Wilkinson Gregg S, Kuo Yong-Fang, Freeman Jean L, Goodwin James S
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1153, USA.
J Natl Cancer Inst. 2007 Jul 4;99(13):1016-24. doi: 10.1093/jnci/djm025. Epub 2007 Jun 27.
Recent reports have identified an association between osteonecrosis of the jaw or facial bones and treatment with nitrogen-containing intravenous bisphosphonates. We investigated this association by use of data from the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare claims.
We identified 16,073 cancer patients who were diagnosed between January 1, 1986, and December 31, 2002, and were treated intravenously with the bisphosphonates pamidronate and/or zoledronic acid between January 1, 1995, and December 31, 2003. We matched 28,698 bisphosphonate nonusers, at a 2:1 ratio, to 14,349 bisphosphonate users on month and year of the first bisphosphonate administration received by users, cancer type, age, sex, risk factors for osteonecrosis (diabetes, alcoholism, cigarette smoking, obesity, hyperlipemia, pancreatitis, or chemotherapy with L-asparaginase), bone metastasis, and SEER program geographic region. Patients were followed until the study's end on December 31, 2003; loss of coverage from Medicare Parts A and B; or one of the following outcomes: a diagnosis of inflammatory conditions or osteomyelitis of the jaw, surgery on the facial bones, or death, whichever occurred first.
Use of intravenous bisphosphonates was associated with an increased risk of jaw or facial bone surgery (hazard ratio [HR] = 3.15, 95% confidence interval [CI] = 1.86 to 5.32) and an increased risk of being diagnosed with inflammatory conditions or osteomyelitis of the jaw (HR = 11.48, 95% CI = 6.49 to 20.33), compared with nonuse. The absolute risk at 6 years for any jaw toxicity was 5.48 events per 100 patients using intravenous bisphosphonates and 0.30 events per 100 patients not using such drugs. The risk of each outcome increased as cumulative dose increased (e.g., for 4-8 infusions, HR for operations on the jaw and facial bones = 3.63, 95% CI = 0.77 to 17.08; for more than 21 infusions, HR = 9.18, 95% CI = 1.74 to 48.53).
Users of intravenous bisphosphonates had an increased risk of inflammatory conditions, osteomyelitis, and surgical procedures of the jaw and facial bones. The increased risk may reflect an increased risk for osteonecrosis of the jaw.
最近的报告已确定颌骨或面骨坏死与含氮静脉注射双膦酸盐治疗之间存在关联。我们通过使用与医疗保险索赔相关的监测、流行病学和最终结果（SEER）计划的数据来研究这种关联。
我们确定了16073例癌症患者，他们在1986年1月1日至2002年12月31日期间被诊断，并在1995年1月1日至2003年12月31日期间接受了双膦酸盐帕米膦酸和/或唑来膦酸的静脉注射治疗。我们按照2:1的比例，将28698例未使用双膦酸盐的患者与14349例使用双膦酸盐的患者进行匹配，匹配因素包括使用者首次接受双膦酸盐治疗的月份和年份、癌症类型、年龄、性别、骨坏死风险因素（糖尿病、酗酒、吸烟、肥胖、高脂血症、胰腺炎或L-天冬酰胺酶化疗）、骨转移以及SEER计划地理区域。对患者进行随访，直至2003年12月31日研究结束、医疗保险A部分和B部分的保险覆盖中断，或出现以下任何一种结果：颌骨炎症性疾病或骨髓炎的诊断、面骨手术或死亡，以先发生者为准。
与未使用者相比，静脉注射双膦酸盐与颌骨或面骨手术风险增加相关（风险比[HR]=3.15，95%置信区间[CI]=1.86至5.32），以及被诊断为颌骨炎症性疾病或骨髓炎的风险增加（HR=11.48，95%CI=6.49至20.33）。使用静脉注射双膦酸盐的患者每100例中6年时任何颌骨毒性的绝对风险为5.48例事件，未使用此类药物的患者每100例中为0.30例事件。随着累积剂量增加，每种结果的风险均增加（例如，对于4 - 8次输注，颌骨和面骨手术的HR=3.63，95%CI=0.77至17.08；对于超过21次输注，HR=9.18，95%CI=1.74至48.53）。
静脉注射双膦酸盐的使用者发生颌骨和面骨炎症性疾病、骨髓炎及手术的风险增加。风险增加可能反映颌骨坏死风险增加。
