Lipocalin 2 serum levels correlate with age and bone turnover biomarkers in healthy subjects but not in postmenopausal osteoporotic women

Abstract Abstract 3780 Background: Gaucher Disease (GD) is an autosomal recessive hereditary disorder of glycosphingolipid metabolism, characterized by accumulation of glucosylceramide in cells of the reticulo-endothelial system, due to the deficient activity of the lysosomal enzyme glucocerebrosidase. Bone manifestations are frequent in GD; nevertheless the pathophysiology of skeletal involvement is still not well understood. Aim: to investigate the role of the bone turnover biochemical markers in GD. In particular we evaluated markers involved in bone formation: Osteoprotegerin (OPG), carboxyterminal propeptide of type I procollagen (PICP), osteocalcin (OST) and in bone resorption: receptor activator of nuclear factor (NF)-kb ligand (RANKL), tartrate resistant acid phosphatase (TRAP5b). Methods: Bone turnover biochemical markers were evaluated on sera obtained from 5 GD patients and 5 healthy subjects matched for age and sex, by Elisa commercial available kits according to the manufacturers‘ instructions. Results: In GD patients we observed an increase of RANKL and a significant reduction of OPG, with a consequent significantly lower OPG/RANKL ratio. Despite of higher levels of TRAP5b and lowest levels of PICP in GD compared to healthy subjects the differences did not achieve statistical significance, likely due to the small number of subjects involved in the study. No differences we observed in serum levels of OST compared with controls. Data (means ± DS) are reported in Table 1. Conclusions: Our data confirm the presence of unbalanced bone turnover in GD patients, characterized by an altered modulation of the OPG/RANKL system (due mainly to reduced expression of OPG, besides increased production of RANKL), an increased resorption phase (TRAP5b) and a decreased neoformation phase (PICP), all of them contributing to skeletal alterations characteristics of these patients. Disclosures: No relevant conflicts of interest to declare.

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Status of circulating bone turnover markers in elderly osteoporosis/osteopenia patients in comparison with healthy subjects

Asian Biomedicine ◽

10.1515/abm-2020-0015 ◽

2020 ◽

Vol 14 (3) ◽

pp. 97-106

Author(s):

Sadra Samavarchi Tehrani ◽

Maryam Moallem ◽

Reyhane Ebrahimi ◽

Seyed Reza Hosseini ◽

Hajighorban Nooreddini ◽

...

Keyword(s):

Bone Turnover ◽

Bone Turnover Markers ◽

Healthy Subjects ◽

Serum Levels ◽

Elderly Subjects ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Mineral Density ◽

Major Health Problem ◽

Turnover Markers

AbstractBackgroundIn the aging individuals, osteoporosis is a major health problem. Due to the various limitations of dual X-ray absorptiometry (DEXA) for diagnosis osteoporosis, serum-based biochemical markers have been suggested for the discrimination between the patients and healthy subjects.ObjectiveTo investigate the serum levels of bone turnover markers in elderly osteoporosis patients.MethodsThe serum samples from elderly subjects (osteoporosis (n = 28), osteopenia (n = 28), and healthy ones (n = 28) were collected from Amirkola Health and Ageing Project study. Furthermore, serum levels of bone formation and bone resorption markers as well as estrogen and progesterone were measured by enzyme-linked immunosorbent assay. Kruskal–Wallis test and receiver operating characteristic curve analysis were used for statistical analysis using SPSS.ResultsLevels of bone alkaline phosphatase (B-ALP) and procollagen type I N-terminal propeptide (PINP) differed between groups (P = 0.003 and 0.009, respectively). Furthermore, PINP and B-ALP levels had the best area under the curve, sensitivity, and specificity for the discrimination between patients with osteoporosis and healthy individuals.ConclusionIn conditions in which we are not able to assess the bone mineral density by DEXA, analysis of the B-ALP and PINP levels may be a helpful tool.

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Detection and Quantification of 7-Hydroxydehydroepiandrosterone Epimers in Three Body Fluids

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20020010 ◽

2002 ◽

Vol 67 (1) ◽

pp. 10-18 ◽

Cited By ~ 1

Author(s):

Richard Hampl ◽

Martin Hill ◽

Luboslav Stárka

Keyword(s):

Healthy Subjects ◽

Serum Levels ◽

Body Fluids ◽

Gas Chromatography Mass Spectrometry ◽

Specific Radioimmunoassay ◽

Order Of Magnitude ◽

Three Body ◽

First Time ◽

Nanomolar Range ◽

Detection And Quantification

3β,7α-Dihydroxyandrost-5-en-17-one (1) (7α-OH-DHEA) and its 7β-hydroxy epimer 2 (7β-OH-DHEA) - 7α- and 7β-hydroxydehydroepiandrosterone - were detected and quantified in three human body fluids: in blood serum, saliva and ejaculate. Specific radioimmunoassay and gas chromatography-mass spectrometry have been used. For the first time the data on changes of these dehydroepiandrosterone metabolites are reported for a representative group of healthy subjects of both sexes (172 females and 217 males) during the life span. The serum levels of both 7-hydroxydehydroepiandrosterone epimers in serum and also in semen were in the low nanomolar range, while concentrations by one order of magnitude lower were found in saliva, but still within the detection limit. The results will serve as a basis for comparative studies of 7-hydroxydehydroepiandrosterone levels under various pathophysiological conditions, with a particular respect to autoimmune disorders.

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Gallium nitrate inhibits accelerated bone turnover in patients with bone metastases.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.2.292 ◽

1987 ◽

Vol 5 (2) ◽

pp. 292-298 ◽

Cited By ~ 40

Author(s):

R P Warrell ◽

N W Alcock ◽

R S Bockman

Keyword(s):

Bone Turnover ◽

Bone Metastases ◽

Vitamin D3 ◽

Biochemical Parameters ◽

Serum Levels ◽

Calcium Excretion ◽

Gallium Nitrate ◽

Clinical Effects ◽

Short Term Treatment

Bone metastases are a major source of morbidity in patients with cancer. Previously, we found that gallium nitrate was a highly effective treatment for cancer-related hypercalcemia. Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We evaluated the clinical effects of gallium nitrate on biochemical parameters of increased bone turnover in 22 patients with bone metastases. Treatment with gallium nitrate for five to seven days caused a median reduction in 24-hour urinary calcium excretion of 66% relative to baseline measurements (P less than .01). Hydroxyproline (OHP) excretion was also significantly reduced (P less than .01). The greatest reduction in hydroxyprolinuria occurred in patients with high baseline excretion. Ionized serum calcium and serum phosphorous declined significantly after treatment (P less than .01 for each). Serum immunoreactive parathyroid hormone (PTH) increased significantly (P less than .01), as did serum levels of 1,25 (OH)2-vitamin D3 (P less than .05). Urinary phosphorous excretion and serum levels of 25-OH-vitamin D3 were not significantly changed. No major toxic reactions occurred as a result of this treatment. These results indicate that gallium nitrate significantly reduces biochemical parameters associated with accelerated bone turnover and that this agent may be useful for preventing pathologic conditions associated with bone metastases.

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The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18126282 ◽

2021 ◽

Vol 18 (12) ◽

pp. 6282

Author(s):

Magda Wiśniewska ◽

Natalia Serwin ◽

Violetta Dziedziejko ◽

Małgorzata Marchelek-Myśliwiec ◽

Barbara Dołęgowska ◽

...

Keyword(s):

Healthy Subjects ◽

Plasma Concentrations ◽

Serum Levels ◽

Hemodialysis Patients ◽

Pressure Regulation ◽

Serum Concentrations ◽

Monoamine Oxidase Activity ◽

Normal Kidney ◽

Bilateral Nephrectomy ◽

Arterial Blood

Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01). Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.

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POS1002 BASELINE CALPROTECTIN AND VISFATIN LEVELS PREDICT RADIOGRAPHIC SPINAL PROGRESSION AFTER 2 YEARS IN ANKYLOSING SPONDYLITIS PATIENTS ON TNF INHIBITOR THERAPY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3059 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 769.2-770

Author(s):

J. Rademacher ◽

M. Siderius ◽

L. Gellert ◽

F. Wink ◽

M. Verba ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Ankylosing Spondylitis ◽

Bone Formation ◽

Bone Turnover ◽

Radiographic Progression ◽

Serum Levels ◽

Tnf Inhibitor ◽

Research Support

Background:Radiographic spinal progression determinates functional status and mobility in ankylosing spondylitis (AS)1.Objectives:To analyse whether biomarker of inflammation, bone turnover and adipokines at baseline or their change after 3 months or 2 years can predict spinal radiographic progression after 2 years in AS patients treated with TNF-α inhibitors (TNFi).Methods:Consecutive AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort2 starting TNFi between 2004 and 2012 were included. The following serum biomarkers were measured at baseline, 3 months and 2 years of follow-up with ELISA: - Markers of inflammation: calprotectin, matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF) - Markers of bone turnover: bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide (sCTX), osteocalcin (OC), osteoprotegerin (OPG), procollagen typ I and II N-terminal propeptide (PINP; PIINP), sclerostin. - Adipokines: high molecular weight (HMW) adiponectin, leptin, visfatinTwo independent readers assessed spinal radiographs at baseline and 2 years of follow-up according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Radiographic spinal progression was defined as mSASSS change ≥2 units or the formation of ≥1 new syndesmophyte over 2 years. Logistic regression was performed to examine the association between biomarker values at baseline, their change after 3 months and 2 years and radiographic spinal progression. Multivariable models for each biomarker were adjusted for mSASSS or syndesmophytes at baseline, elevated CRP (≥5mg/l), smoking status, male gender, symptom duration, BMI, and baseline biomarker level (the latter only in models with biomarker change).Results:Of the 137 included AS patients, 72% were male, 79% HLAB27+; mean age at baseline was 42 years (SD 10.8), ASDAScrp 3.8 (0.8) and mSASSS 10.6 (16.1). After 2 years of follow-up, 33% showed mSASSS change ≥2 units and 24% had developed ≥1 new syndesmophyte. Serum levels of biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, whereas adipokine levels were not altered from baseline (Figure 1).Univariable logistic regression revealed a significant association of baseline visfatin (odds ratio OR [95% confidence interval] 1.106 [1.007-1.215]) and sclerostin serum levels (OR 1.006 [1.001-1.011]) with mSASSS progression after 2 years. Baseline sclerostin levels were also associated with syndesmophyte progression (OR 1.007 [1.001-1.013]). In multivariable logistic analysis, only baseline visfatin level remained significantly associated (OR 1.465 [1.137-1.889]) with mSASSS progression. Furthermore, baseline calprotectin showed a positive association with both, mSASSS (OR 1.195 [1.055-1.355]) and syndesmophyte progression (OR 1.107 [1.001-1.225]) when adjusting for known risk factors for radiographic progression.Univariable logistic regression showed that change of sclerostin after 3 months was associated with syndesmophytes progression (OR 1.007 [1.000-1.015), change of PINP level after 2 years was associated with mSASSS progression (OR 1.027 [1.003-1.052]) and change of visfatin after 2 years was associated with both measures of radiographic progression – mSASSS (OR 1.108 [1.004-1.224]) and syndesmophyte formation (OR 1.115; [1.002-1.24]). However, those associations were lost in multivariable analysis.Conclusion:Independent of known risk factors, baseline calprotectin and visfatin levels were associated with radiographic spinal progression after 2 years of TNFi. Although biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, these changes were not significantly related to radiographic spinal progression in our cohort of AS patients.References:[1]Poddubnyy et al 2018[2]Maas et al 2019Acknowledgements:Dr. Judith Rademacher is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health.Disclosure of Interests:Judith Rademacher: None declared, Mark Siderius: None declared, Laura Gellert: None declared, Freke Wink Consultant of: AbbVie, Maryna Verba: None declared, Fiona Maas: None declared, Lorraine M Tietz: None declared, Denis Poddubnyy: None declared, Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, UCB, Lilly and Novartis, Grant/research support from: Abbvie, Pfizer, UCB, Novartis, Suzanne Arends Grant/research support from: Pfizer.

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Serum levels of bone formation and resorption markers in relation to vitamin D status in professional gymnastics and physically active men during upper and lower body high-intensity exercise

Journal of the International Society of Sports Nutrition ◽

10.1186/s12970-021-00430-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Jan Mieszkowski ◽

Andrzej Kochanowicz ◽

Elżbieta Piskorska ◽

Bartłomiej Niespodziński ◽

Joanna Siódmiak ◽

...

Keyword(s):

Vitamin D ◽

Bone Formation ◽

Bone Turnover ◽

Bone Turnover Markers ◽

Type I Collagen ◽

Serum Levels ◽

Type I ◽

Vitamin D Metabolites ◽

Physically Active ◽

Turnover Markers

Abstract Purpose/introduction To compare serum levels of bone turnover markers in athletes and non-athletes, and to evaluate the relationship between serum levels of vitamin D metabolites and exercise-induced changes in biomarker levels. Methods Sixteen elite male artistic gymnasts (EG; 21.4 ± 0.8 years-old) and 16 physically active men (the control group, PAM; 20.9 ± 1.2 years-old) performed lower and upper body 30-s Wingate anaerobic tests (LBWT and UBWT, respectively). For biomarker analysis, blood samples were collected before, and 5 and 30 min after exercise. Samples for vitamin D levels were collected before exercise. N-terminal propeptide of type I collagen (PINP) was analysed as a marker of bone formation. C-terminal telopeptide of type I collagen (CTX) was analysed as a marker of bone resorption. Results UBWT fitness readings were better in the EG group than in the PAM group, with no difference in LBWT readings between the groups. UBWT mean power was 8.8% higher in subjects with 25(OH)D3 levels over 22.50 ng/ml and in those with 24,25(OH)2D3 levels over 1.27 ng/ml. Serum CTX levels increased after both tests in the PAM group, with no change in the EG group. PINP levels did not change in either group; however, in PAM subjects with 25(OH)D3 levels above the median, they were higher than those in EG subjects. Conclusion Vitamin D metabolites affect the anaerobic performance and bone turnover markers at rest and after exercise. Further, adaptation to physical activity modulates the effect of anaerobic exercise on bone metabolism markers.

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Bone Pain in Multiple Myeloma (BPMM)—A Protocol for a Prospective, Longitudinal, Observational Study

Cancers ◽

10.3390/cancers13071596 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1596

Author(s):

Marta Diaz-delCastillo ◽

Rebecca E. Andrews ◽

Aritri Mandal ◽

Thomas L. Andersen ◽

Andrew D. Chantry ◽

...

Keyword(s):

Quality Of Life ◽

Multiple Myeloma ◽

Observational Study ◽

Bone Turnover ◽

Bone Pain ◽

Subjective Experience ◽

Prospective Longitudinal ◽

Bone Turnover Biomarkers

Multiple myeloma (MM) is a bone marrow neoplasia that causes bone pain in 70% patients. While preclinical models of MM have suggested that both nerve sprouting and nerve injury may be causative for the pain, there is a lack of clinical data. Thus, the primary aims of this clinical study are: (1) to provide a deep characterization of the subjective experience of pain and quality of life in MM patients; (2) to investigate disturbances in the bone innervation of MM patients. Secondary aims include exploring correlations between pain and serum inflammatory and bone turnover biomarkers. In a prospective, observational study (clinicaltrials.gov: NCT04273425), patients with suspected MM requiring a diagnostic iliac crest biopsy at Sheffield Teaching Hospital (UK) are invited to participate. Consenting patients answer seven standardized questionnaires assessing pain, quality of life and catastrophizing. Bone turnover biomarkers and inflammatory cytokines are measured in fasting serum samples, and bone innervation is evaluated in diagnostic biopsies. MM patients are invited to a follow-up upon completion of first line treatment. This will be the first deep characterization of pain in MM patients and its correlation with disturbances in bone innervation. Understanding how bone turnover and inflammation correlate to pain in MM is crucial to identify novel analgesic targets for this condition.

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The holding temperature of blood during a delay to processing can affect serum and plasma protein measurements

Scientific Reports ◽

10.1038/s41598-021-85052-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Milton Ashworth ◽

Benjamin Small ◽

Lucy Oldfield ◽

Anthony Evans ◽

William Greenhalf ◽

...

Keyword(s):

Healthy Subjects ◽

Room Temperature ◽

Serum Levels ◽

Data Interpretation ◽

Blood Samples ◽

Specific Manner ◽

Associated Proteins ◽

Holding Temperature ◽

Pai 1 ◽

Meaningful Data

AbstractAccurate blood-borne biomarkers are sought for diagnosis, prognosis and treatment stratification. Consistent handling of blood is essential for meaningful data interpretation, however, delays during processing are occasionally unavoidable. We investigated the effects of immediately placing blood samples on ice versus room temperature for 1 h (reference protocol), and holding samples on ice versus room temperature during a 3 h delay to processing. Using Luminex multi-plex assays to assess cytokines (n = 29) and diabetes-associated proteins (n = 15) in healthy subjects, we observed that placing blood samples immediately on ice decreased the serum levels of several cytokines, including PAI-1, MIP1-β, IL-9, RANTES and IL-8. During a delay to processing, some analytes, e.g. leptin and insulin, showed little change in serum or plasma values. However, for approximately half of the analytes studied, a delay, regardless of the holding temperature, altered the measured levels compared to the reference protocol. Effects differed between serum and plasma and for some analytes the direction of change in level varied across individuals. The optimal holding temperature for samples during a delay was analyte-specific. In conclusion, deviations from protocol can lead to significant changes in blood analyte levels. Where possible, protocols for blood handling should be pre-determined in an analyte-specific manner.

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