O'Donnell Elizabeth K, Raje Noopur S
Harvard Medical School, Boston, Massachusetts.
Clin Adv Hematol Oncol. 2017 Apr;15(4):285-295.
Bone involvement manifesting as osteolytic bone disease (OBD) or osteopenia is one of the defining features of multiple myeloma (MM). Osteolytic lesions develop in nearly 90% of patients with MM, and these are frequently complicated by skeleton-related events (SREs) such as severe bone pain, pathologic fractures, vertebral collapse, hypercalcemia, and spinal cord compression. SREs have a negative effect on patients' quality of life and affect their long-term outcomes, including survival. In MM, the delicate balance between bone formation and bone destruction is perturbed. OBD is a consequence of increased osteoclast activation along with osteoblast inhibition, which alter bone remodeling. Although MM remains incurable, tremendous progress has been made in the treatment of the disease. As such, there is a need to address the symptoms of the disease that affect quality of life and, ultimately, overall survival. Novel agents targeting OBD are promising therapeutic strategies not only for the treatment of MM OBD but also for the treatment of MM itself. In addition to bisphosphonates, several novel agents are currently under investigation for their positive effect on bone remodeling via osteoclast inhibition or osteoblast stimulation. Future studies will look to combine or sequence all of these agents to improve quality of life, decrease the symptoms of MM OBD, and enhance antitumor activity.
表现为溶骨性骨病（OBD）或骨质减少的骨骼受累是多发性骨髓瘤（MM）的关键特征之一。近90%的MM患者会出现溶骨性病变，并且这些病变常并发骨骼相关事件（SREs），如严重骨痛、病理性骨折、椎体塌陷、高钙血症和脊髓压迫。SREs对患者的生活质量有负面影响，并影响其长期预后，包括生存。在MM中，骨形成与骨破坏之间的微妙平衡受到干扰。OBD是破骨细胞激活增加以及成骨细胞抑制的结果，这会改变骨重塑。尽管MM仍然无法治愈，但在该疾病的治疗方面已经取得了巨大进展。因此，有必要解决影响生活质量并最终影响总生存的疾病症状。靶向OBD的新型药物不仅是治疗MM OBD的有前景的治疗策略，也是治疗MM本身的有前景的治疗策略。除双膦酸盐外，目前正在研究几种新型药物，它们通过抑制破骨细胞或刺激成骨细胞对骨重塑具有积极作用。未来的研究将寻求联合使用或按顺序使用所有这些药物，以改善生活质量、减轻MM OBD的症状并增强抗肿瘤活性。
