Tartrate-resistant acid phosphatase 5b is a potential biomarker for rheumatoid arthritis： a pilot study in Han Chinese

Background Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis （RA） chronic disability.Serum tartrate-resistant acid phosphatase 5b （TRACP-5b） is secreted by osteoclasts,its activity can be used as a clinically relevant bone resorption marker.The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy.Methods Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin （RhCTLA4-lg）,infliximab or methotrexate （MTX）.The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks.Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay （ELISA） at 0,12 and 24 weeks.Hand X-rays were obtained at baseline.Results At baseline,the levels of TRACP-5b correlated with the severity of X-ray damage,disease duration （r=0.332,P=0.012）,and tender joint count （r=0.408,P=0.002）.The 24 weeks values of TRACP-5b for RhCTLA4-lg group and infliximab group differed significantly from the baseline values in each group （P 〈0.05; P 〈0.05）,whereas only the value for RhCTLA4-lg group differed significantly from the 24 weeks value for the MTX group （P 〈0.01）.Considering the two biologics-treated groups together,the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level （P 〈0.05）.Conclusions Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity,treatment with certain biologics,and degree of response to therapy.TRACP-5b should be investigated further as a potential biomarker to predict response to therapy,including slowing of radiographic progression.

中医健脾单元疗法对强直性脊柱炎患者疗效及BGP、TRACP的影响

目的探讨中医健脾单元疗法对强直性脊柱炎(Ankylosing Spondylitis,AS)患者疗效及对血清骨钙素(bone gla protein,BGP)、抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRACP)的影响。方法按随机数字表将60例强直性脊柱炎患者分成治疗组(34例)和对照组(26例),治疗组采用中医健脾单元疗法,即新风胶囊+中医辨证论治+中药熏蒸治疗,对照组采用柳氮磺嘧啶(SASP)+中医辨证论治+中药熏蒸治疗。比较两组患者疗效、治疗前后生活质量、症状体征、急性时相反应物指标及对血清BGP、TRACP等指标变化。结果①中医证候疗效评价结果示两组总有效率与显效率比较,差异有统计学意义(P<0.05)。②两组患者治疗后生活质量总积分、焦虑自评量表(SAS)、抑郁自评量表(SDS)、疼痛严重性评估(VAS)、疾病活动指数(BASDAI)、躯体功能指数BASFI)、整体指数(BAS-G)、中医证候积分、超敏C反应蛋白(hs-CRP)、α酸性糖蛋白(α-AGP)与治疗前比较,差异均有统计学意义(P<0.01);治疗组治疗后血沉(ESR)与治疗前比较,差异有统计学意义(P<0.01);治疗后组间比较,两组生活质量总积分、SAS、SDS、VAS、BASDAI、BASFI、BAS-G、中医证候积分差异均有统计学意义(P<0.01)。③治疗后两组患者血清BGP及TRACP与治疗前比较,差异均有统计学意义(P<0.01),治疗后组间比较,差异亦有统计学意义(P<0.01)。结论中医健脾单元疗法能够提高AS患者的生活质量,改善临床症状体征、焦虑抑郁情绪及实验室指标,疗效优于对照组,其机制可能是通过上调BGP、下调TRACP,改善骨代谢水平,降低组织炎症反应,从而改善全身症状。

The evaluation of Tracp5b as a marker for monitoring treatment results of bone metastasis in breast cancer patients

Objective ：To evaluate the sensitivity of serum tartrate-resistant acid phosphatase 5b（Tracp5b） activity in monitoring bisphosphonate treatment results of bone metastasis in breast cancer（BC） patients. Methods：The serum activities of Tracp5b, CEA, CA153 were measured in 58 BC patients, including 26 without bone metastasis, 32 with bone metastasis. The serum activities of TracpSb, CEA, CA153 were also measured in 19 patients with bone metastasis after 3 months of bisphosphonate treatment. Eighteen healthy women with age from 34 to 70 served as control. Results：Serum TracpSb was significantly elevated in patients with bone metastasis compared with that in all any other groups（P〈 0.05）. The sensitivity of TracpSb was 78.13% and the specificity was 86.36%. The sensitivity of CA153 was 37.50% and the specificity was 77.27%. The sensitivity of CEA was 21.88% and the specificity was 84.09%. The serum activity of TracpSb decreased significantly（P 〈 0.05） after 3 months of bisphosphonate treatment, while the levels of CA153 and CEA were unchanged. Conclusion：Serum Tracp5b activity is a useful diagnostic marker for bone metastasis in BC patients and can be used to evaluate the treatment results of bisphosphonate.

第二代骨吸收生化标志物——血清抗酒石酸酸性磷酸酶5b的临床研究

目的 对血清TRACP5b作为骨吸收生化标志物进行临床研究。方法 利用BoneTRAP试剂盒 ,对 473例正常及骨质疏松患者血清做TRACP5b检测及分析。结果 男性和女性 ,随年龄的增加 ,特别是男性更年期及女性绝经期后 ,血清TRACP5b水平均不断升高 ,表明骨吸收增强 ;当患有骨质疏松后 ,血清中TRACP5b的水平高于同龄人 ,且男性及女性骨质疏松患者血清TRACP5b水平均高于正常人 ,统计学提示有显著性差异。

中医不同治法对骨质疏松症大鼠抗酒石酸酸性磷酸酶含量影响的比较研究

目的观察中医不同治法对糖皮质激素诱导骨质疏松症大鼠骨抗酒石酸酸性磷酸酶含量的影响,探讨中医防治骨质疏松症的作用机制。方法将120只雌雄各半的大鼠随机分为正常对照组、模型对照组、补肾中药组、健脾中药组、活血化瘀中药组和骨疏康中药组6个组,用地塞米松肌注造模。实验结束后,腹主动脉取血处死大鼠,用酶联免疫法检测各组大鼠血清抗酒石酸酸性磷酸酶的含量。结果与正常组比较,模型组大鼠血清TRACP含量升高极为显著(P<0.01);与模型组比较,各治疗组大鼠血清TRACP含量均明显降低,其中以补肾组和骨疏康组降低最为明显,与其他各组比较具有极显著差异(P<0.01)。结论补肾方法通过降低抗酒石酸酸性磷酸酶含量对骨质疏松症具有一定的防治作用。

中国老年学学会骨质疏松委员会骨代谢生化指标临床应用专家共识

骨代谢生化指标包括:钙磷代谢调节指标、骨吸收标志物、骨形成标志物。骨代谢生化指标分别来源于骨、软骨、软组织、皮肤、肝、肾、小肠、血液及内分泌腺体等,是由成骨细胞或破骨细胞分泌的酶和激素,以及骨基质的胶原蛋白代谢产物或非胶原蛋白。骨代谢生化指标可及时反映骨转换状态,灵敏度高、特异性强,用于骨质疏松诊断分型、预测骨折风险、抗骨质疏松治疗疗效评价,以及代谢性骨病的鉴别诊断。并且在骨质疏松发病机制、骨质疏松药物的研究及流行病学研究方面具有重要临床意义。随着骨代谢生化指标检测技术逐渐成熟,临床应用日趋广泛,但不同来源的标本、不同方法、不同设备、不同试剂、人的不同年龄段、不同种族和不同性别等,检测结果存在差异。至今,骨代谢生化指标测定国内外尚无统一检测标准;为此,将骨代谢生化指标的生物学作用及临床意义、技术应用与质量控制,分别整理、凝炼成一篇为各位同仁可读、可用、可参考的文字材料。期待通过"共识"为推动临床骨代谢生化指标检测技术的提高,规范检测流程,建立科学的参考范围,使骨代谢生化指标在骨质疏松规范诊断、规范治疗、抗骨质疏松药物疗效评价及科研工作中发挥重要作用。

Effects of the Drug(BSZGC)-containing Serum on Proliferation of Rat's Osteoclasts and TRACP Activity in vitro

Objective： To observe effects of the drug-containing serum ofBu Shen Zhuang Gu Capsule （BSZGC 补肾壮骨胶囊 Capsule for Tonifying the Kidney to Strengthen the Bones） on proliferation of the rat＇s osteoclasts and tartrate-resistant acid phosphatase （TRACP） activity in vitro so as to delve into the mechanisms of its preventive and therapeutic actions on osteoporosis. Methods： Forty female Sprague-Dawley rats aged three months were randomly divided into high dosage BSZGC group, medium dosage BSZGC group, low dosage BSZGC group, and the control group. BSZGC was orally administered into the rats of high, medium, and low dosage groups at different dosages for 12 days, and isometric normal saline was orally administered to the rats of the control group. The drug-containing serum and control serum were prepared. Osteoclasts isolated mechanically from the femur and tibia of Sprague-Dawley rats aged one week were cultured with medium added with different drug-containing sera and control serum. The growth of osteoclasts was observed under an inverted phase-contrast microscope, and optic density （OD） value of osteoclasts was determined by MTT colorimetric assay. TRACP activity was measured by the diazol method. Results： OD value of osteoclasts in the high dosage drug-containing serum group, medium dosage drug-containing serum group, and low dosage drug-containing serum group was significantly lower than that in the control serum group （P〈0.05） with a dose-effect correlation. TRACP activity in high dosage drug-containing serum group, medium dosage drug-containing serum group, low dosage drug-containing serum group was significantly lower than that of the control serum group （P〈0.01）, and no significant differences in TRACP activity were not found among the different dosages drug-containing serum groups. Conclusions： BSZGC can inhibit the proliferation of the osteoclasts and reduce TRACP activity, which may be one of the mechanisms of its preventive and theraoeutic actions on osteooorosis.

补肾益气活血方对去势大鼠Wnt7b/β-catenin信号通路的调控机制

目的:基于Wnt7b/β-catenin信号通路研究补肾益气活血方对绝经后骨质疏松症大鼠股骨的作用及影响。方法:将90只雌性SD大鼠随机分成正常组,模空组,补肾益气活血方高、低剂量组和福善美组,每组18只。除正常组外,其余各组大鼠采用一次性摘除大鼠双侧卵巢法建立骨质疏松症动物模型,正常组、模空组大鼠给予0.9%氯化钠溶液灌胃,其余各组给予相应药物灌胃,共灌胃12周后,取材。采用双能X线吸收测量法(DAX)检测股骨骨密度;采用ELISA法检测血清ALP、TRACP水平以及股骨Wnt7b、Axin2、Runx2蛋白表达水平;采用qRTPCR法检测股骨Wnt7b、Axin2、Runx2 mRNA表达水平。结果:与模空组比较,补肾益气活血方高、低剂量组能够增加股骨骨密度(P<0.01),下调血清ALP和TRACP水平(P<0.01),补肾益气活血方高剂量组能够上调Wnt7b/β-catenin信号通路Wnt7b、Axin2和Runx2 mRNA及蛋白表达(P<0.05,P<0.01),补肾益气活血方低剂量组能够上调Wnt7b、Axin2蛋白表达(P<0.01)。结论:补肾益气活血方可以通过上调Wnt7b/β-catenin信号通路以促进成骨分化来防治绝经后骨质疏松症。

骨代谢生化指标测定在老年人骨质疏松症中的应用

目的探讨骨代谢生化指标测定在老年人骨质疏松症中的应用。方法采用酶联免疫吸附法(ELISA)测定抗酒石酸酸性磷酸酶-5b(TRACP-5b)、骨特异性碱性磷酸酶(BALP)和骨钙素N端中分子片段(N-MID);用化学发光免疫法定量测定25-羟维生素D3[25-(OH)-VD3]。结果骨质疏松女性组除TRACP和25-(OH)-VD3外,N-MID与对照女性组有明显的降低(P<0.05),而BALP与对照女性组有明显的升高(P<0.05)。骨质疏松男性组除25-(OH)-VD3外,N-MID与对照男性组的有明显的降低(P<0.05),而TRACP和BALP与对照男性组的均有明显的升高(P<0.05)。结论测定血清中的TRACP-5b、BALP、N-MID可在一定范围内了解体内骨代谢情况,并可作为骨质疏松症的检测指标。