蛋白酶体抑制剂对骨髓瘤骨病患者血清骨代谢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

目的探讨蛋白酶体抑制剂对骨髓瘤骨病(MBD)血清骨代谢物抗酒石酸酸性磷酸酶5b同工酶(TRACP-5b)、Ⅰ型胶原羧基端肽β特殊序列(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。方法自2015年4月至2018年6月在河南省人民医院新诊断的MBD患者68例,均给予以蛋白酶体抑制剂-硼替佐米为主的方案治疗,检测治疗前、治疗4个和8个疗程后患者血清TRACP-5b、β-CTX、PINP、维生素D3浓度及影像学变化。结果TRACP-5b、β-CTX和维生素D3在患者治疗4个(68例)和8个疗程(63例)后都较治疗前减低,差异均有统计学意义(P<0.05);PINP治疗前浓度为(78.1±44.9)ng/L,4个疗程后为(94.5±56.1)ng/L,两组比较差异无统计学意义(t=-1.871,P=0.063),8个疗程后升高至(173.3±80.5)ng/L,与治疗前比较差异有统计学意义(t=-8.272,P<0.001)。治疗前影像学骨病分级≥3级的患者比例为66.2%,4个疗程后降至60.3%,两者差异无统计学意义(χ^2=0.569,P=0.477);8个疗程后降至44.5%,与治疗前比较差异有统计学意义(χ^2=6.260,P=0.012)。8个疗程后,可评估患者63例,其中治疗有效者50例,无效者13例,有效组患者血清PINP浓度为(190.7±78.5)ng/L,高于无效组(106.5±47.3)ng/L(t=5.762,P<0.001),维生素D3浓度为(11.7±4.8)μg/L,低于无效组(15.6±5.5)μg/L(t=-2.478,P=0.016),骨病分级≥3级的患者比例为38.0%,也低于无效组的69.2%(χ^2=4.076,P=0.044),结果比较差异均有统计学意义,但两组血清TRACP-5b和β-CTX差异无统计学意义。结论以蛋白酶体抑制剂为主的方案治疗后,MBD患者血清中反映破骨细胞活性的TRACP-5b、β-CTX和维生素D3减低,反映成骨细胞活性的PINP升高,影像学骨病分级下降。

Objective 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 peptideβ(β-CTX),type I procollagen amino terminal prolongation peptide(PINP)and vitamin D3 in patients with myeloma bone disease(MBD).Methods 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.Results After 4 and 8 cycles of chemotherapy,serum levels of TRACP-5b,β-CTX and vitamin D3 were decreased significantly(P<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(t=-1.871,P=0.063).Moreover,it increased to(173.3±80.5)ng/L after 8 cycles of chemotherapy with significant difference(t=-8.272,P<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,P=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,P=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,t=5.762,P<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,t=-2.478,P=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,P=0.044).There was no significant difference in the serum concentration of TRACP-5b andβ-CTX between two groups.Conclusion 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.