Lahtinen R, Laakso M, Palva I, Virkkunen P, Elomaa I
Department of Medicine, Kuopio University Hospital, Finland.
Lancet. 1992 Oct 31;340(8827):1049-52. doi: 10.1016/0140-6736(92)93075-x.
Osteolytic lesions and pathological fractures are common in multiple myeloma. Because clodronate inhibits osteoclastic resorption, we did a randomised, controlled trial in 350 patients from 23 hospitals. All patients received standard melphalan-prednisolone, and were randomised to receive clodronate 2.4 g daily or placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group (n = 168 at baseline) than in the clodronate group (n = 168 at baseline) in an intention-to-treat analysis (24 vs 12%, p = 0.026). Progression of vertebral fractures was lower in the clodronate group, but the difference was not significant (30 vs 40%). Serum calcium and urinary calcium excretion decreased significantly in both groups, but the changes were greater in the clodronate group. The percentage of patients feeling no pain increased more in the clodronate group (from 24 to 54%, p < 0.001) than in the placebo group (from 29 to 44%, p < 0.01). Side-effects were similar in both groups. We conclude that clodronate is an effective and safe adjunct in the management of multiple myeloma. The drug delays osteolytic bone lesions, reduces the degree of hypercalcaemia and hypercalciuria, and decreases pain.
溶骨性病变和病理性骨折在多发性骨髓瘤中很常见。由于氯膦酸盐可抑制破骨细胞的吸收，我们在来自23家医院的350例患者中进行了一项随机对照试验。所有患者均接受标准的美法仑-泼尼松治疗，并被随机分为两组，一组每天接受2.4 g氯膦酸盐治疗，另一组接受安慰剂治疗，为期24个月。在意向性分析中，安慰剂组（基线时n = 168）溶骨性骨病变进展患者的比例是氯膦酸盐组（基线时n = 168）的两倍（24% 对12%，p = 0.026）。氯膦酸盐组椎体骨折的进展较低，但差异不显著（30% 对40%）。两组患者的血清钙和尿钙排泄均显著下降，但氯膦酸盐组的变化更大。氯膦酸盐组感觉无痛的患者百分比增加幅度大于安慰剂组（从24% 增至54%，p < 0.001）（从29% 增至44%，p < 0.01）。两组的副作用相似。我们得出结论，氯膦酸盐是治疗多发性骨髓瘤有效且安全的辅助药物。该药可延缓溶骨性骨病变，降低高钙血症和高钙尿症的程度，并减轻疼痛。
