scholarly journals Serum Sclerostin Levels Are Decreased in Adult Patients With Different Types of Osteogenesis Imperfecta

2014 ◽  
Vol 99 (2) ◽  
pp. E311-E319 ◽  
Author(s):  
Roland Kocijan ◽  
Christian Muschitz ◽  
Astrid Fahrleitner-Pammer ◽  
Karin Amrein ◽  
Peter Pietschmann ◽  
...  
Keyword(s):  
Body Composition ◽  
Mineral Content ◽  
Adult Patients ◽  
Type I ◽  
Healthy Controls ◽  
Amino Terminal ◽  
Type I Procollagen ◽  
Different Types ◽  
Turnover Markers

Context: There are no specific biochemical bone markers available for osteogenesis imperfecta (OI), and the role of sclerostin as a key regulator of bone formation in OI is unknown. Objectives: We aimed to evaluate the role of sclerostin and its association with bone turnover markers as well as body composition parameters in adult patients with different types of OI. Design, Setting, and Participants: This was a case-control study in 27 adult patients and 50 healthy age- and gender-matched controls. Main Outcome Measures: Serum sclerostin levels and bone turnover markers including serum osteocalcin, amino terminal propeptide of type I procollagen, and CrossLaps as well as body composition parameters were determined in mild OI stage I (OI-I) and moderate-severe OI stages III-IV (OI-III-IV), according to Sillence classification. Data were compared with healthy controls. Results: Sclerostin levels were significantly lower in OI-I (19.9 ± 10.9 pmol/L; P < .001) and OI-III-IV (13.3 ± 10.0 pmol/L; P < .001) compared with healthy adults (45.3 ± 14.9 pmol/L), even after adjustment for age, sex, bone mineral content, and body mass index. CrossLaps and PTH were significantly lower in OI-I (0.197 ± 0.15 ng/L; P = .007 and 33.7 ± 19.1 pg/L; P = .033, respectively) and OI-III-IV (0.221 ± 0.18 ng/L; P = .039, and 27.9 ± 14.7 pg/L; P = .001, respectively) than in healthy controls (0.322 ± 0.15 ng/L and 45.0 ± 16.6 pg/L). Amino-terminal propeptide of type I procollagen was below the reference range for OI-I and OI-III-IV. Patients with OI were shorter and lighter and had a decreased bone mineral content (P < .001) but similar fat distribution and lean body mass, compared with controls. Serum sclerostin levels were not related to any bone marker except osteocalcin, the number of prevalent fractures, or body composition readings. Conclusion: Decreased sclerostin levels in OI might reflect a down-regulation or negative feedback mechanism to prevent further bone loss.

scholarly journals Acute Decline in Serum Sclerostin in Response to PTH Infusion in Healthy Men

2011 ◽  
Vol 96 (11) ◽  
pp. E1848-E1851 ◽  
Author(s):  
Elaine W. Yu ◽  
Ruchit Kumbhani ◽  
Erica Siwila-Sackman ◽  
Benjamin Z. Leder
Keyword(s):  
Wnt Pathway ◽  
Healthy Adult ◽  
Serum Levels ◽  
Ionized Calcium ◽  
Type I ◽  
Amino Terminal ◽  
Adult Men ◽  
Type I Procollagen ◽  
Serum Ionized Calcium ◽  
Turnover Markers

Abstract Context: Animal models suggest that the osteoblast-stimulating actions of PTH are mediated by acute suppression of sclerostin, an inhibitor of the anabolic Wnt pathway. The immediate physiological changes in serum sclerostin in response to PTH infusion have not been reported in human studies. Objective: We sought to determine the acute physiological effects of PTH infusion on serum sclerostin and bone turnover markers in healthy adult men. Design, Setting, and Participants: Fifty-three healthy adult men underwent an 18-h iv infusion of human PTH(1-34) at a dose of 0.55 U/kg · h. Outcomes: Serum levels of ionized calcium, sclerostin, and markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and bone resorption (C-telopeptide and N-telopeptide) were obtained at 0, 6, 12, and 18 h. Results: Serum ionized calcium, C-telopeptide, and N-telopeptide increased, and osteocalcin and amino-terminal propeptide of type I procollagen fell linearly throughout the PTH infusion (P < 0.001 for all). Average ± sem sclerostin levels declined from 936 ± 65 to 813 ± 63 pg/ml at 6 h (P < 0.001) and remained stably suppressed for the duration of the PTH infusion. There were no significant correlations between change in sclerostin and change in bone markers. Conclusions: Serum sclerostin declined in response to acute PTH infusion within 6 h in healthy adult men. The early plateau in sclerostin suppression may indicate that maximal stimulation of the Wnt pathway is achieved quickly after exposure to PTH. Our findings support the hypothesis that PTH may mediate its anabolic effects in part via suppression of sclerostin.

Role of the amino-terminal extrahelical region of type I collagen in directing the 4D overlap in fibrillogenesis

Biopolymers ◽  
1979 ◽  
Vol 18 (12) ◽  
pp. 3005-3014 ◽  
Author(s):  
Donald L. Helseth ◽  
Joseph H. Lechner ◽  
Arthur Veis
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Amino Terminal

scholarly journals A multicenter study to evaluate harmonization of assays for N-terminal propeptide of type I procollagen (PINP): a report from the IFCC-IOF Joint Committee for Bone Metabolism

2019 ◽  
Vol 57 (10) ◽  
pp. 1546-1555 ◽  
Author(s):  
Etienne Cavalier ◽  
Richard Eastell ◽  
Niklas Rye Jørgensen ◽  
Konstantinos Makris ◽  
Symeon Tournis ◽  
...  
Keyword(s):  
Multicenter Study ◽  
Evaluation Method ◽  
Clinical Laboratory ◽  
Cellular Level ◽  
Type I ◽  
Type I Procollagen ◽  
Edta Plasma ◽  
Turnover Markers ◽  
Routine Clinical Laboratory ◽  
The Relationship

Abstract Background Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies. Methods We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [UK]) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers’ instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method and the concordance correlation coefficient for PINP values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Results We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods. Conclusions Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals.

Antithrombin Dublin (p.Val30Glu): a relatively common variant with moderate thrombosis risk of causing transient antithrombin deficiency

2016 ◽  
Vol 116 (07) ◽  
pp. 146-154 ◽  
Author(s):  
José Navarro-Fernández ◽  
María Morena-Barrio ◽  
José Padilla ◽  
Antonia Miñano ◽  
Nataliya Bohdan ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Thrombotic Event ◽  
Type I ◽  
Antithrombin Deficiency ◽  
Amino Terminal ◽  
Thrombosis Risk ◽  
Functional Consequences ◽  
Low Incidence ◽  
Two Populations

SummaryThe key haemostatic role of antithrombin and the risk of thrombosis associated with its deficiency support that the low incidence of antithrombin deficiency among patients with thrombosis might be explained by underestimation of this disorder. It was our aim to identify mutations in SERPINC1 causing transient antithrombin deficiency. SERPINC1 was sequenced in 214 cases with a positive test for antithrombin deficiency, including 67 with no deficiency in the sample delivered to our laboratory. The p.Val30Glu mutation (Antithrombin Dublin) was identified in five out of these 67 cases, as well as in three out of 127 cases with other SERPINC1 mutations. Genotyping in 1593 patients with venous thrombosis and 2592 controls from two populations, revealed a low prevalent polymorphism (0.3 %) that moderately increased the risk of venous thrombosis (OR: 2.9; 95 % CI: 1.07–8.09; p= 0.03) and identified one homozygous patient with an early thrombotic event. Carriers had normal anti-FXa activity, and plasma antithrombin was not sensitive to heat stress or proteolytic cleavage. Analysis of one sample with transient deficit revealed a type I deficiency, without aberrant or increased latent forms. The recombinant variant, which lacked the two amino-terminal residues, had reduced secretion from HEK-EBNA cells, formed hyperstable disulphidelinked polymers, and had negligible activity. In conclusion, p.Val30Glu by affecting the cleavage of antithrombin’s signal peptide, results in a mature protein lacking the N-terminal dipeptide with no functional consequences in normal conditions, but that increases the sensitivity to be folded intracellularly into polymers, facilitating transient antithrombin deficiency and the subsequent risk of thrombosis.

scholarly journals Reduced Appendicular Lean Body Mass, Muscle Strength, and Size of Type II Muscle Fibers in Patients with Spondyloarthritis versus Healthy Controls: A Cross-Sectional Study

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kristine Røren Nordén ◽  
Hanne Dagfinrud ◽  
Amund Løvstad ◽  
Truls Raastad
Keyword(s):  
Body Composition ◽  
Muscle Strength ◽  
Lean Body Mass ◽  
Body Mass ◽  
Muscle Fibers ◽  
Type I ◽  
Healthy Controls ◽  
Type Ii ◽  
Mineral Density ◽  
Cross Sectional

Introduction. The purpose of this study was to investigate body composition, muscle function, and muscle morphology in patients with spondyloarthritis (SpA).Methods. Ten male SpA patients (mean ± SD age39±4.1years) were compared with ten healthy controls matched for sex, age, body mass index, and self-reported level of physical exercise. Body composition was measured by dual energy X-ray absorptiometry. Musculus quadriceps femoris (QF) strength was assessed by maximal isometric contractions prior to test of muscular endurance. Magnetic resonance imaging of QF was used to measure muscle size and calculate specific muscle strength. Percutaneous needle biopsy samples were taken fromm. vastus lateralis.Results. SpA patients presented with significantly lower appendicular lean body mass (LBM) (p=0.02), but there was no difference in bone mineral density, fat mass, or total LBM. Absolute QF strength was significantly lower in SpA patients (p=0.03) with a parallel trend for specific strength (p=0.08). Biopsy samples from the SpA patients revealed significantly smaller cross-sectional area (CSA) of type II muscle fibers (p=0.04), but no difference in CSA type I fibers.Conclusions. Results indicate that the presence of SpA disease is associated with reduced appendicular LBM, muscle strength, and type II fiber CSA.

Physical properties of the amino-terminal precursor-specific portion of type I procollagen

Biochemistry ◽  
1977 ◽  
Vol 16 (18) ◽  
pp. 4026-4033 ◽  
Author(s):  
Jurgen Engel ◽  
Peter Bruckner ◽  
Udo Becker ◽  
Rupert Timpl ◽  
Bea Rutschmann
Keyword(s):  
Physical Properties ◽  
Type I ◽  
Amino Terminal ◽  
Type I Procollagen

scholarly journals SAT-021 Effects of E2/P4 Oral Capsules on Bone Turnover in Women with Vasomotor Symptoms

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ginger Constantine ◽  
Michael R McClung ◽  
Risa Kagan ◽  
Shelli Graham ◽  
Brian Bernick ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Osteoporotic Fractures ◽  
Vasomotor Symptoms ◽  
Type I ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen ◽  
Turnover Markers ◽  
Mean Differences ◽  
Post Hoc

Abstract Menopausal hormone therapy slows bone turnover and reduces the risk of osteoporotic fractures. The objective of this post hoc analysis was to evaluate bone turnover markers (BTM) in the phase 3 REPLENISH trial, which evaluated vasomotor symptoms (VMS) with an oral estradiol/progesterone (E2/P4) in postmenopausal women with a uterus. Eligible women for this analysis had ≥50 moderate to severe VMS/week, <5 years since last menstrual period, and BTM measurements at baseline, and months 6 and 12. Percent changes for 3 BTM (bone specific alkaline phosphatase [BSAP], C-terminal telopeptide of type I collagen [CTX-1], and N-terminal propeptide of type I procollagen [PINP]) assessed by immunoassay methods were evaluated from baseline to months 6 and 12 for the 1/100, 0.5/100 and placebo groups. A total of 157 women (40–61 years, 69% White) were analyzed (56 for each 1/100 and 0.5/100; 45 for placebo). Mean baseline values ranged from 14.0–14.3 U/L for BSAP, 0.34–0.39 ng/mL for CTX-1, and 76.9–79.3 ng/mL for PINP. Mean differences in percent change from baseline versus placebo significantly decreased with both E2/P4 doses for all 3 BTM at months 6 and 12. Mean differences from placebo for E2/P4 at months 6/12 ranged from -8.1% to -17.8% for BSAP (all, P≤0.02), -30% to -41% for CTX-1 (all, P≤0.001), and -14% to -29% for PINP (all, P≤0.007). REPLENISH data provide support for a potential skeletal benefit of E2/P4 when used for the treatment of moderate to severe VMS.

scholarly journals Associations of Circulating Osteoglycin With Bone Parameters and Metabolic Markers in Patients With Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Jakob Kau Starup-Linde ◽  
Rikke Viggers ◽  
Bente Langdahl ◽  
Soeren Gregersen ◽  
Simon Lykkeboe ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Microvascular Complications ◽  
Whole Body ◽  
Type I ◽  
Amino Terminal ◽  
Patients With Diabetes ◽  
Turnover Markers

ObjectiveCirculating osteoglycin may facilitate the crosstalk between bone and pancreas to empower adaptation of bone mass to whole body energy balance. We aimed to examine whether osteoglycin is associated with bone and metabolic parameters and if osteoglycin levels differ between patients with type 1 and 2 diabetes (T1D and T2D).Design and methodsA cross-sectional study of 190 patients with diabetes mellitus and stable hemoglobin A1c (HbA1c) (97 T1D and 93 T2D) was conducted. S-osteoglycin was analyzed by ELISA. Unpaired t-tests were performed to test differences between patients with T1D and T2D and linear regression analyses were performed to investigate associations between osteoglycin, glycemic markers, bone turnover markers and characteristics.ResultsS-osteoglycin did not differ between patients with T1D and T2D (p=0.10). No associations were present between osteoglycin and age, gender, microvascular complications, HbA1c, or plasma glucose in T1D or T2D patients (p>0.05 for all). S-osteoglycin was not associated with levels of bone turnover markers (C-terminal cross-linked telopeptide of type-I collagen (CTX), P-procollagen type 1 amino terminal propeptide (P1NP), P-osteocalcin (OC), P-sclerostin, S-osteoprotegerin (OPG) or S-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL)) in neither T1D or T2D patients (p>0.05 for all).ConclusionOsteoglycin levels were similar in T1D and T2D patients. Osteoglycin did not correlate with glucose, HbA1c or any other biochemical marker of bone turnover. Thus, we did not find evidence supporting the existence of an osteoglycin-bone-pancreas axis.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01870557.

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