea. Cobas e411-quantified bone markers may be useful for determining bone metabolism indices.
Topics: Adolescent; Adult; Biomarkers; Bone Remodeling; Bone and Bones; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Osteocalcin; Peptide Fragments; Procollagen; Reference Values; Republic of Korea; Young Adult
PubMed: 31769248
DOI: 10.3349/ymj.2019.60.12.1174 -
Journal of Bone and Mineral Research :... Jul 2017This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin... (Randomized Controlled Trial)
Randomized Controlled Trial
This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin antibody, in adults with moderate osteogenesis imperfecta (OI). Patients received BPS804 (three escalating doses each separated by 2 weeks [5, 10, and 20 mg/kg]) or no treatment (reference group). The primary efficacy endpoints were mean changes from baseline to day 43 in: procollagen type 1 N-terminal propeptide (P1NP), procollagen type 1 C-terminal propeptide (P1CP), bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and type 1 collagen cross-linked C-telopeptide (CTX-1). Mean change from baseline to day 141 in lumbar spine areal bone mineral density (aBMD) was also assessed. BPS804 safety and tolerability were assessed every 2 weeks. Overall, 14 adults were enrolled (BPS804 group: n = 9, mean age 30.7 years, mean aBMD Z-score -2.6; reference group, n = 5, mean age 27.4 years, mean aBMD Z-score -2.2). In the BPS804 group, P1NP, P1CP, BSAP, and OC were increased by 84% (p < 0.001), 53% (p = 0.003), 59% (p < 0.001), and 44% (p = 0.012), respectively, versus baseline (reference: P1NP, +6% [p = 0.651]; P1CP, +5% [p = 0.600]; BSAP, -13% [p = 0.582]; OC, -19% [p = 0.436]). BPS804 treatment downregulated CTX-1 by 44% from baseline (reference: -7%; significance was not tested for this biomarker), and increased aBMD by 4% (p = 0.038; reference group: +1%; p = 0.138). BPS804 was generally well tolerated. There were 32 adverse events reported in nine patients; none was suspected to be treatment-related. There were no treatment-related fractures. BPS804 stimulates bone formation, reduces bone resorption, and increases lumbar spine aBMD in adults with moderate OI. This paves the way for a longer-term, phase 3 trial into the efficacy, safety, and tolerability of BPS804 in patients with OI. © 2017 American Society for Bone and Mineral Research.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Adult; Alkaline Phosphatase; Antibodies, Monoclonal; Bone Density; Bone Morphogenetic Proteins; Female; Genetic Markers; Humans; Male; Osteocalcin; Osteogenesis Imperfecta; Peptide Fragments; Procollagen
PubMed: 28370407
DOI: 10.1002/jbmr.3143 -
Cells Mar 2024Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix (ECM), causing lung...
Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix (ECM), causing lung distortions and dysfunction. Animal models of human IPF can provide great insight into the mechanistic pathways underlying disease progression and a means for evaluating novel therapeutic approaches. In this study, we describe the effect of bleomycin concentration on disease progression in the classical rat bleomycin model. In a dose-response study (1.5, 2, 2.5 U/kg i.t), we characterized lung fibrosis at day 14 after bleomycin challenge using endpoints including clinical signs, inflammatory cell infiltration, collagen content, and bronchoalveolar lavage fluid-soluble profibrotic mediators. Furthermore, we investigated fibrotic disease progression after 2 U/kg i.t. bleomycin administration at days 3, 7, and 14 by quantifying the expression of clinically relevant signaling molecules and pathways, epithelial mesenchymal transition (EMT) biomarkers, ECM components, and histopathology of the lung. A single bleomycin challenge resulted in a progressive fibrotic response in rat lung tissue over 14 days based on lung collagen content, histopathological changes, and modified Ashcroft score. The early fibrogenesis phase (days 3 to 7) is associated with an increase in profibrotic mediators including TGFβ1, IL6, TNFα, IL1β, CINC1, WISP1, VEGF, and TIMP1. In the mid and late fibrotic stages, the TGFβ/Smad and PDGF/AKT signaling pathways are involved, and clinically relevant proteins targeting galectin-3, LPA1, transglutaminase-2, and lysyl oxidase 2 are upregulated on days 7 and 14. Between days 7 and 14, the expressions of vimentin and α-SMA proteins increase, which is a sign of EMT activation. We confirmed ECM formation by increased expressions of procollagen-1Aα, procollagen-3Aα, fibronectin, and CTGF in the lung on days 7 and 14. Our data provide insights on a complex network of several soluble mediators, clinically relevant signaling pathways, and target proteins that contribute to drive the progressive fibrotic phenotype from the early to late phase (active) in the rat bleomycin model. The framework of endpoints of our study highlights the translational value for pharmacological interventions and mechanistic studies using this model.
Topics: Rats; Humans; Animals; Procollagen; Idiopathic Pulmonary Fibrosis; Fibrosis; Collagen; Bleomycin; Disease Progression
PubMed: 38534359
DOI: 10.3390/cells13060515 -
Archivos de Bronconeumologia Sep 2015Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases.
BACKGROUND
Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases.
OBJECTIVES
To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc.
METHODS
Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups.
RESULTS
Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58μg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26μg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045).
CONCLUSIONS
PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc.
Topics: Collagen Type I; Cross-Sectional Studies; Disease Progression; Female; Humans; Lung Diseases, Interstitial; Mexico; Middle Aged; Peptide Fragments; Procollagen; Scleroderma, Systemic; Severity of Illness Index
PubMed: 25301411
DOI: 10.1016/j.arbres.2014.06.018 -
Acta Orthopaedica Et Traumatologica... Jan 2023The aim of this study was to evaluate the effects of vitamin K2 on fracture healing.
OBJECTIVE
The aim of this study was to evaluate the effects of vitamin K2 on fracture healing.
METHODS
Twenty-four 6-week-old male Wistar albino rats that had open tibia fractures induced were included in this study. They were divided into 2 groups of 12, a group that had vitamin K2 administered over 30 consecutive days and a control group. After 30 days, the rats were sacrificed, and from each group, 6 tibiae were selected for biomechanical testing to examine the mechanical strength of the callus tissue using the Instron 3-point bending test and 6 tibiae were selected for histological analysis to examine the density and organization of callus tissue using Allen's grading system and Huo et al's grading system. Furthermore, weekly x-rays were taken to evaluate bone union described by Lane and Sandhu, and osteocalcin, procollagen I N-terminal propeptide, and procollagen I C-terminal propeptide were examined in blood samples taken by intracardiac puncture during sacrification.
RESULTS
Breaking force (P = .047), breaking time (P = .019), stiffness (P = .039), fracture strength (P = .041), and Young's modulus (P = .032) showed a statistically significant increase in the K2 group. Procollagen I C-terminal propeptide (P = .024), procollagen I N-terminal propeptide (.047), and osteocalcin (.048) levels were significantly higher in the K2 group compared to the control group. Furthermore, 3rd-week x-rays showed higher bone union scores according to the Lane and Sandhu method in the K2 group (P = .014). However, the histological grading systems of Allen and Huo et al did not show statistically significant differences between groups (P = .086, P = .07, respectively).
CONCLUSION
In light of these findings, it could be concluded that vitamin K2 has a significant positive effect on fracture healing.
Topics: Animals; Rats; Male; Fracture Healing; Vitamin K 2; Tibia; Osteocalcin; Procollagen; Rats, Wistar; Tibial Fractures; Biomechanical Phenomena
PubMed: 36939360
DOI: 10.5152/j.aott.2023.21013 -
European Journal of Endocrinology Jan 2018Bone turnover markers (BTMs) are useful in clinical practice as they are inexpensive, and they have proven useful for treatment monitoring and identification of poor... (Review)
Review
Bone turnover markers (BTMs) are useful in clinical practice as they are inexpensive, and they have proven useful for treatment monitoring and identification of poor adherence. BTMs cannot be used in individual patients for identifying accelerated bone loss or an increase in fracture risk or in deciding on the optimal therapy. They are useful for monitoring both anti-resorptive and anabolic treatment. Response can be defined as a result that exceeds an absolute target, or by a change greater than the least significant change; if such a response is not present, then poor compliance or secondary osteoporosis are likely causes. A baseline BTM measurement is not always made; in that case, a value of BTM on anti-resorptive treatment that is low or low normal or above the reference interval for anabolic therapy may be taken to indicate a satisfactory response. We provide an approach to using these bone turnover markers in clinical practice by describing algorithms for anti-resorptive and anabolic therapy and describing the changes we observe in the clinical practice setting.
Topics: Biomarkers; Bone Density; Bone Remodeling; Bone Resorption; Endocrine System Diseases; Humans; Osteocalcin; Peptide Fragments; Procollagen
PubMed: 29046326
DOI: 10.1530/EJE-17-0585 -
Journal of Psychiatric Research Feb 2023Higher levels of neurofilament light chain (NfL) and proinflammatory cytokines (i.e., tumor necrosis factor [TNF]-α) were observed in patients with bipolar disorder...
Procollagen type 1 N-terminal propeptide, neurofilament light chain, proinflammatory cytokines, and cognitive function in bipolar and major depressive disorders: An exploratory study of brain- bone axis and systemic inflammation.
BACKGROUND
Higher levels of neurofilament light chain (NfL) and proinflammatory cytokines (i.e., tumor necrosis factor [TNF]-α) were observed in patients with bipolar disorder (BD) and major depressive disorder (MDD). Procollagen type 1 N-terminal propeptide (P1NP), a bone turnover biomarker, is related to MDD. The association among the brain-bone axis, systemic inflammation, and cognitive function remains unclear in severe affective disorders.
METHODS
Overall, 25 patients with BD, 24 with MDD, and 29 matched controls were enrolled in the current study and underwent the measurements of the NfL, P1NP, and proinflammatory cytokine levels and 1-back and 2-back working memory tasks. Generalized linear models (GLMs) were used to examine the aforementioned biomarkers between the groups and clarify the association with each other.
RESULTS
GLMs showed increased levels of NfL (p = 0.001, p = 0.020) and P1NP (p = 0.050, p = 0.032) in the patients with BD and MDD than in the controls and suggested significant correlations between the NfL level and the mean time of the 2-back working memory task (p = 0.038) and between P1NL and TNF-α levels (p < 0.001).
DISCUSSION
Our study revealed the dysregulated brain-bone axis, indicated by elevated NfL and P1NP levels, and related cognitive impairment and systemic inflammation in the patients with BD and MDD. Additional studies are necessary to elucidate definite pathomechanisms underlying those conditions.
Topics: Humans; Depressive Disorder, Major; Bipolar Disorder; Cytokines; Procollagen; Intermediate Filaments; Brain; Cognition; Inflammation; Tumor Necrosis Factor-alpha; Biomarkers
PubMed: 36657346
DOI: 10.1016/j.jpsychires.2023.01.012 -
Frontiers in Endocrinology 2022Undercarboxylated osteocalcin (ucOC) is one form of osteocalcin lacking full carboxylation, which plays an important role in bone homeostasis, glucose homeostasis, and...
Undercarboxylated Osteocalcin and Its Associations With Bone Mineral Density, Bone Turnover Markers, and Prevalence of Osteopenia and Osteoporosis in Chinese Population: A Cross-Sectional Study.
OBJECTIVE
Undercarboxylated osteocalcin (ucOC) is one form of osteocalcin lacking full carboxylation, which plays an important role in bone homeostasis, glucose homeostasis, and energy metabolism. Our aim is to obtain the profile of serum ucOC level according to gender and age and explore its associations with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteopenia and osteoporosis in the Chinese population.
METHODS
This is a cross-sectional study with 900 subjects, composed of 431 men and 469 women. Clinical information was collected, and BMD values of the lumbar spine (L1-4), left femoral neck, and total hip were scanned. Biochemical markers including hepatic and renal function, serum calcium, serum phosphorus, procollagen type 1 N-propeptide (P1NP) β-CrossLaps of type I collagen-containing cross-linked C-telopeptide (β-CTX) intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ucOC were measured.
RESULTS
We found that the median ucOC level was higher in men than women [men, 2.6 ng/ml; women, 1.6 ng/ml; < 0.001]. The profile according to age showed that ucOC levels were the lowest at the age of 40-49 years in both men [2.55 ng/ml (95% CI = 1.96-3.13 ng/ml)] and women [1.57 ng/ml (95% CI = 1.12-2.03 ng/ml)]; in patients younger than 49 years, they decreased with age; then over 50 years, they quickly increased. Furthermore, we found that a higher ucOC level was correlated with lower BMD values at the lumbar spine (men, r = -0.128, = 0.013; women, r = -0.321, < 0.001), femoral neck (men, r = -0.095, = 0.062; women, r = -0.260, < 0.001), and total hip (men, r = -0.123, = 0.015; women, r = -0.209, < 0.001) and higher P1NP (men, r = 0.307, < 0.001; women, r = 0.239, < 0.001) and β-CTX (men, r = 0.169, = 0.001; women, r = 0.354, < 0.001) levels in both men and women. Furthermore, we also showed that a 1 - SD increase in ucOC was associated with an odds ratio (OR) of 1.63 and 1.70 for having osteopenia or osteoporosis in men and women, respectively (men, 95% CI = 1.25-2.13, = 0.004; women, 95% CI = 1.19-2.42, = 0.004).
CONCLUSIONS
We first revealed the profile of serum ucOC levels according to gender and age in the Chinese population and demonstrated the associations of ucOC with BMD and BTMs and the risk of prevalent osteopenia or osteoporosis. Our findings provide a clue to elucidate the function of ucOC in bone metabolism.
Topics: Adult; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; China; Cross-Sectional Studies; Female; Femur Neck; Humans; Male; Middle Aged; Osteocalcin; Osteoporosis; Peptide Fragments; Prevalence; Procollagen
PubMed: 35898467
DOI: 10.3389/fendo.2022.843912 -
International Journal of Clinical... 2023To determine the bone metabolic marker changes from childhood to adolescence and to provide reference values for monitoring bone development in children in Southwest...
OBJECTIVES
To determine the bone metabolic marker changes from childhood to adolescence and to provide reference values for monitoring bone development in children in Southwest China.
METHODS
We surveyed 703 participants attending physical examinations from April 2019 and August 2021. Twenty-eight participants were excluded for lack of laboratory tests, and 14 people were excluded for diseases that might affect bone metabolism. A total of 661 children were selected for the study. According to the main developmental periods, the children were divided into preschool, preadolescence, and adolescence groups. Serum bone turnover markers including -isomerized C-terminal telopeptide of type I collagen (-CTx), N-terminal midfragment of osteocalcin (N-MID), and procollagen type 1 N-propeptide (P1NP) as well as growth and development indices such as serum calcium (Ca), phosphorus (Pi), alkaline phosphatase (ALP), and vitamin D were measured. The changes in bone metabolism-related markers and the correlations between the indices were analyzed.
RESULTS
During the development in boys, the levels of -CTx and N-MID increased with age from preschool to adolescence, while the levels of P1NP decreased and then increased. In girls, the levels of -CTx and N-MID plateaued in early adolescence and showed little change in subsequent adolescence, while the levels of P1NP exhibited a downward trend. The correlations between bone metabolism markers and vitamin D were not significant.
CONCLUSIONS
The levels of bone metabolism markers differed between boys and girls. Reference intervals can be used as essential tools to examine the levels of bone metabolism markers reasonably.
Topics: Male; Child; Female; Humans; Child, Preschool; Adolescent; Peptide Fragments; Procollagen; Vitamin D; Bone and Bones; Biomarkers; Vitamins; Bone Remodeling
PubMed: 37547099
DOI: 10.1155/2023/5537182