牙周維護性治療期使用局部抗生素或光動力治療於殘餘囊袋之輔助成效：隨機控制臨床試驗

Abstract

牙周維護性治療是牙周治療中重要一環，主要在預防牙周疾病復發，目前非手術治療 (洗牙及牙根整平術) 為其最主要之治療方式，但效果會因個體之疾病易感性、是否有深度破壞的牙周囊袋、牙根解剖構造或是細菌的再增生而受影響。因此，相關的輔助治療陸續被提出作為在牙周維護期治療殘餘囊袋的方法。本研究旨在觀察輔助性抗菌光動力治療或局部投予米諾環素凝膠相較於傳統洗牙及牙根整平術在牙周維護期治療殘餘囊袋之臨床療效。 本隨機控制臨床試驗納入58顆牙齒（來自34位病患），隨機分派至三組，分別為單純進行洗牙及牙根整平術 (組別A)、洗牙及牙根整平術加上光動力治療 (組別B)、洗牙及牙根整平術加上局部投予米諾環素凝膠 (組別C)，連續治療兩週。第一次治療時，每組先進行洗牙及牙根整平，其中兩組額外分別加入光動力治療和米諾環素凝膠。第二次治療時，每組皆先進行全口洗牙，接下來，單純洗牙及牙根整平之組別只使用生理食鹽水沖洗以作為安慰劑，另兩組則如同第一次治療，再次分別使用光動力治療和米諾環素凝膠。並於治療前、治療後三個月、六個月及十二個月搜集牙齦溝液以進行發炎細胞激素分析(白介素-1、白介素-8、基質金屬蛋白?-8)，以及紀錄臨床檢查數值(探測流血、牙周囊袋深度、牙周附連數值)。在一年期間每三個月回診時，皆進行全口洗牙及口腔衛教。 總共55顆牙齒完成試驗。在治療後的三個月追蹤可觀察到，組別C有較他組明顯的探測流血減少、牙周囊袋深度降低以及牙周附連增加。組別A、B、C在三個月之牙周囊袋降低量分別為1.12 ± 0.70mm、1.00 ± 0.91mm及1.38 ± 1.36m ; 牙周附連增加量分別為0.65 ± 0.93mm、0.72 ± 1.36mm及1.38 ± 1.36mm。在一年的追蹤結果中，三組臨床檢查數值皆有改善但無統計顯著差異，經由廣義估計方程式(generalized estimating equation, GEE)檢定後，組別B、C在探測流血、牙周囊袋深度降低之改善較組別A多。在發炎細胞激素表現部分，相較於治療前，三組皆顯著下降，而組別C之細胞激素表現顯著低於組別A。一年追蹤時之白介素-1、白介素-8及基質金屬蛋白?-8於組別A、B、C為0.0173 ± 0.0119pg、0.0079 ± 0.0068pg 及0.0075 ± 0.0064pg ; 0.1236 ± 0.0745pg、0.0815 ± 0.0748pg及0.0587 ± 0.0535pg ; 0.1932 ± 0.1898ng、0.0938 ± 0.0830pg及0.0721 ± 0.0743ng。 基於上述結果，可證實三種治療方式皆能有效改善牙周維持期之殘餘囊袋，但輔助性抗菌光動力治療及輔助性局部投予米諾環素凝膠對於降低牙周囊袋及產生牙周附連增加無法提供顯著額外臨床效果。另外可觀察到，輔助性局部給予米諾環素凝膠在三個月內有較明顯之臨床數值的改善和發炎細胞激素的下降。

Background: Supportive periodontal therapy (SPT) is an important maintenance phase to prevent the recurrence of disease progression. Professional scaling and root planning (Sc/RP) in SPT provides periodontal stability and improvement. However, residual pockets still exist during the SPT, especially in the patients with susceptible to periodontal disease, the sites with initial deep probing depth (PD), or anatomical variations, which make the complete removal of calculus difficult. In addition, microbial repopulation may also be a risk of disease recurrence. Therefore, several methods have been introduced as adjunctives to Sc/RP in treating residual pockets in SPT. This study aimed to conduct a randomized controlled clinical trial to investigate the treatment effect of Sc/RP-alone, Sc/RP combined with photodynamic therapy (PDT), and Sc/RP combined with locally administrated minocycline gel on treating residual pockets during SPT. Materials and Methods: Fifty-eight teeth recruited from thirty-four patients with residual pockets during SPT were randomly divided into three groups (Group A: Sc/RP-alone, Group B: Sc/RP + PDT, Group C: Sc/RP + minocycline gel). Sc/RP was performed in all groups over the target sites in the first week. Then, the photosensitizer (methylene blue) was applied and activated by the diode laser in Group B. Minocycline gel was locally delivered in Group C. In the second week, full mouth scaling was performed in all groups. Then, subgingival irrigation with normal saline (placebo) was performed in Group A. In Group B and Group C, PDT and minocycline gel were conducted again. Clinical parameters, including bleeding on probing (BOP), PD, and clinical attachment level (CAL) and gingival crevicular fluid (GCF) sampling for cytokine evaluation (IL-1??, IL-8, and MMP-8) were collected at different timepoints (baseline, post-treatment three months, six months, and twelve months). Full mouth scaling and oral hygiene instruction (OHI) were performed every three months for a year. Results: A total of 55 teeth were completed in the trial. The clinical status of the three groups was similar at baseline. Three months after treatments, better outcome of PD reduction and CAL gain in Group C was noticed. The PD reduction in Group A, Group B, and Group C at three-month follow-up were 1.12 ± 0.70mm, 1.00 ± 0.91mm, and 1.38 ± 1.36mm. Attachment gain were 0.65 ± 0.93mm, 0.72 ± 1.36mm, and 1.38 ± 1.36mm. In the one-year follow-up, clinical parameters were improved in all groups. Although there was no significant difference between groups, Group B and C had better improvement in PD and CAL than Group A confirmed by generalized estimating equations (GEE). Besides, IL-1??, IL-8, and MMP-8 were reduced in all groups after treatment and were significantly higher in Group A than in Group C at one-year follow-up. The IL-1??, IL-8, and MMP-8 in Group A, Group B and Group C at one-year follow-up were 0.0173 ± 0.0119pg, 0.0079 ± 0.0068pg and 0.0075 ± 0.0064pg, 0.1236 ± 0.0745pg, 0.0815 ± 0.0748pg, and 0.0587 ± 0.0535pg, 0.1932 ± 0.1898 ng, 0.0938 ± 0.0830pg and 0.0721 ± 0.0743ng. Conclusions: All treatments were effective in treating residual pockets during SPT. However, there was no significant difference between groups in clinical parameters, indicating that the adjunctive treatments of locally delivered minocycline gel or PDT on treating residual pockets during SPT did not offer benefits in terms of PD reduction and attachment gain, although both treatments reduced the periodontal inflammatory mediators within one year. Minocycline gel + Sc/RP tended to have a more short-term (three months) effectiveness than PDT + Sc/RP in the improvement of clinical parameters and the reduction of cytokines expression.