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Background Procollagen-derived propeptides reflect the rate of collagen synthesis and type I cross-linked collagen telopeptides ( ICTP) collagen I degradation. We studied the collagen metabolism to find out if changes seen in acute respiratory distress syndrome patients are observed in patients with acute respiratory failure ( ARF), and whether multiple organ dysfunction ( MOD) has impact on it. Methods ARF patients with prolonged hospitalisation at least 21 days were included to the study. Blood samples for serum procollagen aminoterminal propeptide I ( PINP) and III ( PIIINP), and ICTP measurements were collected at study admission (day 0) and on days 2, 7, and 21. Results The study population comprised 68 patients. Forty-three patients (63%) developed MOD during the first week. PIIINP levels increased in all patients over time. The increase was slightly more pronounced in patients with MOD. During the first week, the synthesis of PIIINP increased more than PINP, and PINP degradation exceeded its production. By day 21, the balance of collagen metabolites returned to baseline. Conclusion The collagen metabolism was altered in ARF patients. The first week was dominated by degradation of type I collagen and production of type III collagen, but by day 21, the collagen composition returned to more stable form. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the effect of high alpine grazing, associated with varying pasture grass qualities and more pronounced exercise on typically steep slopes, on bone metabolism by improving bone density and enhancing bone turnover in growing sheep. Twenty-four 5-month-old sheep were randomly assigned to two groups. One group was kept at high altitude (HA; 2000-2200 m a.s.l.) for 3 months, and the other group (C; control) remained in the lowlands (400 m a.s.l.). Both groups were kept in grazing pastures with access to good-quality swards. Before the start of the experiment, blood samples were taken, the sheep were weighed, and the left metatarsus of each animal was analysed by quantitative computer tomography. After 1 month, blood samples were taken and body weight was measured, followed by biweekly sampling. Finally, the animals were slaughtered, and the bones were collected for analysis of various bone parameters. Body weight development did not differ between the groups. Concentrations of 25-OH-Vitamin D, carboxy-terminal telopeptide of type I collagen and activities of bone-specific alkaline phosphatase were always higher in the HA group than in the C group, except on the last two sampling dates. Bone mineral content and density increased in both groups during the experiment, but more intensively in the HA group. In addition, the cortical thickness of the HA group increased. The present study demonstrates an increase in bone turnover and mineral content of the bones of the growing sheep grazing in high alpine pastures. The factors associated with HA grazing, therefore, clearly seem to improve bone composition. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether benign joint hypermobility (BJH) is associated with urogenital prolapse and altered collagen metabolism. Methods: 43 postmenopausal women with previous vaginal hysterectomy operated due to genitourinary prolapse were recruited. Each patient was also evaluated for joint hypermobility. The collagen metabolism was studied measuring serum concentrations of type I and III procollagen aminoterminal propeptides and trivalently cross-linked carboxyterminal telopeptide of type I collagen. Results: Clinical joint hypermobility was found in 35% patients. Women with joint hypermobility had higher concentration of aminoterminal propeptide for type I procollagen and the values were statistically significant ( P < 0.0178). Recurrent prolapse was found in 47% of the patients with BJH as compared to non-hypermobile group (25%). In this subgroup the results were statistically significant ( P < 0.0085) for type III collagen. Also, the mean serum concentration for type III procollagen was significantly increased above the reference limit. Conclusions: Women with joint hypermobility have more recurrent genital prolapse as compared to women with normal joint mobility. Plain hypermobility was associated with higher concentrations for type I procollagen. Patients with recurrent prolapse and joint hypermobility have significantly high concentrations for type III procollagen. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The excellent poster painter Henri de Toulouse-Lautrec is the most famous patient with cathepsin K-deficient pycnodysostosis. Cathepsin K is believed to play a major role in osteoclast-driven bone resorption. In this study we explored the role of cathepsin K in bone resorption in a patient with a cathepsin K mutation causing pycnodysostosis in whom psoriatic arthritis also developed. We hypothesized that the patient would develop only inflammatory synovitis but would not develop bone erosions or other osteolytic changes. METHODS: Monocytes from the patient with pycnodysostosis and normal control monocytes were isolated and stimulated to fuse and form multinuclear osteoclast-like cells, which were identified by evaluating messenger RNA expression of osteoclast markers. The ability to resorb bone was assessed by determining the extent of pit formation and levels of collagen degradation products generated by cathepsin K (C-terminal crosslinking telopeptide of type I collagen [CTX]) and matrix metalloproteinases (pyridinoline crosslinked C-terminal telopeptide of type I collagen). These experiments were also done in normal control cells after incubation with the cathepsin K inhibitor E64 during bone resorption. RESULTS: In contrast to our a priori hypothesis, the patient developed a mutilating disease with extensive bony erosions associated with lysis of some of the distal phalanges of her hands and feet. After stimulation of monocytes from this patient, the cells formed multinuclear tartrate-resistant acid phosphatase-positive and calcitonin receptor-positive multikaryons, which, however, totally lacked cathepsin K. These multinuclear cells were able to resorb bone but, in contrast to normal control osteoclasts, did not produce CTX. The resorption pattern was abnormal in that, unlike normal control osteoclasts, both osteoclasts from the patient and E64-inhibited osteoclasts did not leave extensive osteoclast trails, but were relatively sessile. CONCLUSION: In this 'experiment of nature' we observed that cathepsin K is not necessary for bone degradation. These findings may be pertinent to our understanding of the functions of cathepsin K inhibitors, which are currently being developed as drugs to treat metabolic bone diseases. [ABSTRACT FROM AUTHOR]

Objective: To assess whether serum C-terminal cross-linking telopeptide of type I collagen (ICTP), a marker of type I collagen degradation, has any additional value in the assessment of treatment effect in patients with early rheumatoid arthritis (RA). Methods: A total of 182 patients were randomized to treatment either with three disease-modifying anti-rheumatic drugs (DMARDs) and low-dose prednisolone (COMBI) or with a single DMARD with or without low-dose prednisolone (SINGLE). We investigated the prognostic value of serum ICTP level for the progression of joint destruction in X-rays (Larsen's score) from baseline to 2 years. Results: There was a statistically significant decrease in serum ICTP levels from baseline to 1 year. At 6 months, the serum ICTP level was lower in the COMBI patients compared to that of the SINGLE cases (p = 0.008, after adjustment for baseline ICTP). When grouping the patients according to serum ICTP tertiles at 6 months, there was a statistically significant trend for increasing median change in Larsen score from baseline to 2 years from lowest to highest ICTP tertile in the SINGLE patients [p = 0.008, after adjustment for 28-joint Disease Activity Score (DAS28) score and RF status at baseline], while in the COMBI, the change remained low in all ICTP tertiles. Conclusions: The COMBI strategy for recent-onset RA results in early suppression of type I collagen degradation, which is reflected in radiological joint damage at 2 years. Serum ICTP at 6 months may be useful for identifying those RA patients whose treatment should be intensified to prevent further joint damage. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most frequent clinical arrhythmia. Atrial fibrosis is an important factor in initiating and maintaining AF. However, the collagen turnover and its regulation in AF has not been completely elucidated. We tested the hypothesis that the extracellular matrix changes are more severe in patients with permanent AF in comparison with those in patients in sinus rhythm (SR). Intraoperative biopsies from the right atrial appendages (RAA) and free walls (RFW) from 24 patients with AF undergoing a mini-Maze procedure and 24 patients in SR were investigated with qualitative and quantitative immunofluorescent and Western blot analyses. As compared with SR, all patients with AF exhibited dysregulations in collagen type I and type III synthesis/degradation. Tissue inhibitors of metalloproteinases (TIMP2) was significantly enhanced only in RAA-AF. As compared with SR, collagen VI, matrix metalloproteinases MMP2, MMP9 and TIMP1 were significantly increased while TIMP3 and TIMP4 remained unchanged in all AF groups. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a newly discovered MMPs inhibitor, was elevated in RFW as compared to RAA-AF (P<0.05) and RFW-SR (P<0.05). The level of transforming growth factor (TGF)-β1 was higher in AF than SR. Smad2 and phosphorylated Smad2 showed an elevation in RFW-AF as compared to RFW-SR, RAA-AF, and RAA-SR groups (P<0.05). Conclusions: Atrial fibrosis in AF is characterized by severe alterations in collagen I and III synthesis/degradation associated with disturbed MMP/TIMP systems and increased levels of RECK. TGF- β1 contributes to atrial fibrosis via TGF-β1-Smad pathway by phosphorylating Smad2. These processes culminate in accumulations of fibrillar and non-fibrillar collagens leading to excessive atrial fibrosis and maintainance of AF. [ABSTRACT FROM AUTHOR]

Substantial losses of skeletal tissue occur during late pregnancy and lactation. The goal of the present study was to follow these changes in pregnant and lactating goats and sheep, compare these two species during their second lactation, and also compare the results to the first lactation. Blood samples were collected from 12 adult dairy goats (Saanen goat) and sheep (Ostfriesen milk sheep) monthly during gestation, 2 or 3 days postpartum (pp), 2 weeks pp, 4 weeks pp, and then monthly during lactation until 7 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography (pQCT) at the same intervals as the blood was taken. Bone resorption was assessed in serum using two different domains of the carboxyterminal telopeptide of type I collagen (ICTP and crosslaps). Bone formation was quantified in serum with osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25 dihydroxy vitamin D (VITD) were determined in serum. The same procedure was done during the first and second gestation and lactation. Mean ICTP and crosslaps concentrations of the two animal species showed an increase in the last month of gestation. In contrast, mean OC concentrations decreased slowly from the 2nd month of pregnancy until the first week pp. Also mean bAP activities showed a similar time course. Total BMC and BMD decreased until the first week pp in both species. Afterwards, BMC increased again during lactation. BMD levels of sheep and goats returned to prepartum levels during lactation. Vitamin D concentrations peaked in the first week pp. Only VITD concentrations in goats stayed elevated compared with prepartum values throughout the whole lactation during the second lactation. Around parturition and at the beginning of lactation, the bone resorptive phase of bone remodelling is accelerated, but is uncoupled from the process of bone formation. The mineral decrease in bone of these lactating animals seems to be reversible. Since during lactation, bone remodelling has bone resorption and formation phases tightly coupled. Interestingly, in these species, the bone loss in the second pregnancy and lactation measured with BMC and BMD is not as prominent as in the first lactation, but shows almost the same course, although the animals gave more milk in the second lactation. It seems that the organism adapts to the circumstances more easily in the second lactation compared to the first lactation in these two species. [ABSTRACT FROM AUTHOR]

Objective: To assess the state of the disease and verify the diagnoses during a 7-24-month follow-up of adult patients with newly diagnosed inflammatory joint diseases in a defined population. Methods: Patients with previously undiagnosed synovitis in at least one peripheral joint or signs of inflammation in sacroiliac, glenohumeral or hip joints were enrolled on their first hospital visit in 2000 and followed-up for up to 24 months in Kuopio. Results: A total of 138/173 adult patients completed a mean 13-month follow-up. During the follow-up the diagnosis was specified for 15/81 (19%) patients previously classified as undifferentiated arthritis (UA). Eight patients developed rheumatoid arthritis (RA). Of 28 patients with RA, 92% were on disease-modifying anti-rheumatic drugs (DMARDs) and 75% had a combination treatment with two or more DMARDs. According to the diagnosis at baseline, 75% of cases with RA, 38% with spondyloarthropathies (SpAs) and 42% with UA had active synovitis or arthralgia at follow-up. In multivariate analysis, older patients at disease onset were less likely to be in remission (p = 0.011). Conclusion: The diagnosis could be specified for 19% of patients with UA. Fifteen of 20 patients with RA had an active disease despite treatment with DMARDs. Patients with SpAs and UA had a better short-term outcome. Patients with active disease need aggressive therapy in all age groups. [ABSTRACT FROM AUTHOR]

At the initiation of lactation, Ca homeostatic mechanisms have to react to a tremendous increase in demand for Ca. Mobilization of Ca from bone and increased absorption from the gastrointestinal tract are required to re-establish homeostasis. It has been shown that dietary anions play an important role in the prevention of milk fever by mobilizing Ca from bone and by increasing Ca absorption in the GI tract. The purpose of the present study was to investigate the influence of different Ca contents in diets supplemented with anionic salts on bone metabolism of dairy cows. Twenty-four holstein cows (housed inside, second to fourth lactation) without a milk fever history were divided into four groups (A, B, C, D). Each group was fed a different diet which was given from day 263 of gestation till the day of parturition. Group A and B received a low calcium diet (4 g/kg DM) whereas group C and D received a high Ca diet (8 g/kg DM). In addition group B and D received anionic salts. The DCAD was calculated with the formula: DCAD (mEq/kg DM) = (0.2 Ca2++0.16 Mg2++Na++K+) − (Cl−+0.6 S2−+0.65 P3−). Blood and urine samples were collected on days 256, 270 and 277 of gestation, on the day of parturition as well as the following 5 days and on days 9, 14 and 19 after parturition. Serum Ca, P, Mg, ICTP, OC, VITD, PTH and urinary pH were analysed. The bone resorption marker ICTP showed a significant increase after parturition in all the groups. On the contrary, the bone formation marker OC decreased after parturition in all the groups. The VITD concentrations in group D and the urinary pH in group B were significantly lower compared to the other groups (p < 0.05). The Ca concentrations tended to be higher in group B around parturition than in all the other groups. No significant influence of the four different diets on all the other parameters could be shown. In conclusion, this data showed that the addition of anions and the different Ca contents had no significant influence on bone resorption and bone formation markers. This may be because of the fact that the dietary cation–anion balance was not low enough (DCAD – group A: 181 mEq/kg DM, group B: −48 mEq/kg DM, group C: 210 mEq/kg DM and group D: 28 mEq/kg DM) to induce a metabolic acidosis with all its positive effects on calcium metabolism. [ABSTRACT FROM AUTHOR]

Biochemical markers of bone turnover originating from type I procollagen synthesis or type I collagen breakdown were examined in men using a classic twin study design based on monozygotic (MZ) and dizygotic (DZ) twins. The aim was to estimate the influence of heredity (genes and shared family childhood elements) and constitutional factors in determining procollagen type I amino-terminal propeptide (PINP), type I collagen carboxy-terminal telopeptide (ICTP), and urinary amino-terminal type I collagen telopeptide (NTx) marker levels in a sample of in 98 MZ and 108 DZ male twin pairs. We are not aware of any prior studies conducted in men that address the influence of genetic factors on bone turnover marker variability. The findings support a dominant role for heredity in the variation of bone resorption marker levels in men, with additive genetic effects explaining two-thirds of the variance in the bone resorption markers NTx and ICTP. Genetic factors may contribute less for PINP, a marker of bone formation. The genetic loci influencing PINP or NTx and body weight/disc axial area, although related in part, appeared to be largely independent, indicating that genetic effects on bone turnover are unlikely to be to a large degree a result of genetic regulation of individual body weight. [ABSTRACT FROM AUTHOR]

Measurement of bone turnover markers has been proposed as a potentially valuable clinical laboratory aid in osteoporosis risk assessment. These markers may allow quantitative evaluation of rates of bone loss, and thereby identify persons at risk for osteoporosis at an earlier stage. As far as we know, this is the longest longitudinal study on bone turnover markers conducted in adult men. The objectives of this study were to determine whether markers of bone formation (type I procollagen amino-terminal propeptide, PINP, and carboxy-terminal propeptide, PICP), and of bone resorption (type I collagen carboxy-terminal telopeptide, ICTP), are predictive of changes in lumbar spine and femoral neck BMD over a 5-year period, and to determine the ability of the bone resorption marker urine amino-terminal telopeptide (NTx) to explain the variance in BMD change over the past 5 years in a group of men 35–69 years old. In this group, NTx was the only marker to correlate significantly with BMD changes at the femoral neck (r = -0.21), but not at the spine. The use of the biochemical markers studied to predict change in bone density in adult men in middle-aged years is of very limited value. [ABSTRACT FROM AUTHOR]

Osteoclastic tartrate-resistant acid phosphatase activity in serum (S-TRACP 5b) was measured in postmenopausal women ( n =59, mean age 56.1 years) with vertebral osteopenia before and during 2-year treatment with an 800-mg daily dose of clodronate, with a non-amino bisphosphonate. Changes in TRACP 5b were compared with those in urinary excretion of type I collagen amino-terminal telopeptide (U-NTX), corrected for creatinine excretion, a well-established marker of bone resorption, and to serum type I procollagen amino-terminal propeptide (S-PINP), a marker of bone formation. Marker changes 1 year after start of treatment were correlated with changes in bone mineral density (BMD). The least significant change (LSC) for each marker and BMD was calculated from values for subjects receiving placebo. Responders to treatment were those exhibiting a change larger than LSC. In response to clodronate treatment S-TRACP 5b (mean change up to −18%) decreased less than did U-NTX (up to −51%) or S-PINP (up to −46%). Marker changes correlated with changes in lumbar spine and trochanter BMD. The most efficient marker for finding responders to treatment was S-PINP, which changed more than the LSC (32%) in 72% of the subjects at the 1-year time point and in 79% at the 2-year time point. S-TRACP 5b change exceeded the LSC (27%) in 40% and 34% of the subjects at each time point, while U-NTX change exceeded the LSC (55%) in 55% and 40%, respectively. We conclude that, in terms of the proportion of subjects exhibiting any change exceeding the LSC, S-TRACP 5b did not appear to be superior to U-NTX and S-PINP in the follow-up of clodronate treatment. The reason may lie in the mechanism of action of clodronate, which rather than reducing the number of TRACP 5b-secreting osteoclasts, reduces the activity of bone proteolytic enzymes and thus the rate of bone organic matrix degradation. This is seen in decreased amounts of type I collagen breakdown products (U-NTX), and through coupling of bone resorption with bone formation, in a decrease in circulating levels of the marker that reflects new collagen formation (S-PINP). [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate, if different Ca concentrations in diets have an influence on bone mineral metabolism in growing goats and sheep. Twelve growing goats and sheep were divided into two groups. The two control groups received 6.1 g calcium/day (nG) and 6.7 g calcium/day (nS) for goat and sheep respectively. The other two groups were fed 17.7 g calcium/day (hG) and 18.5 g calcium/day (hS). Blood samples were taken 2, 4, 5 and 6 weeks after the start of the experiment. In serum Ca and vitamin D were determined and bone metabolism was measured usingcrosslinked carboxyterminal telopeptide of type I collagen (ICTP), crosslaps, bone-specific alkaline phosphatase and osteocalcin (OC). Bone mineral density (BMD) was quantified using quantitative computed tomography. Bone resorption marker (ICTP) concentrations were significantly different between both groups control sheep/control goat and hS/hG, but no significant differences were evident in the different feeding groups within one species. OC concentrations showed a similar course to ICTP. The goats had significantly higher concentrations compared with sheep. The 1,25 dihydroxyvitamin D (VITD) concentrations in both hCa groups were significantly lower than in the control groups. BMD increased in the hCa groups compared with the control groups with the time, but significant differences were only evident in sheep in week 2. The hCa diet did not induce differences between the groups within one species for all bone markers. The control Ca diet seems to improve the active Ca absorption via VITD whereas the hCa diet leads to a higher amount of Ca apparently digested. Higher BMD was only observed in group hS compared with nS. [ABSTRACT FROM AUTHOR]

The purpose of the study was to find out if the supplementation of phytase to a diet of gestating and lactating sows has any effects on performance and bone parameters of the animals. Forty primiparous gilts were assigned into four groups: group A with phytase [4.2 g total phosphorus (P)/kg (gestation) and 4.5 g total P/kg (lactation)], group B without phytase (with phytase supplementation in diet for rearing) and same P content as group A, group C without phytase and higher P contents [5.0 g total P/kg (gestation) and 5.5 g total P/kg (lactation)] and group D with the same diet as group B (no phytase during the rearing). A 6-phytase was used in this trial (750 FTU/kg diet). The four diets were fed during gestation and lactation. Faeces were collected to determine apparent digestibility of minerals. Blood samples were taken to analyse minerals and bone markers. After weaning the sows were slaughtered and the bones of one hind leg were prepared to measure bone mineral density (BMD) and bone mineral content (BMC) of the tibia. Bone ash and mineral content of the phalanx III were determined. Mean P concentrations in serum decreased during gestation and lactation. But there were no significant differences between the groups. Bone formation marker bone-specific alkaline phosphatase decreased at the beginning of lactation whereas bone resorption marker serum crosslaps increased. The BMD and BMC of the tibia were slightly higher in the groups fed higher concentrations of P and phytase. The ash and mineral contents of the phalanx were the highest for the group fed the highest concentration of P. The apparent digestibility of P increased during gestation mostly in group A (57%→ 69%). In conclusion, high P content and addition of phytase to the diet induced a slightly higher ash content of the bones. It is of high importance, that sows during gestation absorb enough P, to avoid lamenesses and sudden fractures. As not many studies with phytase have been performed during gestation and lactation in sows yet, we can recommend, that phytase as supplement can be used to keep P in the diet at a lower level without negative consequences for bone health. [ABSTRACT FROM AUTHOR]

Glucocorticoids have anti-anabolic effects on many tissues and can cause muscle atrophy. However, their effects on type IV collagen gene expression and degradation in skeletal muscle have not been studied previously. Rats were treated daily with dexamethasone or saline. Half the groups of experimental and control animals were also subjected to daily endurance or uphill running exercise to determine the possible preventive effects of exercise. After an experimental period of 3 or 10 days, the extensor digitorum longus, soleus and tibialis anterior muscles were studied. Dexamethasone treatment for 10 days reduced muscle weight and type IV collagen mRNA abundance in all muscles. Gene expression of matrix metalloproteinase-2 (MMP-2) was decreased in fast muscles. However, the effects of this decrease were possibly attenuated by the simultaneous decrease in the activity of tissue inhibitor of metalloproteinases (TIMP-2). The amount of type IV collagen was not changed during dexamethasone treatment or exercise. The regulation of type IV collagen degradation during dexamethasone treatment varied between slow and fast muscles. Although endurance running prevented muscle atrophy, exercise could not compensate the changes observed in the regulation of type IV collagen gene expression and degradation during dexamethasone treatment. [ABSTRACT FROM AUTHOR]

Twelve 6-month-old growing, female goats and sheep were used in this study. Blood samples were obtained in the morning before goats and sheep were given food and then at 2-h intervals for 24 h (part I). This procedure was repeated 2 weeks later (part II). Concentrations of osteocalcin (OC), activities of total (tAP) and bone-specific alkaline phosphatase (bAP), degradation products of C-terminal telopeptide of type-I collagen (CrossLaps™ CL), and carboxyterminal telopeptide of type-I collagen (ICTP) were measured in serum. In both parts of the study, all bone marker concentrations were significantly higher in goats than in sheep. The OC concentrations in goats increased in the late afternoon/evening and decreased thereafter to reach values similar to those obtained at the beginning. The ICTP concentrations in goats slowly decreased until 14:00 h, increased, and decreased again. The concentrations in sheep decreased continuously but not significantly, towards the morning sampling. The CL concentrations increased in both sheep and goats during the night but at 06:00 h started to decrease to levels `found at the beginning of testing. The bAP activities decreased in goats from 20:00 to 22:00 h. Changes in the concentrations of bone markers were mainly observed in goats of this study. As documented for bone resorption and formation in other species, circadian rhythms were evident`for concentrations of ICTP, CL, bAP and OC. The present study indicates that growing goats may have a physiologically higher bone turn-over than growing sheep, because the bone marker concentrations were always higher. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of dexamethasone treatment on collagen turnover in preterm infants.Methods: The serum concentrations of the amino-terminal propeptide of type I and III procollagens (PINP and PIIINP), which reflect rates of type I and III collagen synthesis, respectively, and the carboxy-terminal telopeptide of type I procollagen (ICTP), which reflects the rate of type I collagen degradation, were monitored in 13 preterm infants receiving dexamethasone and 13 matched control infants without glucocorticoid treatment for a total period of 12 mo. Dexamethasone was started at a median age of 12 d and continued at tapering doses for a median total duration of 10 d. Blood samples were taken immediately after birth, at 7, 14 and 28 d of age and at 2, 3, 6, 9 and 12 mo. The same markers were also measured just before the initiation of dexamethasone and on days 1, 3, and 7 of treatment.Results: A striking decrease in all of the markers was already observed in every case on day 1 of dexamethasone, the suppression being greatest on day 3 and still considerable on day 7. The percentages from the pretreatment levels recorded on days 1, 3 and 7 were: for PINP 51, 26 and 45%; for PIIINP 63, 44% and 52%; and for ICTP 64, 41 and 51%. A rebound rise in PINP levels was seen in dexamethasone-treated infants, the levels exceeding those of the controls at 3 and 6 mo of age. A similar phenomenon was noted concerning PIIINP at 3 mo. The levels settled down at 9 and 12 mo.Conclusion: Dexamethasone causes an immediate, inevitable, deep suppression of type I and III collagen synthesis and also type I collagen degradation. This should be taken into consideration, e.g. when assessing for the indications for steroid treatment in sick preterm infants and its dosing and duration. [ABSTRACT FROM AUTHOR]

Summary Background Glucocorticoids have been shown to downregulate collagen synthesis in human skin in vivo , thereby contributing to skin atrophy. Objectives To compare the effects of continuous and intermittent use of topical hydrocortisone on skin collagen synthesis and, furthermore, to elucidate the mechanism of collagen synthesis reduction induced by hydrocortisone. Methods Collagen propeptides reflecting the synthesis rate of type I and III collagens were studied from suction blister fluids in nine healthy subjects after 3 weeks of continuous (twice daily) or intermittent (on three consecutive days weekly) topical hydrocortisone treatment and 2 weeks after the termination of treatment. Type I collagen mRNA was studied in the same subjects from skin biopsies by using in situ hybridization (ISH) after 3 weeks of treatment. Results Three weeks of continuous treatment decreased the types I and III collagen propeptides in suction blister fluid by 89% and 82%, respectively, while intermittent treatment resulted in a corresponding decrease of 53% and 50%. ISH studies from skin biopsies showed type I collagen mRNA to be markedly reduced in fibroblasts after continuous and intermittent steroid treatment. After a 2-week drug-free interval, the synthesis rate was completely restored in both areas, and some subjects even showed upregulation of synthesis in previously steroid-treated skin. Conclusions Continuous hydrocortisone for 3 weeks markedly decreases collagen propeptides and corresponding mRNA in human skin. Intermittent hydrocortisone has a less marked effect on the collagen synthesis rate. [ABSTRACT FROM AUTHOR]

This study was conducted to examine if substantial bone loss occurs in growing pigs fed a vegetarian diet in comparison with a diet containing fishmeal. Twelve 6-week-old weaned pigs were assigned to two groups: group V [vegetarian diet; 0.61% phosphorus (P) in dry matter until 25 kg and 0.46% P until the end of the experiment] and group F (fishmeal diet; 0.61% P in dry matter until 25 kg and 0.46% P until the end of the experiment). Phytase was added to both diets. These two diets were fed to the two groups for a period of 6 weeks. Blood samples were collected weekly, faeces were collected three times a week. Concentrations of osteocalcin (OC) and carboxyterminal telopeptide of type I collagen (ICTP) were measured in serum, using a radioimmunoassay, and bone-specific alkaline phosphatase (bAP) was measured using an enzyme immunoassay. Bone mineral density (BMD) and content (BMC) were determined by peripheral quantitative computer tomography (pQCT) in the tibia and phalanx. In addition, 1,25-dihydroxyvitamin D (VitD) and parathyroid hormone (PTH) were measured in serum. The digestibility of P was significantly decreased in group V. Significant changes in bAP activities and OC concentrations occurred with time during the 6 weeks. ICTP concentrations were significantly higher in group V. Total BMC and BMD in the tibia and BMD in the phalanx significantly decreased in group V. The results show that a vegetarian diet induces a significant loss of bone and a higher bone formation in group V compared with group F, although phytase was added to both diets. The dietary requirements for P in pigs, especially in the context of feeding vegetarian diets and adding an appropriate amount of phytase, should be investigated further. [ABSTRACT FROM AUTHOR]

Summary Background Smoking is associated with premature facial wrinkling and aberrant wound healing, but the underlying mechanisms of skin injury are poorly understood. Objectives To compare the in vivo collagen synthesis and degradation in the skin of smokers and non-smokers. Methods The study population consisted of 47 current smokers and 51 individuals who had never smoked from northern Finland. Suction blisters were induced in the sun-protected upper inner arm of the study subjects, after which suction blister fluid (SBF) was collected for analyses of the levels of aminoterminal procollagen propeptides of type I and III collagens (PINP and PIIINP, respectively), matrix metalloproteinase (MMP)-8 and tissue inhibitor of MMP (TIMP)-1. PINP, PIIINP and TIMP-1 were also determined from serum samples. The levels of active and pro MMP-1 were assessed from deep-frozen skin biopsies by Western blotting. Results The synthesis rates of type I and III collagens were lower by 18% and 22%, respectively, in the SBF of the smokers compared with the non-smokers. The levels of MMP-8 were higher by 100% in the SBF of the smokers. The levels of MMP-1 in the skin biopsies did not differ significantly between the groups. The levels of TIMP-1 in SBF were 14% lower in the smokers than in the non-smokers, whereas the serum concentrations of TIMP-1 did not differ between the groups. Conclusions Smoking decreases the synthesis rates of type I and III collagens in skin in vivo and alters the balance of extracellular matrix turnover in skin. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine if substantial bone loss occurs in weaned pigs by feeding a phosphorus-deficient diet with or without fumaric acid. Eighteen weaned pigs were used. The animals were assigned to three groups: group C (control; 0.65% P on DM basis), group LP (low phosphorus; 0.37% P on DM basis) and group LPF (low phosphorus plus fumaric acid; 0.35% P on DM basis plus 2% fumaric acid). These three diets were fed to the groups for a period of four weeks after a two-week adaptation period. Blood samples were collected once a week. Carboxyterminal telopeptide of type I collagen (ICTP) in serum was used as a bone resorption marker. Osteocalcin (OC) and bone-specific alkaline phosphatase (bAP) were used as bone formation markers. Bone mineral density (BMD) and content (BMC) were determined by peripheral quantitative computer tomography. BAP activities significantly increased (24%) in group LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. In contrast, ICTP concentrations significantly increased with time in group LP and LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. BMD and BMC in femur and tibia significantly decreased in group LP and LPF. The results show that P-deficient diets induce a bone loss. Fumaric acid did not influence the degree of bone loss. With a better understanding of its effect on bone, dietary phosphorus requirements in pigs could be more precisely defined. [ABSTRACT FROM AUTHOR]

To assess the effects of antenatal corticoid administration on foetal collagen metabolism, cord serum concentrations of the aminoterminal propeptide and carboxyterminal telopeptide of type I procollagen (PINP and ICTP), which reflect rates of type I collagen synthesis and degradation, respectively, were measured in 67 consecutive preterm infants with gestational ages ranging from 24 to 32 wk. The samples were divided into three groups, depending on the administration and timing of antenatal corticosteroid treatment for enhancement of foetal lung maturity: cases in which the mothers had received a full 2-dose administration of dexamethasone on consecutive days 1 to 6 d before delivery (n = 23; Complete-Dexa), those who had received only a single dose of dexamethasone less than 24 h before delivery (n = 17; Partial-Dexa) and those who had not received any antenatal steroids (n = 27; No-Dexa). Infants in the Complete-Dexa group had significantly lower median PINP levels than those in the No-Dexa group (3326 vs 4028 µg/l; p = 0.036); the median PINP level in the Partial-Dexa group (3999 µg/l) was close to that of the No-Dexa group. No significant differences in ICTP concentrations were seen between the groups. [ABSTRACT FROM AUTHOR]

High levels of dietary sucrose affect the metabolism of the pulp-dentin complex and enhance the caries process in dentin. The high-sucrose diet reduces dentin formation in young rats (Tjäderhane et al., 1994; Hietala and Larmas, 1995; Tjäderhane, 1996) and in pups of rat dams fed high-sucrose diet during lactation (Pekkala et ah, 2000a). However, the mechanisms behind the effects are unknown. A direct effect of elevated blood glucose or an indirect effect via insulin has been suggested. We investigated the effects of high glucose and insulin on type I collagen synthesis in human odontoblasts and pulp tissue in vitro, using an organ culture method for functional post-mitotic odontoblasts. Odontoblasts and pulp tissue were cultured separately for 10 days in DMEM with 15% FBS containing additional glucose (G) (4.45 g/L) or insulin (I) (0.6 µg/mL) or both together (GI). We evaluated type I collagen synthesis with RIA, measuring the level of N-terminal propeptide of type I collagen (PINP) secreted into the culture media. PINP secretion decreased in odontoblasts and pulp tissue in G and GI groups when compared with the control and insulin samples (p = 0.001 in both groups in the pulp samples). Insulin alone did not affect PINP secretion distinctly. The results indicate that high levels of glucose, but not insulin, directly down-regulate the type I collagen synthesis in young, differentiated human odontoblasts and pulp tissue. Insulin does not affect the inhibitory effect of high sucrose. These in vitro findings indicate that the high-sucrose diet may alter odontoblast function independently of insulin. [ABSTRACT FROM AUTHOR]

Background The serum concentration of the N-terminal propeptide of type I procollagen (PINP) reflects the synthesis rate of type I collagen, whereas the corresponding C-terminal telopeptide (ICTP) mirrors its degradation. Design PINP and ICTP were measured in a total of 690 cord serum samples from 592 appropriate-for-gestational-age (AGA) infants and 98 smal-for-gestational-age (SGA) infants. These markers were compared between AGA and SGA infants of different gestational ages, ranging from 23 to 41 weeks, and birth weights, from 620 to 4555 g. Results Both PINP and ICTP levels were very high in the preterm AGA infants and declined significantly with advancing gestational age, paralleling the shape of the fetal growth velocity curve. Regardless of the quite large interindividual variations observed in these markers, PINP was significantly lower in both the preterm and term AGA infants than in the SGA infants. This was also the case for ICTP in the preterm infants of gestational age less than 36 weeks. In stepwise multiple regression analyses, gestational age, being either AGA or SGA and head circumference were significant factors to explain the levels of PINP and ICTP. The levels of PINP and ICTP were correlated with each other highly significantly in both the AGA and SGA infants (rs = 0·700 and 0·692, respectively; P < 0·001 in both). Conclusions The levels of type I collagen markers seem to follow closely the shape of the fetal growth velocity curve during different stages of gestation. However, because of the large interindividual variations observed, further studies are needed before the significance of these markers for the assessment of normal and abnormal fetal growth can be established. [ABSTRACT FROM AUTHOR]

Since growth factors have been suggested to regulate dentin collagen formation in response to external irritation, we investigated the effect of TGF-β1 on proα1(I) collagen mRNA expression in cultured mature human odontoblasts and pulpal fibroblasts, as well as cultured human pulp tissue, using quantitative PCR. Cultured gingival fibroblasts (GF) and osteoblasts (OB) served as controls. Also, type I collagen synthesis in cultured odontoblasts and pulp tissue, as well as type III collagen synthesis in odontoblasts, were studied by measuring respective procollagen (PINP and PIIINP) secretion into culture media with radioimmunoassay (RIA). Odontoblasts expressed significantly higher basic level of type I collagen mRNA than pulp tissue or pulp fibroblasts in culture, but markedly lower level than GF and OB cells. TGF-β1 (10 ng/ml) had negligible effects on type I collagen mRNA expression or PINP synthesis in cultured odontoblasts and pulp tissue, and PIIINP synthesis in the odontoblasts. In PF cells, the effect of TGF-β1 depended on culturing conditions; a 6-fold increase in mRNA expression was observed using serum-free medium but no effect was seen in the cells cultured with 10% FBS. In contrast, GF cells serving as controls were not markedly affected by the culture conditions, with 2-3-fold increase in mRNA expression by TGF-β1. These experiments demonstrate that mature human odontoblasts are capable of synthesizing type III collagen protein, and that TGF-β1 has negligible effect on mature human odontoblast and pulp tissue collagen expression. [ABSTRACT FROM AUTHOR]

Summary The collagen metabolites hydroxyproline (HYP), deoxypyridinoline (DPD), and the carboxyterminal telopeptide of type I collagen (ICTP) are suitable markers for bone resorption in humans and several animal species. The purpose of this study was to describe the course of bone resorption markers during short-term hypocalcemia induced with disodium ethylenediaminetetraacetic acid (Na2EDTA) and to investigate whether bone resorption is increased in dairy cows under these conditions. EDTA infusions have been used as a model for periparturient paresis in dairy cows and to estimate the calcium mobilization rate from body reserves in ruminants. In this study, hypocalcemia was induced by means of a 5 % Na2EDTA infusion (0.55 mg/kg/min Na2EDTA for 5 h = total dose of 100.6 g). Two experiments were conducted: (1) Six 4–11 years-old Brown Swiss cows were infused intravenously with EDTA for 5 h. Blood and urine samples were taken repeatedly from 1 day before until 10 days after infusion. (2) Towards the end of the lactation, the experiment was repeated with the same animals after a 14-day-period of feeding a low calcium diet (26 g/animal per day). The EDTA-infusion induced hypocalcemia and hypophosphatemia. The HYP-, DPD- and ICTP-concentration remained mainly unaffected during both infusions. Only DPD showed an increase during infusion and HYP an increase 2 days after the infusion. In conclusion, the EDTA infusion had little effect on the concentrations of the measured bone markers, which may be due to the fact that the serum calcium pool was refilled by increased absorption of Ca via the gastrointestinal tract. From these results, it can be concluded that bone resorption was not influenced by EDTA infusion. [ABSTRACT FROM AUTHOR]

Background: Collagens are major proteins in the extracellular matrix, providing tissues with tensile strength. They are also important for cell adhesion and the invasion of malignant tumours. Methods: Thirty-nine samples of human colon (24 diverticulosis, 6 malignant tumours, 9 controls) were collected during elective surgery. Immunoassays for different domains of type I and III collagens and procollagens were used in soluble tissue extracts and trypsin digests of tissue samples. Results: The contents of cross-linked type I and III collagen telopeptides and total collagen were similar in diverticulosis and healthy tissue, whereas in malignant tissue maturely cross-linked type III collagen was scarce. Furthermore, some of the cross-linked type I telopeptide antigens were exceptionally small in size, indicating that the cross-linking of type I collagen in collagen fibres is impaired in cancer. The rate of type I collagen synthesis was clearly increased in malignancy, but not significantly in diverticulosis. However, type III collagen synthesis was increased in diverticulosis, but not in malignancy. Conclusions: In colon malignancy, the collagen cross-linking process was aberrant and the synthesis of type I collagen increased. In diverticulosis, the synthesis of type III collagen was increased, suggesting only moderately increased metabolic activity. [ABSTRACT FROM AUTHOR]

Radiation-induced fibrosis is a common side-effect of cancer treatment. The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synthesis, skin thickness, gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for breast cancer with surgery and radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non-treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIMP-1 and TIMP-2) and MMP-9 and MMP-2/TIMP-2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for PIIINP. In irradiated skin, PINP, PIIINP, TIMP-1 and MMP-2/TIMP-2 complex levels in SBF and the number of PINP-positive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of TIMP-2 in irradiated and non-irradiated skin were similar. MMP-9 could not be detected in SBF with the assay used. The serum levels of MMP-9 were higher in the treated subjects than the reference values. The serum values of PINP, PIIINP, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were not significantly affected. These results indicate increased local collagen synthesis and accumulation of connective tissue in irradiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis. [ABSTRACT FROM AUTHOR]

Malignant tumours often induce a fibroproliferative response in the adjacent stroma, characterized by increased expression of type I and type III procollagens. In normal tissues, fibrillar collagens normally undergo extensive intermolecular cross-linking that provides tensile strength to the tissue. Here we set out to characterize collagen cross-linking in human ovarian carcinoma tissue in vivo. Biochemical and immunochemical methods were used for cross-linked telopeptides of type I and III collagens in samples of benign and malignant serous tumours. The locations and staining patterns of these proteins were visualized immunohistochemically. The contents of both total collagen and the cross-linked type I and type III collagens in the malignant samples were only about 20% of those in the benign tumours. The cross-linked telopeptide antigens derived from the collagens were smaller and more heterogeneous in size in the malignant than in the benign tumours, indicating a defective cross-linking process scarcely leading to the formation of mature cross-links in the collagen fibres in malignancy. Immunostaining revealed disorganized type I and type III collagen bundles in carcinomas. These findings suggest that the collagen cross-linking process is aberrant in malignant tumours, possibly resulting in increased susceptibility of tumour collagens for the proteolysis often associated with tumour invasion. [ABSTRACT FROM AUTHOR]

To assess the mechanisms of osteopenia in inflammatory bowel disease (IBD), the serum markers of bone formation (osteocalcin and carboxyterminal propeptide of type I procollagen (PICP)) and bone degradation (carboxyterminal telopeptide of type I collagen (ICTP)), the bone mineral density (BMD) of the lumbar spine and the proximal femur and calcium intake of 150 unselected IBD patients and 73 healthy controls were investigated. The patients had higher ICTP values (3.69 (SD 1.40) microgram/l) than the healthy controls (3.25 (1.00) microgram/l, p = 0.035), but no differences in serum PICP and osteocalcin between these groups were detected. In the patients, the ICTP, PICP, and osteocalcin values did not have any significant correlation with BMD, but the patients with ICTP values above 3.6 microgram/l had significantly lower Z scores than those with lower ICTP. In the controls, however, a positive correlation between serum ICTP and BMD was found. The ulcerative colitis patients with total colitis had higher values of ICTP (3.96 (1.58) microgram/l) than those with a left sided disease (3.04 (0.86) micrograms/l, p = 0.009). The patients with a history of clinically active disease (n = 20) had higher ICTP (4.58 (1.55) microgram/l) and osteocalcin (12.56 (5.64) microgram/l) values than the patients (n = 130) with quiescent disease (ICTP 3.56 (1.33), p = 0.002, and osteocalcin 9.76 (3.62), p = 0.017). Increased serum osteocalcin, PICP, and ICTP concentrations and reduced BMD Z scores were found in a subgroup of Crohn's disease patients with a history of an active disease (n = 11). Raised serum ICTP and normal values of osteocalcin and PICP in IBD patients show increased breakdown of type I collagen without a compensatory increase in its synthesis suggesting an increased rate of bone degradation as a probable mechanism for osteopenia in IBD. Raised ICTP values are related to reduced bone mineral densities. [ABSTRACT FROM PUBLISHER]

Serum concentrations of the markers of collagen synthesis and degradation, collagen I propeptide (PICP), collagen III propeptide (PIIINP) and the cross-linked telopeptide of type I collagen (ICTP) were measured in young male dermatological patients and in control subjects. No significant differences were noted between patients suffering from atopic eczema ( n=24), other eczemas ( n=11), acne ( n=8), psoriasis ( n=7) or tinea ( n=9) and the control subjects ( n=24). In the total study population representing patients with common skin diseases and control subjects there was a significant correlation between the serum concentrations of PICP and PIIINP and between the concentrations of PICP and ICTP. This suggests that synthesis of type I and III collagens in vivo is coordinated and that the degradation and synthesis of type I collagen is balanced. These markers were also measured in older patients suffering from psoriasis, eczema and various connective tissue diseases. It was noted that the degree of skin involvement in these diseases was not related to the serum concentrations of the markers of collagen metabolism. The highest levels of PICP and PIIINP were observed in a patient with systemic mastocytosis (PICP 309 Μg/1 and PIIINP 8.0 Μg/1). Increased levels of PIIINP were also found in patients with a high alcohol consumption. We have previously demonstrated that systemic glucocorticoids reduce collagen propeptide levels in serum. In the present study we also proved that systemic gluocorticoids have no effect on collagen degradation. Thus the side effects of glucocorticoids, such as growth inhibition, skin atrophy and decrease in bone mass, are a result of inhibition of the synthesis of collagen and other macromolecules. The results indicate that local or generalized skin diseases do not markedly alter serum markers of collagen synthesis or degradation. The alterations in collagen metabolism determined by measurements in serum are thus mostly related to systemic involvement and medication (especially glucocorticoids). [ABSTRACT FROM AUTHOR]

The value of serum procollagen peptide (PICP) as a non-invasive index of bone formation was studied in 18 patients established on haemodialysis. There was a significant correlation between PICP and serum alkaline phosphatase activity (ALP; =0.55, <0.05), and between PICP and osteocalcin (=0.53, <0.05). PICP also correlated significantly with histomorphometric indices of bone formation, particularly bone formation rates (BFR) as estimated by the tetracycline double-labelled technique (=0.74, <0.01), but not with those of bone resorption. There was a similar relationship between BFR and ALP. From the regression analyses, a normal BFR was associated with normal PICP values despite the absence of renal function, suggesting that the impact of renal function on serum concentrations of PICP may not be large. Seven patients had histochemical evidence for significant aluminium overload. th these patients the expected sup pression in biochemical and histological indices of bone formation was associated with inappropriately raised PICP concentrations. The mechanism of this discrepancy is not clear, but caution is advocated in the interpretation of PICP in the presence of significant aluminium overload. Our findings otherwise suggest that PICP may be a useful non-invasive index of bone formation in patients on haemodialysis. [ABSTRACT FROM PUBLISHER]

We investigated the effect of the menopause and postmenopausal hormone replacement therapy (HRT) on the serum concentration of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), a potential new biochemical marker of bone resorption. A group of 44 healthy postmenopausal women, aged 45-54 years, had about 19% higher serum ICTP than did a group of 42 healthy premenopausal women aged 35-50 years (3.6±0.8 µg/l v 3.0±0.7 µg/l (mean ±SD); p<0.01), although there was a large overlap in the values. The 44 postmenopausal women also participated in a longitudinal clinical study, in which 20 received HRT and 24 received a placebo. Compared with the placebo group, those who received HRT had a significant ( p<0.05) decrease in ICTP of about 12% at the end of 1 year of treatment, but again there was considerable overlap in the values. The menopause-and HRT-induced changes in ICTP were less than those seen in serum osteocalcin, serum total alkaline phosphatase, and fasting urinary excretion of hydroxyproline, calcium, pyridinoline and deoxypyridinoline. We conclude that the menopause increases and HRT decreases ICTP, although these changes are less pronounced than those seen in other biochemical markers of bone turnover. [ABSTRACT FROM AUTHOR]

Antibodies against the human basement membrane proteins, laminin and the 7-S domain of type IV collagen, were used to study the epidermal basement membrane in lesional skin from four patients with dermatitis herpetiformis. The staining pattern of both antigens was mostly fragmented and sometimes absent on papillary microabscesses, but when present it was attached to the epidermal basal cells. On papillary microblisters and larger blisters the staining of both antigens showed discontinuities and was located in the floor of the blister, except for two cases where tiny fragments of laminin staining were also seen in the roof of larger blisters. These results suggest that blister formation in dermatitis herpetiformis takes place between the epidermal basal cells and the basement membrane. [ABSTRACT FROM AUTHOR]

Calcium deficiency is a major etiological determinant of rickets in Nigerian children and is accompanied by undermineralization of the developing bone matrix which is composed largely of type I collagen. We have assessed types I and III collagen metabolism by measuring the circulating concentrations of teh N- and C-terminal pro-peptides (intact PINP and PICP) and the C-terminal telopeptide (ICTP) of type I collagen, and the N-terminal pro-peptide (PIIINP) of type III collagen in 94 healthy Nigerian children and in 44 children aged 1-5 years with active calcium-deficiency rickets. In active rickets the mean levels of the four collagen metabolites were approximately twofold higher than in the healthy children, despite a wide variation of individual values. Mean intact PINP was 812 +/- 279 versus 403 +/- 189 microg/liter; PICP was 573 +/- 265 versus 348 +/- 299 microg/liter; PIIINP was 16.8 +/- 8.6 versus 10.8 +/- 3.6 microg/liter, and ICTP was 28.4 +/- 17.2 versus 11.9 +/- 4.1 microg/liter (all P < 0.001), in rachitic and healthy children, respectively. Healthy children younger than 3 years had higher levels of all the collagen metabolites than those between 3 and 5 years (all P < 0.05). Alkaline phosphatase was greater in rickets than in the healthy group (P < 0.001) whereas mean osteocalcin levels were slightly lower (P = 0.009). 1,25(OH)2D correlated with all the collagen propeptides, but not with ICTP in the healthy children. No such correlations were found in rickets, where there was a poor inverse correlation between 1,25(OH)2D and ICTP. These data suggest that collagen turnover is elevated in cases of calcium-deficiency rickets, where vitamin D status is adequate, possibly indicating increased turnover of undermineralized osteoid. [ABSTRACT FROM AUTHOR]

In this study , serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r = 0.53, P < 0.02, SEE/Y = 0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high- and low-turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n = 48)], a highly significant positive regression of S-PICP on m was demonstrable (r = 0.50, SEE/Y = 0.63, P < 0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P < 0.001, SEE/Y = 0.41) and 0.42 (P < 0.01, SEE/Y = 0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r = 0.49, P < 0.001, SEE/Y = 0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P < 0.001, SEE/Y = 0.61), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]