Collagen Degradation In Patients Research Articles

A prospective randomized controlled trial of bone metabolism in patients with charcot foot

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcots foot) - is a progressive destructive inflammatory disease of the osteoarticular apparatus of the foot, untimely and inadequate treatment of which can lead to the formation of gross deformities. More often, DNOAP is unilateral, bilateral lesion is relatively rare. It is not always possible to trace the relationship between the debut of DNOAP with trauma and chronic hyperglycemia. There is data demonstrating the role of individual pro-inflammatory factors in the pathogenesis of DNOAP, however, studies combining the evaluation of various metabolic markers of Charcots foot formation are currently extremely poor.
 AIM: To evaluate the hormonal and metabolic markers of bone formation and resorption in patients with DNOAP and without this diabetic complication.
 METHODS: A prospective, controlled trial included 70 patients with type 2 diabetes mellitus (37 men and 43 women) who formed 2 groups: group 1 included patients with DNOAP, group 2 was formed by patients with diabetes without foot skeleton damage. All patients underwent a study of 1,25-OH-vitamin D, sclerostin, pro-MMP-1, C-terminal propeptide type 1 collagen (PICP), type 1 collagen, osteocalcin, PTH, 25-OH-vitamin D, beta-cross-slaps.
 RESULTS: The results of the studies confirmed the presence of vitamin D deficiency in all patients with diabetes mellitus included in the study, revealed the absence of statistically significant differences between the groups in the values of sclerostin, pro-MMP-1; 25-OH-vitamin D, type I collagen, and osteocalcin (p 0.05). However, significant differences were found in the 1.25-OH vitamin D levels: patients with DNOAP presented the lower rates of 1,25-OH-vitamin D in comparison to control group (p 0.05). Beta-cross and PICP levels were significantly higher in DNOAP patients as well (p 0.05). Those findings show the more severe collagen degradation in patients with DNOAP and can be the genetically predisposed cause of DNOAP development. Though further studies are needed.
 CONCLUSION: In patients with DNOAP a decrease in 1,25-OH-vitamin D levels was found, as well as the alteration of the synthesis and destruction of collagen (beta-cross-slaps and PICP) compared to patients with diabetes mellitus without osteoarticular disorders.

A prospective randomized controlled trial of bone metabolism in patients with charcot foot

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot’s foot) - is a progressive destructive inflammatory disease of the osteoarticular apparatus of the foot, untimely and inadequate treatment of which can lead to the formation of gross deformities. More often, DNOAP is unilateral, bilateral lesion is relatively rare. It is not always possible to trace the relationship between the debut of DNOAP with trauma and chronic hyperglycemia. There is data demonstrating the role of individual pro-inflammatory factors in the pathogenesis of DNOAP, however, studies combining the evaluation of various metabolic markers of Charcot’s foot formation are currently extremely poor. AIM: To evaluate the hormonal and metabolic markers of bone formation and resorption in patients with DNOAP and without this diabetic complication. METHODS: A prospective, controlled trial included 70 patients with type 2 diabetes mellitus (37 men and 43 women) who formed 2 groups: group 1 included patients with DNOAP, group 2 was formed by patients with diabetes without foot skeleton damage. All patients underwent a study of 1,25-OH-vitamin D, sclerostin, pro-MMP-1, C-terminal propeptide type 1 collagen (PICP), type 1 collagen, osteocalcin, PTH, 25-OH-vitamin D, beta-cross-slaps. RESULTS: The results of the studies confirmed the presence of vitamin D deficiency in all patients with diabetes mellitus included in the study, revealed the absence of statistically significant differences between the groups in the values of sclerostin, pro-MMP-1; 25-OH-vitamin D, type I collagen, and osteocalcin (p > 0.05). However, significant differences were found in the 1.25-OH vitamin D levels: patients with DNOAP presented the lower rates of 1,25-OH-vitamin D in comparison to control group (p <0.05). Beta-cross and PICP levels were significantly higher in DNOAP patients as well (p <0.05). Those findings show the more severe collagen degradation in patients with DNOAP and can be the genetically predisposed cause of DNOAP development. Though further studies are needed. CONCLUSION: In patients with DNOAP a decrease in 1,25-OH-vitamin D levels was found, as well as the alteration of the synthesis and destruction of collagen (beta-cross-slaps and PICP) compared to patients with diabetes mellitus without osteoarticular disorders.

Triglyceride blood levels and metalloproteinases activity in acute myocardial infarction patients

Aim: Matrix Metalloproteinases MMPs and their inhibitors TIMPs are key enzymes for myocardial collagen degradation in patients (pts) with acute myocardial infarction (AMI). The aim of this study was to investigate the influence of triglyceride blood levels on collagenolytic activity in pts with AMI.

Abstract 17678: The Correlation Between Collagen Degradation and LV Function Following Induction of Beta-Blocker Therapy

Objectives: Beta-blocker therapy inhibits LV remodeling, and improves not only LV systolic function but also LV diastolic function, and improves prognosis of heart failure patients. But it is unknown why beta-blocker therapy improves LV function. Recently, serum collagen markers such as Procollagen type I C-terminal propeptide (PICP) and collagen type I C-terminal telopeptide (CITP), are useful as index of myocardium collagen synthesis and degradation. We investigate correlation between collagen turnover and LV function following induction of beta-blocker therapy with systolic heart failure patients. Methods: Study population consisted of 46 patients with systolic heart failure. Patients were clinically stable within 1 month and on stable medical therapy, including ACEI or ARB and diuretics, and no beta-blocker therapy. We started beta-blocker therapy, initiated at a target dose of from 5 to 10mg/day. Echocardiography was performed before, 2, 6, and 12 months after the initiation of beta-blocker therapy. LV systolic function was estimated using the LV ejection fraction by Simpson biplane method. Peak systolic strain in the radial direction was measured at the anterior and posterior walls in the short-axis view. We measured E- and A-wave peak velocities and deceleration time (DcT) form the mitral inflow profile, and tissue Doppler early diastolic mitral annular velocity (E'). Serum PICP and CITP were determined. Results (table): A total of 46 patients were enrolled. The median age of all patients was 56±14 years. 15 patients were women and 31 patients were men. EF, DcT and E' were improved after induction of beta-blocker therapy. PICP was not changed, but CITP was decreased from 8.9±7.8 to 6.1±1.7ng/ml at 12 months after treatment. The lower %changes in CITP was associated with the higher %changes in DcT (r=0.21, p&lt;0.05), EF (r=0.29, p&lt;0.01) and radial systolic strain (r=0.26, p&lt;0.05), but not E'. The %changes in PICP were not related %changes in DcT and E'. Conclusions: The improvement in LV systolic function as indexes in EF and radial systolic strain and LV diastolic stiffness as indexes in DcT, correlated with inhibition of collagen degradation in patients with LV systolic function.

Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations

Objective We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Patients and methods Sixty-four adult patients with OI (39% women, mean age ± SD: 37 ± 12 years) and 64 healthy age-matched controls (54% women, 39 ± 7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63 ± 8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62 ± 10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (α/β CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Results Patients with OI had CTX-II levels similar to those of subjects with knee OA ( p = 0.89; mean ± SEM; 460 ± 57 ng/mmol Cr for OI group and 547 ± 32 ng/mmol Cr for OA group) and significantly higher than both young (144 ± 7.8 ng/mmol Cr, p < 0.0001) and old controls (247 ± 7 ng/mmol Cr, p < 0.0001). In patients with OI, increased Helix-I ( p < 0.0001) and α/β CTX-I ( p = 0.0067) were independently associated with increased CTX-II and together explained 26% of its variance ( p < 0.0001). In patients with knee OA, increased levels of α/β CTX-I ratio were also associated with higher CTX-II levels. Conclusion Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA.

Prostaglandin E2 role in inhibition of joint cartilage collagen destruction in patients with osteoarthritis

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

A 5-yr longitudinal study of type IIA collagen synthesis and total type II collagen degradation in patients with knee osteoarthritis--association with disease progression

The 5-yr longitudinal study tested the hypothesis that serum and urinary markers of type II collagen metabolism would be associated with radiological progression of disease in patients with mild-to-moderate knee osteoarthritis (OA). Synthesis of type IIA collagen and degradation of total type II collagen were assessed in 135 patients with mild-to-moderate knee OA over 5 yrs using serum concentration of the N-propeptide of collagen type IIA (PIIANP) and urinary excretion of crosslinked C-telopeptide (CTX-II), respectively. The markers were measured at baseline, 2, 3 and 5 yrs' follow-up corresponding to X-ray time points. Analysis of variance (ANOVA) was performed to determine longitudinal changes over 5 yrs in the biomarkers in all patients and between progressors and non-progressors. Complete X-ray progression data over 5 yrs, serum PIIANP and urinary CTX-II were available for 84/135 patients. There were 24 progressors and 60 non-progressors. Overall, over the 5-yr study period average PIIANP and CTX-II levels were higher in progressors compared with non-progressors (P < 0.05 for both, ANOVA). The patients with serum PIIANP in the highest quartile of 5-yr levels of PIIANP had a significantly higher risk of progression than the other patients [relative risk (95% CI): 3.2 (1.1-9.2)]. Increased levels of urinary CTX-II were also associated with a higher risk of progression with a relative risk (95% CI) of 3.4 (1.2-9.4) in patients with 5-yr levels above the median. The risk of progression was highest in patients with 5-yr levels of PIIANP in the highest quartile and/or CTX-II in the two highest quartiles with a relative risk (95% CI) of progression, 11.8 (2.5-54). The data presented here suggest that progression of knee OA is associated with alterations of systemic levels of biological markers of type II collagen metabolism. The data also suggest that the combined measurement of serum PIIANP and urinary CTX-II may be useful to identify patients with knee OA at increased risk of disease progression.

An Inverse Relationship Between Markers of Fibrogenesis and Collagen Degradation in Patients With or Without Alcoholic Liver Disease

Excessive deposition of collagen leading to cirrhosis is a major complication of alcohol abuse. However, the mechanisms behind the accumulation of the extracellular matrix proteins are poorly understood. We measured serum markers of collagen degradation (beta-CTx), fibrogenesis (PINP, PIIINP), and pro- and anti-inflammatory cytokines from 84 male heavy drinkers, who were either with (N = 52) or without (N = 32) clinical or histological signs of alcoholic liver disease (ALD), and from 20 healthy nonalcoholic controls. Serum beta-CTx levels in ALD patients were significantly lower than in healthy controls or in the alcoholics without liver disease, while PINP and PIIINP, reflecting type I and type III collagen synthesis, respectively, were significantly increased. The alcoholics without liver disease showed values, that were not significantly different from those of healthy controls. Serum beta-CTx correlated negatively with serum PIIINP and proinflammatory cytokines (IL-2, IL-6, IL-8, TNF-alpha), and positively with anti-inflammatory cytokines (IL-1, TGF-beta), whereas serum PIIINP correlated positively with these proinflammatory cytokines and negatively with the anti-inflammatory cytokines. Calculation of PIIINP/beta-CTx ratio was found to yield an excellent sensitivity (94%) and specificity (98%) in differentiating the alcoholics with liver disease. The present findings indicate a positive relationship between markers of collagen biosynthesis and proinflammatory cytokines, and a negative relationship between these markers and a marker of collagen degradation and anti-inflammatory cytokines, suggesting that a disturbed balance in these cellular responses may facilitate fibrogenesis and play a pivotal role in the pathogenesis of ALD. These findings should also be implicated in the development of noninvasive tools for discriminating individuals at risk for fibrogenesis.

50 Left ventricular unloading effects of NT-proBNP are associated with increased collagen degradation in patients with acute decompensation of chronic heart failure

50 Left ventricular unloading effects of NT-proBNP are associated with increased collagen degradation in patients with acute decompensation of chronic heart failure

Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy.

Left ventricular (LV) dilation and myocardial remodelling are hallmarks of heart failure in idiopathic dilated cardiomyopathy (DCM). Interstitial collagen is essential for LV integrity and function while degradation of collagen by collagenases, especially matrix-metalloproteinases (MMPs), are suggested to contribute to ventricular dilation. In the present study, serological markers of collagen metabolism were investigated. Serum levels of MMP-1 and its inhibitor (TIMP-1), the markers for collagen degradation type I (collagen carboxyterminal telopeptide (ICTP)) and synthesis (carboxyterminal propeptide of type I procollagen (PICP)) were quantified by ELISA and RIA of 43 patients with DCM and 47 age-matched control subjects. Free MMP-1 serum concentration was significantly increased in the DCM group (5.29+/-0.83 vs. 2.22+/-0.29 ng/ml; P=0.01) as well as the free TIMP-1 concentration (206.54+/-12.65 vs. 181.44+/-8.55 ng/ml; P=0.05). The free MMP-1/TIMP-1-ratio was higher in DCM than in the control group (0.030+/-0.005 vs. 0.012+/-0.001; P=0.01). ICTP was significantly increased (7.60+/-1.21 vs. 3.44+/-0.19 microg/l; P<0.001). PICP was not significantly increased (125.29+/-8.93 microg/l vs. 113.11+/-5.47 microg/l; P=n.s.). Free MMP-1 and MMP-1/TIMP-1-ratio correlated with LV end diastolic diameter [cm/m(2) body surface area (BSA)] (r=0.28; P=0.03 and r=0.34; P=0.01, respectively) as well as with cardiac index (CI) (r=-0.32; P=0.04 and r=-0.33; P=0.04, respectively) in patients with DCM. Serum markers of collagen degradation are elevated and might be valuable markers for progression of LV dilation in patients with DCM.

The bisphosphonate zoledronate decreases type II collagen breakdown in patients with Paget’s disease of bone

Bisphosphonates have been suggested to be partially chondroprotective in animal models of arthritis. The aim of this study was to assess the short-term effect of the bisphosphonate zoledronate on type II collagen degradation in patients with Paget’s disease of bone. Twenty-six patients with active Paget’s disease who were a part of a double-blind, placebo-controlled, randomized study comparing the effects of several doses of a single injection of zoledronate, a potent bisphosphonate, were studied. Type II collagen destruction was assessed by urinary levels of type II collagen C-telopeptide (CTX-II) using a new immunoassay. Bone resorption was assessed by measuring the urinary excretion of nonisomerized type I collagen C-telopeptide (α CTX-I). Biochemical markers were measured at baseline and 5, 10, 30, and 60 days after injection. At baseline, no significant increase of CTX-II was observed in patients with Paget’s disease compared with a group of 27 gender-and age-matched controls, in contrast to the ninefold ( p < 0.0001) increase of urinary α CTX-I. After a single intravenous injection of zoledronate (200 or 400 μg), urinary CTX-II transiently decreased by a median of 25% 5 days after the injection of zoledronate ( p = 0.0023 vs. placebo), then increased to pretreatment levels after 10 days. In contrast, urinary α CTX-I decreased within 5 days with a maximal decrease of 51% at day 10 ( p < 0.001 vs. baseline and placebo), and levels remained suppressed during the 2 months of the study. Zoledronate not only reduces bone turnover but also directly decreases type II collagen degradation in patients with Paget’s disease, suggesting that bisphosphonates may have chondroprotective effects in humans. Measurement of type II collagen breakdown by a new urinary biochemical marker may be useful for in vivo assessment of the effects of drugs that potentially inhibit cartilage destruction.

Effect of the Angiotensin Receptor Blocker Valsartan on Morbidity and Mortality in Heart Failure: the Valsartan Heart Failure Trial (Val-HeFT)

In order to assess the efficacy of the angiotensin receptor blocker valsartan in the treatment of heart failure (HF), 5010 patients were studied in 16 countries on 4 continents. Patients with chronic HF [NYHA II (62%), III (36%) and IV (2%)], ejection fraction (EF) <40% and …

Circulating Biochemical Marker Levels of Collagen Metabolism Are Abnormal in Patients with Abdominal Aortic Aneurysm

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type Icollagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex-matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concentrations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 +/- 16.4 vs 111.3 +/- 40.3 ng/mL; p < 0.01), but those in patients with ASO (105.4 +/- 55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 +/- 5.6 ng/mL; ASO, 21.4 +/- 13.8 ng/mL; AAA, 24.5 +/- 11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 +/- 0.18 vs 0.20 +/- 0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 +/- 61.2 ng/mL) or ASO (327.6 +/- 54.9 ng/mL) were significantly higher than in HC (227.3 +/- 60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.

Monitoring collagen degradation in patients with arthritis. The search for suitable surrogates.

Monitoring collagen degradation in patients with arthritis. The search for suitable surrogates.

Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease

Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease

Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease.

We have used a new enzyme-linked immunoassay (ELISA) to measure the urinary excretion of type I collagen peptides (CrossLaps) released during bone matrix degradation in a sample of healthy adults comprising 146 women and 60 men, aged 31-89 yr, and in patients with metabolic bone disease. The intra- and interassay coefficients of variation were less than 10% and 13%, respectively. The recovery of CrossLaps antigen from urine samples ranged from 92-115%, and the ELISA was linear for serial sample dilutions. The CrossLaps assay does not cross-react with either free pyridinoline (Pyr) or free deoxypyridinoline (D-Pyr). CrossLaps measured by ELISA and the total excretion of Pyr measured by high performance liquid chromatography were highly correlated in normal women (n = 91; r = 0.73; P < 0.001). Urinary CrossLaps excretion increased with age in women, but not in men. In women, the menopause was reflected by a mean 141% increase in CrossLaps excretion [from an average 217 to 524 micrograms/mmol creatinine (Cr)] that was higher than the mean increase in total D-Pyr (+91%) and total Pyr (+47%) measured by HPLC and the mean increase in bone alkaline phophatase (+48%) and osteocalcin (+41%). Urinary CrossLaps excretion was increased from control values in Paget's disease (n = 32; mean, 1810 +/- 2300 micrograms/mmol Cr; P < 0.001), in patients with primary hyperparathyroidism (n = 10; mean, 780 +/- 380 micrograms/mmol Cr; P < 0.001), and in patients with hyperthyroidism (n = 27; mean, 1280 +/- 970 micrograms/mmol Cr; P < 0.001), with Z-scores (number of SD from the mean of sex- and age-matched controls) of 4.4 +/- 6.6, 1.5 +/- 1.2, and 6.7 +/- 6.5, respectively. In patients with Paget's disease, CrossLaps values were highly correlated with urinary hydroxyproline levels (r = 0.91; P < 0.001), and the decrease in urinary CrossLaps excretion was greater than that in urinary hydroxyproline (-71% vs. -17%; P < 0.001) after 3 days of i.v. treatment with the bisphosphonate pamidronate. In patients with hyperthyroidism, CrossLaps excretion was elevated above the normal range in most patients (78%) and returned to normal within 1 month of treatment for hyperthyroidism. It is concluded that this new convenient assay represents a sensitive and specific index of the bone resorption rate, and that it should be useful for the clinical investigation and therapeutic monitoring of patients with osteoporosis and other metabolic bone diseases.

Measurement of the cross-linking compounds pyridinoline and deoxypyridinoline in urine as an index of collagen degradation in patients with surgical menopause

Surgical menopause, a disorder of ovariectomized women, is characterized by a wide spectrum of bone turnover abnormalities. Conventional biochemical markers of bone resorption lack specificity and do not reflect bone resorption assessed from histology. We measured the urinary excretion of the pyridinoline crosslinks pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), a specific marker of bone and cartilage collagen degradation, in 10 women with bone loss due to surgical menopause and in 10 nonmenopausal women. Urinary pyridinoline crosslinks correlated with collagen degradation and reabsorption, as assessed by the mean values of Pyr and D-Pyr in surgical patients, are significantly higher compared with those seen in the controls. These data indicate that Pyr and D-Pyr are sensitive markers of bone turnover in women with surgical menopause and that they can be considered a good index for determining the degree of collagen degradation.

Measurement of the cross linking compounds pyridinoline and deoxypyridinoline in urine as an index of collagen degradation in patients suffering from surgical menopause

Measurement of the cross linking compounds pyridinoline and deoxypyridinoline in urine as an index of collagen degradation in patients suffering from surgical menopause