Bataille R, Chappard D, Basle M F
Laboratoire d'Hematologie, Institut de Biologie, Nantes, France.
Blood. 1996 Jun 1;87(11):4762-9.
To determine if excessive osteoclastic-mediated bone resorption (BR) is an early tumor-induced event in multiple myeloma (MM), BR was assessed at first presentation on quantitative bone biopsy in 87 individuals evaluated for monoclonal gammopathy of undetermined significance (MGUS) and reinterpreted according to the presenting features and subsequent follow-up evaluation. As a reference population, 48 patients with previously untreated overt MM were evaluated under similar conditions. The median level of BR was significantly higher in 48 overt MM versus 87 MGUS patients (12.2% v 5.1% [normal level, <6%], P <.01). Actually, 93% of overt MM patients had an excessive BR versus 45% of MGUS patients at presentation (P <.01) According to simple presenting parameters (> or <5% plasma cells within the bone marrow, presence or absence of mild anemia/neutropenia), 31 individuals were classified as low-risk MGUS, 32 high-risk MGUS, and 24 indolent MM. An excessive BR was observed in 16% of low-risk MGUS, 46% of high-risk MGUS (P <.01 v low-risk MGUS), 79% of indolent MM (P <.05 v high-risk MGUS), and 93% of overt MM patients. Of major interest, the level of BR in indolent MM (11.2%) was identical to that in overt MM (12.2%) but significantly higher than in both low-risk (4%, P <.01) and high-risk (5.6%, P <.01) MGUS. When considering the follow-up evaluation of MGUS patients, an excessive BR at presentation was observed in 52% of MGUS cases that turned out to be unstable or developed subsequent MM, but in only 4% of stable MGUS (P <.01). More precisely the level of BR of low-risk MGUS that either turned out to be unstable or that developed into MM was significantly higher at presentation than that of subsequent stable MGUS (4.4% v 2.9%, P <.05). The same difference was observed in both high-risk MGUS and indolent MM according to subsequent follow-up studies (8.1% v 3.4% and 11.7% v 6%, respectively, P <.05). Of major interest, the level of BR in 11 stable high-risk MGUS cases actually fulfilling the diagnostic criteria of smoldering MM was very low (3.4%) and similar to that in stable low-risk MGUS (2.9%). We conclude that a quantifiable excess of BR in MGUS is significantly associated with progression and thus is an early symptom of malignancy in these individuals.
为了确定破骨细胞介导的过度骨吸收（BR）是否是多发性骨髓瘤（MM）中早期肿瘤诱导的事件，我们对87例意义未明的单克隆丙种球蛋白病（MGUS）患者进行了首次定量骨活检，评估其BR情况，并根据其临床表现和后续随访评估重新解读。作为对照人群，我们在相似条件下评估了48例未经治疗的显性MM患者。48例显性MM患者的BR中位数水平显著高于87例MGUS患者（12.2%对5.1%[正常水平，<6%]，P<.01）。实际上，93%的显性MM患者在初诊时存在过度BR，而MGUS患者为45%（P<.01）。根据简单的临床表现参数（骨髓内浆细胞>或<5%，是否存在轻度贫血/中性粒细胞减少），31例个体被分类为低风险MGUS，32例为高风险MGUS，24例为惰性MM。低风险MGUS患者中16%、高风险MGUS患者中46%（与低风险MGUS相比P<.01）、惰性MM患者中79%（与高风险MGUS相比P<.05）以及显性MM患者中93%观察到过度BR。最值得关注的是，惰性MM患者的BR水平（11.2%）与显性MM患者（12.2%）相同，但显著高于低风险（4%，P<.01）和高风险（5.6%，P<.01）MGUS患者。考虑MGUS患者的随访评估时，在最终被证明不稳定或发展为后续MM的MGUS病例中，52%在初诊时存在过度BR，但稳定MGUS患者中仅4%（P<.01）。更确切地说，最终被证明不稳定或发展为MM的低风险MGUS患者初诊时的BR水平显著高于后续稳定的MGUS患者（4.4%对2.9%，P<.05）。根据后续随访研究，高风险MGUS和惰性MM也观察到同样的差异（分别为8.1%对3.4%和11.7%对6%，P<.05）。最值得关注的是，11例实际上符合冒烟型MM诊断标准的稳定高风险MGUS病例的BR水平非常低（3.4%），与稳定低风险MGUS患者相似（2.9%）。我们得出结论，MGUS中可量化的BR过量与疾病进展显著相关，因此是这些个体恶性肿瘤的早期症状。
