Eom Ki-Seong, Kim Seok Jin, Lee Je-Jung, Suh Cheolwon, Kim Jin Seok, Yoon Sung-Soo, Kim Byung Soo, Kang Hye Jin, Choi Young Jin, Kim Chul Soo, Kim Yang Soo, Kwak Jae-Yong, Kim Yoo Jin, Joo Young Don, Mun Yeung-Chul, Jo Deog Yeon, Park Joon Seong, Park Chi-Young, Kim Sung-Hyun, Min Chang-Ki
Division of Hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Republic of Korea.
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
Biomed Res Int. 2014;2014:245247. doi: 10.1155/2014/245247. Epub 2014 Jun 23.
We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n = 89). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.
我们开展了一项前瞻性多中心研究,通过骨转换标志物确定硼替佐米对复发或难治性浆细胞骨髓瘤(PCM)患者骨吸收和骨形成的作用。共有104例患者接受了至少1个周期的硼替佐米治疗。其中大多数患者病情已进展(n = 89)。其中,75例患者完成了4个周期的治疗。大多数患者(81.7%)接受了与类固醇联合的治疗。在第4周期治疗后,75例患者中有47例达到完全缓解(CR)、严格意义上的完全缓解(nCR)、非常好的部分缓解(VGPR)和部分缓解(PR)(64.4%),而26例患者缓解程度低于PR(35.6%)。随着患者接受更多治疗周期,达到≥PR的患者比例增加,在第8周期后达到90%。治疗后DKK-1水平显著下降。骨形成标志物(骨碱性磷酸酶和骨钙素)以及破骨细胞调节因子如可溶性核因子κB受体活化因子配体(sRANKL)也显著下降。这些发现主要在接受类固醇治疗且病程较长的患者中观察到。虽然治疗后sRANKL显著降低,但骨保护素(OPG)水平在治疗后没有显著变化,导致sRANKL/OPG比值降低(P = 0.037)。总之,我们的临床数据表明,硼替佐米和类固醇治疗可能会重新调整PCM中破骨细胞与成骨细胞活性之间的代谢平衡。