Bone destruction and hypercalcemia in plasma cell myeloma.
Bone destruction and hypercalcemia in plasma cell myeloma.
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DOI：
10.5555/uri:pii:0093775486900059
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发表时间：
1986-09
影响因子：
4
通讯作者：
G. Mundy;D. Bertolini
中科院分区：
文献类型：
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作者：
G. Mundy;D. Bertolini
骨髓瘤几乎总是伴随着破坏性溶骨性骨损害的显著增加。骨髓瘤的骨破坏是这种疾病最令人痛苦的临床特征，包括顽固性骨痛，自发或轻微损伤后发生的骨折，以及伴随其伴随的症状和体征的高钙血症。80%的患者以骨痛为主要症状。骨骼损伤有几种模式。有时，患者会出现与孤立性浆细胞瘤相关的单发溶骨性病变。一些患者有弥漫性骨量减少，这类似于骨质疏松症的表现，是由于骨髓瘤细胞扩散到整个中轴骨骼。在大多数患者中，在骨髓瘤细胞沉积或巢的部位有多个离散的溶解病变。骨髓瘤的骨扫描显示几乎没有异常。同位素骨扫描是用标记的双膦酸盐进行的，这些双膦酸盐在矿物质沉积部位被摄取，并反映骨形成细胞活性增加。骨髓瘤的特点是分散的溶骨性病变，几乎不增加形成，这可能是骨髓瘤的骨扫描与乳腺癌的骨扫描不同的原因，乳腺癌的成骨细胞活性经常增加。同样，骨髓瘤患者的血清碱性磷酸酶通常不会升高，除非他们同时存在病理性骨折。碱性磷酸酶也反映了成骨细胞的活性。大多数现有证据表明，骨髓瘤的骨破坏机制主要是破骨细胞。这首先是在一项研究中提出的，在这项研究中，对37名骨髓瘤患者的尸检和活检样本进行了形态检查。在本组中，活跃的破骨细胞性骨吸收主要发生在骨髓瘤细胞浸润率超过20%的标本中。在骨髓瘤患者的骨标本中，很少或不含有骨髓瘤细胞，几乎没有破骨细胞活性或有活跃的骨吸收的证据。这表明骨髓瘤细胞引起破骨细胞活动，从而导致骨吸收增加。在后来的一项研究中，通过对118例骨髓瘤患者未脱钙的过渡骨活检，采用定量骨组织形态计量学技术证实了骨吸收表面破骨细胞增加与重度骨髓瘤细胞浸润区域之间的关联。3令人惊讶的是，平均骨小梁体积没有减少，但骨形成异常。远离重度骨髓瘤细胞浸润区的骨形成表面增加，但类骨缝厚度减少，钙化率降低。作者认为，在许多骨髓瘤患者中，单个成骨细胞的活性可能降低，这是后面这些发现的原因。进一步的证据表明，骨髓瘤的骨吸收机制主要是破骨细胞的，数据表明，作为破骨细胞活性的特异性抑制剂的药物，如双膦酸盐、米曲霉素和皮质类固醇，通常在降低骨髓瘤患者的血清钙方面非常有效。4，“16并非所有的工作人员都发现骨髓瘤的骨弹性吸收增加。谢克特等人在他们研究的患者中几乎没有发现破骨活性的证据。麦克唐纳等人认为，小鼠骨髓瘤细胞具有在体外直接破坏骨的能力，不依赖于破骨细胞，就像早先描述的人类乳腺癌细胞的类似方式。这种现象是否具有活体意义目前尚不清楚，在一些骨髓瘤、骨硬化患者中
M YELOMA is almost always associated with a marked increase in destructive osteolytic bone lesions. Bone destruction in myeloma is responsible for the most distressing clinical features of this disease, including intractable bone pain, fractures occurring either spontaneously or following trivial injury, and hypercalcemia with its attendant symptoms and signs. Eighty percent of patients present with bone pain as a predominant symptom.’ The bone lesions occur in several patterns. Occasionally, patients develop single osteolytic lesions that are associated with solitary plasmacytomas. Some patients have diffuse osteopenia, which mimics the appearance of osteoporosis, and is due to the myeloma cells being spread diffusely throughout the axial skeleton. In most patients there are multiple discrete lytic lesions occurring at the site of deposits or nests of myeloma cells. Bone scans in myeloma show very little abnormality. Isotopic bone scans are performed with labeled bisphosphonates that are taken up at sites of mineral deposition and reflect increased activity of bone forming cells. Myeloma is characterized by discrete lytic lesions with little increase in formation and this is probably the explanation for the difference in appearance between the bone scan in myeloma and the bone scan in breast cancer, where osteoblast activity is frequently increased. Similarly, serum alkaline phosphatase, which also reflects osteoblast activity, is usually not increased in patients with myeloma, unless they have coexistent pathological fractures. Most available evidence suggests that the mechanism of bone destruction in myeloma is primarily osteoclastic. This was first suggested in a study in which morphologic examination was performed on autopsy and biopsy samples of bone from a series of 37 patients with myeloma.’ In this series, active osteoclastic bone resorption was found predominantly in specimens that contained more than 20% marrow myeloma cell infiltration. In specimens of bone from myeloma patients that contained few or no myeloma cells, little osteoclast activity or evidence of active bone resorption was observed. This suggested that the myeloma cells caused the osteoclast activity that led to increased bone resorption. The association between increased osteoclasts on bone resorbing surfaces and areas of heavy myeloma cell infiltration was confirmed in a later study using the technique of quantitative bone histomorphometry on undecalcified transiliac bone biopsies from 118 patients with myeloma.3 Surprisingly, no decrease in mean trabecular bone volume was observed, but abnormalities were observed in bone formation. Bone forming surfaces were increased away from the areas of heavy myeloma cell infiltration but the osteoid seams were reduced in thickness and had a lowered calcification rate. The authors suggested that the activity of individual osteoblasts may be reduced in many patients with myeloma, accounting for these latter findings. Further evidence that the mechanism of bone resorption in myeloma is primarily osteoclastic is provided by data that show drugs that are specific inhibitors of osteoclast activity such as the bisphosphonates, mithramycin, and corticosteroids are usually very effective in lowering the serum calcium in patients with myeloma.4,“16 Not all workers have found increased osteoelastic resorption in myeloma. Schechter et al’ saw little evidence of osteoclastic activity in the patients they studied. MacDonald et al” suggested that murine myeloma cells had the capacity to destroy bone directly in vitro independent of osteoclasts, in a similar manner described earlier for human breast cancer cells.’ Whether this phenomenon has an in vivo significance is not currently known, In some patients with myeloma, osteosclerosis