Ⅰ型胶原吡啶交联终肽在结肠肿瘤诊断中的应用

目的 检测良性结肠肿瘤、恶性结肠肿瘤患者及健康对照组血清中的Ⅰ型胶原吡啶交联终肽(ICTP)活性,探讨ICTP在良恶性结肠肿瘤诊断和鉴别诊断中的价值.方法 选取75例恶性胃肠肿瘤患者,设为A组,其中71例为原发性恶性结肠肿瘤、4例为转移性肿瘤患者,另选43例良性结肠肿瘤患者为B组,同时,设52例同龄健康人为C组,均采用酶免疫测定(EIA)方法测定血清中的ICTP活性.结果 B组患者血清ICTP活性为(6.75 ±3.34) μg/L,C组血清ICTP活性为(4.68±2.91) μg/L,A组患者血清ICTP活性为(14.84±8.49) μg/L,其中,原发性恶性结肠肿瘤患者和转移性结肠肿瘤患者的血清ICTP活性分别为(17.47±10.86) μg/L和(8.14 ±5.45) μg/L.A组中两类患者的血清ICTP活性与B、C组比较差异均有统计学意义(P＜0.05),B组患者与C组比较差异无统计学意义(P＞0.05).而A组中原发性恶性结肠肿瘤与转移性肿瘤组之间的差异也有统计学意义(P＜0.05).结论 血清ICTP是反映结肠肿瘤骨代谢的一个灵敏而简便的检测指标,并有助于良恶性结肠肿瘤的诊断及鉴别诊断.     

I型胶原吡啶交联末端肽在评价类风湿关节炎 患者病情活动和骨丢失中的临床意义

目的探讨Ⅰ型胶原吡啶交联末端肽(ⅠCTP)在评价类风湿关节炎(RA)病情活动和骨丢失中的重要意义。方法对125例RA女性患者血清,采用酶联免疫吸附试验(ELISA)方法定量检测血清骨代谢指标ⅠCTP、I型胶原羧基末端肽(C区)β降解产物(β-CTX)、Ⅰ型原胶原氨基端前肽(PINP)的浓度,使用DAS28评估RA患者疾病活动指数,影像学sharp评分评估骨侵蚀与狭窄程度,用双能X线吸收仪测定骨密度,并了解患者服用糖皮质激素情况。结果 RA疾病活动组ⅠCTP值明显高于RA疾病稳定组(P<0.01),在排除了糖皮质激素的影响后,差异仍显示有统计学意义。并且血清ⅠCTP值与局部骨侵蚀、狭窄评分呈正相关,与RA全身骨密度无相关性,而血清β-CTX值与全身骨密度呈负相关,与局部骨侵蚀、狭窄评分无相关性。结论Ⅰ型胶原吡啶交联末端肽(ⅠCTP)是评价RA病情活动及局部骨丢失的有效辅助诊断指标,临床观察到ⅠCTP值明显升高时应积极使用RA病情控制药物以防治进一步关节骨破坏。     

Ⅰ型胶原交联氨基末端肽在前列腺癌骨转移诊断中的意义

目的 探讨前列腺癌患者尿液中Ⅰ型胶原交联氨基末端肽(NTx)含量与骨转移发生之间的关系.方法 采用ELISA法测定前列腺癌患者尿液中的NTx含量,将临床明确诊断骨转移与无骨转移两组进行对照并进行统计学分析.结果 S4例前列腺癌患者中骨转移组24例,非骨转移组30例.骨转移组患者的尿液NTx含量平均385.22 nmol BCE/mmol Cr,非骨转移组为73.76 nmol BCE/mmol Cr,两组之间的差异有统计学意义(P=0.029).以NTx含量诊断骨转移的特异度和敏感度分别为76.5%和71.4%.结论 NTx在前列腺癌骨转移诊断中有较为重要的意义.     

不同年龄段健康人群骨代谢指标Ⅰ型前胶原N末端前肽的特点分析

目的确定健康中国人群中Ⅰ型前胶原N末端前肽(type Ⅰ procollagen propeptide,PⅠNP)的年龄和性别特异性参考区间。方法采用骨密度测定法测定骨密度正常的中国人群599份血清,建立参考区间。年龄组分为20～29岁、30～39岁、40～49岁、50～59岁、≥60岁。结果在划分中国男性和女性人群的年龄组时,不同年龄组的总PINP存在显著差异。在男性人群中,PⅠNP水平随着年龄的增长而降低,然后在中年后保持稳定。在女性人群中,与男性人群相似的下降趋势与50～59岁年龄组的急剧增加相似。结论本研究初步建立了具有正常骨密度的中国男性和女性人群与年龄相关的PⅠNP参考区间。     

血清ICTP与TRACP 5b联合检测在乳腺癌骨转移诊断中的价值

目的:探讨溶骨性骨代谢标志物血Ⅰ型胶原交联羧基末端肽(ICTP)和血抗酒石酸酸性磷酸酶5b(TRACP 5b)的检测对诊断乳腺癌骨转移的价值.方法:用ELISA法测定78例乳腺癌患者及40例乳腺良性肿瘤患者血清ICTP和TRACP 5b水平,比较两者水平在骨转移、非骨转移乳腺癌患者及良性乳腺肿瘤患者中的差异及其相关性.结果:乳腺癌骨转移患者血清ICTP和TRACP 5b水平均明显高于无骨转移及乳腺良性肿瘤患者(均P＜0.001),而后两者间无统计学差异(均P＞0.05).乳腺癌患者血清ICTP与TRACP 5b浓度表达呈正相关(r=0.63,P＜0.01).血清ICTP和TRACP诊断乳腺癌骨转移的敏感性、特异性和准确性分别为55.3％,92.5％,81.4％和84.2％,83.8％,83.9％,两者联合检测分别为94.7％,81.3％,85.6％.结论:血清ICTP和TRACP 5b对乳腺癌骨转移的诊断均有重要价值,两者联合检测有助于提高诊断的敏感性和准确性.     

男性骨特异性碱性磷酸酶、骨钙素、I型胶原氨基末端肽与骨密度的关系

目的探讨男性人群血清骨特异性碱性磷酸酶(BAP)、血清骨钙素(sOC)和血清Ⅰ型胶原氨基末端肽(sNTX)与BMD的相互关系。方法用ELISA方法测定309名20~80岁男性志愿者的血清骨特异性碱性磷酸酶(sBAP)、血清骨钙素(sOC)和血清Ⅰ型胶原氨基末端肽(sNTX),用DEXA(双能X线吸收法)测定腰椎正位(AP)L1-L4总体、腰椎侧位、股骨颈、Wards区(华氏区)及髋部总体的面积BMD。结果(1)直线相关分析显示,sOC、sNTX与腰椎正位总体BMD呈负相关,r分别为-0.007,-0.100。BAP与腰椎正位总体、腰椎侧位、髋部总体、股骨颈及Wards区BMD均负相关,r分别为-0.190、-0.087、-0.175、-0.128、-0.128(P<0.05)。(2)校正年龄、体重指数和吸烟的影响后,sOC和各部位BMD相关性消失;sNTX与腰椎正位总体BMD;BAP与腰椎正位总体、髋部总体、股骨颈及Wards区BMD相关性仍存在,r分别为-0.164、-0.171、-0.148、-0.191、-0.105(P<0.05)。(3)以50岁为切点,将所有样本按年龄分两段,偏相关分析显示50岁以前sOC、sNTX和BAP与各部位BMD无显著相关;50岁以后除腰椎侧位外,BAP与腰椎正位总体、髋部总体、股骨颈及Wards区BMD负相关,偏相关系数分别为-0.206、-0.256、-0.183、-0.126(P<0.05)。sOC与各部位BMD无显著相关,sNTX与腰椎正位总体显著负相关,偏相关系数为-0.202(P<0.05)。(4)按BMD分组,方差分析显示50岁以上年龄匹配男性骨质疏松组BAP高于正常对照组与低骨量组,NTX高于正常对照组(P<0.05)。(5)分别以各部位BMD为应变量,年龄、BMI、吸烟(每日吸烟数量×烟龄)、BAP、sOC和sNTX为自变量,进行多元逐步线性回归分析。年龄、体重指数为各部位BMD的独立决定因子;吸烟为腰椎正位总体、髋部总体及Wards区BMD的独立决定因子。BAP为腰椎正位总体,髋部总体,股骨颈及Wards区BMD的独立决定因子,解释其BMD变化的百分数分别为16.5%、18.0%、13.4%、10.8%。(P均<0.05);sNTX为腰椎正位总体BMD的独立决定因子,解释腰椎正位总体BMD变化的15.7%。结论(1)校正年龄、体重指数和吸烟后,50岁以上男性BAP与腰椎正位总体、髋部总体、股骨颈及Wards区BMD,sNTX与腰椎正位总体BMD均呈负相关,BAP与sNTX均为50岁以上男性BMD的独立决定因子。(2)50岁以上男性骨质疏松组BAP显著高于正常对照组与低骨量组,NTX高于正常对照组,较高的骨代谢转换水平与较低的BMD相关联。(3)年龄、体重指数与吸烟均为各部位BMD的独立影响因素。     

骨代谢生化指标临床应用专家共识(2023修订版)

骨代谢生化指标的临床应用，为骨质疏松的诊断、鉴别诊断、预测骨折风险及抗骨质疏松治疗疗效评价提供了分子生物学依据，并在骨质疏松流行病学研究、发病机制、骨质疏松药物开发研究方面具有重要意义。由于骨代谢生化指标检测特异性强、灵敏度高，其应用日趋广泛。该文检索了大量中外文献，编审了《骨代谢生化指标临床应用专家共识》(2023修订版),对骨代谢生化指标的分类、骨代谢生化指标的方法学以及生物学意义、骨代谢指标的检测变异等进行了论述。     

B型超声在甲状腺肿瘤中的诊断价值(附161例临床分析)

本文对161例甲状腺肿瘤术前进行B超检查,并与术后病理结果对照.结果表明,术前B超对甲状腺肿瘤的诊断符合146例(90.6％).不符合15例(9.4％),诊断符合率较高,并能发现细小早期病灶。     

SPECT-PET显像在分化型甲状腺癌~(131)I治疗预后中的应用价值

目的探讨SPECT及PET显像在诊断甲状腺癌放射治疗后复发和转移中的应用价值。方法对103例接受131I治疗的分化型甲状腺癌(DTC)患者的核医学显像资料、影像学资料及血浆Tg、TSH的水平测定结果进行分析,其中的85例为有效病例,作为本研究的研究对象,分为实验组和对照组,实验组行131I SPECT/CT、131I-WBS显像,对照组行124I-PET和FDG SPECT/CT显像,并同期测定患者的血浆Tg、TSH水平及常规检查,同时让患者口服重组人促甲状腺激素(rhTSH)后再次显像,分析其显像资料及血浆Tg、TSH水平,结合患者的临床表现,综合分析患者同期的各项影像学检查结果(131I SPECT/CT断层显像、18F-FDG显像、CT、B超、MRI等)及血清TSH、Tg水平测定值,对患者是否发生分化型甲状腺癌术后转移复发进行判断,并以此做出诊断。血浆Tg水平诊断肿瘤复发转移的判断阈值为>10 ng/mL。结果以Tg血浆水平>10 ng/mL做为肿瘤复发转移判断界值得出SPECT/CT较131I全身显像具有更高的灵敏度;124I-PET较131 I-WBS有着更好的空间分辨率和灵敏度,可提高DTC定位诊断的准确性;18F-FDGPET/CT显像对Tg水平明显增高的甲状腺癌复发和转移患者有重要的诊断价值;服rhTSH可进一步提高18F-FDG检查的准确性。结论 131I SPECT-PET显像,可提高病灶定位的准确性,为肿瘤预后的评价提供了更准确的判断依据,将进一步推动分化型甲状腺癌临床诊疗水平的提升。     

Changes in serum carboxyterminal telopeptide of type I collagen in an experimental model of canine osteomyelitis

Blood biochemical indices of bone turnover were followed up for 1 month in six dogs with experimental osteomyelitis. The bone infection resulted in significant increase in parameters of bone formation (serum bone alkaline phosphatase and serum osteocalcin) and bone resorption [serum carboxyterminal telopeptide of type I collagen (i-ICTP)] as early as the end of the second week after the operation and inoculation. There was strong evidence that serum i-ICTP levels could be useful for the early diagnosis of postoperative complications in veterinary orthopedics, such as posttraumatic osteomyelitis.     

Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen in uremic hyperparathyroidism

SUMMARY: We compared the serum level of the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) with clinical parameters of bone formation and skeletal symptoms to investigate whether I-CTP can predict the degree of renal osteodystrophy. Serum I-CTP was measured in 41 patients with secondary hyperparathyroidism who underwent total parathyroidectomy and autoimplantation (PTx). Measurement was done by using radioimmunoassay. Blood samples were collected before surgery and at 1, 3, 6, 9, 12, 15, and 18 months afterwards for the measurement of bone formation parameters. Serum I-CTP levels were significantly higher in patients with Jensen grade 3–5 renal osteodystrophy than in patients with grade 0–2 renal osteodystrophy. the I-CTP levels were also significantly higher in patients with bone or joint pain compared with patients without pain. There was a significant negative correlation between the serum I-CTP level and the lumbar vertebral (L2-4) bone mineral density. Serum I-CTP was significantly correlated with the serum levels of alkaline phosphatase, calcium, and phosphate, as well as the serum calcium x phosphate product, and the intact parathyroid hormone level. These findings suggest that serum I-CTP could be used as a marker for evaluating osteodystrophy in uremic hyperparathyroidism.     

Cross-linked N-telopeptide of type I collagen (NTx) in urine as a predictor of periprosthetic osteolysis.

Periprosthetic osteolysis is often nonsymptomatic and hard to visualize by conventional radiography. Cross-linked N-telopeptide of type I collagen (NTx), a marker of osteoclast mediated bone resorption, has been suggested to evaluate local particulate-induced osteolysis in patients operated on with a total hip prosthesis. Urine specimens were sampled after hip joint replacement in 160 patients. NTx was analyzed by a commercially available ELISA kit. Osteolysis was identified in the acetabulum and confirmed at operation. Using analysis of covariance to correct for differences in age, gender, and time after operation, NTx (mean SD) was 36+/-12 BCE/nM creatinine in patients with osteolysis (n=33) and 27+/-13 BCE/nM creatinine in patients without osteolysis (n=127) (p=0.003). Eighteen hips of 38 (47%), demonstrating an annual wear of more than 0.2 mm and an NTx value above 29 BCE/nM creatinine, had been revised due to osteolysis. The osteolysis prevalence in this group was increased 10 times (CI 4-23, p<0.05). Indeed, NTx release and annual wear were both associated with increased prevalence of osteolysis, however, independently of each other. NTx seems a feasible marker of periprosthetic osteolysis. A preoperative baseline NTx level is likely needed for its use as a predictor of periprosthetic osteolysis in individual cases.     

Oncological validation of bone turnover markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) in patients with prostate cancer and bone metastases

BackgroundBone formation markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) were reported to be increased in patients with prostate cancer (PC) and bone metastases. The objective of the presented study was to investigate the utility of serum 1CTP and P1NP values in the diagnosis of bone metastases and in predicting oncological outcome in patients with PC.MethodsIn total, serum samples of 186 patients were included retrospectively including 53 (28.50%) benign prostatic hyperplasia (BPH) patients and 133 (71.50%) PC-patients. The group of patients with PC consisted of 58 patients with non-metastatic PC (cM0) (43.61%) and 70 (52.63%) patients with bone metastases (cM1b). Serum 1CTP and P1NP were measured by radioimmunoassay (RIA). Results were compared to clinical variables including oncologic follow-up data by univariate and multivariate analyses.ResultsMedian 1CTP concentrations were significantly higher in patients with PC compared to the BPH group [5.08 (range, 1.73–158.00) vs. 4.00 (range, 2.18–34.19) µg/L, P=0.019]. However, no significant difference of P1NP levels could be shown for these groups. With median values of 6.04 (1.73–158.00) and 3.91 µg/L (2.04–34.51) for 1CTP and 48.60 (9.12–1,074.37) and 33.90 (8.72–149.30) for P1NP both markers were altered in cM1b patients compared to cM0 patients (P=0.001 each). Furthermore, cancer-specific survival (CSS) and overall survival (OS) were significantly shorter in cM1b patients with higher 1CTP concentrations (P=0.037 and P=0.019, respectively), whereas no associations of P1NP and outcomes were observed.ConclusionsThe present study confirms that increased levels of 1CTP and P1NP concentrations are associated with presence of metastatic disease in the bone. Moreover, these markers are able to predict clinical course in PC patients with bone metastases. The potential use of these markers for treatment selection in advanced PC remains to be determined.     

N-terminal telopeptides of type I collagen and bone mineral density for early diagnosis of nonunion: An experimental study in rabbits

Background:The diagnosis and treatment of bone nonunion have been studied extensively. Diagnosis and treatment of nonunion are mainly performed based on the interpretation of clinico-radiographic findings, which depend on the clinician''s experience and the degree of bone callus formation during the fracture-healing process. However, resolution may be compromised when the bone mineral content is <25%. A feasible method of monitoring bone-healing is therefore needed. We monitored a rabbit model of bone nonunion by regular radiographic examinations, QCT detection, and biomarker concentrations.Results:BMD and NTX concentrations were significantly lower at 5 weeks postoperatively compared to the preoperative values and were significantly different between the two groups. OC showed no significant difference before and after surgery.Conclusions:BMD and NTX concentrations may be useful for early detection of bone nonunion in rabbits.     

Establishing a Reference Interval for Bone Turnover Markers in 637 Healthy,Young, Premenopausal Women From the United Kingdom,France, Belgium,and the United States

Robust reference intervals are needed for the interpretation of bone turnover markers in large phase III fracture trials. The objectives of the study were to (1) estimate reference intervals for serum bone alkaline phosphatase (bone ALP), serum procollagen type I N propeptide (PINP), serum β cross‐linked C‐telopeptides of type I collagen (S‐βCTX), and urinary cross‐linked N‐telopeptides of type I collagen (U‐NTX) in healthy young premenopausal women; (2) examine geographical differences on bone turnover markers; and (3) assess factors known to influence bone turnover and test whether these explain any regional differences. We studied 637 eligible women from four countries that participated in the Horizon‐PFT study (United Kingdom, France, Belgium, United States). The women were 30–39 yr of age (mean, 34.6 yr), with regular cyclic menses. Subjects completed a medical and lifestyle questionnaire. Two‐sided 95% reference intervals were estimated on transformed values and transformed back to the original scale using the proposed methodology of the International Federation of Clinical Chemistry. S‐βCTX was significantly higher in France relative to the United Kingdom (p = 0.01), and PINP was higher in France (p < 0.001) and Belgium (p = 0.02) relative to the United Kingdom and significantly higher in France relative to the United States (p < 0.01) by ANOVA. Overall, one could associate low bone turnover markers with nonsmoking, use of a contraceptive pill, exercise, being close to the time of ovulation, and having high 25‐hydroxyvitamin D levels. Countries differed by these characteristics, and once allowed for in the statistical model, any country differences were attenuated or removed.     

Comparison of serum levels of pyridinoline and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen as markers of bone resorption in patients receiving maintenance hemodialysis

Background Serum levels of pyridinoline, measured by high-performance liquid chromatography, and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), measured by a newly developed radioimmunoassay kit, were compared and analyzed to determine whether ICTP can replace pyridinoline as a marker of bone resorption in hemodialysis patients. Methods Thirty-five patients receiving maintenance hemodialysis were studied. Ten of the 35 patients were selected for an investigation of the kinetics of ICTP during hemodialysis treatment to compare with that of pyridinoline. Pyridinoline, ICTP, and other known bone metabolic markers were measured in all 35 patients immediately before hemodialysis. The correlation between pyridinoline and ICTP was analyzed by using relative amounts of these markers and the findings of bone resorption on a plain roentgenogram of the hands. Results The mean removal and recovery rates of ICTP were 25.3% and 103.4%, respectively. The correlation coefficient between pyridinoline and ICTP was 0.756 (P<0.001). Pyridinoline, but not ICTP, positively correlated with intact parathryroid hormone (iPTH) and osteocalcin. A higher correlation was shown between iPTH and pyridinoline than between iPTH and ICTP. ICTP was better correlated with lower levels of pyridinoline (r=0.651,P<0.005) than higher ones (r=0.230, not significant). A positive correlation was observed between pyridinoline and ICTP in patients without subperiosteal resorption. Conclusion ICTP is not superior to pyridinoline as a marker of bone resorption in hemodialysis patients, especially in those with a progressed state of bone resorption.     

The Use of Bone Markers in a 6-Week Study to Assess the Efficacy of Oral Clodronate in Patients with Metastatic Bone Disease

Biochemical markers of bone metabolism are strongly associated with skeletal complications in metastatic bone disease. The bisphosphonate clodronate reduces skeletal morbidity by inhibiting bone resorption. This study investigated the use of bone markers to assess the efficacy of oral clodronate across a range of clinically relevant doses. There were 125 patients with metastatic bone disease randomized to daily oral clodronate (800, 1,600, 2,400 and 3,200 mg) or placebo in a double-blind, multicenter study. Urinary N-terminal telopeptide of type I collagen (U-NTX), serum C-terminal telopeptide of type I collagen (S-CTX), urinary calcium (U-Ca), and bone alkaline phosphatase were measured weekly for a 6-week treatment period. Doses of ≥1,600 mg clodronate produced mean reductions of >40% in U-NTX, S-CTX and U-Ca, all significantly different from placebo (P = 0.0015, 0.001, 0.0036, respectively), after 6 weeks. Evaluation of least significant changes in markers suggested that the commonly used 1,600 mg dose was most appropriate for breast cancer patients. However, this dose was suboptimal for other (mainly prostate cancer) patients, who showed better response to 2,400 mg. The number of adverse events in the treatment arms was not significantly different from that in placebo, but a higher number of patients had diarrhea in the 3,200 mg arm and withdrew from the study. This trial is the first to explore the dose-response relationship of clodronate in oncology using specific markers of bone turnover. It has confirmed that the 1,600 mg dose is safe and effective for breast cancer patients but may be suboptimal for the other tumors studied.