抗骨吸收藥物對牙科植體成敗之影響

Abstract

抑制骨質吸收的藥物(Anit-resorption Agents, ARA)常用於治療骨質疏鬆症或是抑制惡性腫瘤發生骨轉移。今了解，ARA的病患接受牙科手術時，易引起顎骨壞死。然，ARA對牙科植體之影響，學界意見不同。為釐清此爭議，本研究分別以流行病學、統合分析及病例對照研究為方法探討。 流行病學研究方面，調查台大醫院(National Taiwan University Hospital , NTUH)顎骨壞死(medicine related osteonecrosis of jaws, ONJ)的盛行率。比對牙科部之環口全景顎X光片，分析牙科植體與ONJ之關係。結果顯示，ONJ之盛行率為0.24%。比對牙科影像資料，其中兩位ONJ之病因和牙科植體相關。 統合分析研究方面，依據實證醫學的步驟，進行研究。共蒐集1661篇文章，共有11項文獻研究納入統合分析。分析得知，總共7007支植體，其中有1148支植體脫落。微弱證據顯示使用ARA之患者比未使用者具有較高的植體失敗率（OR=1.3），故引用回朔性世代研究調查植體失敗的危險因子。 回朔性世代研究方面，自台大醫院資料庫搜集攝護腺癌、乳癌、多發性骨髓瘤及骨質疏鬆之患者，納入具有植體的患者100名，蒐集其年齡、性別、用藥特性、用藥原因等因子。統計學方面，使用卡方檢定(chi-square)，羅吉斯回歸(Logistic regression)等探討牙科植體失敗率及ARA之相關性。結果顯示，使用ARA與否是為影響牙科植體失敗率之關鍵因子，其勝算比為10.47 ( p= 0.00)。多變項迴歸分析顯示下列三項為植體脫落的獨立危險因子: 牙周病與否 (adjusted OR=2.56),使用藥物的原因 (adjusted OR=6.5)，使用ARA與否 (adjusted OR=18.4); 使用ARA患者植牙後使用比起植牙前使用有較高失敗率(p=0.04)。女性患者失敗率較高(p=0.01)。有牙周病之患者失敗率較高(p=0.03)。脫落之植體依其形態可分為兩種， 35%為類植體周圍炎樣 (peri-implantitis type)，可見齒槽骨由齒槽嵴頂吸收，且呈現類似火山口狀。另外，65%為類骨塊脫離樣 (en-block type)，植體仍與骨緊密結合，但有一腐骨中且包含具骨整合植體之病灶產生，與顎骨分離。 藉由本研究，可以見得使用ARA患者其植體成功率為73.6%。女性患有牙周病及在使用抗吸收藥物前已有骨整合之植體，為植體脫落之高危險群。骨塊脫離樣之脫落植體應被定義為真正的植體相關顎骨壞死。綜合以上，牙科植體之手術醫師應謹慎評估當患者曾經使用ARA或是正在使用ARA，仍需注意成功的牙科植體亦可能於患者使用ARA後脫落。此外，基於本研究之限制，仍需要更進一步的前瞻性隨機性研究，方能斷定ARA對牙科植體的影響。

The anti-resorption agents (ARA) can inhibit the osteoclast to reduce bone resorption, which were commonly used in patients with osteoporosis or malignant tumors. To our best knowledge, the alveolar bone surgery induced medicine related osteonecrosis of jaw (ONJ) easily in the patient taking ARA. The prognosis of implants in ARA patients is controversial. In order to investigate this issue, this research was designed as three parts including epidemiology survey, meta-analysis and retrospective study in the relationship of ARA and dental implant prognosis.. Firstly, all the patients under ARA in NTUH were recruited from 2010 to 2016. The study reported the prevalence of ONJ in those patients. The patient with the dental implant who receiving ARA was identified via cross matching the dental panoramic radiograph and the database of prescription. Prevalence of ONJ in NTUH was 0.24%. Two patients had ONJ related to dental implant failure. Secondly, a meta-analysis was conducted to evaluate the impact of the ARA on the dental implantation. In this part, the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was used. For the meta-analysis, the search resulted in 1661 articles. After selection according to the eligibility criteria, 11 studies were included, with a total of 7007 implants placed, 1148 loss of implants. Patients treated with ARA had more implant failure than those without (OR: 1.3), but the evidence was not strong. There are many of risk factors could not be survey in the meta-analysis, therefor the retrospective study was performed to investigate the risk factors of dental implant failure for patients taking ARA.. Lastly, a retrospective cohort study was performed to identify the key factors, which affected the failure rate of the dental implantation with taking ARA. The patients with osteoporosis or malignant tumors who received dental implants were divided into two groups according to taking ARA or not. The relation of gender, history of systemic disease, age, drug duration, drug types, and primary diseases as risk factors of dental implant failure were reported. For statistics, Chi-square test, logistic regression and odds ratios were calculated for the association of risk factors to ONJ. The study showed that the key factor of implant failure was taking ARA or not (OR= 10.47). The multivariate regression analysis showed that periodontitis condition (OR=2.56), the indication for ARA (OR=6.5), taking the ARA (OR= 18.4) were risk factors of implant loss. The implant failure rate was higher in the patients receiving implantation before anti-resorptive therapy (p=0.04), female patients (p=0.01) and patients with periodontitis (p=0.03). Two patterns of implants loss were noted in this study. Thirty-five percentage of implants loss was “peri-implantitis” type. The marginal ridge resorption was showed on the dental radiography in this type. Another 65% implants loss was “en block” type. A whole bone block with osseointegrated implant was loss like a sequestrum. The retrospective study supported that the successful rate of implant in the patient with ARA was 73.6%. The female patients with osseointegrated implants and periodontitis were high-risk populations of implant loss after anti-resorptive therapy. The implant loss with en block pattern should be defined as real implant-related ONJ. The interests were that the failure of an osseointegrated implant might occur after the anti-resoptive therapies. Further prospective randomized studies with long follow-up period were necessary to identify the influence of ARA on the dental implant failure.