Ripamonti C I, Maniezzo M, Boldini S, Pessi M A, Mariani L, Cislaghi E
Supportive Care in Cancer Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Italy.
Dental Team, Fondazione IRCCS, Istituto Nazionale dei Tumori, Italy.
J Bone Oncol. 2012 Sep 24;1(3):81-7. doi: 10.1016/j.jbo.2012.08.001. eCollection 2012 Dec.
Osteonecrosis of the Jaw (ONJ) is an adverse event reported especially in patients receiving cancer treatments regimen, bisphosphonates (BPs), and denosumab. We performed an open-label, prospective study in patients treated with zoledronic acid who developed ONJ lesions >2.5 cm, and had no benefit after the treatment with the standard therapy, to evaluate the efficacy and tolerability of medical ozone (O3) treatment delivered as gas insufflations on each ONJ lesions. Twenty-four patients (mean age 62.5, range 41-80; 12 female) with bone metastases due to breast (11), prostate (4)and lung (4)cancers, myeloma (2), or osteoporosis (3), previously treated with zoledronic acid and not underwent dental preventive measures and with ONJ lesions >2.5 cm, were observed and treated with topical O3 gas insufflation every third day for a minimum of 10 for each pathological area or till necrotic bone sequestrum or surgery. We used a special insufflation bell-shaped device adjusted to the specific characteristics of the patient, capable of eliminating any residue of O3 diffusion by degrading it and releasing O2 into the air. Azithromicin 500 mg/day was administered for 10 days in all patients before the first three gas insufflation although they had previously received various cycles of antibiotics. Ten patients required more than 10 O3 gas insufflations due to multiple lesions and/or purulent sovrainfections; one patient received two further O3 insufflations while waiting the day of surgery. Six of 24 patients interrupted the O3 gas therapy for oncological disease progression (five patients) and for fear of an experimental therapy (one patient). Six patients had the sequestrum and complete or partial (one patient) spontaneous expulsion of the necrotic bone followed by oral mucosa re-epithelization after a range of 4-27 of O3 gas insufflations. No patient reported adverse events. In 12 patients with the largest and deeper ONJ lesions, O3 gas therapy produced the sequestrum of the necrotic bone after 10 to 38 insufflations; surgery was necessary to remove it (11 patients). Of interest, removal was possible without the resection of healthy mandible edge because of the presence of bone sequestrum. All together the response rate was 75.0% (95% CI, 53.3-90.2%) in ITT analysis and 100% (95% CI, 81.5-100%) in the PP analysis. In all patients treated with O3 gas ± surgery, no ONJ relapse appeared (follow-up mean 18 months, range 1-3 years). Medical O3 gas insufflations is an effective and safe treatment for patients treated with BPs who developed ONJ lesions >2.5 cm. Short abstract: ONJ is an adverse event reported in patients receiving cancer treatments regimen, bisphosphonates and denosumab. We performed an open-label, prospective study in 24 patients with solid tumours, myeloma or osteoporosis due to hormonal therapy, treated with zoledronic acid without previuos preventive dental screening, who developed ONJ lesions >2.5 cm, and had no benefit after standard therapy, to evaluate the efficacy and tolerability of medical ozone (O3) treatment delivered as gas insufflations on each ONJ lesions. The patients were treated with O3 every third day for a minimum of 10 for each pathological area or till necrotic bone sequestrum or surgery. Eleven patients required more than ten O3 gas insufflations. Six of 24 patients interrupted the therapy for oncological disease progression. Six patients had the sequestrum and complete or partial (one patient) spontaneous expulsion of the necrotic bone followed by oral mucosa re-epithelization after a range of 4 to 27 of O3 gas insufflations. No patient reported adverse events. In 12 patients with the largest and deeper ONJ lesions, O3 gas therapy produced the sequestrum of the necrotic bone after 10 to 38 insufflations; surgery was necessary to remove it (11 patients). Of interest, removal was possible without the resection of healthy mandible edge because of the presence of bone sequestrum. All together the response rate was 75.0% (95% CI, 53.3-90.2%) in ITT analysis and 100% (95% CI, 81.5-100%) in the PP analysis. In all patients treated with O3 gas ± surgery, no ONJ relapse appeared (follow-up mean 18 months, range 1-3 years).
颌骨坏死（ONJ）是一种不良事件，尤其在接受癌症治疗方案、双膦酸盐（BPs）和地诺单抗治疗的患者中报道。我们对接受唑来膦酸治疗且发生>2.5 cm ONJ病变、经标准治疗后无改善的患者进行了一项开放标签的前瞻性研究，以评估医用臭氧（O3）以气体吹入方式对每个ONJ病变进行治疗的疗效和耐受性。24例患者（平均年龄62.5岁，范围41 - 80岁；12例女性）因乳腺癌（11例）、前列腺癌（4例）、肺癌（4例）、骨髓瘤（2例）或骨质疏松症（3例）发生骨转移，此前接受过唑来膦酸治疗，未采取牙科预防措施且ONJ病变>2.5 cm，对其进行观察并每三天对每个病理区域进行一次局部O3气体吹入治疗，最少10次，或直至坏死骨痂或手术。我们使用一种根据患者具体特征调整的特殊钟形吹入装置，该装置能够通过降解O3消除任何扩散残留并将O2释放到空气中。尽管所有患者此前已接受过多个周期的抗生素治疗，但在首次三次气体吹入前，所有患者均给予阿奇霉素500 mg/天，共10天。由于多处病变和/或脓性继发感染，10例患者需要超过10次O3气体吹入；1例患者在等待手术当天又接受了两次O3吹入。24例患者中有6例因肿瘤疾病进展（5例患者）和对实验性治疗的恐惧（1例患者）中断了O3气体治疗。6例患者出现了骨痂，坏死骨完全或部分（1例患者）自发排出，在进行了4 - 27次O3气体吹入后口腔黏膜重新上皮化。无患者报告不良事件。在12例ONJ病变最大且最深的患者中，O3气体治疗在吹入10至38次后产生了坏死骨痂；需要手术切除（11例患者）。有趣的是，由于存在骨痂，无需切除健康的下颌边缘即可进行切除。在意向性分析中，总有效率为75.0%（95% CI，53.3 - 90.2%），在符合方案分析中为100%（95% CI，81.5 - 100%）。在所有接受O3气体±手术治疗的患者中，未出现ONJ复发（随访平均18个月，范围1 - 3年）。医用O3气体吹入对接受BPs治疗且发生>2.5 cm ONJ病变的患者是一种有效且安全的治疗方法。简短摘要：ONJ是在接受癌症治疗方案、双膦酸盐和地诺单抗治疗的患者中报道的一种不良事件。我们对24例因激素治疗导致实体瘤、骨髓瘤或骨质疏松症、接受唑来膦酸治疗且未进行过预防性牙科筛查、发生>2.5 cm ONJ病变且经标准治疗后无改善的患者进行了一项开放标签的前瞻性研究，以评估医用臭氧（O3）以气体吹入方式对每个ONJ病变进行治疗的疗效和耐受性。患者每三天接受一次O3治疗，每个病理区域最少10次，或直至坏死骨痂或手术。11例患者需要超过十次O3气体吹入。24例患者中有6例因肿瘤疾病进展中断治疗。6例患者出现了骨痂，坏死骨完全或部分（1例患者）自发排出，在进行了4至27次O3气体吹入后口腔黏膜重新上皮化。无患者报告不良事件。在12例ONJ病变最大且最深的患者中，O3气体治疗在吹入10至38次后产生了坏死骨痂；需要手术切除（11例患者）。有趣的是，由于存在骨痂，无需切除健康的下颌边缘即可进行切除。在意向性分析中，总有效率为75.0%（95% CI，53.3 - 90.2%），在符合方案分析中为100%（95% CI，81.5 - 100%）。在所有接受O3气体±手术治疗的患者中，未出现ONJ复发（随访平均18个月，范围1 - 3年）。
