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蛋白酶体抑制剂对骨髓瘤骨病患者血清骨代谢标志物的影响及临床意义

[The influence and clinical significance of proteasome inhibitor on serum bone metabolite markers in patients with myeloma bone disease].

作者信息

Ma R J, Yang S W, Yuan X L, Jiang L, Yang J, Wang Z, Zhang Y, Lei P C, Zhang L, Shang B J, Cheng L N, Zhu Z M

机构信息

Department of Hematology, Henan Provincial People's Hospital; Institute of Hematology, Henan Provincial People's Hospital, Henan Key Laboratory of Stem Cell Differnetiation and Modification, Zhengzhou 450003, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2020 Jul 14;100(26):2032-2035. doi: 10.3760/cma.j.cn112137-20200328-00988.

DOI:10.3760/cma.j.cn112137-20200328-00988
PMID:32654448
Abstract

To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide β(β-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、β-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, β-CTX and vitamin D3 were decreased significantly (0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (-1.871, 0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (-8.272, 0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, 0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, 0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,5.762, 0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) μg/L vs (15.6±5.5) μg/L, -2.478, 0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, 0.044). There was no significant difference in the serum concentration of TRACP-5b and β-CTX between two groups. After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, β-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.

摘要

探讨蛋白酶体抑制剂对骨髓瘤骨病(MBD)患者血清骨代谢标志物包括抗酒石酸酸性磷酸酶5b同工酶(TRACP-5b)、Ⅰ型胶原羧基末端肽β(β-CTX)、Ⅰ型前胶原氨基端延长肽(PINP)及维生素D3的影响及临床意义。选取2015年4月至2018年6月我院收治的68例新诊断MBD患者,采用基于蛋白酶体抑制剂的方案进行治疗。于治疗前及化疗4个周期、8个周期后检测血清TRACP-5b、β-CTX、PINP及维生素D3浓度,并观察影像学变化。化疗4个周期和8个周期后,血清TRACP-5b、β-CTX及维生素D3水平均显著下降(P<0.05)。化疗前PINP血清浓度为(78.1±44.9)ng/L,化疗4个周期后变为(94.5±56.1)ng/L,差异无统计学意义(t=-1.871,P=0.063);化疗8个周期后升至(173.3±80.5)ng/L,差异有统计学意义(t=-8.272,P=0.001)。所有患者中影像学分级≥3级者占66.2%,化疗4个周期后降至60.3%,差异无统计学意义(χ2=0.569,P=0.477);化疗8个周期后影像学分级≥3级者占比降至44.5%,显著低于治疗前(χ2=6.260,P=0.012)。化疗8个周期后,63例患者可评价疗效,其中50例有效,13例无效。有效组PINP血清浓度高于无效组((190.7±78.5)ng/L比(106.5±47.3)ng/L,t=5.762,P=0.001),有效组维生素D3血清浓度低于无效组((11.7±4.8)μg/L比(15.6±5.5)μg/L,t=-2.478,P=0.016)。有效组骨病≥3级患者比例也显著低于无效组(38.0%比69.2%,χ2=4.076,P=0.044)。两组TRACP-5b、β-CTX血清浓度差异无统计学意义。采用基于蛋白酶体抑制剂的方案治疗后,反映MBD患者破骨细胞活性的血清TRACP-5b、β-CTX及维生素D3浓度降低,提示成骨细胞活性的PINP血清浓度升高,骨病影像学分级降低。

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