University of Newcastle, Newcastle-upon-Tyne, UK.
Br J Haematol. 2014 Jul;166(1):109-17. doi: 10.1111/bjh.12861. Epub 2014 Mar 27.
Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long-term follow-up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21-28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5.9-year median follow-up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5.2% vs. CLO 5.8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3.7% vs. CLO 0.5%; P < 0.0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23.7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.
双膦酸盐推荐用于多发性骨髓瘤继发溶骨性病变的患者。我们报告了 Medical Research Council Myeloma IX 研究中双膦酸盐治疗的安全性，该研究进行了长期随访。新诊断的多发性骨髓瘤患者被随机分配至唑来膦酸（ZOL；4 mg 静脉注射，每 21-28 天 1 次）或氯膦酸（CLO；1600 mg/d 口服）联合化疗。在 1960 例患者（中位随访 5.9 年）中，两种双膦酸盐均具有良好的耐受性。两组急性肾衰竭事件相似（ZOL 组 2 年时为 5.2%，CLO 组为 5.8%；此后发生率趋于平稳）。确诊的颌骨骨坏死（ONJ）总发生率较低，但 ZOL 组更高（ZOL 组为 3.7%，CLO 组为 0.5%；P<0.0001）。ONJ 事件通常为低级别，大多数发生在 8 至 30 个月（ONJ 中位时间为 23.7 个月）。在 10 例有 ONJ 恢复数据的患者中，ZOL 组的 4 例患者完全恢复，2 例患者改善，3 例患者无改善；CLO 组的 1 例患者无改善。ZOL 组的 6 例患者在发生 ONJ 前均进行了牙科手术或外伤。ZOL 和 CLO 的肾脏不良事件发生率相似。ONJ 发生率仍然较低，CLO 组低于 ZOL 组。迄今为止，我们未再见到新的 ONJ 病例。
