The fate of intraperitoneally retained gallstones with different morphologic and microbiologic characteristics: an experimental study

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.     

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.     

Three paediatric cases of primary sclerosing cholangitis treated with ursodeoxycholic acid and sulphasalazine

The aim of this study was to reveal the relationship of the plasma levels of the carboxy terminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide domains of type I collagen (ICTP) to age and height velocity (HV), and to compare PICP and ICTP levels in those who have not reached their final height with those who have. PICP and ICTP levels were measured by RIA in 271 healthy children (161M, 110F) aged from 10 to 15 y. The HV was calculated from their health check-up cards. The subjects were divided into two groups in this study: the final height (FH) group whose HV was <1.0 cm/y, and the non-final height (NFH) group whose HV in the last year was > or =1.0 cm/y. PICP and ICTP levels almost paralleled the values of age-related changes of HV. Furthermore PICP and ICTP levels significantly correlated with HV. PICP and ICTP levels of the FH group were higher than those of adults previously reported. The values will be useful as reference for healthy children and growth disorder. Before reaching final height, PICP and ICTP can be useful makers of not only bone turnover but also of linear growth. Bone turnover rate is still increasingly active just after linear growth has been completed, and then it become similar to the levels of adults.     

Carcinogenic responses of transgenic heterozygous p53 knockout mice to inhaled 239PuO2 or metallic beryllium

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

Comparison of biochemical markers of bone turnover in Paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links

We have compared the use of new markers of bone turnover in the assessment and treatment of Paget disease and made observations on the mechanisms of bone resorption. Urine hydroxyproline (Hyp) as a bone resorption marker and serum alkaline phosphatase (ALP) as a bone formation marker have traditionally been used to biochemically assess and monitor treatment of Paget disease. Hyp and total ALP were compared with total urine pyridinoline (Pyd) and deoxypyridinoline (Dpd), free urine Pyd and Dpd, urine type I collagen N-terminal cross-linked telopeptide (NTX), type I collagen C-terminal propeptide (PICP), serum osteocalcin, and bone ALP in Paget patients treated with pamidronate. Patients were divided into three biochemical severity-based treatment groups by their fasting urine hydroxyprolline excretion (HypE) levels (Le., group 1, HypE < 5.0 mumol/l of glomerular filtrate [GF]; group 2, HypE of 5.0-9.9 mumol/l of GF; group 3, HypE > 10 mumol/l of GF). Group 1 received one 60 mg intravenous infusion of pamidronate, and groups 2 and 3 received four and six 60 mg infusions at weekly intervals, respectively. Fasting serum and morning urine specimens were taken before and at 2, 6, 13, and 26 weeks after starting treatment. Baseline Z scores were used to compare separation of patient results from normal, and the difference in Z scores from baseline to 13 weeks was used to compare response to treatment. Baseline discrimination and response to treatment at all disease activity levels was greatest for NTX and was poor for osteocalcin, PICP, and C-terminal cross-linked telopeptide of type I collagen (ICTP). The other markers showed good discrimination and response at medium and high levels of disease activity. NTX, total Pyd and Dpd, free Pyd and Dpd, and ICTP are all pyridinoline cross-link-based markers, but discrimination and response by NTX was generally much greater than for the others. Determination of the mechanism of the difference between NTX and other cross-link measures is necessary for appropriate use of the markers and may also lead to a better understanding of the bone resorption process. It has been proposed that the greater sensitivity and discrimination of NTX is because it is more bone-specific than the other cross-link markers with significant amounts of free Pyd and Dpd coming from nonbone sources. We propose another model where the proportion of peptide-bound cross-links such as NTX may be increased in high bone turnover states partly due to a rate-limiting step in their degradation to free cross-links. Conditions with high bone resorption rates would have high levels of NTX that would decline rapidly when resorption rates fall to a level where the capacity to degrade NTX matches the rate of production.     

Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability

Biochemical markers of bone turnover may be useful to monitor patients taking hormone replacement therapy (HRT). The aim of this study was to assess the utility of markers in monitoring HRT by comparing the response of a large panel of markers to HRT with their within subject variability. We measured the response of markers to transdermal estradiol in 11 postmenopausal women over 24 weeks. We measured the within subject variability of markers in 11 untreated healthy postmenopausal women over the same period. The mean decrease in markers of bone formation after 24 weeks treatment ranged from 19% for procollagen type I C-terminal propeptide (PICP) to 40% for procollagen type I N-terminal propeptide (PINP). The mean decrease in markers of bone resorption ranged from 10% for tartrate-resistant acid phosphatase (TRAP) to 67% for C-terminal cross-linked telopeptide The least significant change (LSC at p < 0.05), calculated from the within subject variability in the untreated group, was used to define response. LSC for osteocalcin was 21%, bone alkaline phosphatase 28%, PICP 24%, PINP 21%, type I collagen telopeptide 28%, TRAP 17%, urinary calcium 90%, hydroxyproline 75%, total deoxypyridinoline 47%, free pyridinoline 36%, free deoxypyridinoline 26%, N-terminal cross-linked telopeptide 70%, and C-terminal cross-linked telopeptide 132%. The greatest number of responders after 24 weeks of treatment were found using PINP and osteocalcin (9 each), and free deoxypyridinoline (8 each) and total deoxypyridinoline (8 each) and total deoxypyridinoline (7 each). Lumbar spine bone mineral density defined four patients as responders. The ability to detect a response differs between markers and is not dependent on the magnitude of response to therapy.     

Clinical usefulness of blood PICP, PINP and ICTP concentrations as bone metastasis markers in prostate cancer patients

PICP and PINP are considered markers of bone formation, and ICTP is considered to be a marker of bone resorption. We measured these three markers as indicators of bone metastasis of prostatic cancer, and assessed their clinical usefulness. Serum PICP, PINP and ICTP were significant higher in patients with bone metastasis than localized cancer or controlled bone metastasis. Serum PSA increased initially with the LH-RH agonist during the course of bone metastasis. All these markers were subsequently observed to increase. Change in PICP of patients with bone metastasis was slight compared to PINP during endocrine treatment. Serum PICP, PINP and ICTP reflect the extent of metastasis in bone and are useful for monitoring the response of this condition to therapy.     

Biochemical effects of calcium supplementation in postmenopausal women: influence of dietary calcium intake

We studied the biochemical effects of calcium supplementation during a 2-mo course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y since menopause). The effects on calcium homeostasis and bone remodeling were assessed after 1 and 2 mo of daily administration of either calcium carbonate (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium intake assessed before the beginning of calcium supplementation was 786 mg/d. We found a significant inverse relation between baseline intact parathyroid hormone (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002). A significant increase in urinary excretion of pyridinoline was observed when the dietary calcium intake was lower than the median value. Calcium supplementation resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a significant reduction of bone alkaline phosphatase at 2 mo and of all bone-resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and 2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations. When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium supplementation was responsible for a greater increase in urinary calcium excretion and a greater decrease in markers of bone turnover. The greatest variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05) and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium supplementation in postmenopausal women was efficient in reducing markers of bone turnover, with a greater effect in women with a low dietary calcium intake.     

Bone metabolism markers in patients with Basedow-Graves disease

Collagen type I is the main collagen type found in bones. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it might represent an useful marker of bone formation similarly to osteocalcin. PICP, osteocalcin, alkaline phosphatase, serum and urinary calcium excretion were measured in 58 premenopausal females affected by Graves' disease and also 28 of them after attainment of euthyroidism by methimazole treatment to study these biochemical indices of bone remodelling before and after treatment. Before therapy PICP (mean +/- S.D.: 244.2 +/- 112.3 vs. 136.8 +/- 32.4 micrograms/l), osteocalcin (mean +/- S.D.: 17.8 +/- 6.7 vs. 7.5 +/- 2.7 micrograms/l) and other markers were significantly (p < 0.05) higher than sex and age matched controls (n = 24). Treatment induced a significant decrease of PICP, alkaline phosphatase, calcaemia and calciuria compared to pretreatment values, while osteocalcin did not significantly differ (mean +/- S. D.: 17.8 +/- 6.7 vs. 14.7 +/- 8.7 micrograms/l). These data suggest that hyperthyroidism due to Graves' disease causes an increase of serum levels of these markers, but further studies are necessary to asses the differences between PICP and osteocalcin as markers of osteoblast activity in hyperthyroidism.     

Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction

The elderly subject is prone to both vitamin B insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphates (phosphatases), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 +/- 10.2 vs 30.2 +/- 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiently and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.     

Diagnostic validity of bone metabolic markers for bone metastasis

We measured bone resorption markers in tumor patients with and without bone metastases and evaluated the diagnostic validity of these biochemical parameters in the diagnosis of neoplastic bone involvement. On the basis of radiography and bone scintigraphy findings, subjects were divided into 3 groups, 83 patients without bone metastases (META(-)), 22 patients with 1 or 2 bone metastases (META(+)) and 22 patients with more than 3 bone metastases (META(++)). Among the biochemical markers, urinary pyridinoline (PYR), circulating C-terminal telopeptide of type I collagen (ICTP) and urinary N-terminal telopeptide of type I collagen (NTx) were especially sensitive and specific and increased significantly not only in META(++) but also even in META(+). The efficacy of several bone metabolic markers in differentiating between patients with and without bone metastases was evaluated by receiver-operating characteristic (ROC) analysis, and PYR, ICTP and NTx were proved to have high diagnostic validity (area under the ROC curve; 0.75 for PYR, 0.77 for ICTP and 0.77 for NTx). Furthermore, their odds ratios showed significantly high values for both META(+) and META(++)(to META(++); 7.91 for PYR, 5.33 for ICTP and 5.70 for NTx). On the other hand, urinary deoxypyridinoline (DPYR) and serum total alkaline phosphatase (ALP) showed relatively low sensitivities, the odds ratio of ALP in particular being insignificant. In conclusion, several bone metabolic markers were proved to be useful in the diagnosis of bone metastases in patients with malignancies, particularly PYR, ICTP and NTx had rather high diagnostic validities among all markers examined in this study.     

Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty-two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked N-telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D-Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X-ray absorptiometry both at lumbar spine and at three femoral sites (Ward's triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D-Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.     

Applicability of SSCP analysis for MHC genotyping: fingerprinting of Ovar-DRB1 exon 2 alleles from Finnish and Russian breeds

Recent studies have implicated leptin in the modulation of bone mass during skeletal development. Whether leptin also exerts an influence on bone after growth has stopped is unknown at present. In this cross-sectional study on 94 women (60 premenopausal, 34 postmenopausal) aged 40-60 years, we analyzed the relationship between serum leptin and bone density and bone cortex geometry and bone metabolism. Total and trabecular bone density as well as total and cortical bone area were determined by quantitative computed tomography (QCT) at the distal radius. Bone metabolism was assessed by measuring bone-specific alkaline phosphatase, osteocalcin, procollagen type I C-terminal propeptide (PICP) and collagen type I C-terminal telopeptide in serum, and deoxypyridinoline in urine samples. None of the indices of bone density or geometry was significantly related to leptin serum concentrations (P > 0.05) before or after adjustment for body mass index (BMI). PICP was associated with serum leptin in the postmenopausal group only (r = -0.40 after adjustment for BMI; P = 0.009). Yet, as none of the other markers of bone metabolism exhibited a significant correlation with serum leptin in any of the menopausal groups, this association is likely to be due to the influence of extraskeletal factors on PICP serum levels. Thus, it appears that leptin has less influence on the mature than on the growing skeleton.     

Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.     

The effects of inhaled glucocorticoids on bone mass and biochemical markers of bone homeostasis: a 1-year study of beclomethasone versus budesonide

Bone mass and biochemical bone markers were prospectively studied in 33 patients with chronic obstructive pulmonary disease treated for 1 year with inhaled beclomethasone 200 micrograms/q.i.d. (group A, 8 men and 4 women), inhaled budesonide 200 micrograms/q.i.d. (group B, 6 men and 5 women), or not requiring steroids (group C, 6 men and 4 women). Both inhaled corticosteroids decreased serum concentrations of the osteoblastic markers, osteocalcin and carboxy-terminal propeptide of type I collagen (PICP). The osteoclastic marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) increased significantly more in patients on beclomethasone than in those on budesonide. The decrease in bone mineral density was more pronounced in patients treated with beclomethasone (1.1% in the spine 1.7% in the hip P < 0.05) compared to those treated with budesonide (0.6% in both spine and hip) or in the control group. Inhaled corticosteroids affect biochemical bone markers and bone mineral density, but there is a different effect for the two corticosteroids evaluated in the present study.     

Time-dependent changes of serum carboxy-terminal peptide of type I procollagen and carboxy-terminal telopeptide of type I collagen concentrations in patients with acute myocardial infarction after successful reperfusion: correlation with left ventricular volume indices

To test the hypothesis that in patients with acute myocardial infarction (AMI), changes in the concentrations of the serum carboxy-terminal peptide of type I procollagen (PICP) and the carboxy-terminal telopeptide of type I collagen (ICTP) reflect extracellular matrix reformation and degradation, respectively, in the infarct healing processes, we measured these serum concentrations by RIA and compared their values with left ventricular (LV) indices obtained by left ventriculography. We studied 13 consecutive patients with their first AMI who underwent successful reperfusion. Blood samples were taken the day of admission and on days 2, 3, 4, 5, 7, and 14. LV volume indices were determined at 1 month after AMI, when LV remodeling was almost completed. The serum concentrations of both PICP and ICTP changed in a time-dependent manner. The average serum PICP concentration was lower than 1 SD below the mean control values on days 2 and 3 and increased thereafter, returning to the lower end of the control range at day 14. The area under the curve (AUC) for PICP was significantly correlated with the LV end systolic (ES) and end diastolic (ED) volume indices and LV ejection fraction for the first 14 days after AMI. The serum PICP on days 5-14 was inversely correlated or tended to be correlated with the LVES and LVED volume indices. The average serum ICTP concentrations on admission were within the control range, began to increase on day 2, and reached maximal concentrations on day 5, remaining at a plateau concentration until day 14. Although the AUC of ICTP for 14 days, the ICTP concentrations on days 1 and 14, and the minimal and maximal concentrations were significantly correlated with creatine kinase (CK) release and the period from AMI onset to the peak CK time, the concentrations were not significantly correlated with any LV indices except for the concentration on day 4, which was weakly correlated with the LVES volume index. The serum concentrations of PICP showed a significant time-dependent change that correlated with LV indices, indicating that PICP may provide additional information for evaluating the healing process because it affects LV remodeling after AMI. Although the serum concentration of ICTP changed in association with CK release, the ICTP concentration was found to be a poor indicator for LV indices.     

Magnesium deficiency and bone loss after cardiac transplantation

Magnesium depletion adversely affects many phases of skeletal metabolism and has been implicated as a risk factor in several forms of osteoporosis. Magnesium deficiency has also been reported after cardiac transplantation. To evaluate whether altered magnesium homeostasis could be related to the pathogenesis of early bone loss after cardiac transplantation, we prospectively measured serum and urinary magnesium and evaluated them with respect to biochemical indices of mineral metabolism and rates of bone loss. The study population included 60 patients (45 men, 15 women) aged 53 +/- 11 years (SD) with measurements of biochemistries and bone mineral density by dual-energy X-ray absorptiometry before and 3 months after transplantation. All received prednisone, cyclosporine A, and azathioprine, plus calcium (1000 mg) and vitamin D (400 IU). After transplantation, serum magnesium decreased by 16 +/- 15% (SD) from 2. 0 +/- 0.3 mg/dl to 1.6 +/- 0.2 mg/dl (normal 1.8-2.2 mg/dl; p < 0. 0001), accompanied by an increase in the fractional excretion of magnesium (7.1 +/- 3.9% to 13.3 +/- 5.6%; p < 0.0017). Forty-three patients with low 3-month serum magnesium levels (相似文献   

The hamstring index

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Similar changes in remodeling are seen in osteoporosis. To study the pathogenetic role of thyroid hormone in osteoporosis, we measured concentrations of free and total thyroid hormones and investigated the sensitivity of the skeleton toward thyroid hormones in 14 osteoporotic, 16 estrogen-treated, and 15 normal postmenopausal women with comparable thyroid status. Triiodothyronine (T3, 60 microg/day for 7 days) was administered to the three groups. The skeletal response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin (BGP), and pyridinium cross-linked telopeptide domain of type I collagen (ICTP) in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and deoxypyridinoline (DPR) at days 0, 8, 15, and 57. Women on estrogen replacement therapy exhibited lower bone turnover than the normal postmenopausal women. Markers of bone formation were reduced by 19-43% and markers of resorption by 22-48%. The osteoporotic women displayed lower bone mass at the lumbar spine and the distal forearm (p < 0.01-0.001), but the levels of biochemical markers of bone formation and resorption were comparable to values obtained in the normal postmenopausal women. T3 stimulation caused significant increases (p values ranging between 0.05-0.001) in all three groups of the resorptive markers: ICTP (47%, 47%, 45%), OHP (29%, 30%, 33%), PYR (43%, 27%, 51%), and DPR (42%, 24%, 59%). Of the formative markers, only BGP increased significantly (32%, 40%, 47%) (p < 0.001). At day 57, however, all three formative markers increased compared with day 15 (p < 0.05-0.001). No significant differences in bone markers were demonstrated between groups. In the osteoporotic group, as the only group, serum calcium increased (p < 0.05) and serum PTH fell (p < 0.05). In conclusion, osteoporosis and estrogen substitution are not characterized by altered concentrations of thyroid hormones or responsiveness to thyroid hormones at the level of individual bone cells; however, altered responses pertaining to PTH and calcium were detected.     

Budesonide and beclamethasone dipropionate inhalation powders. The effect on bone and collagen turnover in children

The objective of the study was to assess bone and collagen turnover in asthmatic children treated with dry powder budesonide from the Turbohaler and dry powder beclomethasone dipropionate from the Diskhaler in a dose of 800 micrograms/day. Thirteen prepubertal children with asthma were studied. The study was conducted as an open crossover study with two treatment periods and treatment free run-in and wash-out periods. All periods were of two weeks' duration. At day 14 in each period blood samples were taken for assessment of serum osteocalcin, the carboxyterminal propeptide of type I collagen (PICP), and the aminoterminal propeptide of type III collagen (PIIINP). At the same time urine was collected for assessment of creatinine corrected pyridinoline (uPYR/cr) and deoxypyridinoline (udPYR/cr) crosslinks. Results: Osteocalcin concentrations were not influenced by any of the treatments. During budesonide treatment PICP was reduced by 18% (p = 0.03), PIIINP by 24% (p = 0.0002), uPYR/cr by 16% (p = 0.03) and udPYR/cr by 21% (p = 0.12). During treatment with beclomethasone dipropionate PICP was reduced by 20% (p = 0.01), PIIINP by 36% (p = 0.0002), uPYR/cr by 18% (p = 0.004) and udPYR/cr by 13% (p = 0.02). The suppressive effect of beclomethasone dipropionate on PIIINP was more marked than that of budesonide (p = 0.001). It is concluded that treatment with dry powder budesonide and beclomethasone dipropionate 800 micrograms/day is associated with suppression of bone and collagen turnover. The suppression seems to be more marked during treatment with beclomethasone dipropionate. Long term effects and effects of lower doses of budesonide and beclomethasone dipropionate on bone and collagen markers needs further study.     

Markers of bone turnover in hyperthyroidism and the effects of treatment

Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary pyridinoline cross-link (Pyr) excretion, reflecting bone resorption, have been measured in 27 patients with hyperthyroidism and 30 age-matched controls using direct and novel immunoassays. Hyperthyroid patients had higher (P < 0.001) levels of all 3 markers compared with control values: Pyr, 246 +/- 181 nmol/mmol creatinine vs. 40 +/- 12 (+515%); OC, 55 +/- 23 vs. 23 +/- 7.4 micrograms/L (+139%); and B-ALP, 22 +/- 17 vs. 10.0 +/- 5.0 micrograms/L (+120%). OC and Pyr levels were elevated above the normal range in most patients and were significantly correlated with serum free T3 concentrations (r = 0.53; P < 0.01 and r = 0.76; P < 0.001; for OC and Pyr, respectively). B-ALP levels were elevated in 11 of the 27 patients and did not correlate with serum thyroid hormone concentrations. After therapy for hyperthyroidism, Pyr and OC levels returned to normal within 1 month, whereas B-ALP transiently increased after 1 month before falling to baseline levels. The relapse of hyperthyroidism observed in 1 patient was associated with a steep increase in bone markers. These results indicate that Pyr, measured using a new and convenient immunoassay, is a highly sensitive marker for altered bone metabolism in hyperthyroidism. The increases in OC and B-ALP were less impressive, suggesting an imbalance between resorption and formation with subsequent rapid bone loss in untreated hyperthyroidism. OC and B-ALP also appear to reflect different aspects of osteoblast metabolism during the treatment of hyperthyroid patients.