Veterans Affairs Pittsburgh Healthcare System, Research and Development, Pittsburgh, Pennsylvania, USA.
Bone. 2011 Jan;48(1):135-40. doi: 10.1016/j.bone.2010.06.016. Epub 2010 Jun 19.
Multiple myeloma (MM) is the most frequent cancer to involve the skeleton and results in purely osteolytic lesions that rarely heal. MM bone disease is responsible for some of the most devastating complications of MM. The marrow microenvironment plays a key role in MM bone disease as well as in the initiation, expansion and chemoresistance of MM cells. How this microenvironment becomes so supportive of MM, and the contribution and interaction of the various components of the microenvironment to enhancing MM growth are only beginning to be understood. However, it is clear that suppression of osteoblast activity plays a key role in the bone destructive process as well as progression of the tumor burden in myeloma. The impairment of osteoblast activity in MM results primarily from blockade of osteogenic differentiation of mesenchymal progenitors to mature osteoblasts. MM patients have low to normal levels of bone formation markers, such as alkaline phosphatase and osteocalcin in the setting of increased bone resorption. In contrast, MM patients without bone lesions display balanced bone remodeling with increased osteoclastogenesis and normal or increased bone formation rates. Both soluble factors and cell-to-cell contact between MM cells and osteoblast progenitors are responsible for the suppression of osteoblast differentiation in MM. In this article, the mechanism responsible for osteoblast suppression will be reviewed, and the effects of novel bone anabolic agents on myeloma bone disease will be discussed.
多发性骨髓瘤（MM）是最常累及骨骼的癌症，导致纯溶骨性病变，很少愈合。MM 骨病是 MM 最具破坏性并发症的部分原因。骨髓微环境在 MM 骨病以及 MM 细胞的起始、扩增和化疗耐药中起关键作用。这种微环境如何变得如此有利于 MM，以及微环境的各个组成部分对增强 MM 生长的贡献和相互作用才刚刚开始被理解。然而，很明显，抑制成骨细胞活性在骨破坏过程以及骨髓瘤肿瘤负担的进展中起着关键作用。MM 中破骨细胞活性的损害主要是由于阻断间充质祖细胞向成熟成骨细胞的成骨分化。在骨吸收增加的情况下，MM 患者的碱性磷酸酶和骨钙素等骨形成标志物水平低至正常。相比之下，无骨病变的 MM 患者表现出平衡的骨重塑，破骨细胞生成增加，骨形成率正常或增加。MM 细胞和成骨细胞祖细胞之间的可溶性因子和细胞间接触都负责抑制 MM 中的成骨细胞分化。本文将回顾负责成骨细胞抑制的机制，并讨论新型骨合成代谢药物对 MM 骨病的影响。
