The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD. The current study involved 74 subjects (41 NDMM patients, 33 controls). MBD was assessed by whole-body low-dose computed tomography. sRANKL, periostin, and osteopontin were assayed by commercial ELISA kits. At diagnosis, all tested parameters were significantly higher in NDMM patients compared to the controls (p< 0.0001), correlating with disease stage, MBD grade, and BM infiltration by MPCs. During therapy, the serum levels of all tested proteins decrease, most prominently after autologous stem cell transplantation (p< 0.0001). A significant reduction was established in patients achieving complete and very-good partial response compared to all others (p< 0.05). In conclusion, sRANKL, periostin, and osteopontin reflect MBD severity and could be promising markers for MBD monitoring and the effect of myeloma treatment.
多发性骨髓瘤的标志性特征是骨髓瘤相关骨病。骨髓瘤浆细胞、基质细胞与骨髓微环境之间的相互作用在骨髓瘤骨病的发病机制中起关键作用。骨重塑过程严重失调，破骨细胞活性占主导地位。本研究旨在评估新诊断多发性骨髓瘤患者初诊及治疗过程中作为破骨细胞激活因子的可溶性核因子κB受体活化因子配体、骨膜蛋白和骨桥蛋白的循环水平，分析其与临床及实验室数据的相关性，并评估其作为骨髓瘤骨病评估附加生物标志物的潜力。本研究纳入74名受试者（41例新诊断多发性骨髓瘤患者，33例对照）。通过全身低剂量计算机断层扫描评估骨髓瘤骨病。采用商业ELISA试剂盒检测可溶性核因子κB受体活化因子配体、骨膜蛋白和骨桥蛋白。初诊时，新诊断多发性骨髓瘤患者所有检测参数均显著高于对照组（p<0.0001），且与疾病分期、骨髓瘤骨病分级及骨髓瘤浆细胞骨髓浸润程度相关。治疗期间所有检测蛋白的血清水平均下降，自体干细胞移植后下降最为显著（p<0.0001）。与未达标的患者相比，达到完全缓解和非常好的部分缓解的患者血清蛋白水平显著降低（p<0.05）。综上所述，可溶性核因子κB受体活化因子配体、骨膜蛋白和骨桥蛋白可反映骨髓瘤骨病严重程度，有望成为监测骨髓瘤骨病及评估骨髓瘤治疗效果的重要标志物。
肿瘤(癌症)患者之家