PICP Levels Research Articles

Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover

Heart failure with preserved ejection fraction (HF-PEF) can be difficult to diagnose in clinical practice. Myocardial fibrosis is a major determinant of diastolic dysfunction (DD), potentially contributing to the progression of HF-PEF. The aim of this study was to analyse whether serological markers of collagen turnover may predict HF-PEF and DD. We included 85 Caucasian treated hypertensive patients (DD n=65; both DD and HF-PEF n=32). Serum carboxy (PICP), amino (PINP), and carboxytelo (CITP) peptides of procollagen type I, amino (PIIINP) peptide of procollagen type III, matrix metalloproteinases (MMP-1, MMP-2, and MMP-9), and tissue inhibitor of MMP levels were assayed. Using receiver operating characteristic curve analysis, MMP-2 (AUC=0.91; 95% CI: 0.84, 0.98), CITP (0.83; 0.72, 0.92), PICP (0.82; 0.72, 0.92), B-type natriuretic peptide (BNP) (0.82; 0.73, 0.91), MMP-9 (0.79; 0.68, 0.89), and PIIINP (0.78; 0.66, 0.89) levels were significant predictors of HF-PEF (P<0.01 for all). Carboxytelo peptides of procollagen type I (AUC=0.74; 95% CI: 0.62, 0.86), MMP-2 (0.73; 0.62, 0.84), PIIINP (0.73; 0.60, 0.85), BNP (0.69; 0.55, 0.83) and PICP (0.66; 0.54, 0.78) levels were significant predictors of DD (P<0.05 for all). A cutoff of 1585 ng/mL for MMP-2 provided 91% sensitivity and 76% specificity for predicting HF-PEF and combinations of biomarkers could be used to adjust either sensitivity or specificity. Markers of collagen turnover identify patients with HF-PEF and DD. Matrix metalloproteinase 2 may be more useful than BNP in the identification of HF-PEF. This suggests that these new biochemical tools may assist in identifying patients with these diagnostically challenging conditions.

Increased Myocardial Collagen Turnover in Patients with Progressive Cardiac Conduction Disease

Histopathologically, progressive cardiac conduction disease (PCCD) is characterized by progressive fibrosis and sclerodegenerative changes in the proximal and distal conduction system of the heart. Therefore, we sought to determine the serum levels of myocardial collagen turnover markers, extracellular matrix components, transforming growth factor beta(1) (TGFbeta(1)), and bone morphogenic protein-7 (BMP-7) in this population. Study population included 20 patients (6 M/14 F, mean age 76 +/- 8 years) with acquired, permanent 2:1, or complete atrioventricular block and compared with age- and sex-matched, asymptomatic, healthy control subjects (n = 18, 6 M/12 F, mean age 75 +/- 7 years). Serum myocardial collagen turnover markers:matrix metalloproteinases (MMP-1, 2, 9), tissue inhibitor of matrix metalloproteinase (TIMP-1), amino-terminal propeptide of procollagen type I (PINP) and type III (PIIINP), carboxy-terminal telopeptide of collagen type I (CITP), and carboxy-terminal propeptide of procollagen type I (PICP), serum extracellular matrix components (laminin and fibronectin), TGFbeta(1), and BMP-7 levels were measured in both groups. Serum PICP (849 +/- 396 vs 631 +/- 294 ng/mL, P = 0.04), PIIINP (3.7 +/- 1.3 vs 3 +/- 1 mug/L, P = 0.03), CITP (0.68 +/- 0.35 vs 0.48 +/- 0.25 ng/mL, P = 0.037), and plasma MMP-9 (58.8 +/- 56 vs 25.9 +/- 17.3 ng/mL, P = 0.006) levels were higher in patient population compared to control subjects. Serum MMP-1 (24.1 +/- 20.5 vs 13.6 +/- 7.5 ng/mL, P = 0.045) and MMP-2 (1310 +/- 139 vs 1186 +/- 163 ng/mL, P = 0.01) levels were higher in control subjects compared to patient population. There was no difference in serum TIMP-1, PINP, laminin, fibronectin, TGFbeta(1), and BMP-7 levels between two groups. Our findings demonstrate the presence of increased myocardial collagen turnover and active fibrotic process in patients with PCCD compared to control subjects.

Bone marrow and serum connective tissue polypeptides in idiopathic myelofibrosis.

The distribution of collagen type VI and tenascin has been determined in both normal and myelofibrotic bone marrow by immunohistological techniques. In normal sections positivity was demonstrated in the periosteum (collagen type VI and tenascin) and in the walls of small blood vessels (tenascin). In contrast, myelofibrotic bone marrow showed an increased deposition of both proteins, especially collagen type VI, although this increase was restricted to the later fibrotic stages of the disease. Serum concentrations of collagen type I (PICP), collagen type III (PIIIP) and laminin (laminin P1) related polypeptides were determined in a further 26 patients. PIIIP levels were significantly raised, in contrast to PICP and laminin P1 concentrations. All three markers, however, were significantly elevated in patients with active/transforming disease. Laminin P1 and PICP levels showed a strong correlation, indicating a relationship between basement membrane and interstitial collagen metabolism, although they do not appear to offer any advantage over PIIIP for the monitoring of disease activity.

Osteochondrale Molekülmarker als quantitative Verlaufsparameter nach matrixgekoppelter autologer Chondrozytentransplantation CaRes®

In this study we attempt to evaluate whether or not osteochondral markers of the synovial fluid can be helpful in defining objectively the repair process following matrix-based autologous chondrocyte implantation (ACI) CaReS (Cartilage Regeneration System). As a part of a clinical prospective pilot study, synovial fluid of 19 patients was examined before, as well as 6, 12, 26, and 52 weeks after matrix-based ACI. A synovial fluid analysis was performed and markers of bone and cartilage metabolism were evaluated. Molecular markers routinely examined included MMP-1, MMP-3, MMP-13, TIMP, hCOMP, PICP und MIA. The levels were referenced to the total protein concentration of the synovial fluid and compared with clinical parameters (IKDC) and magnetic resonance imaging (MRI). With the exception of MMP3 all markers showed a drop of the concentration below preoperative levels at 6 weeks. All marker levels returned to below the preoperative concentration at 26 as well as 52 weeks after surgery. The MIA, MMP-3, PICP, hCOMP and TIMP levels showed significant changes over the period of 52 weeks (p<0.01). Statistically significant correlations between the marker levels and the clinical scores could only be observed at several times of assessment. Under consideration of missing correlations to clinical parameters (IKDC/MRI) non-specific osteochondral marker proteins of the synovial fluid cannot be used without further scrutiny to document changes in cartilage and osseous metabolism following matrix-supported ACI over the time of 52 weeks objectively. The drop of the concentrations below preoperative levels at 6 weeks can possibly be explained by the reduced traumatization of the joint with the CaRes procedure compared to the classic ACI. Specific markers for cartilage metabolism should be defined to permit a direct and objective comparison of the various conservative and operative methods presently available for the treatment of chondral lesions of the knee joint.

Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)

Hypertensive left ventricular hypertrophy (LVH) is associated with cardiomyocyte hypertrophy and an excess in myocardial collagen. Myocardial fibrosis may cause diastolic dysfunction and heart failure. Circulating levels of the carboxy-terminal propeptide of procollagen type I (PICP), an index of collagen type I synthesis, correlate with the extent of myocardial fibrosis. This study examines myocardial fibrosis in relation to blood pressure, left ventricular mass (LVM), and diastolic function. We examined PICP levels in 115 patients with hypertensive LVH, 38 with hypertension but no hypertrophy, and 38 normotensive subjects. Patients with LVH were subsequently randomly assigned to the angiotensin II type 1 receptor blocker irbesartan or the beta1 receptor blocker atenolol for 48 weeks. Diastolic function was evaluated by tissue velocity echocardiography (n=134). We measured basal septal wall velocities of early (Em) and late (Am) diastolic myocardial wall motion, Em velocity deceleration time (E-decm), and isovolumic relaxation time (IVRTm). Compared with the normotensive group, PICP was elevated and left ventricular diastolic function was impaired in the hypertensive groups, with little difference between patients with and without LVH. PICP related to blood pressure, IVRTm, Em, and E/Em, but not to LVM. Irbesartan and atenolol reduced PICP similarly. Only in the irbesartan group did changes in PICP relate to changes in IVRTm, and LVM. Myocardial fibrosis and diastolic dysfunction are present in hypertension before LVH develops. The findings with irbesartan suggest a role for angiotensin II in the control of myocardial fibrosis and diastolic function in patients with hypertension with LVH.

Markers of Inflammation and Fibrosis Are Related to Cardiovascular Damage in Hypertensive Patients with Metabolic Syndrome

Previous studies have shown that metabolic syndrome (MS) is associated with an increased susceptibility to develop cardiovascular damage (CD). Experimental evidence indicates that inflammation and fibrosis could play a critical role in the development of CD in hypertension. This issue has not been clarified yet in patients with MS. The aim of our study was to investigate the relationship between markers of inflammation and fibrosis with CD in hypertensive patients with and without MS. One hundred twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, biochemical parameters, 24-h urinary albumin excretion rate (UAER), levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured. All patients underwent an echocardiographic examination with transmitral Doppler and tissue Doppler imaging (TDI). Left ventricular mass indexed by height(2.7) (LVM/h(2.7)) (P < .001), early diastolic peak flow velocity/early myocardial diastolic velocity ratio (E/Em ratio), a TDI index of diastolic function (P < .001), and 24-h UAER (P < .05) were significantly higher in the group with MS, whereas peak myocardial systolic velocity (Sm), a TDI index of systolic function (P < .001), was lower. Serum levels of CRP (P < .001), TNF-alpha (P < .05), TGF-beta (P < .01), and PICP (P < .001) were significantly increased in MS. These markers were significantly related to higher LVMI(2.7), higher E/Em ratio, and increased 24-h UAER and a lower Sm in the whole population, with a further significant enhancement in MS. Cardiovascular damage is more frequent in hypertensives with MS than in hypertensives without MS, and this is significantly related to the increased levels of inflammation and fibrosis found in hypertensives with MS.

Levels of bone collagen markers in preterm infants: relation to antenatal glucocorticoid treatment

Although the beneficial effects of antenatally administered glucocorticoids are well documented, data on the potential of adverse consequences are limited. The objective of this study was to determine the effects of antenatally administered glucocorticoids on biochemical markers of bone metabolism of 55 preterm infants with a gestational age of 24-34 weeks who were enrolled in the study. Neonates were divided into two groups according to antenatal exposure to corticosteroids. There were no significant differences between the groups in clinical characteristics and anthropometric variables. We studied blood levels of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) at the time of delivery, on postnatal day 10, and at 2 and 4 months of life. Comparing the groups, we found statistically significant reduction in PICP levels at birth in corticosteroid-exposed neonates (P < 0.05). The levels of bone markers increased progressively on the first days of life. There were no significant differences between groups in bone markers at 10 days or at 2 and 4 months of life. We found no significant difference for bone markers between groups of infants exposed to single or repeated maternal corticosteroid treatments. In summary, antenatal glucocorticoid treatments are suggested to have a negative impact on fetal bone formation as reflected by low PICP levels at birth. However, this negative effect on bone markers seems to be a temporary effect that subsides on the first days of life and afterward.

Changes of Bone Turnover Markers after Marathon Running over 245 km

We evaluated bone turn over markers, cortisol and parathyroid hormone (PTH) levels in male athletes after 245 km of marathon running. Sixteen athletes were studied five days before, immediately after, and 1, 3, and 5 days after the run. We used T-test and Pearson correlation for statistical analysis. Osteocalcin levels were significantly decreased from 4.6 microg/lit to 3.8 microg/lit (p < 0.05). Activity of b-ALP was significantly decreased from 66 U/lit to 61.5 U/lit (p < 0.05). PICP levels were also significantly decreased from 168 microg/lit to 153 microg/lit (p < 0.05). Hydroxyproline levels decreased after the run from 70 mmol/min to 65 mmol/min (p < 0.05). ICTP levels increased after the run but without being statistically significant, from 6.62 microg/lit to 7.0 microg/lit. Urine calcium decreased significantly by 68 %, immediately after the run. Cortisol increased from 212 ng/ml to 455 ng/ml, and PTH levels increased from 12 pg/lit to 16 pg/lit immediately after the race (p < 0.05). Cortisol levels were significantly negatively correlated with osteocalcin (r = - 0.61, p < 0.05) and b-ALP (r = - 0.98, p < 0.05). PTH levels were significantly negatively correlated only with serum osteocalcin (r = - 0.8, p < 0.05). These findings suggest a transient suppression in osteoblast function during the marathon run probably due to cortisol and PTH levels elevation.

QRS DURATION AND Q-TC INTERVAL DO NOT CORRELATE WITH SERUM MARKER OF MYOCARDIAL FIBROSIS IN PATIENTS WITH ADVANCED SYSTOLIC HEART FAILURE.

Purpose QRS duration is currently used to select patients with advanced systolic heart failure (HF) for device therapy. Q-Tc prolongation has long been associated with increased risk of ventricular arrhythmias. We hypothesized that the degree of fibrosis within the myocardium may influence QRS duration and Q-Tc interval in patients with advanced systolic HF. Methods Thirty-six patients with systolic HF and EF Results The mean left ventricular ejection fraction (EF), QRS duration, and Q-Tc interval were 23.0 ± 5.4%, 125.8 ± 33.9 milliseconds, 487.6 ± 42.0, respectively. Mean PICP level was 997.4 ± 455.1 ng/mL. Conclusions In this small study of patients with advanced systolic HF, the degree of myocardial fibrosis as determined by serum levels of PICP did not correlate with QRS duration or Q-Tc interval. Q-Tc, on the other hand, significantly correlated with EF.

SERUM MARKER OF FIBROSIS I IS THE STRONGEST INDEPENDENT PREDICTOR OF DIASTOLIC FUNCTION IN PATIENTS WITH ADVANCED SYSTOLIC HEART FAILURE.

Background Severe diastolic dysfunction, known as restrictive filling pattern, has been correlated with worse outcome in patients with advanced systolic heart failure. However, the degree of diastolic dysfunction in these patients is highly variable. The major determinants of diastolic function in patients with advanced systolic heart failure have not been well described. Methods We enrolled 40 patients with heart failure and left ventricular ejection fraction (LVEF) Results Mean age was 58.7 ± 13.9 years. Mean LVEF was 25.1 ± 6.4%. Female and ischemic etiology of systolic dysfunction was present in 28% and 48%, respectively. Mean PICP levels were significantly higher in patients with severe diastolic dysfunction (DD) versus the nonsevere group, 1,308.31 ± 466.79 ng/mL versus 864.97 ± 366.19 mg/mL, respectively (p Conclusion In patients with advanced systolic heart failure, PICP, a serum marker of fibrosis, is significantly higher in those with severe diastolic dysfunction. Among parameters tested, PICP is the strongest independent predictor of diastolic function.

Ventricular remodeling following acute myocardial infarction: The role of altered collagen homeostasis

Ventricular remodeling following myocardial infarction, characterized by detrimental changes on ventricular size, shape and function, is considered to be one of the most powerful predictors of adverse outcomes after myocardial infarction [1,2]. Recently, McGavigan et al. [3] have evaluated the role of impaired collagen homeostasis in predicting the development of early ventricular remodeling following acute myocardial infarction. Fifty-one patients with acute myocardial infarction have been included in this study. Twenty-three of these patients had normal left ventricular wall motion index and 28 have had abnormal wall motion index. C-propeptide for type-I collagen (PICP) andC-telopeptide for type-I collagen (CITP) have been measured as the markers of collagen synthesis and degradation, respectively. Patients who manifested early left ventricular remodeling following acute myocardial infarction have increased degradation and reduced synthesis of collagen, favoring net collagen breakdown. Both groups with normal and abnormalwall motion index have shown to have increased in PICP and CITP over time. However mean admission of CITP levels, indicating collagen degradation, has been detected to be significantly higher in patients with abnormal wall motion index. In contrary, admission of PICP levels, indicating collagen synthesis, has been shown to be significantly lower in abnormal wall motion index group. In addition admission of CITP levels had a positive correlation with wall motion index. CITPN3.2 ng/ml has been reported to

Analysis of Bone Mineral Density and Turnover in Patients with Cystic Fibrosis: Associations between the IGF System and Inflammatory Cytokines

Background: Cystic fibrosis (CF) patients present an increased risk of osteoporosis, and increased fracture rate. Several factors have been identified as modulators of bone metabolism and bone mineral density (BMD). Aims: To evaluate BMD and serum markers of bone turnover and establish their relationships with serum concentrations of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α, IGF-I, IGF-II, IGF binding protein (IGFBP)-2, IGFBP-3, and parathyroid hormone (PTH) in young adult CF patients. Methods: Seventeen young adult CF patients (4 M, 13 F; mean age: 26.6 ± 1.1 years) were enrolled in the study and analysed as a whole and as two subgroups according to the Shwachman-Kulczycki score. BMD was assessed at the lumbar spine (L1–L4) by dual energy X-ray absorptiometry (DXA Hologic QDR 2000). Bone turnover was assessed by measuring serum levels of osteocalcin (OC) and serum carboxyterminal propeptide of type I collagen (PICP) as markers of bone formation, and serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as a marker of bone resorption. Serum IGFs, IGFBPs, and cytokines were assayed using special commercial kits. Daily calcium intake and weekly physical activity were estimated by questionnaires. Forced expiratory volume in one second was used to assess pulmonary function. Results: Lumbar BMD was normal, although there was a tendency to be lower in the patients with a lower clinical score. Both OC and PICP were increased, whereas ICTP was normal. Lumbar BMD was positively correlated with pulmonary function. IL-6 and C-reactive protein (markers of inflammation) were inversely correlated with PICP. Serum ICTP levels were correlated with serum IGF-I levels.No significant relationship was detected among lumbar BMD, markers of bone turnover and PTH, IGF-I, IGF-II, IGFBP-2, IGFBP-3, TNF-α, IL-1β, and body mass index Z-score. Conclusions: Bone turnover is abnormal in CF patients. Young adult CF patients with satisfying clinical status and nutritional conditions have normal BMD and increased serum OC and PICP levels.

Type 1 Collagen Marker of Bone Turnover, Insulin-Like Growth Factor, and Leptin in Dichorionic Twins with Discordant Birth Weight

We investigated the relationship between IGF-I-IGF binding protein (IGFBP)-1 and leptin levels with type 1 collagen markers of bone turnover in dichorionic twins with or without discordant birth weight of 20% or greater. Maternal and cord bloods were collected from gestational age-matched dichorionic twins with (n = 16) or without (n = 16) discordant birth weight. The samples were assayed for cross-linked carboxyl terminal telopeptide (ICTP, a marker of bone resorption) and propeptide (PICP, a marker of bone formation) of type I collagen, leptin, IGF-I, and IGFBP-1 by RIA. The intrauterine growth-restricted (IUGR) twins of the discordant group had higher fetal ICTP (P < 0.001) and IGFBP-1 (P < 0.001) levels, whereas PICP (P < 0.001), IGF-I (P < 0.001), and leptin (P < 0.001) were lower than the cotwins with normal weight (AGA). In contrast, concentrations of IGF-I, IGFBP-1, ICTP, PICP, and leptin were comparable between concordant twin pairs. Leptin levels were positively correlated with PICP (r = 0.61; P < 0.001) and negatively with ICTP (r = -0.57; P < 0.001) in concordant and AGA twins but not in IUGR twins. In IUGR twins, IGF-I had positive association with PICP (r = 0.76; P < 0.001) and negative association with ICTP (r= -0.76; P < 0.001), whereas IGFBP-1 was negatively correlated with PICP levels (r = -0.65; P < 0.01). No such association was found in concordant and AGA twins. These data suggest that IUGR twins had high bone turnover, which is independent of maternal factors and perhaps may be due to altered IGF axis.

Changes of collagen metabolism predict the left ventricular remodeling after myocardial infarction

To analyze the predictive value of cardiac collagen metabolism "in vivo" in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). Forty-five patients (age 66 +/- 8.27) underwent biochemical analysis for cardiac collagen metabolism (groups A, B and C); 30 patients with their first MI were treated with successful PCI (group A; n = 30), group B (n = 5) were MI patients with unsuccessful PCI. Group C were patients without MI (n = 10), they underwent elective diagnostic coronary angiography only. The collagen metabolism was analyzed in acute and subacute MI phases by using serum blood markers: the carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP). Furthermore, the ejection fraction (EF) and left ventricular end-diastolic volume maximal changes in the course of 6 months were measured by echocardiography. A significant increase of both PICP and PIIINP on day 4 following MI was detected. Furthermore, PICP and PIIINP level assessed on the 30th day was significantly higher in the PCI unsuccessful group versus successful group. PICP level on day 4 above 110 microg/l and PIIINP level above 4 microg/l was significantly often found in the subgroup of patients with the EF improvement less than 10% or worsening and with significant left ventricular dilatation during 6 months follow-up. Cardiac catheterization itself does not affect collagen metabolism. We concluded that collagen metabolism markers enable to study in vivo the MI healing and to predict left ventricular functional and volume changes.

The effect of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with cystic fibrosis

Impaired vitamin K status in cystic fibrosis (CF) has been considered as a newly emerged pathogenetic factor for reduced bone mineral density (BMD). Our aim was to evaluate the effectiveness of vitamin K supplementation in managing bone formation abnormalities in children and adolescents with CF. The statuses of vitamins K and D in relation to biochemical markers of bone metabolism and BMD were examined in 20 CF children receiving vitamin D supplements but not vitamin K supplements. Laboratory tests were carried out at the beginning of the study period and after 1 year of vitamin K supplementation (10 mg single oral dose/week) and the results were compared; the results were also compared with those of 25 healthy controls. Ten of the CF patients had BMD z-score<or=2.5 (n=5) or between -1 and -2.5 (n=5). Biochemical tests on patients before vitamin K supplementation revealed that the levels of osteoblastic activity markers, namely, bone alkaline phosphatase (BAP), serum osteocalcin (Gla-OC), serum carboxy-terminal propeptide of type I procollagen (PICP) and serum amino-terminal propeptide of type I procollagen (PINP), were significantly reduced compared with those of the controls. These patients had also lower 25-hydroxy-vitamin D (25(OH)D) and vitamin K serum levels, higher undercaboxylated osteocalcin (Glu-OC) and parathormone (PTH) levels and a higher calcium to creatinine ratio (Ca/Cr) than the controls. Vitamin K intake was associated with an increase in Gla-OC, PINP, PICP levels and a decrease in Glu-OC levels. PTH levels were lower after vitamin K supplementation without any difference in BMD z-scores. Our data indicate that vitamin K supplementation may have a beneficial role in bone health in CF children.

Elevated Carboxy-Terminal Peptide of Procollagen Type I in Elderly Patients with Diastolic Dysfunction

Diastolic dysfunction (DD) is common in elderly people. Myocardial fibrosis is a major determinant of diastolic function. Increased myocardial fibrosis has been observed with advancing age. We hypothesized that plasma levels of carboxy-terminal peptide of procollagen type I (PICP), a marker of fibrosis, is elevated in elderly subjects with DD compared to healthy control subjects. PICP levels were measured in 29 elderly subjects with DD and 25 healthy control subjects. The relationship between PICP levels and age, gender, hypertension, and the presence of left ventricular hypertrophy were then assessed. PICP levels were significantly higher in elderly subjects with DD than in healthy control subjects (301.0 +/- 52.0 vs. 262.9 +/- 45.3 ng/mL; P = .006). PICP levels were higher in elderly with DD regardless of the presence of left ventricular hypertrophy. Additionally, PICP levels were not found to correlate with age. PICP levels are elevated in elderly people with DD. PICP may be a useful marker to determine the level of fibrotic activity in this population.

Elevated IGFBP-1 cause high bone turnover in growth-restricted monochorionic twins with discordant birth weight

Objective To test the hypothesis that low birth weight twins have a higher risk of osteoportotic fracture in later life, we investigated the association between fetal IGF axis and type-1 collagen markers of bone turnover in monochorionic (MC) twins with or without discordant birth weight of ≥20%. Methods Maternal and cord bloods were collected from gestational age matched MC twins of discordant ( n = 16) and concordant birth weights ( n = 16). The samples were assayed for cross linked carboxyl terminal telopeptide (ICTP, a marker of bone resorption) and pro-peptide (PICP, a marker of bone formation) of type I collagen, IGF-1, and IGFBP-1 by radio-immunoassay. Results The growth-restricted twins (IUGR) of discordant group had higher fetal IGFBP-1 and ICTP ( P < 0.001) levels, while PICP ( P < 0.001) was lower than the co-twins with normal weight (AGA). In contrast, cord blood levels of IGF-1, IGFBP-1, ICTP, and PICP in concordant twin pairs were comparable to AGA twins. The concordant and AGA twins had a positive correlation between ICTP and PICP levels ( y = 23 x − 711; r = 0.84; P < 0.001; n = 48) but no such association was found in IUGR twins. Instead, IGFBP-1 levels in IUGR twins had a negative association with PICP ( r = 0.81; P < 0.001; n = 16) and a positive correlation with ICTP ( r− = 0.51; P < 0.05; n = 16). No such association was found in concordant and AGA twins. Conclusion These data suggest that growth-restricted twins had high bone turnover, due to elevated IGFBP-1. This association seems to be independent of maternal and genetic factors.

Spironolactone improves diastolic function in the elderly

Diastolic dysfunction is common in the elderly. Increased myocardial fibrosis, a major determinant of diastolic function, has been observed with advancing age. Spironolactone prevents age-related increases in myocardial fibrosis in old normotensive rats. Spironolactone, via its antifibrotic activity, can improve diastolic function in the elderly with isolated diastolic dysfunction. The study was a prospective, double-blind, randomized, placebo-controlled trial. Thirty elderly subjects between 60 and 85 years of age with isolated diastolic dysfunction and no contraindications for spironolactone were randomized to 25 mg/day of spironolactone or placebo for 4 months. Mitral E/A and deceleration time, plasma levels of carboxy-terminal of procollagen type I (PICP), and brain natriuretic peptide (BNP) were measured at baseline and at the end of 4 months. Plasma level of potassium was also monitored to prevent clinically significant hyperkalemia. There was no serious adverse event or clinically significant hyperkalemia in the spironolactone group. Compared with baseline values, spironolactone significantly improved mitral E/A ratio (0.71 +/- 0.08 vs. 0.84 +/- 0.19, p = 0.025) and deceleration time (285.5 +/- 73.1 vs. 230.0 +/- 54.7, p = 0.035). There were no significant differences in the magnitude of change in the levels of PICP and BNP between the two treatment groups. Spironolactone may improve diastolic function in the elderly.

Feto-maternal Bone Remodeling in Normal Pregnancy and Preeclampsia

To investigate feto-maternal bone turnover in normal pregnancy and preeclampsia and to test the hypothesis whether the reported low bone mass at birth in small-for-gestational age infants is associated with decreased bone formation or increased bone resorption. Thirty-two patients with preeclampsia (17 mild and 15 severe) and 20 normotensive women (controls) with singleton gestations in the third trimester participated in this study. Furthermore, 25 nonpregnant healthy women were chosen as nonpregnant controls. Maternal 24-hour urine specimens and venous blood samples were collected. In addition, fetal cord blood and the first voided neonatal urine were also collected. The freshly separated sera were assayed for osteocalcin (OC) and carboxy-terminal propeptide of type 1 collagen (PICP) by radioimmunoassay. Urine samples were assayed for N-telopeptide of type 1 collagen (NTx) by enzyme-linked immunosorbent assay. Maternal and cord serum OC and PICP levels were significantly decreased in severe preeclampsia, whereas maternal and first-voided neonatal urinary NTx level were significantly increased compared to the corresponding levels of controls. In both mother and fetus, the coupling index of markers of bone turnover in normal pregnancy or mild preeclampsia was in favor of bone formation, whereas in severe preeclampsia the markers suggested marked bone resorption. Increased bone resorption and decreased bone formation occur in preeclampsia in both mother and fetus, being more pronounced in the latter. The increased osteoclastic activity in preeclampsia may be attributed to increased RANKL induced by increased interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor beta2 (TGF-beta2) production.

Effects of combined estrogen/testosterone therapy on bone and body composition in oophorectomized women

Objective. To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen therapy on bone markers, bone mineral density and body composition in oophorectomized women.Methods. Fifty women, 45–60 years old, who had undergone a hysterectomy and bilateral salpingo-oophorectomy for benign disorders, were randomly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily. Twenty-four weeks later, cross-over was performed to the other treatment regimen. Forty-four women completed the study. Their serum concentrations of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, osteocalcin, carboxyterminal telopeptide aminoterminal (ICTP), of type I collagen propeptide of type I procollagen (PICP) and interleukin (IL)-1 receptor antagonist were measured at baseline and after 24 weeks of both treatments, as were also their body mass index (BMI) and blood pressure. Bone mineral density of the total body, spine and hip and total body fat, total lean body mass, trunk fat and trunk lean mass were determined by dual-energy X-ray absorptiometry measurements at baseline and after 24 weeks of both regimens.Results. During treatment, the addition of testosterone counteracted the decrease in IGF-I and PICP seen with estrogen therapy alone. Osteocalcin and ICTP were significantly reduced to the same extent by both therapies. No change ocurred in the IL-1 receptor antagonist. A significant increase was seen in total lean body mass with the estrogen/testosterone regimen, but the total fat mass, trunk lean or fat mass remained unchanged after 24 weeks of both treatments. No effect was detected on total, hip or spinal bone mineral density after treatment with estrogen alone or estrogen/testosterone. Likewise, BMI and blood pressure were unaffected.Conclusions. The addition of testosterone to oral estrogen might have positive effects on bone as suggested by the fact that it counteracted the decline in IGF-I and PICP levels. An anabolic effect on muscle was reflected by an increase in the total lean body mass. No adverse effects were noted on BMI, fat distribution or blood pressure during the 6-month treatment with oral testosterone undecanoate.