Serum Carboxyterminal Propeptide Of Type Research Articles

Bone status and adipokine levels in children on vegetarian and omnivorous diets

Measurements of bone mineral density (BMD) reflect bone status but not the dynamics of bone turnover. Biochemical markers, which show global skeletal activity, were validated for the assessment of bone formation and resorption processes. Adipokines also play a significant role in the regulation of bone metabolism. To assess body composition, bone mineral density, bone turnover markers and adipokine levels in relation to vegetarian and omnivorous diets. The study included 53 vegetarian and 53 omnivorous prepubertal healthy children matched for age and sex (median age 7.0 years). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. 25-hydroxyvitamin D and parathormone levels were measured by chemiluminescence method. Serum carboxy-terminal propeptide of type I collagen (CICP), total osteocalcin (OC) and its forms carboxylated (c-OC) and undercarboxylated (uc-OC), C-terminal cross-linking telopeptide of collagen type I (CTX), leptin and adiponectin levels were determined using immunoenzymatic assays. Both groups of children were comparable in terms of body composition, except for the percentage of fat mass, which was lower (19.24 vs. 21.77%, p=0.018) in vegetarians. Mean values of total BMD z-score and lumbar spine BMD z-score were lower (-0.583 vs.-0.194, p=0.009 and-0.877 vs.-0.496, p=0.019, respectively) in vegetarians compared with omnivores. Serum leptin level was about 2-fold lower (1.39 vs. 2.94ng/mL, p<0.001) in vegetarians, however, adiponectin concentration was similar in both groups. Vegetarians had similar concentration of 25-hydroxyvitamin D, but higher parathormone (40.8 vs. 32.1pg/mL, p=0.015) and CTX (1.94 vs. 1.76ng/mL, p=0.077) levels than omnivores. Total osteocalcin and CICP concentrations were comparable in both groups, however, c-OC/uc-OC ratio was higher (1.43 vs. 1.04ng/mL, p<0.05) in vegetarians. We found positive correlation between c-OC and nutritional parameters adjusted for total energy intake (plant protein, phosphorus, magnesium and fiber intakes) in vegetarian children. Prepubertal children on a vegetarian diet had significantly lower total and lumbar spine BMD z-scores, but absolute values of bone mineral density did not differ. BMD z-scores did not correlate with bone metabolism markers and nutritional variables, but were positively associated with anthropometric parameters. Lower leptin levels in vegetarian children reflect lower body fat. Longitudinal studies are necessary to evaluate the impact of the observed association on bone health at adulthood.

Bone Remodelling Markers in Rheumatoid Arthritis

Bone loss in rheumatoid arthritis (RA) patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin), serum aminoterminal propeptide of type I collagen (PINP), serum carboxyterminal propeptide of type I collagen (ICTP), bone alkaline phosphatase (BAP), osteocalcin (OC), and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX), N-terminal telopeptide of type 1 collagen (I-NTX), pyridinolines (DPD and PYD), and tartrate-resistant acid phosphatase (TRAP). Bone resorption can be seen either in periarticular bone (demineralization and erosion) or in the total skeleton (osteoporosis). Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

Circulating carboxy-terminal propeptide of type I procollagen is increased in rheumatic heart disease

Mitral valve is mostly affected in rheumatic heart disease which is prevalent in developing countries [1–3] and thousands of new cases are being diagnosed worldwide every year [1–3]. It is known that extensive fibrosis occurs in the rheumatic valve [4]. Serum carboxyterminal propeptide of type I procollagen (PICP), the marker of collagen synthesis was reported as a marker of extracellular matrix (ECM) remodelling in various heart diseases [5–8]. We therefore, measured the levels of circulating PICP to explore the severity of ECM remodelling in rheumatic heart disease.

Serum carboxy-terminal propeptide of type I procollagen (PIP) is a marker of diastolic dysfunction in patients with early type 2 diabetes mellitus

This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of myocardial fibrosis, is related to changes of the ventricular filling dynamics in patients with early type 2 diabetes mellitus (T2DM). The T2DM group had lower mitral and tricuspid E/ A ratios than the control group. Serum PIP was higher in patients with T2DM than in controls (131.1 ± 45.6 vs. 109.3 ± 32.5 ng/mL, p = 0.039). A–Ar, an estimate of passive diastolic function, was inversely related to serum PIP levels in T2DM ( r = − 0.42, p = 0.03). These results show a relation between LV diastolic function and serum PIP levels in early T2DM.

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.

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.

Relation between Serum Carboxy-Terminal Propeptide of Type 1 Procollagen(PIP), a Marker of Myocardial Fibrosis, and Left Ventricular Diastolic Function in Patients with Early Type 2 Diabetes Mellitus

Background and Objectives:This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I PIP, a marker of myocardial fibrosis, was related to the change of the ventricular filling dynamics in patients with early type 2 diabetes mellitus (DM). Subjects and Methods:Echocardiography was performed in 28 patients with type 2 DM and 32 age-matched healthy controls, ranging from 31-69 years of age, with normal left ventricular (LV) systolic function and ECG at rest. Subjects with diabetic complications, including microalbuminuria, nephropathy (Cr>1.3 mg/dL), severe obesity (BMI≥30 kg/m), LV hypertrophy (LV septal thickness and/or posterior wall thickness 12 mm on M-mode) and hypertension, were excluded. The serum concentrations of PIP and Transforming growth factor TGF-β1 were measured by enzyme immunoassay methods. Results:The type 2 DM group had lower mitral (Type 2 DM vs. Control: 0.88±0.28 vs. 1.17±0.34, p<0.01) and tricuspid E/A ratios (1.15±0.25 vs. 1.30±0.25, p=0.01) than the control group. The level of serum PIP was higher (p<0.05) in patients with type 2 DM than in the control group (131.1±45.6 vs. 109.3±32.5). The difference in the duration between transmitral forward (A) and pulmonary venous retrograde (Ar) waves (A-Ar) was considered an estimate of a passive diastolic function. A-Ar was inversely related with the serum PIP level in type 2 diabetes (r=-0.43, p=0.03). Conclusion:These results show a relationship between the LV diastolic function and the serum concentration of PIP in early type 2 DM. These findings suggest that the determination of the serum level of PIP is a useful method for the screening and early diagnosis of myocardial fibrosis associated with DM. (Korean Circulation J 2005;35:500-506)

The relation between myocardial cyclic variation of integrated backscatter and serum concentrations of procollagen propeptides in hypertensive patients

Cyclic variation of integrated backscatter (IBS), or CVIBS, provides a noninvasive method to measure myocardial collagen deposition and ischemia in hypertensive patients. We hypothesized that serum procollagen propeptides can offer additional values to CVIBS for evaluating cardiac changes related to fibrosis or ischemia. A total of 21 patients were enrolled in this study and were divided into three groups according to the presence of hypertension and serum carboxyterminal propeptide of type I procollagen (PICP) concentration; these were: 7 hypertensive patients with PICP ≥ 127 μg/L (group 1), 7 hypertensive patients with PICP < 127 μg/L (group 2), 7 normotensive subjects with PICP < 127 μg/L (group 3). In addition to PICP, serum aminoterminal propeptide of type III procollagen (PIIINP), stress 201thalium scintigraphy and CVIBS were examined. Phase-compensated amplitudes of CVIBS at mid posterior and mid anteroseptal segments were significantly lower in group 1 ( p < 0.05). Patients with fixed 201thallium perfusion defects had lower phase-compensated amplitudes of CVIBS at mid anteroseptal segment and higher PIIINP concentrations ( p < 0.05). In conclusions, decrease of myocardial phase-compensated amplitude accompanied with increase of serum PICP concentration may be indicative of the underlying fibrotic process of hypertensive myocardium. Decrease of this CVIBS parameter with increase of serum PIIINP implies concomitant myocardial ischemia. (E-mail: lun0630@ha.mc.ntu.edu.tw)

Circulating osteoprotegerin in women during GnRH-agonist treatment and their relationships with mineral components and biomarkers of bone turnover

A novel cytokine termed osteoprotegerin (OPG) that is also called osteoclastogenesis-inhibitory factor, which inhibits osteoclast maturation and activity, was recently isolated. In order to determine the influence of estrogen deficiency on the levels of circulating OPG in women, we studied the changes in the levels of circulating OPG in 10 Japanese women ages 25–49 (mean ± SD, 34.0 ± 6.9) years with endometriosis receiving gonadotropin-releasing hormone agonists (GnRH-a) therapy. We further analyzed whether the levels of circulating OPG have relations with the levels of the biomarkers of bone turnover or those of circulating mineral components in these patients during GnRH-a treatment. The patients were treated with a monthly injection of 3.75 mg leuprolide acetate depot for 6 months. In all patients, the concentrations of serum estradiol decreased after 6 months of GnRH-a treatment. The bone mineral density of the lumber spines in these patients significantly ( P < 0.01) decreased (percentage change: mean ± SD, −5.4 ± 2.1%), while circulating OPG levels significantly ( P < 0.01) increased after 6 months of treatment. The values of circulating OPG had significant correlations with those of urinary pyridinoline ( r = 0.59, P < 0.01), urinary deoxypylridinoline (Dpd) ( r = 0.46, P < 0.05), and serum alkaline phosphatase ( r = 0.66, P < 0.01) but not with those of serum carboxy-terminal propeptide of type I procollagen during GnRH-a treatment. The values of circulating OPG also correlated significantly with those of serum calcium (Ca) and phosphorus (P) ( r = 0.65 and 0.72, P < 0.01). Further analyses revealed that the percentage change in the value of circulating OPG had a significant correlation with that of urinary Dpd ( r = 0.84, P < 0.01). These results suggest that circulating OPG levels rise against the increase in osteoblastic bone resorption and circulating Ca levels in the case of estrogen deficiency, possibly as a compensatory mechanism serving to limit circulating Ca levels and bone density.

Circulating osteoprotegerin in women during GnRH-agonist treatment and their relationships with mineral components and biomarkers of bone turnover

A novel cytokine termed osteoprotegerin (OPG) that is also called osteoclastogenesis-inhibitory factor, which inhibits osteoclast maturation and activity, was recently isolated. In order to determine the influence of estrogen deficiency on the levels of circulating OPG in women, we studied the changes in the levels of circulating OPG in 10 Japanese women ages 25–49 (mean ± SD, 34.0 ± 6.9) years with endometriosis receiving gonadotropin-releasing hormone agonists (GnRH-a) therapy. We further analyzed whether the levels of circulating OPG have relations with the levels of the biomarkers of bone turnover or those of circulating mineral components in these patients during GnRH-a treatment. The patients were treated with a monthly injection of 3.75 mg leuprolide acetate depot for 6 months. In all patients, the concentrations of serum estradiol decreased after 6 months of GnRH-a treatment. The bone mineral density of the lumber spines in these patients significantly ( P < 0.01) decreased (percentage change: mean ± SD, −5.4 ± 2.1%), while circulating OPG levels significantly ( P < 0.01) increased after 6 months of treatment. The values of circulating OPG had significant correlations with those of urinary pyridinoline ( r = 0.59, P < 0.01), urinary deoxypylridinoline (Dpd) ( r = 0.46, P < 0.05), and serum alkaline phosphatase ( r = 0.66, P < 0.01) but not with those of serum carboxy-terminal propeptide of type I procollagen during GnRH-a treatment. The values of circulating OPG also correlated significantly with those of serum calcium (Ca) and phosphorus (P) ( r = 0.65 and 0.72, P < 0.01). Further analyses revealed that the percentage change in the value of circulating OPG had a significant correlation with that of urinary Dpd ( r = 0.84, P < 0.01). These results suggest that circulating OPG levels rise against the increase in osteoblastic bone resorption and circulating Ca levels in the case of estrogen deficiency, possibly as a compensatory mechanism serving to limit circulating Ca levels and bone density.

The effect of supraphysiological doses of anabolic androgenic steroids on collagen metabolism.

We examined the effect of supraphysiological doses of anabolic androgenic steroids (AAS) on collagen metabolism and whether the changes reflect the alterations in muscle, bone, and tendon collagen metabolism, possibly in a tissue-specific manner. Serum carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), aminoterminal propeptide of type III procollagen (PIIINP), urine hydroxylysylpyridinoline (HP), and lysylpyridinoline (LP) as well as urine creatinine were determined from 17 men abusing AAS. Measurements were made twice during the intake of AAS and twice during the subsequent withdrawal period. When the volunteers were on steroids, their serum PIIINP concentrations and urine HP/LP ratio were significantly higher and their serum ICTP concentrations were significantly lower than during the withdrawal period (p < 0.05). Serum PIIINP correlated with total cumulative doses of injectable intramuscular steroids, and serum ICTP correlated with the duration of the steroid intake period (p<0.05). The results suggest that high doses of AAS decrease the degradation and seem to increase the synthesis of type I collagen. Furthermore, high doses of AAS are suggested to enhance soft tissue collagen metabolism on the basis of increased type III collagen synthesis and elevated HP/LP ratio during the steroid administration period. Although the tissue-specific turnover of collagen of soft connective tissues remains unknown, the turnover of bone collagen seems not to change following the use of high doses of AAS, at least within the time interval of the present study.

Serum Markers of Type I Collagen Synthesis and Degradation in Amyotrophic Lateral Sclerosis

Collagen abnormalities in the skin and spinal cord have been reported in amyotrophic lateral sclerosis (ALS) patients. Serum carboxyterminal propeptide of type I procollagen (PICP) and the carboxyterminal cross-linked telopeptide of type I collagen (ICTP) reflect type I collagen synthesis and degradation, respectively. However, there has been no study concerning PICP or ICTP in ALS. We studied collagen contents of the skin and measured serum levels of PICP and ICTP in patients with ALS and control subjects. Serum PICP levels were significantly lower in ALS patients than in controls. Serum ICTP levels were significantly higher in ALS patients than in controls, and there was an appreciable positive correlation between serum ICTP levels and the duration of illness in ALS patients. In ALS patients, the collagen content of the skin was significantly smaller than in controls and indicated a progressive decrease in relation to illness. In addition, there was a significant negative correlation between serum ICTP concentrations and the collagen content of the skin in ALS patients. These data suggest that increased ICTP levels and decreased serum PICP levels may reflect unique changes in the skin, with a predominance of degradation compared to the synthesis of type I collagen in ALS.

Acute and early effects of triiodothyronine administration on serum markers of bone and mineral metabolism.

There have been few studies on acute changes of bone metabolism in humans by thyroid hormone. This study aimed to examine the effects of triiodothyronine on serum markers of bone and mineral metabolism during a 7-d course of daily 75 microg therapy in 14 normal volunteers by drawing blood on 1, 2, 3, 5, and 7 d of therapy. Serum calcium concentrations did not significantly change during the course of therapy, while serum phosphorus concentrations were significantly (p < 0.05) decreased from 3.21 +/- 0.43 mg/dL (mean +/- SD) to 2.85 +/- 0.46 mg/dL on the 7th d. Serum PTH concentrations were significantly decreased from 339 +/- 116 pg/mL to 316 +/- 29 pg/mL. Serum concentrations of alkali-phosphatase and bone-specific alkali-phosphatase were not significantly changed, but serum osteocalcin concentrations were significantly increased from 5.71 +/- 1.98 mg/dL to 6.73 +/- 2.24 mg/dL. Serum carboxy-terminal propeptide of type I collagen concentrations were significantly decreased from 137.8 +/- 33.7 microg/L to 119.2 +/- 33.6 microg/L. Serum pyridinoline cross-linked telopeptide domain of type I collagen concentrations, a bone resorption marker, were significantly increased from 3.40 +/- 0.77 to 3.87 +/- 1.05 microg/L, and such significant increase was obtained from the 3rd day. The results indicate that some of bone and mineral markers change rapidly in response to triiodothyronine-induced acute thyrotoxicosis, but the manner of change is not the same as that of chronic thyrotoxicosis.

Characteristics of Biochemical Markers in Patients with Metabolic Bone Disorders.

Biochemical markers of bone turnover are expected to have some different characteristics among bone metabolic disorders. We compared bone formation markers: serum total alkaline phosphatase (s-Alp), serum osteocalcin (s-OC) and serum carboxy-terminal propeptide of type I collagen (s-PICP); and bone resoiption markers: serum carboxy-terminal telopeptide of type I collagen (s-ICTP), urinary pyridinoline (u-Pyr) and urinary deoxypyridinoline (u-Dpyr) to examine which marker is the most suitable and reliable to evaluate bone turnover in patients with osteoporosis (n = 29), osteomalacia (n = 10), primary hyperparathyroidism (n = 6) and renal osteodystrophy (n = 21). The value of s-Alp in the osteomalacia group was significantly higher than those in the normal control group and the osteoporosis group (p<0.001), and T-score of s-Alp was significantly higher than those of s-OC and s-PICP in the osteomalacia group. The values of u-Pyr and u-Dpyr in the primary hyperparathyroidism group were significantly higher than those in the other groups (p < 0.001). S-PICP, which are not dependent upon renal function, was much higher in the renal osteodystrophy group man in all other groups. In the osteoporosis group, T-score of s-ICTP was significantly higher than those of s-OC. Thus, s-Alp was a good marker in osteomalacia, u-Pyr and u-Dpyr in primary hyperparathyroidism, s-PICP in renal osteodystrophy, and s-ICTP in osteoporosis.

Bone-turnover metabolites as clinical markers of bone metastasis in patients with prostatic carcinoma.

Candidate markers of prostatic metastases to bone, urinary deoxypyridinoline, serum carboxy-terminal propeptide of type 1 procollagen (P1CP), and pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP), were measured to evaluate their prognostic efficacy. Urinary levels (mean +/- SD) of deoxypyridinoline were measured by a competitive immunoassay, and serum levels of P1CP and 1CTP were measured by radioimmunoassay in 30 patients with benign prostatic hyperplasia, 18 patients with prostatic carcinoma without bone metastases, and 27 patients with prostatic carcinoma and bone metastases. Urinary concentrations of deoxypyridinoline (pmol/micromol creatinine) in patients with prostatic carcinoma and bone metastases (10.4 +/- 7.7) were significantly higher than those in similar patients without bone metastases (4.3 +/- 1.3) and those in patients with benign prostatic hyperplasia (3.8 +/- 1.2). Serum levels of P1CP and 1CTP (ng/mL) in patients with prostatic carcinoma and bone metastases (262.6 +/- 188.7 and 10.3 +/- 9.5, respectively) were significantly higher than those in similar patients without bone metastases (118.1 +/- 30.2 and 4.3 +/- 1.4, respectively) and those in patients with benign prostatic hyperplasia (93.9 +/- 25.1 and 3.3 +/- 1.1, respectively). Serial measurements of urinary deoxypyridinoline and serum P1CP and 1CTP were correlated with a positive response to treatment (reduced measurements) and with the clinical progression of disease (increased measurements) before detection of new bone lesions by bone scintigram. Urinary deoxypyridinoline, serum P1CP, and serum 1CTP should be useful markers in confirming and monitoring prostatic carcinoma metastases to bone.

The Value of Serum Carboxyterminal Propeptide of Type 1 Procollagen in Predicting Bone Metastases in Prostate Cancer

The Value of Serum Carboxyterminal Propeptide of Type 1 Procollagen in Predicting Bone Metastases in Prostate Cancer

The Value of Serum Carboxyterminal Propeptide of Type 1 Procollagen in Predicting Bone Metastases in Prostate Cancer

Purpose Carboxyterminal propeptide of type 1 procollagen (P1CP) is believed to be a marker of new bone formation. We investigated the possible application of serum P1CP as a biochemical marker for bone metastases in patients with prostate cancer. Materials and Methods Prostate specific antigen (PSA), prostatic acid phosphatase (PAP), P1CP and alkaline phosphatase were measured in 136 serum samples from 79 patients with untreated prostate cancer, 29 with stage D2 disease in remission and 28 with progressive stage D2 carcinoma. Results Serum P1CP and alkaline phosphatase were significantly elevated in untreated patients with a positive bone scan (278.9 +/− 61.9 ng./ml. and 826.5 +/− 176.3 international units per l., respectively) compared to those with a negative bone scan (104.2 +/− 4.2 and 200.8 +/− 9.1, respectively, p <0.05). The areas under receiver operating characteristics curves were 0.86 for P1CP, 0.87 for alkaline phosphatase, 0.88 for PSA and 0.85 for PAP. The best accuracy rates for P1CP, alkaline phosphatase, PSA and PAP to predict bone lesions were 84, 87, 86 and 84%, respectively. P1CP provided a greater specificity and positive predictive value. These serum markers correlated significantly with the extent of disease on bone scan (p <0.05). The incidence of positive serum P1CP and alkaline phosphatase decreased significantly in response to endocrine therapy in patients with bone metastasis, and increased progressively in association with progression of the tumor (p <0.05) parallel to PSA and PAP. Conclusions These findings suggest that serum P1CP is a useful indicator for predicting bone metastases.

Normal serum indices of bone collagen biosynthesis and degradation in small for gestational age infants.

Serum carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), new markers of bone collagen type I biosynthesis and degradation, have not been studied in small for gestational age (SGA) infants. In an earlier study, we found a lower bone mineral content (BMC) and decreased serum osteocalcin in SGA than in appropriate for gestational age (AGA) infants, supporting the thesis that decreased fetal bone formation is a cause of lower BMC in SGA. In view of the role of insulin-like growth factor-I (IGF-I) in the regulation of collagen type I synthesis and degradation, and low serum IGF-I concentrations in SGA infants, we hypothesized that serum PICP would be lower and serum ICTP would be higher in SGA than in AGA infants, reflecting decreased bone collagen type I biosynthesis or enhancement of bone collagen type I degradation in SGA. We studied 19 term SGA and 38 term AGA infants that were matched specifically 1:2 by gestation and birth month. There were no differences between SGA and AGA infants in serum PICP nor ICTP concentrations. Serum ICTP was correlated with osteocalcin and with PICP in SGA infants but not in AGA infants. Thus, serum biochemical indices of bone collagen type I biosynthesis and degradation in term SGA infants are similar to those in term AGA infants. These findings are not consistent with the thesis of altered fetal bone collagen type I biosynthesis or degradation in SGA. We suggest that the reduced bone mineral content in SGA infants is predominantly related to a lower supply of minerals rather than defective regulation of bone collagen type I metabolism.

Clinical usefulness of serum carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer.

A study was undertaken to evaluate the clinical usefulness of measurements of serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as parameters of bone metastasis in patients with prostate cancer. Serum PICP, ICTP, prostate-specific antigen (PSA), and alkaline phosphatase (ALP) were evaluated in 82 patients with prostate cancer and 26 patients with benign prostatic hyperplasia (BPH). These markers were measured serially in 16 prostate cancer patients during treatment. The serum levels of PICP, ICTP, ALP, and PSA were significantly higher in prostate cancer patients with bone metastasis than in patients with either BPH or prostate cancer without bone metastasis. Although the rate of detection of bone metastasis with PICP and ICTP was slightly lower than that with PSA determined by the receiver operating characteristic curve, the correlation between both PICP and ICTP and the extent of disease was much higher than that of PSA. PICP and ICTP levels varied with ALP and PSA levels, the patient's clinical course after the start of endocrine therapy and the progression of bone metastasis. The levels of PICP and ICTP did not change substantially in patients who developed local regrowth or lymph node metastasis, and decreased as bone metastases responded to radiotherapy. PICP and ICTP thus reflect the metastatic burden in bone and are useful for monitoring the response of bone metastasis to therapy.

Biochemical evaluation of bone turnover in cancer patients with bone metastases: relationship with radiograph appearances and disease extension

Serum bone alkaline phosphatase (BALP), serum carboxy-terminal propeptide of type I procollagen (PICP) and serum bone gla protein (BGP) as markers of bone formation, serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of collagen resorption and fasting molar ratio of urinary calcium to creatinine (CaCr) and serum parathyroid hormone (PTH) were determined in two groups of cancer patients: 48 with advanced or metastatic disease with negative bone scan and 174 with bone metastases categorised as having lytic, mixed or blastic lesions and with more or fewer than or equal to three sites involved. In patients without apparent bone involvement, bone formation markers were rarely elevated. Conversely, serum ICTP was frequently found to be supranormal, showing it to be a non-specific marker for early detection of bone metastases. As expected, values of bone formation markers progressively increased in patients with lytic, mixed and blastic lesions, but ICTP levels did not show any differences according to the types of bone appearances, confirming previous reports of elevated osteoclast activity also in patients with apparent blastic lesions. Serum PTH increased significantly in patients with lytic compared with patients with mixed and blastic appearances, paralleling the bone formation markers, but CaCr showed the opposite pattern. These data are compatible with calcium entrapment in the bone in patients with increased osteoblast activity. This so called 'bone hunger syndrome' is further confirmed by the finding that in the subgroup of blastic appearances CaCr diminished whereas both ICTP and PTH increased according to the extent of tumour load in the bone.