Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates
Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates
复制标题
DOI：
10.1359/jbmr.080205
复制
发表时间：
2008-06-01
影响因子：
6.2
通讯作者：
Hortobagyi, Gabriel N.
中科院分区：
文献类型：
--
作者：
Hoff, Ana O.;Toth, Bela B.;Hortobagyi, Gabriel N.
简介：颌骨骨坏死（ONJ）已报道患者接受双膦酸盐治疗。与这种疾病相关的发病率和危险因素尚未明确界定。材料和方法：我们对1996年至2004年间静脉注射双膦酸盐治疗的4019例患者进行了回顾性分析。我们的目标是估计频率，了解临床表现，并确定与ONJ发展相关的危险因素。结果：1338例乳腺癌患者中有16例（1.2%），548例多发性骨髓瘤患者中有13例（2.4%）发生ONJ。在ONJ患者中，帕米膦酸盐或唑来膦酸治疗的中位剂量和持续时间显著高于对照组（p < 0.0001）。多因素Cox比例风险回归分析发现，唑来膦酸治疗（风险比[HR]， 15.01; 95% CI: 2.41-93.48; p = 0.0037）、帕米膦酸治疗后再服用唑来膦酸（风险比[HR]， 4.00; 95% CI: 0.86-18.70; p = 0.078）和拔牙（风险比，53.19;95% CI: 18.20-155.46; p < 0.0001）是乳腺癌ONJ的显著风险。在多发性骨髓瘤中，拔牙（HR, 9.78; 95% CI: 3.07-31.14; p = 0.0001）和骨质疏松（HR, 6.11; 95% Cl: 1.56-23.98; p = 0.0095）是在控制双膦酸盐治疗的情况下的显著危险因素。29例患者中有13例随访时间中位数为17.1个月（范围7-67个月）；3例患者在此期间病变愈合。结论：ONJ是一种罕见但持久的疾病，主要发生在静脉注射双膦酸盐治疗的乳腺癌和多发性骨髓瘤患者中。高累积剂量的双膦酸盐、口腔健康状况不佳和拔牙可能是ONJ发生的重要危险因素。23%的保守治疗患者的ONJ得到缓解。
Introduction: Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The incidence and risk factors associated with this disorder have not been clearly defined.Materials and Methods: We conducted a retrospective analysis of 4019 patients treated with intravenous bisphosphonates between 1996 and 2004. Our goals were to estimate the frequency, understand the clinical presentation, and identify risk factors associated with ONJ development.Results: Sixteen of 1338 patients with breast cancer (1.2%) and 13 of 548 patients with multiple myeloma (2.4%) developed ONJ. The median dose and duration of treatment with pamidronate or zoledronic acid were significantly higher in patients with ONJ (p < 0.0001). Multivariate Cox proportional hazards regression analysis identified treatment with zoledronic acid (hazards ratio [HR], 15.01; 95 % CI: 2.41-93.48; p = 0.0037), treatment with pamidronate followed by zoledronic acid (HR, 4.00; 95 % CI: 0.86-18.70; p = 0.078), and dental extractions (HR, 53.19; 95% CI: 18.20-155.46; p < 0.0001) as significant risks for ONJ in breast cancer. In multiple myeloma, dental extractions (HR, 9.78; 95 % CI: 3.07-31.14; p = 0.0001) and osteoporosis (HR, 6.11; 95% Cl: 1.56-23.98; p = 0.0095) were significant risk factors while controlling for bisphosphonate therapy. Thirteen of 29 patients were followed for a median of 17.1 mo (range, 7-67 mo); lesions healed in 3 patients during this period.Conclusions: ONJ is an uncommon but long-lasting disorder that occurs mainly in breast cancer and multiple myeloma patients treated with intravenous bisphosphonates. High cumulative doses of bisphosphonates, poor oral health, and dental extractions may be significant risk factors for ONJ development. ONJ resolved in 23% of patients with conservative therapy.