scholarly journals Comparison of Bone Turnover Biomarkers in Serum and Urine Measured on an Automated Analytical Platform

Author(s):  
Brittany M Wilson ◽  
Ryan D Ross ◽  
Joshua J Jacobs ◽  
Dale Rick Sumner

Abstract Background Matched serum and urine samples from patients who had total hip replacement were used to assess serum-validated immunoassay reagents for use in urine. Methods Samples were evaluated by an automated electrochemiluminescent immunoassay (cobas e411; Roche Diagnostics) for C-terminal telopeptide of type I collagen isoform β (β-Crosslaps), osteocalcin N-terminal midfragment (N-MID OC), N-terminal propeptide of type I collagen (PINP), and interleukin 6 (IL-6). Spike and recovery experiments were utilized to assess urinary matrix effects. Correlations between serum and both raw and creatinine-corrected urinary measures were assessed. Short-term precision was assessed. Results Spike and recovery experiments indicated minimal matrix effects of urine for the β-Crosslaps assay. Potential matrix effects were observed for the other analytes because N-MID OC and IL-6 tended to be slightly overrecovered, whereas PINP was underrecovered. There were strong correlations between serum β-Crosslaps and raw (Spearman ρ [rs] = 0.725, P < 0.0001) and creatinine-corrected (rs = 0.793, P < 0.0001) urinary measures and moderate correlations between serum N-MID OC and raw (rs = 0.582, P < 0.0001) and creatinine-corrected (rs = 0.482, P < 0.0001) urinary measures. PINP was not detected in urine, and no significant serum–urine correlations were found for IL-6. Short-term precision for urinary levels of β-Crosslaps, N-MID OC, and IL-6 were 1.6%, 6.3% and 14.4%, respectively. Conclusions Urinary measurements of β-Crosslaps and N-MID OC assays were correlated with serum measurements and had good short-term precision. Urinary PINP was not detectable. IL-6 can be measured in urine using this technology, but the levels did not correlate with serum levels, and the short-term precision was variable.

Author(s):  
Jan Mieszkowski ◽  
Andrzej Kochanowicz ◽  
Elżbieta Piskorska ◽  
Bartłomiej Niespodziński ◽  
Joanna Siódmiak ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Julia Mentzel ◽  
Tabea Kynast ◽  
Johannes Kohlmann ◽  
Holger Kirsten ◽  
Matthias Blüher ◽  
...  

Psoriasis is a chronic inflammatory disease of the skin and joints. More recent data emphasize an association with dysregulated glucose and fatty acid metabolism, obesity, elevated blood pressure and cardiac disease, summarized as metabolic syndrome. TNF-α and IL-17, central players in the pathogenesis of psoriasis, are known to impair bone formation. Therefore, the relation between psoriasis and bone metabolism parameters was investigated. Two serum markers of either bone formation—N-terminal propeptide of type I procollagen (P1NP) or bone resorption—C-terminal telopeptide of type I collagen (CTX-I)—were analyzed in a cohort of patients with psoriasis vulgaris. In patients with psoriasis, P1NP serum levels were reduced compared to gender-, age-, and body mass index-matched healthy controls. CTX-I levels were indistinguishable between patients with psoriasis and controls. Consistently, induction of psoriasis-like skin inflammation in mice decreases bone volume and activity of osteoblasts. Moreover, efficient anti-psoriatic treatment improved psoriasis severity, but did not reverse decreased P1NP level suggesting that independent of efficient skin treatment psoriasis did affect bone metabolism and might favor the development of osteoporosis. Taken together, evidence is provided that bone metabolism might be affected by psoriatic inflammation, which may have consequences for future patient counseling and disease monitoring.


1999 ◽  
Vol 45 (9) ◽  
pp. 1510-1516 ◽  
Author(s):  
Alessandro Rubinacci ◽  
Raffaella Melzi ◽  
Maria Zampino ◽  
Armando Soldarini ◽  
Isabella Villa

Abstract Background: Deoxypyridinoline (Dpd) is one of the two pyridinium cross-links that provide structural rigidity to type I collagen in bone. During osteoclastic resorption, Dpd is released into circulation and is excreted in the urine in free and peptide-bound forms. Free and total Dpd are highly correlated, but whether the free-to-total cross-link ratio is constant in both normal and high bone turnover states remains controversial. To compare free and total Dpd performance in a physiological condition, urinary free and total Dpd were measured after a short-term inhibition of osteoclast activity such as that induced by an oral calcium load. Methods: Total and free Dpd were measured by HPLC and by immunosorbent assay, respectively, in two groups of subjects, one (calcium-treated; n = 16) taking calcium and the other not (control; n = 9). Results: The urinary excretion of total Dpd at 2 and 4 h after oral calcium loading was decreased compared with controls. By contrast, changes in free Dpd were similar in the calcium-treated and control groups, reflecting only circadian rhythm. Conclusions: Total and free Dpd do not show comparable sensitivity in detecting short-term inhibition of osteoclast activity. The degradation process of peptide-bound to free Dpd could render free Dpd insensitive to acute changes of osteoclast activity.


1995 ◽  
Vol 28 (5) ◽  
pp. 541-545 ◽  
Author(s):  
John K. Scariano ◽  
Elizabeth A. Walter ◽  
Robert H. Glew ◽  
Bruce W. Hollis ◽  
Allison Henry ◽  
...  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4003-4003
Author(s):  
Lara Pochintesta ◽  
Silvia Mangiacavalli ◽  
Federica Cocito ◽  
Cristiana Pascutto ◽  
Alessandra Pompa ◽  
...  

Abstract Abstract 4003 Skeletal related events (SREs) are a significant cause of morbidity and mortality in multiple myeloma (MM). Markers of bone turn-over, in particular serum C-terminal telopeptide of type I collagen (CTX), can be used for monitoring early signs of bone damage either in osteoporosis or in neoplasm such as Multiple Myeloma. Since serum CTX levels are significantly decreased during bisphosphonate treatments (Dennis, N Engl J Med 2008), it is not clear whether serum CTX monitoring still retain a role in predicting SREs once bisphosphonate treatments was started. Aim of this study was to test whether serum CTX monitoring significantly correlates with active bone disease in a population of MM patients irrespective of concomitant bisphosphonate treatment. An unselected cohort of 87 patients with multiple myeloma diagnosed at our Hematology Division with the following characteristics entered this study: the availability of a baseline determination of serum CTX prior to start bisphosphonate therapy, multiple sequential serum CTX determinations (≥2 performed with an interval of at least 4 weeks), a radiologic evaluation available at the time of any SREs. The study was approved by our local ethical committee and conducted according to Helsinki Declaration guidelines. Patients baseline characteristics were the following: M/F 59%/41%, median age 60 (range 37–86), Durie and Salmon stage I/II/III (11%/14%/75%). During the study period (median follow-up 2.8 year, range 0.4–21 years), 73 patients (83%) experienced at least one SRE. Development of SRE was evaluated by standard skeletal x-ray, CT or MRI scan. Serum CTX was measured by an enzyme chemiluminescence method. A total of 260 serum CTX determinations were available for statistical analysis (median number of determinations for each patient 3, range 2–9). Univariate analysis found a statistically significant association between serum CTX and bone disease status with higher values in patients with active lytic lesions when compared to patients without radiological evidence of bone disease (median value 0.411 vs 0.356, p<0.001). By contrast, we observed significantly lower serum CTX values in patients under bisphosphonates treatment (median value 0.160 vs 0.355, p=<0.001). Association between serum CTX values, bone disease status and active bisphosphonates treatment was analyzed with a time-series linear model, accounting for measurement being repeated sequentially on each patient (random-effects GLS regression). Bone disease status and bisphosphonates treatment resulted significantly and independently associated to serum CTX (regression coefficient 0.222, 95%CI: 0.107–0.338, p<0.001 and 0.208 95%,CI: 0.320–0.096, p<0.001 respectively for bone disease status and bisphosphonates, cfr Tab 1). In addition, variations of CTX serum levels correlated significantly with the presence of active bone disease even under treatment with bisphosphonates (p<0.001). In conclusion, this study confirmed a positive association between serum CTX and presence of active bone disease. In addition serum CTX levels show a significant decrease under treatment with bisphosphonates. Taking into account these observations, patient-specific variations rather than the absolute serum CTX value should be used for detecting the onset of new SREs during a concomitant bysphosphonates treatment. Tab 1: Levels of serum CTX according to bone disease status and bisphosphonates treatment. Bisphosphonates treatment Progression in bone disease Active None Yes 0.219 (0.03–1.79) 0.533 (0.02–4.14) No 0.139 (0.03–0.69) 0.345 (0.071–1.57) Disclosures: No relevant conflicts of interest to declare.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Yu-Ling Huang ◽  
Yen-Wenn Liu ◽  
Yu-Jou Huang ◽  
Wen-Fei Chiou

Vitis thunbergiiis used in Taiwan as a botanical supplement for inflammatory bone diseases. This study aims to examine its direct effect on bone metabolism. Three-month-old female mice were randomly divided into ovariectomized control (OVX), sham operated (SHAM), and ovariectomy treated with either 17β-estradiol or a special ingredient (VtR) fractionated from an ethanol extract ofV. thunbergiistarted two weeks after ovariectomy. VtR treatment for 8 weeks significantly ameliorated the deterioration of bone mineral density and reversed all the ovariectomy-induced changes in  μ-CT parameters. The antiosteoporotic effect of VtR accompanied decrease in serum levels of C-terminal telopeptides of type I collagen (CTx), interleukin-7, and ration of RANKL/osteoprotegerin (OPG) but rise in osteocalcin concentration. Sparse calcified microarchitecture and less alkaline-phosphatase- (ALP-) positive cells were observed at the femur and vertebral sites in OVX mice while VtR remarkably restored such variation. HPLC analysis showed (+)-vitisin-A, (−)-vitisin-B, and ampelopsin C predominated in VtR. Both (−)-vitisin B and ampelopsin C increased ALP activity and bone nodule formation in cultured osteoblasts. Instead of stimulating osteoblastogenesis, (+)-vitisin A dramatically repressed osteoclasts differentiation and bone resorption. The results suggested VtR composed of diverse components to reciprocally drive osteoblastogenesis and interdict osteoclastogenesis may serve as a potential botanic drug for osteoporosis therapy.


2015 ◽  
Vol 42 (11) ◽  
pp. 2066-2070 ◽  
Author(s):  
Sibel Yilmaz-Oner ◽  
Gulsen Ozen ◽  
Meryem Can ◽  
Pamir Atagunduz ◽  
Haner Direskeneli ◽  
...  

Objective.Remission is the primary aim in the treatment of patients with rheumatoid arthritis (RA). In this study, we aimed to evaluate biomarker profiles of patients in remission by different criteria and compare these profiles with controls.Methods.Serum levels of calprotectin, interleukin 6 (IL-6), type II collagen helical peptide, C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases (ICTP), matrix metalloproteinase 3 (MMP-3), resistin, and leptin were measured by ELISA in 80 patients. The patients were in Disease Activity Score at 28 joints with erythrocyte sedimentation rate (DAS28-ESR) remission, and had these characteristics: female/male 54/26, mean age 51.4 ± 12.1 years, mean disease duration 11.4 ± 8.1 years, rheumatoid factor positivity 68.7% (n = 55), anticyclic citrullinated peptide positivity 60.7% (n = 48). These patients were also evaluated for the American College of Rheumatology/European League Against Rheumatism (Boolean) and Simple Disease Activity Index (SDAI) remissions. Additionally, 80 age-, sex-, and comorbidity-matched individuals without rheumatic diseases were included in the study as controls.Results.At recruitment of 80 patients in DAS28 remission, 33 patients (41.2%) were found in Boolean remission and 39 patients (48.7%) were in SDAI remission. Serum MMP-3, ICTP, resistin, and IL-6 levels of the 80 patients in DAS28 remission were statistically significantly higher than the controls. Patients in Boolean and SDAI remissions had significantly higher serum ICTP, resistin, and IL-6 levels in comparison with the controls.Conclusion.The 3 commonly used remission criteria of RA are almost similar with regard to patients’ biomarker levels. Biomarker profiles of patients may provide complementary information to clinical evaluation of remission and may help to determine the patients under the risk of progression.


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