Serum concentrations of cross-linked N-telopeptides of type I collagen: new marker for bone resorption in hemodialysis patients

BACKGROUND: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). METHODS: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (beta-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient's bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. RESULTS: Serum NTX correlated significantly with beta-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as beta-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, beta-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. CONCLUSION: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.     

Usefulness of bone markers for detection of bone metastases in lung cancer patients

OBJECTIVES: Lung cancer commonly causes destructive bone metastases. The aim of this study was to compare efficiency of biochemical bone markers in the detection of bone metastases in lung cancer patients. DESIGN AND METHODS: We measured serum calcium (Ca), alkaline phosphatase (ALP), bone isoenzyme of alkaline phosphatase (BALP), osteocalcin (OC) and urine deoxypyridinoline crosslinks (DPD) levels in 52 lung cancer patients; 27 patients with the evidence of bone metastases, 25 without metastases in bone when they were first diagnosed. BALP, OC and DPD were measured by specific immunoassays. ALP, Ca and urine creatinine levels were determined by colorimetric methods. RESULTS: Ca, ALP, BALP, OC and DPD levels were significantly higher in the patients with bone metastases than those without bone metastases (p < 0.01 for BALP and OC, p < 0.001 for Ca, ALP and DPD). The sensitivity and specificities of all markers as follows: 89%-44% for BALP, 52%-88% for OC, 81%-76% for DPD, respectively. ROC curves were generated separately for BALP, OC and DPD to assess the diagnostic efficiency of markers in a different manner. DPD showed the best curve characteristics among the studied bone markers, followed by the BALP curve. OC curve showed poor characteristics. CONCLUSIONS: Our results suggest that the measurement of DPD and BALP may be useful in detecting bone metastases in lung cancer patients. Also it could help in the follow-up of bone metastases from lung cancer since they can be repeated more often than roentgenography and bone scintigraphy, at less cost and with less discomfort to the patients.     

Short- and long-term effects of ibandronate treatment on bone turnover in Paget disease of bone

BACKGROUND: In Paget disease of bone (PD), serum total alkaline phosphatase (TAP) is a valid marker of disease activity. The aim of the present longitudinal study was to compare TAP with new and potentially more specific markers of bone turnover in bisphosphonate-treated patients with PD. METHODS: Twenty patients with active PD were studied before and after treatment with 2 mg of intravenous ibandronate over a period of 12 months. TAP (by colorimetry), serum bone-specific alkaline phosphatase (BAP; by enzyme immunoassay), serum osteocalcin (OC; by ELISA), serum bone sialoprotein (BSP; by RIA), and urinary total pyridinoline (PYD; by HPLC) and deoxypyridinoline (DPD; by HPLC) were measured as markers of bone turnover. RESULTS: Before treatment, TAP, BAP, and BSP were increased in all 20 patients, whereas OC was increased in 10, PYD in 13, and DPD in 15 patients. Three months post treatment, nine patients showed normalized TAP values, and a >/=25% re-increase (i.e. , relapse) was observed in all patients after 12 months. A normalization of BAP was achieved in six patients only. No significant changes were found for OC. BSP was decreased significantly at 24 h, and DPD at 48 h post treatment. A normalization of BSP was found in 8, of PYD in 18, and of DPD in 16 cases. Both PYD and DPD increased significantly from 9 months post treatment onward. CONCLUSIONS: Most markers of bone turnover show similar long-term changes after treatment of active PD with ibandronate. With regard to cost-effectiveness and assay performance, TAP remains the marker of choice in therapeutic monitoring of PD. However, more specific markers may improve the biochemical assessment of PD in certain situations.     

Comparison of urinary markers for bone resorption in multiple myeloma

Multiple myeloma causes extensive bone remodeling. Classical biochemical markers such as urinary calcium have poor sensitivity for detecting multiple myeloma bone remodeling. New biochemicals have been developed including a carboxyterminal telopeptide of collagen I (CTX). We used an immunoenzymatic assay to determine urinary CTX in 60 patients with multiple myeloma. This marker was evaluated with regard to total pyridinolines, urinary calcium, radiological features, pain and response to treatment with bisphosphonates. In patients with bone involvement, CTX concentrations were significantly higher (+230%) than those of deoxypyridinoline (DPD) (+175%) and pyridinolines (PYD) (+130%). In all patients we have found a close correlation between CTX and DPD but not between CTX and PYD. Compared to radiological features, CTX was more sensitive (97%) and specific (96%) than DPD. After treatment by bisphosphonates, the fall in CTX concentrations was paralleled to urinary calcium and more marked than pyridinolines. Although our results need to be confirmed, CTX appears to be a potential marker to explore bone involvement in multiple myeloma.     

甲状腺功能亢进症患者尿脱氧吡啶啉的变化

目的　研究甲状腺功能亢进症 (甲亢 )患者新的骨代谢指标的变化。方法　测定 44例甲亢患者及 3 8例健康对照者的血清钙、磷、总碱性磷酸酶 (ALP)、骨钙素 (OC)、尿脱氧吡啶啉 (DPD)的水平。结果　甲亢组除血钙 (2 .40 3± 0 .189vs 2 .40 0± 0 .12 9,P =0 .0 7)与对照组无明显差别外 ,血磷 (1.2 5± 0 .0 9vs 1.12± 0 .0 6,P <0 .0 1)、ALP(10 0 .2 5± 12 .64vs 5 3 .5 5± 8.5 8,P <0 .0 1)、OC(13 .0 7± 3 .0 9vs 6.2 4± 1.5 7,P <0 .0 1)和尿DPD(3 1.62 3± 4.87vs 4.63 4± 0 .945 ,P <0 .0 1)均较对照组有明显增高。骨形成指标OC、ALP分别增高 110 %、87% ,而骨吸收指标尿DPD增高 62 8% ,以尿DPD活性增高更为显著 ,尿DPD与患者年龄、病程不相关。血ALP与T4呈正相关 ,尿DPD、血OC与T3 呈正相关。结论　甲亢患者由于高水平甲状腺激素的作用骨代谢增强 ,骨吸收大于骨形成 ;尿DPD是反映骨吸收的一项敏感而特异的指标     

Changes in biochemical markers after lower limb fractures

BACKGROUND: The bone remodeling sequence after bone fracture changes the concentrations of biochemical bone markers, but the relationships of fracture size and of healing time to changes in biomarkers are unclear. The present pilot study was undertaken to determine the changes found in serum bone markers after plate osteosynthesis of closed distal tibial and malleolar fractures during a study period of 24 weeks. METHODS: We measured tatrate-resistant acid phosphatase (TRACP 5b), collagen type I C-terminal telopeptide (ICTP), bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), and human cartilage glycoprotein 39 (YKL-40) in 20 patients with lower limb fractures (10 malleolar, 10 tibia). A physical examination and radiographs were completed to assess evidence of union. RESULTS: All malleolar fractures healed within 6 weeks, whereas 2 tibial fractures did not show complete bone healing after 24 weeks. Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 microg/L; ICTP: 5.6 vs 3.3 microg/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 microg/L, and 3.5 vs 3.2 microg/L, respectively, in the malleolar fracture group). CONCLUSIONS: In normal bone healing, changes in bone turnover markers were primarily dependent on the fracture size. Delayed tibia fracture healing may involve a disturbance in bone remodeling.     

Biochemical markers of bone turnover.

BACKGROUND: Osteoporosis in many countries has reached epidemic proportions. This has stimulated the development of biochemical markers to assist in the assessment of osteoporotic risk and in monitoring the efficacy of treatment. Biochemical markers of bone turnover are products released from osteoblasts and osteoclasts or collagen breakdown products. MARKERS: Markers of bone formation include bone-specific alkaline phosphatase (BAP), osteocalcin (OC) and procollagen peptides. All of these can be measured easily by immunoassay techniques. Of these markers, OC has been extensively studied. However, OC undergoes in vitro degradation, thus, assay results are variable. BAP, on the other hand, is much more stable and shows less within-person biological variation. Bone resorption markers include tartrate-resistant acid phosphatase (TRAP) and collagen breakdown products, such as pyridinium cross-links, galactosyl hydroxylysine and cross-linked telopeptides, such as CTx and NTx. Of these, deoxypyridinium (DPD) has been extensively studied. DPD shows diurnal variation and the within-individual biological variation is large. Of the newer assays, NTx appear to show large differences at menopause. CONCLUSIONS: Thus, serum BAP and DPD or NTx are the current choice of bone markers.     

Age-related changes in bone turnover markers and ovarian hormones in premenopausal and postmenopausal Indian women

This study characterizes age-related changes in bone turnover markers in relation to ovarian hormones. The data (N = 236) were divided into 5-year age bands and three groups: premenopausal (Group I, N = 139), perimenopausal (Group II, N = 30), and postmenopausal (Group III, N = 67). Age-related increases in mean parathyroid hormone (PTH), osteocalcin (OC), and collagen telopeptide (CTx) levels were observed. Women in Group II (N = 37) with osteopenia had lower levels of E1G (P<0.001) with normal FSH levels as compared to 50 women in the same group with normal bone mineral density (BMD). Their mean OC levels were reduced (P<0.05) and CTx levels were significantly elevated (P<0.01). The mean E1G levels were significantly lower (P<0.001) and mean CTx levels were significantly higher (P<0.001) in 30 perimenopausal women (Group II) compared to premenopausal women. In 28 postmenopausal women (group III) the mean BMD levels and E1G were significantly lower (P<0.001) with elevated FSH levels (P<0.001). Increased CTx levels (P<0.0001) reflected a higher rate of bone resorption. These observations suggest that perimenopausal women with low E1G, elevated FSH should be screened for osteoporosis, and it may be valid to combine simultaneous measurements of bone turnover markers with ovarian hormones when screening women at risk for osteoporosis.     

柠檬酸盐抗凝剂对献血者骨代谢平衡的短期影响

本研究旨在探讨单采血小板模式下柠檬酸盐抗凝剂的应用对机体骨代谢平衡的短期影响,为可能的干预手段提供参考,更好地保护献血者健康。采用自身交叉、安慰剂对照的研究模式,对22名健康献血志愿者以标准化的干预方式分别给予1．5me／（kg·min）的柠檬酸盐抗凝荆（ACD—A）和相同容量的安慰剂（生理盐水）输注,干预洗脱期为2—3周。干预过程中采集系列血样进行骨代谢相关指标,包括骨形成指标骨钙素（osteocalcin,OC）、骨吸收指标Ⅰ型胶原蛋白C端肽（carboxyterminal telopeptide of type Ⅰ collagen,CTX）、全段甲状旁腺素（intactpara-thyroid hormone,PTH）,以及游离钙离子（ionized calcium,iCa^2＋）和无机磷（phosphorus,Pi）的检测,采集系列尿样进行尿钙、尿磷和尿肌酐的检测。结果表明：与对照组比较,柠檬酸盐干预导致：①血清OC和CTX水平大幅升高（P〈0．0001）,并于干预结束时升高至最高点,其中CTX增幅高于OC（P=0．02）,OC／CTX比值降低（P〈0．01）;②血清。PTH水平升高（P〈0．0001）,iCa^2＋（P〈0．0001）和Pi（P〈0．01）水平降低,尿钙排出增加（P〈0．0001）;③女性,Ca^2＋水平降幅高于男性（P=0．007）,但未见iPrrH、OC和CTX水平变化的性别间差异;④血清OC水平变化与CTX正相关（r=0．56,P〈0．0001）,二者均与iCa^2＋水平变化负相关（roc=-0．4J4,rcTx=-0．44,P〈0．0001）;男性iPTH水平变化与Oc相关（r=0．34,P=0．02）,女性无此相关性;⑤上述指标24小时后均恢复至初始水平。结论：普通剂量下单次柠檬酸盐抗凝剂的输注可引发机体骨转换率的短暂提升,并以骨吸收增强为主要特征,同时伴随有尿钙排泄的增加,其对长期、频繁单采献血者骨质健康的影响值得关注。     

绝经后妇女血清基质金属蛋白酶与骨转换生化指标及骨密度的关系

目的探讨绝经后妇女血清基质金属蛋白酶(MMP)-1和MMP-2与骨密度及骨转换生化指标之间的关系。方法采用酶联免疫吸附法测定297名48~80岁女性志愿者的血清MMP-1、MMP-2和血清骨碱性磷酸酶(BAP)、血清骨钙素(OC)及血清Ⅰ型胶原氨基末端肽(NTX),用双能X线吸收法测定腰椎正位1~4总体、股骨颈、华氏区、髋部总体的骨密度。结果MMP-1与骨密度及骨转换生化指标无明显相关性;MMP-2与骨密度呈较弱的负相关,校正年龄与体重指数后,MMP-2与股骨颈、髋部骨密度的相关性消失;MMP-2与BAP、OC、NTX正相关(P<0.01);绝经后骨质疏松症患者血清MMP-2水平高于年龄匹配的正常对照组和骨量减少组(P<0.01)。结论绝经后妇女血清MMP-2与骨转换生化指标相关联,血清MMP-2水平升高可能为高骨代谢转换过程(如绝经后骨质疏松症)中的一种伴随表现。     

Biomarkers of bone turnover and bone mineral density in hyperprolactinemic amenorrheic women.

We tested the hypothesis that biomarkers of bone resorption are increased in hyperprolactinemic amenorrheic patients with estrogen (E) deficiency, augmenting the possible risk of developing osteoporosis. Fifty hyperprolactinemic patients with amenorrhea of more than 12 months and with low serum E2, as well as 30 healthy fertile women (controls), matched for age and body mass index, participated in this study. Bromocriptine was administered orally to hyperprolactinemic patients and blood and urine samples were collected before and 12 weeks after treatment. Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary deoxypridinoline (D-Pyr) and N-telopeptide of type 1 collagen (NTX) excretion, reflecting bone resorption, were measured using direct immunoassays. Hyperprolactinemic patients had higher (p < 0.0005) levels of all the biomarkers compared to control values: (OC, 22+/-1.2 [SE] vs. 14+/-.99 ng/ml (+57 %); B-ALP, 14.2+/-0.7 vs. 7.5+/-0.8 ng/ml (+89 %); D-Pyr, 8.8+/-0.6 vs. 3.2+/-0.3 nmol/mmol creatinine (+175%) and NTX, 65+/-5.1 vs. 25+/-3.2 nmol bone collagen equivalent (BCE)/mmol creatinine (+160%)). These results were associated with significantly decreased lumbar spine bone mineral density (LS-BMD), measured by dual energy X-ray absorptiometry (DEXA). Treatment of hyperprolactinemia with bromocriptine restored normal values of bone formation and resorption markers. In conclusion, hyperprolactinemia with estrogen deficiency exhibits a significant increase of bone resorption which is associated with a significant decrease of LS-BMD. These changes may subject the patient to the possible risk of developing osteoporosis.     

Serum tartrate-resistant acid phosphatase isoforms in rheumatoid arthritis

Objectives: Our objective was to evaluate the significance and source of serum tartrate-resistant acid phosphatase (TRACP) in patients with rheumatoid arthritis (RA). Methods: Thirty-five RA, 32 osteoarthritis (OA) and 16 control subjects were studied. Serum TRACP-5b activity and total TRACP protein were determined by immunoassay. TRACP isoforms were analyzed by non-denaturing polyacrylamide gel electrophoresis (PAGE). Serum bone alkaline phosphatase (BAP), cross-linked N-terminal telopeptides (NTx), and C-terminal telopeptides (ICTP) of type I collagen were estimated as markers of bone turnover. C-reactive protein (CRP) was measured as a marker of chronic inflammation. Macrophages and dendritic cells (DC) were developed from peripheral blood monocytes. Cell lysates and culture supernatants were analyzed for TRACP isoforms by immunoassay and PAGE. Results: In RA, mean TRACP-5b activity was normal, but median total TRACP protein was increased twofold (p<0.001). In OA, TRACP-5b activity and protein were normal. In RA, TRACP-5b activity correlated weakly with ICTP (r=0.56) while TRACP protein levels correlated weakly with NTx (r=0.43). Additionally, TRACP protein, but not TRACP-5b activity correlated significantly with CRP (r=0.42). Macrophage and DC lysates contained TRACP-5b, while tissue culture supernatants contained TRACP-5a. Conclusions: Increased total TRACP protein in RA sera was probably due to TRACP-5a and not derived from osteoclasts. Rather, it could be a secreted product of inflammatory macrophages and DC.     

Different acute responses of serum type I collagen telopeptides, CTX, NTX and ICTP, after repeated ingestion of calcium

BACKGROUND: N- and C-terminal fragments of type I collagen such as NTX, CTX and ICTP are released into circulation during bone resorption and can be quantified in serum. Their respective sensitivity as indices of osteoclastic activity was compared after a short-term inhibition of resorption induced by repeated drinking of calcium-fortified water. METHODS: Serum NTX, CTX and ICTP were measured by specific immunoassays in one group of 15 subjects sampled at 08.00, 11.00, 14.00 and 17.00 (referred to as T0, T3h, T6h and T9h) and having ingested in two experimental periods 660 ml of either low-calcium mineral water or the same low-calcium mineral water fortified with calcium (300 mg/l) at three times (08.00, 11.00 and 14.00). RESULTS: Oral intake of calcium-fortified water resulted in progressive decrease in serum CTX (by 38.7% at T3h, 61.0% at T6h and 60.4% at T9h) and NTX (by 19.0% at T3h, 24.1% at T6h and 25.2% at T9h) while serum ICTP concentrations were not significantly affected. Since ingestion of low-calcium water induced a modest but significant decrease in both CTX (-19.4%) and NTX (-10.6%) we compared the two sets of assays with repeated-measures two-factor analysis of variance with interaction. Ingestion of calcium-fortified water vs. low-calcium water resulted in a significant decrease in both serum CTX (time, P<0.0001; treatment, P<0.0001; time-by treatment, P<0.0001) and NTX (time, P<0.0001; treatment, P=0.0001; time-by treatment, P=0.0066). CONCLUSIONS: CTX is more sensitive than NTX while ICTP is not sensitive to calcium-induced acute changes in osteoclastic activity. The present results stress the importance of choosing appropriate biochemical bone markers to demonstrate the effects of calcium on bone resorption.     

Biochemical markers of bone formation in hemodialysis and after allotransplantation of cadaveric kidney

AIM: To ascertain informative value of estimation of bone forming markers in patients on chronic hemodyalisis (CHD) and recipients of cadaveric kidney (CK). MATERIAL AND METHODS: Parathyroid hormone (PTH), beta-crosslaps (CTX), osteocalcin (OC), amino-terminal procollagen propeptide 1 (PINP), bone alkaline phosphatase (BAP), bone mineral density (BMD) were determined in 152 patients on CHD (89 males and 63 females aged 49 +/- 13 years) and 195 CK recipients (106 males and 89 females aged 42 +/- 12 years) 30 +/- 38 months after kidney transplantation. RESULTS: PTH, CTX and BAP determination specifies skeletal disease (secondary hyperparathyroidism or adynamic bone disease) in CHD patients. In patients with CK recipients osteoporosis differed from osteopenia by higher levels of PTH, CTX, OC in the absence of any differences in BAP, PINP. All bone forming markers were lower than CTX showing suppression of bone forming. Bone fractures in CK recipients' anamnesis were associated with OC and BAP decrease in men and low border of normal OC in women. Determination of bone formation and resorption markers in patients on CHD and CK recipients is of great clinical importance.     

Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study

BACKGROUND: Bone mineral density (BMD) is used to follow gain or loss of bone mass but cannot detect changes within a short period of time. Biochemical markers of bone turnover may be of value for prediction of individual bone loss. METHODS: We studied the relation between common inexpensive markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin (OC), urinary hydroxyproline (OHPr), and calcium (Ca)), BMD, age, and menopause in a combined cross-sectional and longitudinal design comprising 429 pre- and postmenopausal randomly selected women aged 21-79 years (mean 50 years). A follow-up was initiated after 5 years (including 192 of these women), which focused on changes in bone mass and the ability of these four common markers of bone turnover (sampled at baseline) to predict future bone loss. RESULTS: A marked increase was observed for all markers at the beginning of menopause. During the postmenopausal period ALP and Ca decreased to near premenopausal levels, while OC and OHPr remained high even 15 years after menopause. We also found inverse correlations at baseline between the bone markers and BMD, independent of the selected marker or skeletal site, r=-0.14 to -0.46, P<0.05. The correlations between ALP, OC, OHPr, and subsequent bone loss over 5 years, was significant for arm, r=-0.23 to -0.36, P<0.01. Baseline levels of all bone markers correlated significantly at group level with the 5-year follow-up of BMD for all sites. The ability of markers to predict individual bone loss was estimated by a multivariate regression model, which included baseline BMD, age, and body mass index as independent variables. ROC analysis showed a validity of approximately 76% for the forearm model, but was lower for the hip (55%) and lumbar spine (65%). CONCLUSIONS: These data show that the common inexpensive biochemical markers of bone turnover ALP, OC, OHPr, and Ca were related to the current bone mass and, moreover, provides information about future bone loss at the individual level. Future investigations should include an evaluation of the clinical relevance of markers of bone turnover in relation to fracture risk.     

Urinary bone resorption markers in monitoring treatment of symptomatic osteoporosis

We have studied the clinical usefulness of urinary bone resorption markers in postmenopausal women with symptomatic osteoporosis. The study design is a randomised double-blind placebo controlled study, in which the subjects were daily treated for 24 months either with a hormone analogue (2.5 mg Livial, generic name Tibolone, Organon, Amsterdam, Holland) plus 800 mg calcium (n = 14, age 63+/-5 years, range 52-68 years), or with placebo plus 800 mg calcium (n = 19, age 66+/-7 years, range 50-75 years). The laboratory methods for urinary bone resorption markers were enzyme immunoassays (EIA) for urinary pyridoline (PYD) and deoxypyridoline crosslinks (DPD), and for cross-linked N-telopeptides of Type I Collagen (NTx), and an HPLC assay for urinary hydroxyproline (HOP). All the urine assay results were calculated per mmol creatinine. All the resorption markers decreased during the two-year study period in both groups. The Z scores (discriminating power, i.e. ability of the different tests to distinguish the hormone treated subjects from the placebo treated subjects) for HOP and PYD were rather low: 0.06-1.52 for HOP and 0.68-1.47 for PYD. The differences between the two treatment groups were statistically significant for DPD at 12 and 24 months of treatment (P = 0.0471 and P = 0.0466, respectively), the Z scores ranging 0.45-1.90. NTx showed the most prominent decrease from the beginning of the study especially in the hormone treatment group: the differences between the two treatment groups were statistically highly significant for NTx already at 6 months of treatment (P = 0.0015), and the Z scores remained high ranging 2.11-3.82 throughout the two-year study period. Dual X-ray absorptiometry (DXA) of the lumbar spine and femoral neck did not show statistically significant differences between the two treatment groups throughout the two-year study period. After 2 years there was, however, a significant increase in bone density both in the spine (+ 6.6%, P = 0.0002) and in the femoral neck (+ 3.4%, P = 0.0389) in the women with hormone treatment. In the control group a significant increase (+ 5.1%, P = 0.0012) in the spine, whereas a non-significant decrease (-1.5%, n.s.) in the femoral neck was observed. We suggest that measurement of urinary cross-linked peptides derived from Type I collagen (NTx and DPD) might be a useful biochemical method of observing the positive clinical effect (i.e. reduction in bone resorption) following hormone replacement therapy in postmenopausal fracture patients.     

A collection method and high-sensitivity enzyme immunoassay for sweat pyridinoline and deoxypyridinoline cross-links.

BACKGROUND: Collagen cross-link molecules such as pyridinoline (PYD), deoxypyridinoline (DPD), and N-terminal cross-linked peptides (NTX) have been measured in urine as indices of bone resorption. However, very little is known regarding the excretion of pyridinolines into other biological fluids. We report a collection device, normalizing analyte, and high-sensitivity immunoassay for quantitative analysis of free pyridinoline cross-links in sweat. METHODS: Flame atomic emission and ion-selective electrode techniques were used to measure potassium as a sweat volume marker. The Pyrilinks immunoassay for urine free pyridinolines was optimized to increase sensitivity for measurements in sweat. The precision, accuracy, and detection limit of this assay were characterized. To assess values and variability of sweat pyridinolines in human subjects, a nonocclusive skin patch was used to collect sweat samples from a reference group and from a mixed group experiencing accelerated bone resorption, postmenopausal women and men receiving gonadotropin-releasing hormone for prostate cancer. RESULTS: The immunoassay intra- and interassay variations were 相似文献   

老年男性血清睾酮水平变化与骨代谢生化指标的关系

目的探讨老年男性血清睾酮水平变化与骨代谢生化指标的关系。方法106例研究对象根据年龄分为60岁~、70岁~及80岁以上三组,检测各研究对象血清睾酮、骨钙素(BGP)、Ⅰ型胶原羧基肽(PICP)、碱性磷酸酶(ALP)及尿脱氧吡啶啉(DPD)值,进行比较及相关分析。结果随增龄血清睾酮逐渐下降,血清BGP、PICP及ALP也下降,尿DPD逐渐升高(P<0.05 orP<0.01);血清睾酮水平与BGP正相关(r=0.57,P<0.05),与DPD负相关(r=-0.49,P<0.05)。结论随增龄,老年男性骨代谢呈负平衡,且与雄激素的逐渐下降密切相关。     

Bone remodeling markers in the detection of bone metastases in prostate cancer

BACKGROUND: Early detection of bone metastases in prostatic carcinoma is very useful in treatment and prognosis of the disease. The aim of this work was to evaluate the sensitivity and specificity of a group of bone markers in order to discriminate between prostate carcinoma patients without (M(0)) and with (M(1)) bone metastases. METHODS: Sixty-seven non-treated patients with: benign prostate hyperplasia (n=21), prostatic carcinoma in several stages without bone metastases (T(X)M(0)) (n=31) and with bone metastases (T(X)M(1)) (n=15) were studied. The following markers were studied: (A) bone formation: (1) serum bone alkaline phosphatase, IRMA (Tandem Ostase, Beckman); (2) serum procollagen I amino-terminal propeptide (PINP), RIA (Orion Diagnostica); (B) bone resorption: (1) urinary collagen I amino-terminal telopeptide (NTX), ELISA (Ostex); (2) collagen I carboxy terminal telopeptide (CTX): (2A) urinary alpha-CTX, RIA (Osteometer), (2B) serum beta-CTX, Elecsys (Roche); (3) collagen I cross-linked carboxy terminal telopeptide (ICTP), RIA (Orion Diagnostica). RESULTS: Levels of all bone markers were significantly higher in group M(1) than in group M(0). A complete separation of groups M(0) and M(1) was achieved with PINP and beta-CTX (100% sensitivity and specificity). CONCLUSIONS: These results support the use of PINP or beta-CTX as a tool to confirm the presence or absence of bone metastases in the first staging of prostatic carcinoma patients.     

The effect of smoking on bone metabolism: maternal and cord blood bone marker levels

BACKGROUND: To clarify the effect of smoking on bone metabolism in the fetus, we measured osteocalcin (OC), bone isoenzyme of alkaline phosphatase (BALP), procollagen type 1 C-terminal propeptide (PICP) in maternal serum and umbilical cord blood. METHODS: 15 active smoker, 14 passive smoker, 15 nonsmoker women and their newborn were included in this study. OC, BALP, PICP were determined by enzyme immunoassay. RESULTS: Of the bone markers tested only OC was different in the serum of the three groups of women. Infants of smoker women have significantly lower umbilical cord blood OC levels than those of infants from both passive smoker and nonsmoker women.(25.6 +/- 6.6, 35.8 +/- 10.4, 37.2 +/- 16.1 ng/mL respectively, p < 0.05). Infants of smoker women have significantly lower umbilical cord blood BALP levels than those of infants from nonsmoker women. (46 +/- 12, 57 +/- 15 U/L p < 0.05). All bone markers except total ALP were significantly higher in umbilical cord blood as compared to maternal blood levels (p < 0.001 for all). CONCLUSION: High umbilical cord blood bone marker levels may reflect the altered bone metabolism of fetus. Moreover, chronic hypoxia due to smoking may cause the suppression of bone matrix synthesis or placental synthesis as reflected by low OC and BALP levels in umbilical cord blood of infants from smoker women.