Clemens M R, Fessele K, Heim M E
Eberhard-Karls-Universität Tübingen, Abteilung Innere Medizin II, Germany.
Ann Hematol. 1993 Mar;66(3):141-6. doi: 10.1007/BF01697625.
In 1989, a prospective randomized multicenter study was initiated in order to determine the safety and efficacy of oral clodronate in myeloma patients. The primary objective of this long-term trial is to evaluate whether supportive clodronate is able to prevent or retard the progression of bone disease and reduce the occurrence of characteristic complications: pain, pathologic fractures, and hypercalcemia. We now report first results as an interim analysis, including data obtained from 26 patients (total number of Tübingen patients n = 36) who entered the study at the Medizinische Universitätsklinik Tübingen. Patients were randomized to receive either chemotherapy alone (melphalan 15 mg/m2 i.v. on day 1 and prednisolone 60 mg/m2 orally on days 1-4 every 4 weeks (control group) or in combination with 1600 mg clodronate/day orally as a single dose for a period of at least 1 year. Repeated radiologic examinations in addition to hematologic and biochemical analysis were performed in order to evaluate the skeletal status with respect to lytic bone lesions and osteoporosis and the course of serum M protein and light chain excretion into urine. Clodronate treatment resulted in a significant decrease of serum calcium concentrations and of biochemical indices for bone resorption. No clodronate-related toxicity or hypocalcemia was observed. In patients treated with chemotherapy alone, this effect was less marked and discontinuous. Clodronate-treated patients developed fewer progressive bone lesions (significant for lytic, not for osteoporotic lesions). No hypercalcemic episodes occurred in the clodronate-treated patients, but there were six episodes in the control group. Whereas the number of vertebral fractures was evidently less is clodronate-treated patients, three of those patients suffered from multiple fractures of long bones and ribs. All together, 12 pathologic fractures occurred in five clodronate-treated patients, whereas in the control group 23 pathologic fractures occurred in the same number of patients during the whole observation period. The final analysis of all multicenter included patients should clarify these findings. There was a significant finding that clodronate proved to have an analgesic effect.
1989年，开展了一项前瞻性随机多中心研究，以确定口服氯膦酸盐在骨髓瘤患者中的安全性和有效性。这项长期试验的主要目的是评估辅助性氯膦酸盐是否能够预防或延缓骨病进展，并减少典型并发症的发生：疼痛、病理性骨折和高钙血症。我们现在报告首次结果作为中期分析，包括从图宾根大学医学临床中心入组该研究的26例患者（图宾根患者总数n = 36）获得的数据。患者被随机分为两组，一组仅接受化疗（美法仑15 mg/m²静脉注射，第1天给药，泼尼松龙60 mg/m²口服，第1 - 4天给药，每4周重复一次（对照组）），另一组在接受化疗的同时，联合口服1600 mg氯膦酸盐/天，单次给药，持续至少1年。除血液学和生化分析外，还进行了多次放射学检查，以评估溶骨性骨病变和骨质疏松的骨骼状况，以及血清M蛋白和轻链尿排泄的过程。氯膦酸盐治疗导致血清钙浓度和骨吸收生化指标显著降低。未观察到与氯膦酸盐相关的毒性或低钙血症。在仅接受化疗的患者中，这种效果不太明显且不持续。接受氯膦酸盐治疗的患者发生的进行性骨病变较少（溶骨性病变有显著差异，骨质疏松性病变无显著差异）。接受氯膦酸盐治疗的患者未发生高钙血症发作，但对照组有6次发作。虽然接受氯膦酸盐治疗的患者椎体骨折数量明显较少，但其中3例患者发生了长骨和肋骨多处骨折。在整个观察期内，5例接受氯膦酸盐治疗的患者共发生12例病理性骨折，而对照组相同数量的患者发生了23例病理性骨折。对所有多中心纳入患者的最终分析应能阐明这些发现。有一个重要发现是氯膦酸盐被证明具有镇痛作用。
