Serum Levels Of Carboxyterminal Propeptide Research Articles

Preeclampsia – a risk factor for osteoporosis? Analysis of maternal Sclerostin levels and markers of bone turnover in patients with pre-eclampsia

Introduction: The role of preeclampsia (PE) in affecting bone metabolism could not be clarified in the past years. Recently Sclerostin, a new marker of bone metabolism which is known to have an inhibitory effect on bone formation causing osteoporosis, was discovered. Objective: To investigate serum levels of Sclerostin and markers of bone turnover in women with normotensive pregnancies and pregnancies complicated by PE. Methods: In this prospective study we enrolled 22 women with PE and 22 healthy pregnant women to observe serum levels of carboxyterminal propeptide of type I collagen (PICP), cross-linked carboxyl terminal telopeptide of the type I collagen (ICTP), calcium, phosphate, 25-hydroxyvitamin D and parathyroid hormone. In 16 preeclamptic and 16 healthy pregnant women, serum Sclerostin levels were analyzed. Results: Serum levels of Sclerostin (mean ± standard deviation: healthy 10.5 ± 8.1 pmol/l versus PE 11.5 ± 9.4 pmol/l, p = 0.768), ICTP (healthy 0.3 ± 0.2 ng/ml versus PE 0.4 ± 0.1 ng/ml, p = 0.462), PICP (healthy 59.9 ± 49.9 ng/ml versus PE 89.0 ± 62.0 ng/ml, p = 0.094), phosphate (healthy 1.1 ± 0.2 mmol/l versus PE 1.2 ± 0.4 mmol/l, p = 0.162) and parathyroid hormone (healthy 26.9 ± 14 pg/ml versus PE 35.3 ± 17.6 pg/ml, p = 0.08) showed no significant differences between the groups. Significantly lower serum calcium (healthy 2.3 ± 0.1 mmol/l versus PE 2.2 ± 0.2 mmol/l, p < 0.005) and serum 25-Hydroxyvitamin D (healthy 39.3 ± 16.7 nmol/l versus PE 23.9 ± 16.9 nmol/l, p < 0.005) were observed in preeclamptic women. Conclusion: Pregnancies complicated by PE show no signs of high bone turnover and may not lead to a higher risk of osteoporosis in later life.

Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers

IntroductionEarly systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.MethodsSeventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.ResultsThirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.ConclusionThese results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.

Relationships between mandibular cortical bone measures and biochemical markers of bone turnover in elderly Japanese men and women

The aim was to clarify the association between dental panoramic radiography measures of mandibular inferior cortical shape and biochemical markers of bone turnover in elderly men and women. Subjects were 80-year-old men (n = 85) and women (n = 153). Mandibular cortical shape and width were evaluated on dental panoramic radiographs. Bone formation and resorption, respectively, were estimated by serum levels of carboxy-terminal propeptide of type I collagen (PICP) and serum type I collagen carboxy-terminal telopeptide (ICTP). Eroded cortices of the mandible were significantly associated with increased serum PICP levels (P = .005) in women. Lower mandibular cortical width quartiles were also significantly associated with increased serum PICP levels in men (P = .020) and women (P = .006). Mandibular inferior cortical measures detected on dental panoramic radiographs may be associated with bone formation rates and be useful in predicting osteoporosis in elderly Japanese men and women.

骨病変と高カルシウム血症をともなう造血器腫瘍におけるI型プロコラーゲン-C-プロペプチド(PICP),I型コラーゲン-C-テロペフチド(ICTP)とC端副甲状腺ホルモン関連蛋白(C-PTHrP)の臨床的意義

骨病変と高カルシウム血症をともなう造血器腫瘍におけるI型プロコラーゲン-C-プロペプチド(PICP),I型コラーゲン-C-テロペフチド(ICTP)とC端副甲状腺ホルモン関連蛋白(C-PTHrP)の臨床的意義

Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease

Osteoprotegerin (OPG), the neutralizing decoy receptor for the osteoclast activator RANK ligand, was measured in serum taken from patients with multiple myeloma at the time of diagnosis. Median OPG was lower in the patients with myeloma (7.4 ng/mL; range, 2.6-80; n = 225) than in healthy age- and sex-matched controls (9.0 ng/mL; range 5.1-130; n = 40; P =.02). Importantly, OPG levels were associated with degree of radiographically assessed skeletal destruction (P =.01). The median OPG level in patients lacking osteolytic lesions was 9.1 ng/mL, as compared with 7.6 ng/mL and 7.0 ng/mL, respectively, in patients with minor or advanced osteolytic disease. Furthermore, OPG levels were associated with World Health Organization performance status (P =.003) and correlated to serum levels of carboxy-terminal propeptide of type I procollagen (PICP; P <.001) but not with clinical stage or survival. These findings suggest impaired OPG function in myeloma and give a rationale for OPG as a therapeutic agent against myeloma bone disease.

Serum levels of carboxy-terminal propeptide of type I collagen in nonalcoholic steatohepatitis

Serum levels of carboxy-terminal propeptide of type I collagen in nonalcoholic steatohepatitis

Serum levels of carboxy-terminal propeptide of type I collagen in nonalcoholic steatohepatitis

Serum levels of carboxy-terminal propeptide of type I collagen in nonalcoholic steatohepatitis

Serum levels of carboxy-terminal propeptide of human type I procollagen are an indicator for the progression of diabetic nephropathy in patients with Type 2 diabetes mellitus

The finding that glomerular mesangial cells produce human type I collagen suggests that the serum levels of carboxy-terminal propeptide of human type I procollagen (P1CP) may reflect the severity of diabetic nephropathy. We therefore investigated the relationship between serum P1CP levels and the extent of diabetic complications in 100 patients (46 males and 54 females) with Type 2 diabetes and in 64 healthy subjects. Serum P1CP was determined by radioimmunoassay. In diabetes, we defined P1CP levels less than 142 ng/ml as a normal P1CP group (group A), whereas we defined them as equal to or greater than 142 ng/ml as a high P1CP group (group B). The diabetic patients had significantly elevated serum P1CP levels compared with the controls. The prevalence of hypertension, proliferative diabetic retinopathy or macroalbuminuria was significantly higher in group B than in group A. Serum P1CP levels showed a significant positive correlation with urinary albumin excretion, but not with fasting blood glucose, glycosylated hemoglobin A 1c or serum osteocalcin. Macroalbuminuric patients showed significantly higher P1CP levels than the normoalbuminuric patients. In patients in the absence of diabetic nephropathy, no significant differences of P1CP levels were found among the severity of diabetic retinopathy. The present results suggest that serum P1CP levels reflect the progression of diabetic nephropathy in patients with Type 2 diabetes.

Wheat bran supplementation does not affect biochemical markers of bone turnover in young adult women with recommended calcium intake

We investigated the effect of wheat bran on biochemical indicators of Ca and bone metabolism in nineteen healthy women, aged 25.5 (SE 0.9) years. Subjects received six wheat bran biscuits or six white flour biscuits per day for a period of 4 weeks (crossover). Wheat bran consumption increased fibre intake from 17.7 (SE 1.3) to 29.6 (SE 1.3) g/d (7 d food record) and enhanced P intake from 1225 (SE 59) mg/d to 1663 (SE 65) mg/d; P < 0.001. Mean daily Ca intake during wheat bran consumption (1110 (SE 82) mg/d) significantly (P = 0.008) exceeded Ca ingestion during the white flour period (955 (SE 67) mg/d). Wheat bran increased the number of defecations per week from 7.9 (SE 0.8) to 12.2 (SE 1.4) (P = 0.0018). Urinary Ca excretion over 24 h significantly (P = 0.021) decreased from 473 (SE 53) mumol/mmol creatinine (control period) to 339 (SE 37) mumol/mmol creatinine (wheat bran period). Serum 25-hydroxyvitamin D, 2 h fasting urinary Ca/creatinine excretions and 24 h urinary P excretion remained constant. No differences in serum levels of carboxy-terminal propeptide of type I procollagen (biomarker of bone formation) or in 2 h fasting urinary hydroxyproline/creatinine excretions (biomarker of bone resorption) were observed at the end of the two cycles of dietary supplementation. We conclude that a high fibre intake of approximately 30 g/d has no significant adverse effects on bone turnover in subjects with Ca intakes above 1000 mg/d and that the reduction in 24 h urinary Ca excretion is most probably the result of an adaptation process, induced by a decrease in net absorbed Ca.

Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.

Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.

Albumin synthesis and bone collagen formation in human immunodeficiency virus-positive subjects: differential effects of growth hormone administration.

Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined. Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 +/- 15%, P = 0.002), patients with asymptomatic HIV (24 +/- 10%, not significant), patients with AIDS (47 +/- 7%, P < 0.001), and patients with AIDS and > 10% weight loss (21 +/- 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 +/- 7%, P < 0.05), HIV+ subjects (39 +/- 16%, P < 0.05), and patients with AIDS (25 +/- 7%, P < 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 +/- 12%) in response to hrGH. The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.

Studies of type I collagen related substances as bone metastatic markers of prostate carcinoma with special regard to serum carboxyterminal propeptide of type. I. Procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and Urinary deoxypyridinoline levels

To investigate if serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of deoxypyridinoline (D-Pyr) are useful markers of bone metastasis in patients with prostate carcinoma, we measured these markers in patients with untreated benign prostatic hyperplasia (BPH) and untreated prostate carcinoma (PCA). Serum PICP, ICTP and urinary D-Pyr levels were determined in 53 patients; 16 patients with BPH, 15 patients with PCA without bone metastasis (stage A, B, C and D1) and 22 patients with PCA with bone metastasis (stage D2). At the same time correlations among these markers and serum total alkaline phosphatase (ALP) activity were studied. Serum PICP, ICTP and urinary D-Pyr levels in the PCA patients with bone metastasis were significantly higher than those of BPH. The serum levels of PICP in patients with PCA with bone metastasis group were significantly higher than those of without bone metastasis group. The serum levels of ICTP in patients with PCA without bone metastasis group were significantly higher than those of BPH group, while no significant difference was observed between PCA group with and without bone metastasis. In the PCA patients with bone metastasis, serum PICP and serum total alkaline phosphatase (ALP) activity were significantly correlated (r = 0.80). In these patients, serum ICTP and urinary D-Pyr levels were also significantly correlated (r = 0.70). These results suggest that serum PIPC, ICTP and urinary D-Pyr are the useful markers to quantitate bone metastasis in the patients with PCA. Moreover, the determination of serum ICTP levels may be significant for detecting occult bone metastasis in the patients with PCA.

Changes in bone mass and serum markers of bone metabolism after parathyroidectomy

Background . Primary hyperparathyroidism (PHPT) is associated with an increased bone turnover. The simultaneous use of biochemical and bone mass measurements before and after parathyroidectomy is sparsely reported. This study was carried out to evaluate changes in bone mass and markers of bone metabolism in postmenopausal women with PHPT after parathyroidectomy. Methods . Twelve women, mean age of 63 years, were investigated. Measurements of bone mineral density (total body, spine, hip, and forearm bone mineral density) with dual-energy x-ray absorptiometry were performed before operation and at follow-up at a median of 23 months. Concomitantly, changes in serum intact parathyroid hormone, bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal propeptide of type I procollagen, and the immunoactive carboxyterminal telopeptide of type I collagen were recorded. Results . At follow-up a significant increase in bone mineral density of the spine (p < 0.05), femoral neck (p < 0.05), Ward's triangle (p < 0.05), and trochanter (p < 0.01) was observed. No significant changes in the forearm were registered. Levels of parathyroid hormone, B-ALP, and osteocalcin were elevated and intercorrelated before operation. The serum levels of these parameters decreased significantly after operation. Serum levels of carboxyterminal propeptide of type I procollagen and the immunoactive carboxyterminal telopeptide of type I collagen did not significantly differ from a reference population, and no major changes were observed at follow-up. Conclusions . Bone mineral density in the spine and hip is improved after parathyroidectomy in postmenopausal women with primary hyperparathyroidism. Serum levels of B-ALP and osteocalcin are elevated in PHPT and decrease after operation. The clinical usefulness of serum markers of collagen metabolism in investigating bone metabolism in PHPT seems limited.

Serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen and laminin P1 in Duchenne muscular dystrophy.

The striking proliferation of connective tissue in Duchenne muscular dystrophy is attributed, besides other components of the extracellular matrix, to an increase of endomysial and perimysial type III and type I collagen. We investigated if muscle fibrosis correlates to an increased serum concentration of procollagen I or III. Therefore, we measured the serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen and laminin P1 in 20 boys with progressive muscular dystrophy (16 definite Duchenne muscular dystrophy, 2 suspected of Duchenne muscular dystrophy, 2 Becker muscular dystrophy). In contrast to collagen I and III the expression of laminin in the basement membrane is known to be normal in Duchenne muscular dystrophy. There was no significant alteration of serum concentration of procollagen III N-peptide, procollagen I C-peptide and laminin P1 in boys with Duchenne muscular dystrophy. Measuring these parameters is not useful for investigating the extent of muscle fibrosis or for monitoring the effect of therapeutic trials such as steroid treatment.

The changes in serum type I and III procollagen, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with chronic renal failure.

Serum levels of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) can be used as markers of bone formation and the evaluation of children with growth disorders. We measured the serum levels of these collagens by radioimmunoassay (RIA), insulin-like growth factor I (IGF-I) (by immunoradiometric assay) and insulin-like growth factor binding protein-3 (IGFBP-3) (by RIA) levels in 24 children aged between 4 and 14 years with chronic renal failure (CRF) (n = 12 dialysis, n = 12 non-dialysis) and 12 age-matched healthy controls, to find out whether these parameters have a prognostic or therapeutic value on monitoring of growth retardation in CRF. Mean serum IGFBP-3 and PIIINP levels in the dialysis patients were higher than the control group, the difference between the groups was statistically significant (P < 0.05). It seemed that the pubertal stage of the patients did not affect the levels of PICP, PIIINP, and IGFBP-3 while serum IGF-I levels in pubertal patients were significantly higher than those in prepubertal patients (P < 0.001). There was no significant correlation between PICP and PIIINP in any patients. Neither PICP nor PIIINP correlated with height z-score, bone age, IGF-I, or IGFBP-3. It was concluded that the increased serum IGFBP-3 and PIIINP levels in chronic renal disease are poor prognostic indicators leading to progressive renal failure and end-stage renal disease (ESRD). Further investigations into the effects of these collagens on growth failure associated with CRF are needed.

Growth hormone treatment in osteogenesis imperfecta with quantitative defect of type I collagen synthesis

OBJECTIVES: We studied growth rate, bone density, and bone metabolism in patients affected by type I osteogenesis imperfecta (OI) with quantitative defect in type I collagen synthesis during treatment with human growth hormone (hGH), being aware of its collagen-stimulating synthesis activity in vitro. STUDY DESIGN: Fourteen patients (6 boys; ages 4.8 to 10.8 years) were studied. Any structural alteration in the collagen chains was excluded, and reduced production of structurally normal type I collagen (increase in type III/type I collagen; reduction in the messenger ribonucleic acid α1[I]/α2[I] ratio) was demonstrated. The patients were divided into two groups comparable in sex, age, height, and clinical severity of OI; seven patients (three boys) were treated for 12 months with hGH at a dosage of 0.2 mg/kg per week (0.6 IU/kg per week), in six injections subcutaneously, and seven were followed as control subjects. Auxologic data were measured every 3 months, and bone age was determined at the start, after 1 year of treatment, and 1 year after its completion. Every 3 months, serum insulin-like growth factor type I, osteocalcin, carboxyterminal propeptide of type I procollagen, alkaline phosphatase, calcium, and phosphorus levels and urinary hydroxyproline and calcium levels were determined. Bone mass measurements were carried out at the start of the study in all patients and repeated after 12 months in treated patients at the lumbar spine by dual-energy x-ray absorptiometry and by anteroposterior (second, third, and fourth lumbar vertebrae) and lateral (third lumbar vertebra) scan. Results were expressed as areal (anteroposterior and lateral) bone density (in milligrams per square centimeter) and as calculated true density (in milligrams per cubic centimeter). RESULTS: After 12 months, linear growth velocity in treated patients increased significantly in comparison with the pretreatment period (from 3.57 ± 0.55 to 6.04 ± 0.69 cm/yr; p <0.05) and with the untreated group ( p <0.05). Bone age did not advance faster than chronologic age. The fracture index per year was low before treatment, and during therapy no patient had any fractures. Serum osteocalcin levels were statistically lower than in control subjects before treatment and increased significantly after 12 months (3.3 ± 1.0 vs 2.1 ± 0.9 nmol/L; p <0.05). Serum levels of carboxyterminal propeptide of type I procollagen were significantly lower than normal values before treatment (164.6 ± 46.7 vs 310.3 ± 97.6 ng/ml; p <0.05) and rose, but not significantly, during and after treatment. Before therapy, patients with OI had significantly lower lumbar anteroposterior, lateral, and calculated true bone density than the normal population of the same sex compared for both age and height. After hGH treatment, bone density increased significantly in the lumbar spine, in anteroposterior and lateral scans (+2.6% ± 2.5% and +9.8% ± 14.0%, respectively; p <0.05), and in calculated true bone density (+11.4% ± 6.7%; p <0.05). CONCLUSIONS: From our results, we conclude that hGH treatment in moderate OI does not increase the fracture risk in treated patients in the short term, significantly increases the rate of linear growth velocity, and increases bone turnover and mineral content in trabecular bone at the lumbar spine. (J P EDIATR 1996;129:432-9)

Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy.

The aim of the present cross-sectional study was to disclose whether long-term thyroxine replacement therapy (TRT) in primary hypothyroidism causes osteopenia. We compared 36 adult biochemically and clinically euthyroid patients who had received TRT for more than 5 years (mean 13 years) for primary hypothyroidism with 80 sex- and age-matched normal controls. Height, body weight and lean body mass were similar, but the patients had 21% higher fat body mass (p = < 0.01) than their controls. Furthermore, compared to controls the patients had 29% higher serum thyroxine (T4) and 31% higher serum free T4 index (FT4I) levels (p < 0.001), whereas serum triiodothyronine (T3) and FT3I levels were both reduced by 7% (p < 0.05). In the patients, serum TSH was reduced significantly (p < 0.001). No significant differences were observed between patients and normals in regional or total bone mineral content or bone mineral density levels, apart from 20% higher lumbar bone mineral content among the premenopausal patients (p < 0.05). Surprisingly, the mean serum calcium level was slightly elevated (2.38 +/- 0.08 vs 2.33 +/- 0.07 mmol/l, p < 0.001), serum phosphate decreased (1.13 +/- 0.19 vs 1.23 +/- 0.16 mmol/l, p < 0.01) and 24-h renal calcium excretion was reduced by 19% (p < 0.05). No changes were observed in serum magnesium, intact parathyroid hormone or calcitriol. The biochemical markers of bone resorption (serum carboxyterminal telopeptide of type I collagen, renal excretion of hydroxyproline, pyridinoline and deoxypyridinoline) and formation (serum levels of carboxyterminal propeptide of type I procollagen, osteocalcin and total and bone alkaline phosphatase) were similar in the two groups. We conclude that long-term thyroxine replacement therapy in primary hypothyroidism does not exert a negative effect on bone mass or alter bone turnover.

Serum markers of collagen type I metabolism in spontaneously hypertensive rats: relation to myocardial fibrosis.

The assay of serum peptides of extracellular collagen synthesis and degradation could provide an indirect estimate of the rate of fibrillar turnover. This study was designed to investigate whether serum peptides of collagen type I synthesis and degradation are altered in spontaneously hypertensive rats (SHR) with left ventricular hypertrophy and whether these serum collagen-derived peptides are related to myocardial fibrosis. We measured serum levels of carboxyterminal propeptide of procollagen type I (PIP) as a marker of collagen I synthesis and serum levels of the pyridinoline crosslinked telopeptide domain of collagen type I (CITP) as a marker of fibrillar collagen I degradation in ten 36-week-old normotensive Wistar-Kyoto (WKY) rats, ten 36-week-old SHR, and ten 16-week-old SHR treated with the angiotensin-converting enzyme inhibitor quinapril (10 mg /kg body wt per day, orally) for 20 weeks. PIP and CITP were determined by specific radioimmunoassays. Histomorphometric and immunohistochemical studies of the left ventricle were performed in all rats. In untreated SHR compared with WKY rats, we found a more extensive interstitial and perivascular fibrosis, an increased (P<.01) collagen volume fraction, a more marked deposition of collagen type I, an increased (P<.01) serum concentration of PIP, and a similar serum concentration of CITP. In quinapril-treated SHR compared with untreated SHR, we found an absence of left ventricular hypertrophy, a marked decrease of fibrosis, a lower (P<.01) collagen volume fraction, a diminished deposition of collagen type I, a decreased (P<.01) concentration of PIP, and a similar concentration of CITP. A direct correlation was found between the collagen volume fraction and serum PIP (r=.753, P<.05) in untreated SHR. These results suggest that tissue metabolism of collagen type I is abnormal in SHR and can be normalized by treatment with quinapril. On the basis of our findings, we propose that serum PIP may be a marker of collagen type I-dependent myocardial fibrosis in rats with genetic hypertension.

Changes in serum type I and III procollagen levels in children with chronic renal failure.

Serum levels of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) can be used as markers of bone formation and the evaluation of children with growth disorders. We measured the serum levels of these collagens with radioimmunoassay in 24 children aged between 4 and 14 years with chronic renal failure (CRF; n = 12 dialysis, n = 12 nondialysis) and 12 age-matched healthy controls, to find out whether these parameters have a prognostic or therapeutic value in monitoring the growth retardation in CRF. Mean serum PIIINP levels in the dialysis patients were higher than in the control group; the difference between the groups was statistically significant (p < 0.05). It seemed that the pubertal stage of the patients did not affect the levels of PICP and PIIINP. There was no significant correlation between PICP and PIIINP in any patients. Neither PICP nor PIIINP correlated with the height z-score or bone age. It was concluded that the increased serum PIIINP levels in renal patients might be accepted as a poor prognostic factor leading to progressive renal failure and end-stage renal disease. Further investigations into the effects of these collagens on growth failure associated with CRF are needed.

Serum levels of carboxyterminal propeptide of type I procollagen and pyridinoline crosslinked telopeptide of type I collagen in normal children and children with growth hormone (GH) deiciency during GH therapy

In this study, we investigated age-related changes in serum levels of both the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline crosslinked telopeptide of type I collagen (ICTP) to elucidate bone formation and resorption, respectively, in 200 normal Japanese children (141 males and 59 females, age range 0–16 years). Furthermore, to clarify the effect of GH on bone turnover, we measured serum PICP and ICTP in 26 growth hormone (GH)-deficient children (20 males and 6 females, age range 4–15 years) who showed significant bone growth during recombinant human GH therapy. In the normal children, the curves for age-related changes in both serum PICP and ICTP levels almost paralleled that of the standard height velocity curve in both sexes. The serum levels of both peptides were higher than those in adults, and the peak increases corresponded with the timing of the adolescent growth spurt. Furthermore, the serum levels of PICP and ICTP were significantly correlated with the height velocity. In the GH-deficient patients, the serum ICTP levels before GH therapy were lower than those in age- and sex-matched controls. Both PICP and ICTP levels in serum increased significantly at the beginning of GH therapy. Furthermore, the percent increase in PICP after 1 month of GH treatment was positively correlated with the percent increase in height velocity during 1 year of GH treatment. These results suggest that bone turnover is high in normal children, particularly during infancy and puberty, and that GH could affect bone resorption as well as formation. The serum level of PICP is a potential marker for predicting the growth response to long-term GH therapy. ( Bone 17:397-401; 1995)