硼替佐米对多发性骨髓瘤骨病的作用及其机制探讨

The effect and the mechanism of bortezomib on bone disease in patients with multiple myeloma

目的观察硼替佐米联合地塞米松方案(BD方案)对多发性骨髓瘤(MM)骨痛的疗效并初步探讨其作用机制。方法观察2006年10月至2009年4月中山大学附属第一医院血液科收治的59例接受BD方案和33例接受VADM方案(长春新碱、阿霉素、地塞米松与马法兰联合)的MM患者骨痛缓解、活动能力改善及骨事件发生情况;用酶联免疫吸附试验(ELISA)检测其中25例患者治疗前后抗酒石酸酸性磷酸酶(TRACP-5b)、骨碱性磷酸酶(BALP)及Wnt信号通路抑制因子DKK1的浓度。结果BD组在骨痛缓解率、活动能力改善和骨相关事件发生率方面均优于VADM组[分别为75.7%对50.0%,64.9%对20.8%和13.8%对57.8%(P均<0.05)]。与化疗前相比,BD组患者化疗后BALP浓度升高[(15.90±11.88)U/L对(48.98±47.07)U/L],TRACP-5b水平下降[(4.04±1.92)U/L对(2.22±1.53)U/L],DKK1水平下降[(19.08±11.78)μg/L对(9.78±5.14)μg/L],差异有统计学意义(P均<0.05)。结论BD方案对MM患者骨病有显著疗效;可促进骨髓瘤患者的成骨代谢,抑制破骨代谢。

Objective To study whether bortezomib combined with dexamethasone can relieve bone pain of patients with multiple myeloma and to see whether bortezomib have effect on bone metabolism through determining the concentration of bone turnover marks. Methods 59 cases of patients with multiple myeloma treated with BD and 38 cases of patients treated with VADM were observed before and after chemotherapy to compare the alleviation of bone pain, the improvement of the ability to move and the occurrence of skeletal related events between the two groups. The plasma from 25 patients were collected before and after chemotherapy when they were in hospital each time and the concentrations of TRACP-Sb, BALP and DKK1 in plasma were determined by ELISA. Results BD group was better than VADM group in the rate of alleviation of bone pain, the improvement of the ability to move and the incidence of skeletal related events（75.7% vs 50% ,64.9% vs 20. 8% and 13.8% vs 57. 8% ,all P 〈0. 05）. The level of BALP increased and the level of TRACP-5b and DKK1 decreased after the treatment in BD group. Conclusion Bortezomib can relive the bone pain of patients with multiple myeloma,improve the abili- ty to move and decrease the incidence of skeletal related events. Bortezomib can also promote the bone formation and inhibit the bone destruction.