Badros Ashraf, Terpos Evangelos, Katodritou Eirini, Goloubeva Olga, Kastritis Efstathios, Verrou Evgenia, Zervas Kostas, Baer Maria R, Meiller Timothy, Dimopoulos Meletios A
University of Maryland, Greenebaum Cancer Center, 22 South Greene St, Baltimore, MD 21201, USA.
J Clin Oncol. 2008 Dec 20;26(36):5904-9. doi: 10.1200/JCO.2008.16.9300. Epub 2008 Nov 17.
To evaluate the natural history of bisphosphonate-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma.
Ninety-seven patients with myeloma from the United States (n = 37) and Greece (n = 60) were observed prospectively for a minimum 3.2 years after ONJ. Patients characteristics were similar with regard to age, bisphosphonate use, and myeloma therapy, except more autologous transplantations were performed on patients in the United States than in Greece (73% v 28%; P < .0001).
ONJ resolved in 60 patients (62%), resolved and recurred in 12 patients (12%), and did not heal in 25 patients (26%). Dental procedures preceded ONJ in 46 patients (47%) and were more common in those with single episodes (35 of 60, 58%) than recurrent or nonhealing (11 of 37, 30%; P = .007). Recurrent ONJ followed reinitiation of bisphosphonates in six of 12 patients. Greek patients had more bone pain than United States patients (60% v 30%, P = .001) and were less likely to restart bisphosphonates (5% v 35%, P < .0002). Myeloma relapses were more common in patients with recurrent/nonhealing than single-episode ONJ (84% v 62%; P = .02). Median overall survival from myeloma diagnosis was 10.8 years (95% CI; 9.3 years to not reached) and did not differ between patients with single, recurrent, and nonhealing ONJ (P = .2).
ONJ healed in 75% of patients. Patients with spontaneous ONJ have a higher risk of nonhealing and recurrence. Reinitiating bisphosphonates after healing of ONJ is a reasonable option in patients experiencing relapse who are at risk of skeletal complications. Further studies of the pathogenesis and healing of ONJ are needed.
评估多发性骨髓瘤患者双膦酸盐相关颌骨坏死（ONJ）的自然病程。
对来自美国（n = 37）和希腊（n = 60）的97例骨髓瘤患者在发生ONJ后进行了至少3.2年的前瞻性观察。患者在年龄、双膦酸盐使用和骨髓瘤治疗方面的特征相似，但美国患者接受自体移植的比例高于希腊患者（73%对28%；P <.0001）。
60例患者（62%）的ONJ得到缓解，12例患者（12%）缓解后复发，25例患者（26%）未愈合。46例患者（47%）在ONJ发生前接受过牙科治疗，且在单发患者中更常见（60例中的35例，58%），高于复发或未愈合患者（37例中的11例，30%；P =.007）。12例复发ONJ患者中有6例在重新开始使用双膦酸盐后复发。希腊患者比美国患者有更多的骨痛（60%对30%，P =.001），且重新开始使用双膦酸盐的可能性更小（5%对35%，P <.0002）。复发/未愈合ONJ患者的骨髓瘤复发比单发ONJ患者更常见（84%对62%；P =.02）。骨髓瘤诊断后的中位总生存期为10.8年（95%CI；9.3年至未达到），单发、复发和未愈合ONJ患者之间无差异（P =.2）。
75%的患者ONJ愈合。自发性ONJ患者不愈合和复发的风险更高。ONJ愈合后重新开始使用双膦酸盐对于有骨骼并发症风险且出现复发的患者是一个合理的选择。需要对ONJ的发病机制和愈合进行进一步研究。
