Saad Fred, Lipton Allan, Cook Richard, Chen Yin-Miao, Smith Matthew, Coleman Robert
Centre Hospitalier de l'Universite de Montreal, Hopital Notre-Dame, Montreal, Quebec, Canada.
Cancer. 2007 Oct 15;110(8):1860-7. doi: 10.1002/cncr.22991.
Data from randomized, controlled trials of zoledronic acid were retrospectively analyzed to assess the effect of pathologic fractures on survival in patients with malignant bone disease.
A Cox regression model was used to estimate the effect of fractures (time-dependent variable) on survival in patients with stage III multiple myeloma or bone metastases from solid tumors enrolled in 3 large trials. Patients were randomized to receive zoledronic acid, pamidronate, or placebo every 3-4 weeks for up to 24 months (prostate cancer, breast cancer, and multiple myeloma) or up to 21 months (lung and other solid tumors).
A total of 3049 patients with multiple myeloma (n = 513), breast (n = 1130), prostate (n = 640), or lung cancer or other solid tumors (n = 766) were included in this analysis. Patients with multiple myeloma had the highest fracture incidence (43%), followed by breast (35%), prostate (19%), and lung cancer (17%). In all tumor types except lung, pathologic fracture was associated with a significant increase in risk of death, and breast cancer patients had the greatest increased risk. After adjustment for baseline characteristics, including performance status and prior skeletal complications, breast cancer patients who developed a pathologic fracture on study had a significant 32% increased risk of death relative to patients without a fracture (hazard ratio = 1.32; P < .01); patients with multiple myeloma or prostate cancer had a >20% increased risk of death.
These results suggest that fractures are associated with increased risk of death in patients with malignant bone disease. Therefore, preventing fractures is an important goal of therapy.
对唑来膦酸随机对照试验的数据进行回顾性分析，以评估病理性骨折对恶性骨病患者生存的影响。
使用Cox回归模型估计骨折（时间依赖性变量）对参加3项大型试验的III期多发性骨髓瘤或实体瘤骨转移患者生存的影响。患者被随机分组，每3 - 4周接受唑来膦酸、帕米膦酸或安慰剂治疗，最长治疗24个月（前列腺癌、乳腺癌和多发性骨髓瘤）或最长21个月（肺癌和其他实体瘤）。
本分析共纳入3049例多发性骨髓瘤（n = 513）、乳腺癌（n = 1130）、前列腺癌（n = 640）或肺癌及其他实体瘤（n = 766）患者。多发性骨髓瘤患者骨折发生率最高（43%），其次是乳腺癌（35%）、前列腺癌（19%）和肺癌（17%）。除肺癌外，在所有肿瘤类型中，病理性骨折与死亡风险显著增加相关，乳腺癌患者死亡风险增加最大。在对包括体能状态和既往骨骼并发症等基线特征进行调整后，研究期间发生病理性骨折的乳腺癌患者相对于未发生骨折的患者死亡风险显著增加32%（风险比 = 1.32；P <.01）；多发性骨髓瘤或前列腺癌患者死亡风险增加>20%。
这些结果表明，骨折与恶性骨病患者死亡风险增加相关。因此，预防骨折是治疗的一个重要目标。
