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抗骨吸收藥物對植牙的影響

The Effects of Anti-Resorptive Agents on Dental Implant Therapy

摘要


由於可以有效抑制破骨細胞的活性,雙磷酸鹽類及單株抗體製劑如RANKL抑制劑等抗骨吸收藥物,常使用於骨質疏鬆症、癌症產生骨轉移或多發性骨髓瘤之治療。因抗骨吸收藥物會影響骨頭之新陳代謝,一旦顎骨產生傷口,可能會引起癒合不良而形成顎骨壞死的現象,稱之為藥物相關顎骨壞死(medication-related osteonecrosis of the jaws,MRONJ)。隨著植牙技術的進步與高齡化社會的到來,愈來愈多的高齡骨質疏鬆症患者接受植牙補綴的治療;另一方面,現代社會癌症合併骨頭轉移的發生率節節高升,受惠於癌症治療的進展,這些癌症患者的存活期大幅增長,難免也會面對植牙的決定,以增進生活品質,而以上這兩類患者常會使用抗骨吸收藥物治療。由於植牙手術是產生顎骨傷口的重要途徑之一,又屬高單價的治療項目,為了避免上述顎骨壞死後遺症及醫療糾紛的產生,了解抗骨吸收藥物可能對植牙產生的影響是非常的重要。抗骨吸收藥物使用,對於植牙可能產生早發性或遲發性顎骨壞死的現象。對於正在使用抗骨吸收藥物的患者植牙,短期影響可能是無法達到骨整合,植體失敗喪失,嚴重者甚至產生顎骨壞死現象。即使手術成功,己產生骨整合,甚至己補綴完成開始咬合的植體,在長期使用下,可能因受力不當或因為藥物(特別是雙磷酸鹽類)對植體周圍軟組織的毒性,會讓植體周圍骨對口腔細菌之抵抗力降低,使得植體周圍炎發生機率增加,可能導致進一步顎骨壞死現象產生。雖然植牙手術有可能引起顎骨壞死,許多的研究報告認為使用抗骨吸收藥物,並不一定會影響植牙手術之骨整合及成功率。總結而言,對於臨床醫師,只要能術前仔細的評估,排除具高風險因子的患者,對於骨質疏鬆症使用抗骨吸收藥物患者並非不能植牙,但對癌症產生骨轉移正在使用高劑量抗骨吸收藥物患者,由於產生顎骨壞死的機率高很多,因此不建議進行植牙治療。

並列摘要


Anti-resorptive agents, such as bisphosphonates or denosumab, a monoclonal antibody to receptor activator of nuclear factor-κB ligand (RANKL), that potently inhibit osteoclast-mediated bone resorption are commonly used in patients with osteoporosis, cancer with bone metastasis or multiple myeloma. The alteration of bone turnover and remodeling by antiresorptive agents impair wound healing of jaw bones, and potentially result in an adverse event which was termed medication-related osteonecrosis of the jaws (MRONJ). In our aging society, dental implantations are required by more and more elderly osteoporotic patients for improving their chewing function. Also, improving survival period of metastatic cancer patients increases the demand of dental implantations during their life time. Because implant surgery is one of the leading risk factors of MRONJ, how prevent the risk of MRONJ among those patients with anti-resorptive therapy is an important issue, Better understanding of the effects of antiresorptive agents on implant surgery will not only reduce the incidence of side effects, but also the emergence of medical legal problems. The effects of antiresorptive agents on implant therapy include both early and late phases. In the early phase, the failure of osseointegration and loss of implants may happen. Furthermore, the surgical procedures may lead to osteonecrosis. In the late phase, soft tissue toxicity of antiresorptive agents, especially bisphosphonates, may induce microbial attacks to soft tissue around osscointegrated implants, and result in perimplantitis and MRONJ. However, this is a controversial issue that some other researchers found that antiresorptive agents do not compromise osseointegration and success rate of implant therapy. In conclusion, for osteoporotic patients under anti-resorptive therapy, implant therapy is feasible based on cautious preoperative evaluation and case selection. In contrary, metastatic cancer patients using high dose anti-resorptive agents should be considered as high-risk patients for MRONJ, and therefore implant therapy is not a suggested treatment option for dental reconstruction.

參考文獻


Ruggiero SL, Dodson TB, Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg 2014;72:1938-56.
Chiu WY, Yang WS, Chien JY, et al. The influence of alendronate and tooth extraction on the incidence of osteonecrosis of the jaw among osteoporotic subjects. PLOS One 2018;13:e0196419.
Vahtsevanos K, Kyrgidis A, Verrou E, et al. Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 2009;27:5356-62.
Vescovi P, Campisi G, Fusco V, et al. Surgery-triggered and non surgery-triggered Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ): A retrospective analysis of 567 cases in an Italian multicenter study. Oral Oncol 2011;47:191-4.
Saad F, Brown JE, Van Poznak C, et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol 2012;23:1341-7.

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