Serum Carboxyterminal Propeptide Of Type Research Articles

Evolution of circulating C-terminal propeptide of type I procollagen in patients with chronic renal failure pre and post renal transplantation.

The carboxyterminal propeptide of type I procollagen is a biochemical marker of type I collagen synthesis. We evaluated circulating carboxyterminal propetide of type I procollagen levels in patients with terminal renal failure before and after kidney transplantation. Serum carboxyterminal propeptide of type I procollagen, osteocalcin, total alkaline phosphatase, intact parathyrin, creatinine, calcium and phosphate levels were determined in 20 patients, before and 15, 30, 90 and 180 days after surgery. Serum creatinine and intact parathyrin concentrations showed a significant decrease after kidney transplantation. Immunosuppressive treatment consisted of low dose prednisone, cyclosporin and antilymphoblast globulin. In our group, only 5 patients (25%) showed serum carboxyterminal propeptide of type I procollagen levels higher than normal before kidney transplantation. At 15 and 30 days, carboxyterminal propeptide of type I procollagen concentrations showed a decrease, while at 90 and 180 days there was a significant increase above the normal range (p = 0.006; ANOVA). Serum osteocalcin and total alkaline phosphatase levels increased significantly at the same time. We found a significant correlation between carboxyterminal propetide of type I procollagen and osteocalcin at 15 and 30 days after kidney transplantation. We conclude that the significant increase in carboxyterminal propeptide of type I procollagen levels after kidney transplantation reflect an increase in bone turnover. The low doses of steroids employed do not seem to have a significant inhibitory effect on collagen synthesis.

Elevated parathyroid hormone-related peptide levels after human gestation: relationship to changes in bone and mineral metabolism.

PTH-related peptide (PTHrP) can be found in high concentrations in human breast milk and has been implicated in material calcium regulation postpartum. We studied the relationship of plasma PTHrP levels of serum markers of bone turnover and selective cancellous bone density in 35 women (age, 25 +/- 3 yr) 2-3 days postpartum and after 3 and 6 months of lactation. The mean postpartum plasma PTHrP levels measured by immunoradiometric assay was 2.64 +/- 0.19 pmol/L (mean +/- SE) and were elevated compared to that in 35 age- and sex-matched controls (1.34 +/- 0.14; P < 0.0001). PTHrP remained significantly elevated, but decreased during the lactation period of 6 +/- 1 months. Immediately postpartum, serum protein levels were lowest, and serum ionized calcium levels highest. At that time, PTH was suppressed to 50% of control values (P < 0.001). Two or 3 days postpartum, serum ionized calcium was negatively correlated with total serum protein (r = -0.47; P < 0.0001) and positively correlated with plasma PTHrP (r = -0.32; P < 0.008). PTH was inversely correlated with ionized calcium (r = -0.24; P = 0.03) and PTHrP (r = -0.31; P < 0.01). Three and 6 months postpartum, serum protein and PTH levels had returned to normal, and ionized calcium concentrations decreased. There was no indication that PTHrP may have any significant systemic effect after 3 and 6 months of lactation. Long term lactation led to a significant decrease in radial cancellous bone density (-4.5%; P < 0.05) at 6 months and to elevations in serum markers of bone resorption (2- to 3-fold for serum carboxy-terminal telopeptide of type I collagen) and formation (1- to 2-fold for osteocalcin and serum carboxy-terminal propeptide of type I procollagen). Bone turnover balance was clearly negative after 3 months of lactation compared to the control value and indicated net bone loss at a time when estrogen levels were low. With ongoing lactation, estrogen levels increased, and bone turnover balance improved significantly and independently of PTHrP levels. We interpret these results as evidence that PTHrP is elevated during the postgestational period and has a weak and temporary effect on calcium metabolism when serum protein levels are reduced. PTHrP does not seem to participate significantly in the regulation of bone turnover during lactation. Normalization of bone turnover balance at 6 months of lactation suggests that further cancellous bone loss is most likely minimal when breast-feeding is extended beyond that time.

Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones

In order to investigate collagen metabolism in two different types of autosomal dominant osteopetrosis (ADO), eight patients with type I (aged 23-61 years, mean 40.4 years) and nine patients with type II ADO (aged 20-49 years, mean 32.8 years) were compared with ten normal controls (aged 22-54 years, mean 35.4 years). The subjects were treated with 100 micrograms of triiodothyronine (T3) daily for 7 days and followed for a total of 4 weeks. Serum T3 increased in all subjects and a corresponding suppression of thyroid-stimulating hormone (TSH) was observed. Serum carboxy-terminal propeptide of type I collagen (S-PICP) in the control and type I groups showed no difference at baseline, whereas type II was lower than controls (p < 0.01). No significant alterations following stimulation were observed in any of the groups. Serum BGP (osteocalcin) values in the two patient groups were insignificantly lower than controls both at baseline and throughout the study. Following stimulation, a significant response was seen in the three groups (p < 0.001). The increases during the treatment period (delta values) for controls, type I and type II were 47.6% (p < 0.01), 51.7% (p = 0.05) and 34.8% (NS), respectively, with no difference between the groups. Serum bone-specific alkaline phosphatase (S-ALP) was not different between the groups and no alterations were observed in relation to treatment. The serum N-terminal propeptide of type III collagen (S-PIIINP) showed no difference at baseline between type I and controls but was significantly higher (p < 0.003) in type II than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Etretinate administration reduces serum propeptide of type I procollagen level in patients with psoriasis

The serum carboxyterminal propeptide of type I procollagen (PICP) level in 26 patients with psoriasis was significantly lower than in control subjects (124 +/- 47 and 224 +/- 78 ng/ml, respectively; P < 0.001). The patients were divided into two groups, those treated with etretinate and untreated patients. PICP levels in the treated group were significantly lower than those in the untreated group (P < 0.001), but there was no difference between the control and untreated groups. In addition, there was a negative correlation between PICP levels and the serum etretinate concentration in treated patients (r = -0.622, P < 0.05). There was no difference between procollagen type III aminoterminal propeptide (PIIIP) levels in patients and controls, nor was there any significant difference between etretinate-treated and untreated patients. In cell culture studies, etretinate dose-dependently (from 10(-9) to 10(-5) M) decreased the PICP concentration in the medium of fibroblasts from both healthy subjects and patients. In osteoblast cell culture, PICP levels were reduced only in a high concentration of etretinate (10(-5) M). However, no change was observed in preadipose cells. Our in vivo and in vitro observations indicated that psoriasis per se did not affect either serum PICP or PIIIP levels, but that etretinate had an inhibitory effect on collagen synthesis by fibroblasts. Hence, the administration of etretinate to psoriatic patients is, at least in part, responsible for the reduction of serum PICP levels in these patients.

Accelerated bone degradation in thyroid carcinoma patients during thyroxine treatment, measured by determination of the carboxyterminal telopeptide region of type I collagen in serum.

We studied the effects of long-term suppressive thyroxine treatment on serum markers of bone collagen synthesis and degradation in thyroid carcinoma patients, and the relationship of these effects to the serum concentrations of thyrotropin, free thyroxine and free triiodothyronine were investigated. Thirty-seven thyroid carcinoma patients receiving a stable thyroxine dose, and thirty-five controls participated in a cross-sectional study. Bone collagen synthesis and degradation were measured by using specific radioimmunoassays to determine the serum concentrations of carboxyterminal propeptide of type I procollagen, and carboxyterminal telopeptide region of type I collagen, respectively. Serum thyrotropin, free T4 and free T3 were measured by time-resolved fluoroimmunoassays (Delfia). Serum carboxyterminal telopeptide region of type I collagen concentrations of thyroid carcinoma patients were significantly higher than those of the controls (p = 0.0012). Serum carboxyterminal propeptide of type I procollagen concentrations did not differ significantly between the patients and controls (p = 0.85). Significant associations between age or physical activity, and carboxyterminal propeptide of type I procollagen or carboxyterminal telopeptide region of type I collagen were found in the controls, but not in the patients. Thyrotropin, free T4 or free T3 were not significantly associated with carboxyterminal propeptide of type I procollagen or carboxyterminal telopeptide region of type I collagen in either the control or patient group. From these results it is concluded that long-term suppressive thyroxine treatment seems to accelerate bone degradation, but not bone formation, and therefore carries a risk for osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible variation in bone resorption during the normal menstrual cycle.

In order to determine whether bone turnover varies during the normal menstrual cycle, we measured biochemical markers of bone resorption (serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum alkaline phosphatase) in ten healthy premenopausal women every two or three days for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its nadir during the follicular phase and its peak during the luteal phase, and an overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic changes were observed in the urinary parameters of bone resorption or in the biochemical markers of bone formation. We conclude that sICTP, a new biochemical marker of bone resorption, undergoes small variations during a normal menstrual cycle in premenopausal women, whereas the biochemical markers of bone formation remain constant.

Photopheresis in systemic sclerosis: clinical and serological studies using markers of collagen metabolism.

Eight patients with progressive systemic sclerosis were treated with photopheresis or extracorporeal photochemotherapy given on 2 consecutive days every 4 weeks for 5 to 8 months. Previous treatment with immunosuppressive agents or D-penicillamine was discontinued for at least 4 weeks prior to photopheresis. Although IL-2 receptor density in peripheral blood T-lymphocytes decreased significantly in the initial phase of the photopheresis therapy, no substantial clinical improvement occurred. Although the intention had been to treat all patients for at least 8 months with photopheresis alone, it was mandatory due to severe exacerbations to give additional immunotherapy to 4 patients, and 2 of these together with another patient wanted to discontinue photopheresis after 5 and 6 months, as they did not expect an effect. Three of the 4 patients with progression had RNP-antibodies, suggesting that they had their scleroderma as part of a mixed connective tissue disease. The clinical exacerbations were accompanied in all patients by a highly significant increase in serum aminoterminal propeptide of type III procollagen (PIIINP), which has been reported to correlate with involvement of skin and internal organs in systemic sclerosis. Similar but less significant increases were found in serum carboxyterminal propeptide of type I procollagen (PICP); there were no significant changes in serum cross-linked fragment of type I collagen. Plasma levels of 8-methoxypsoralen were all above 80 ng/l, showing that the lack of responses to photopheresis could not be due to poor absorption of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry.

Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p < 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = -0.45, p < 0.05, SEM/Y = 412%). S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p < 0.05) and volume-referent bone formation rate (r = 0.61, p < 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p < 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.

Is serum carboxyterminal propeptide of type I procollagen a useful marker in patients with bone metastases?

Is serum carboxyterminal propeptide of type I procollagen a useful marker in patients with bone metastases?