�� Vol. 43. No. 1 March 2010 The comparison of minocycline oral-rinse and gel on pocket depth Eka fitria augustina Department of Periodontics Faculty of Dentistry Airlangga University Surabaya - Indonesia abstract Background: �n�ecti�n disease is still c�nsidered as a �r��inent disease in �any devel��ing c��ntries, like �nd�nesia. ��e ��st �ral in�ecti�n disease is �eri�d�ntitis. Des�ite scaling and r��t �lanning as t�e �ain t�era�y, �in�cycline as adj�nct t�era�y �as already �een �sed ��r �eri�d�ntitis. ��ere are a l�t �� �edia �sed, s�c� as �ral rinse and gel. �any researc�es even �ave als� s����n t�at t�e �se �� �in�cycline as adj�nct t�era�y can decrease in�la��ati�n in �eri�d�ntitis. Like tetracycline, �in�cycline as an anti in�la��at�ry and antic�llagenase is als� c�nsidered t� �e very e��ective ��r t�e treat�ent �� �eri�d�ntitis. �edia �� �in�cycline t�at are availa�le are gel, �i�er, and �ral rinse, as t�e ne��est �ne. Purpose: ��e ��r��se �� t�is researc� is t� e�a�ine t�e c���aris�n �� 0.2% �ral rinse �in�cycline and 2% �in�cycline gel t� red�ce t�e ��cket de�t�. Method: ��e sa��les ��ere divided int� t��� gr���s, t�e �irst gr��� �sing �ral rinse and t�e sec�nd �ne �sing gel a�ter scaling. result: ��ere ��as n� statistically signi�icant di��erence �et��een t�e gr��� ��it� �in�cycline gel and �ral rinse. Conclusion: ��e a��licati�n �� 2% �in�cycline gel �r 0.2% �in�cycline ���t� ��as� a�ter scaling and r��t �lanning �as t�e sa�e e��ect in red�cing ��cket de�t�.. Key words: �yn�cycline gel, �ral rinse, ��cket de�t� abstrak latar belakang: Penyakit in�eksi �asi� �er��akan kas�s yang �en�nj�l di �anyak negara �erke��ang, se�erti �nd�nesia. �n�eksi r�ngga ��l�t yang �anyak terjadi adala� �eri�d�ntitis. Selain tera�i �ta�a yait� skeling dan r��t �lanning, �engg�nakan �in�siklin se�agai tera�i ta��a�an tela� �anyak dig�nakan, se�erti ��at k���r dan gel. Banyak �enelitian �en�nj�kkan �a���a �engg�naan �in�siklin se�agai tera�i ta��a�an da�at �en�r�nkan keradangan �ada �asien �eri�d�ntitis. Se�erti tetrasiklin, �in�siklin se�agai anti keradangan dan anti k�lagenase, sangat e�ekti� se�agai �era��atan �eri�d�ntitis. �edia �in�siklin yang �anyak dig�nakan di antaranya yait� gel, �i�er, dan ��at k���r yang ter�ar�. tujuan: ��j�an �enelitian adala� �engeta��i �er�andingan antara �engg�naan 0,2% ��at k���r �in�siklin dan 2% �in�siklin gel �nt�k �eng�rangi kedala�an ��ket �eri�d�ntal. Metode: Sa��el di�agi �enjadi d�a gr��, gr�� �erta�a �engg�nakan ��at k���r, dan kel����k ked�a �engg�nakan gel, setela� tera�i skeling. hasil: �idak ada �er�edaan yang signi�ikan antara kel����k �in�siklin ��at k���r dan gel. Kesimpulan: �in�siklin gel dan ��at k���r sa�a-sa�a e�ekti� dala� �eng�rangi kedala�an ��ket. Kata kunci: �in�siklin gel, ��at k���r, kedala�an ��ket C�rres��ndence: Eka Fitria Augustina, c/o: Department of Periodontics Dentistry, Faculty of Dentistry Airlangga University, Jln. Prof Mayjend Moestopo no. 47 Surabaya, Indonesia. E-mail : firstyaugustina@yahoo.com Research Report introduction Periodontitis actually can be defined as an infection disease attacking periodontal tissue caused by specific microorganism with many clinical manifestation, started from bleeding, inflammation, bone resorbtion, dental instability, to dental extraction. Periodontitis, moreover, manifests in various infections with many clinical manifestation of medical history as well as with many treatment responses depended on many factors, including �� Dent. J. (Maj. Ked. Gigi), Vol. 43. No. 1 March 2010: 21-25 bacteria, response of host immune and also environmental factor.1 Periodontitis is usually related with the increasing of the number of bacteria pathogen, such as P�r��yr���nas gingivalis, Prev�tella inter�edia, Bacteri�des ��rsyt�s, and Actin��acill�s actin��icete�c��itans that has already been published widely. Periodontal disease can be classified into advanced chronic periodontitis, refractory periodontitis, and aggressive periodontitis.2 Therefore, eliminating plaque and calculus is considered to be the most prominent stage in periodontitis therapy even though the common recurrence caused by periodontophatogen invading into gingival epithel, cementum, and dentin tubuli cannot be cleaned mechanically. Many researches have already shown that the use of antibiotics either systemically or locally was very useful to support the early periodontal therapy, involving scaling and root planning. Antibiotics can be given systemically per oral or locally like in gel, encapsulated, mouthwash, and others.3 This fact becomes the base of the critical framework that antibiotics is needed to support the success of the treatment for periodontal disease, either systemically or locally. In addition, the use of antibiotics locally is by inducing it directly into the pocket in order to make the level of medicine in pocket increasing, as a result, the medicine can also penetrate into root surface and periodontal smooth tissue, which then is expected to be more effective than systemically antibiotics.2 Locally antibiotics can also prevent and minimize many side effects caused by the use of antibiotics systemically.4 Minocycline, as antibiotics derived from the second generation of tetracycline, has already been improved for therapy of periodontal disease since it can effectively attack periodontal phatogen.4,5 Minocycline, has wide spectrum that can actively attack negative and positive gram bacteria that cause chronic periodontitis. The character of minocycline actually is bacteriostatic which can constrain the protein synthesis from bacteria.6 Minocycline also has anti-inflammatory character which can constrain apoptosis (cell death) by increasing TNF alpha and managing cytokine regulation. The effect of this anti-inflammatory charater is also influenced by direct action of T cell in microglia which can decrease the capability of T cell in connecting with microglia, and then can affect the producing of in signal mediator of cell T and microglia.6 There are many treatments for periodontal disease that have already used the application of minocycline in many media. The most available media of minocycline is gel, but the media of minocycline in mouthwash has been improved, especially for curing reccurent apthous stomatitis (RAS).8 Based on the results of many researchers, it is known that the use of minocycline locally can also reduce the pocket depth, bleeding during probing, and improve clinical adhesion.8 Locally antibiotics is a local anti-microbe that is effective for periodontophatogen, as anti inflammation.2 Based on the above explanation, the writer would like to analyze which kind of minocycline is more effective in reducing the pocket depth. material and method This research is a clinical research for measuring the depth of periodontal pocket before and after the application of minocycline. This experiment was done in Periodonsia Clinic of Faculty of Dentistry Airlangga University, from November 2007 to Januari 2008. Samples are involving patients who must meet the following criteria: 30–50 years old, male or female, having no allergic history with minocycline (tetracycline), not having pregnancy or breastfeeding, not having period, having chronic periodontitis with 3–6 mm periodontal pocket depth, not systemically (per oral) using antibiotics or anti-inflammation and application of gel or mouthwash minimally about 30 days, in good condition or having no systemic abnormality from the beginning to the end of measuring. The samples are divided into two groups, the first group with the application of 2% minocycline gel (Figure 1) and the second one with the application of 0.2% minocycline mouthwash. Based on the previous study, 2% of minocycline is the best concentration for reducing the pocket depth compared with other concentrations.12 Furthermore, 2% minocycline gel is made from 2 grams of pure minocycline powder mixed with 100 grams of unguintum gel (poly prophylene glycol). This mixing process must be done immediately before it is applied and then put into spuit used for inducing it into the pocket. Minocycline mouthwash 0.2% is made by 0.2 grams of pure minocycline powder mixed with 100 ml sterile aquadest, and then is used for mouth-washing. figure 1. Application of 2% minocycline gel in periodontal pocket. For both groups, the measuring of the pocket depth has been done before scaling. After scaling, the application of 2% minocycline gel is done in the first group and redone one week later.11 The measuring of the periodontal pocket depth is redone in the fourth and sixth weeks. Meanwhile, the second group is instructed to wash their mouth with 0.2% minocycline twice a day for seven days.11 The measuring of the pocket depth was also done in the fourth and sixth ��Augustina: The comparison of minocycline oral rinse and gel weeks. Before the fourth week, the measuring of the pocket depth cannot be done since the condition of periodontal table 1. The T test result of the difference of the pocket depth in the group with the application of mouthwash N X SD SE Signif. 2 tailed T Before the application of mouthwash After the application of mouthwash in the fourth week Before the application of mouthwash After the application of mouthwash in the sixth week After the application of mouthwash in the fourth week After the application of mouthwash in the sixth week 15 15 15 15 15 15 3.6667 2.6000 3.6667 2.3333 2.6000 2.3333 0.61721 0.63246 0.61721 0.48795 0.63246 0.48795 0.15936 0.12599 0.16330 0.12599 0.000 0.000 0.104 5.172 8.367 1.174 table 2. The T test result of the difference of the pocket depth in the group with the application of gel N X SD SE Signif 2 tailed T Before the application of gel After the application of gel in the fourth week Before the application of gel After the application of gel in the sixth week After the application of gel in the fourth week After the application of gel in the sixth week 15 15 15 15 15 15 4.3333 3.1333 4.3333 2.8000 3.1333 2.8000 0.61721 0.74322 0.61721 0.56061 0.74323 0.56061 0.15936 0.19190 0.15936 0.14475 0.19190 0.14475 0.000 0.000 0.55 6.874 11.500 2.092 table 3. The T test result of the difference of the pocket depth between the group with the application of mouthwash and that with the application of gel N X SD SE Signif 2 tailed T After the application of mouthwash in the fourth week After the application of gel in the fourth week After the application of mouthwash in the sixth week After the application of gel in the sixth week 15 15 15 15 1.0667 1.2000 1.3333 1.5333 0.79881 0.67612 0.61721 0.57640 0.20625 0.174517 0.15936 0.13333 0.610 0.334 -0.521 -1.000 tissue is still weak. Therefore, if probing is done before the fourth week, it will affect the process of recovery. �� Dent. J. (Maj. Ked. Gigi), Vol. 43. No. 1 March 2010: 21-25 result The difference of the pocket depth before and after the application of 0.2% minocycline mouthwash can be seen in Table 1. There was significant difference between before and after the application of mouthwash in the fourth week (p = 0.000). Similarly, there was also significant difference between before and after the application of mouthwash in the sixth week (p = 0.000). However, there was no significant difference after the application of mouthwash in the fourth week and in the sixth week (p = 0.104). Thus, it can be concluded that there was significant difference in the sample group before and after the application of mouthwash. The comparison of the difference of the pocket depth between before and after the application with minocycline 2% gel can be seen in Table 2. There was significant difference between the group with the application of 2% gel in the fourth week compared with that before the application (p = 0.000). Similarly, it is known that there was also significant difference between the group with the application of 2% gel in the sixth week compared with that before the application (p = 0.000). Nevertheless, there was no significant difference between the group with the application of 2% gel in the fourth week compared with that in the sixth week (p = 0.55). Therefore, it can be concluded that there was significant difference in the sample group before and after the application of gel. The comparison of the difference of the pocket depth between the group with the application of minocycline 2% gel and that with the application of minocycline mouthwash can be seen in following table 3. There was no significant difference between the group with the application of mouthwash and that with the application of gel in the fourth week, about p = 0.610 (p < 0.05). Similarly, there was no significant difference between the group with the application of mouthwash and that with the application of gel in the sixth week, about p = 0.334. Thus, there was no significant difference between the sample group with the application of mouthwash and that with the application of gel. discussion Periodontal disease is marked by the inflammation and the dental supporting tissue damage. This inflammation is marked by the progressive damage of periodontal ligament, alveolar bone, followed by pocket forming (the gingival sulcus pathologically becomes deeper), and gingival recession occurred (the clinical decreasing of gums).2 This periodontal treatment is aimed to maintain the dental function as well as to prevent and reduce the severity of the disease. The success of this treatment can be obtained by decreasing or eliminating bacteria pathogen, and by repairing the capability of tissue in maintaining and repairing itself.2 Many clinical researchs about the use of antibiotics for treating periodontal disease have been conducted. The use of antibiotics even can be done as the single method of the treatment or combined with scaling and root planing in periodontitis treatment. The use of antibiotics is aimed to eliminate bacteria pathogen in periodontal pocket, while scaling and root planing are aimed to repair the gingival health by eliminating all factors that can cause the inflammation on the dental surface. Gel antibiotics in the low concentration can directly applied in the dental surface without causing side effects like in systemically using.2,10 In this research, scaling and root planning together with the measuring of the pocket depth was done in both groups, one group with the application of mouthwash and the other one with the application of gel. The result of the research showed that the pocket depth in the group with the application of mouthwash was decreasing in the fourth week after the application (Table 1). This result is similar with the result of the previous study in which the use of minocycline as the additional therapy together with scaling and root planing can improve the recovery of periodontitis. One of the recovery processes is the decreasing of the pocket depth.11 Meanwhile, unlike before the application of mouthwash, the pocket depth in the group was decreasing after the application in the sixth week (Table 1). The result is similar with the result of the previous studies in which the additional therapy of minocycline with the application of mouthwash is proved to be able to decrease the inflammation.11 Since it can cause the eliminating of bacteria, the recovery of periodontitis can become better than that only with scaling and root planing.3 However, after the application of mouthwash, there was no statistically significant difference between the pocket depth in the fourth week and that in the sixth week. But, based on the data, the bigger decreasing of the pocket depth occurred in the sixth week. Unlike before the application, in the fourth week, the decreasing of the pocket depth was about 1.0667 mm. Meanwhile, in the sixth week the decreasing was about 1.3334 mm (Table 1). It is may be caused by the scaling before the application of mouthwash can eliminate the amount of subgingiva microorganism and can affect the health of periodontal tissue.2 From the fourth week to the sixth week the sample group is predicted to be able to maintain oral hygiene well, therefore, in the sixth week the decreasing of the pocket depth would be better than that in the fourth week. By improving the health of the tissue, the pocket depth would be decreasing because of the improving of the adhesion. The decreasing of the pocket depth actually is clinically important since if the pocket is deep, plaque control will be difficultly done, thus, the abnormality can possibly recurrent.2 There was pocket depth decreasing after the application of 2% minocycline gel in the fourth week (Table 2). This result was similar with the result of the previous finding that minocycline gel is effective to be applied directly in the periodontal pocket in order to effectively attack microorganism relating with periodontitis, such as ��Augustina: The comparison of minocycline oral rinse and gel P�r��yr��inas gingivalis, �. ��rsyt�ia, P. inter�edia, and A. c��itans.12 The significant difference of the decreasing of the pocket depth between before and after the application of 2% minocycline gel, moreover, occurred in the sixth week (Table 2). It is also known that with the application of minocycline gel the reparation of periodontal tissue can involve the decreasing of bleeding on probing (BOP) and the decreasing of the pocket depth in the sample group compared with that in the control group.12 Based on the comparison of the sample group using the application of gel before and after the application in the sixth week, furthermore, there was the decreasing of the pocket depth (Table 2). This result was similar with the result of the previous researches that minocycline gel is effectively used for the additional therapy of periodontal disease, especially for eliminating microorganism, decreasing the pocket depth, decreasing the score of bleeding index, and repairing the adhesion.3 It is also caused by the effective character of minocycline in eliminating the growth of negative gram periodontal pathogen, by the high concentration of gingival crevicular fluid (GCF), and by the slow release in the periodontal pocket.13 Based on the comparison of the sample group using the application of gel in the fourth week and in the sixth week (Table 2) there was no significant difference among them. However, the decreasing of the pocket depth was bigger in the sixth week. In the fourth week, the decreasing of the pocket depth was only about 1.200 mm compared with that before the application. In the sixth week, the decreasing of the pocket depth was about 1.533 mm compared with that before the application (Table 1). The reason is possibly because the patients can maintain oral hygiene as instructed by operator, thus, the decreasing of the pocket depth was better in the sixth week. There was no significant different between the sample group using the application of mouthwash. Nevertheless, it is also known that the decreasing of the pocket depth in the group with the application of gel was better, about 1.0667 mm, than the one with the application of mouthwash, about 1.200 mm (Table 3). The reason is because with the application of gel, the medicine can directly penetrate into periodontal pocket and can eliminate bacteria causing periodontitis in the pocket. Therefore, if the amount of bacteria causing the damage of periodontal tissue is decreasing, the recovery process will be better. Besides that, minocycline also has capability in constraining the protein synthesis of bacteria, and in attacking periodontal pathogen, such as P. gingivalis, P. inter�edia, F. n�cleat��, and A. c��itans. 6 There was no decreasing of the pocket depth in the sample group with the application of mouthwash and the one with the application of gel in the sixth week (Table 3). However, the decreasing of the pocket depth in the group using the application of gel was better, about 1.533mm, than the one using the application of mouthwash, about 1.337 mm. It indicates that scaling and root planing therapies together with the use of minocycline gel can reduce the pocket depth as same as the result of the previous researches. It is related with bacteriostatic effect and resistance activities of metaloproteinase matrix (MMP) derived from minocycline. Minocycline considered as analog of tetracycline, actively attacks bacteria with wide spectrum from periodontal pathogen. The high concentration of local minocycline has anti-infection effect when penetrates into biofilm of plague compared with that used systemically.7 Compared with the application of mouthwash, the application of gel was more useful, cause of directly penetrated into the pocket, and then the release occurred slowly. But, the decreasing of the pocket depth in both groups are the same. Based on the result of this research, it can be concluded the application of 2% minocycline gel or 0.2% minocycline mouth wash often scaling and root planning has the same effects in reducing pocket depth. refferences 1. Kamma JJ, Slots J. Herpesviral-bacterial infection in aggressive periodontitis. J Clin Periodontol. 2003, 30(5): 420–6. 2. Newman MG, Takei HH, Carranza FA. Carranza�s clinicalCarranza�s clinical periodontology. 10th ed. Philadelphia: WB Saunders Co; 2006. p. 798–802, 803–11. 3. Niederman R. Minocycline gel gives adjunctive improvement to scale and polish. Summary Evidence Based Dentistry 2000; 2(3): 654. 4. Cortelli JR, Rodrigues SM, Aquino DR, Ricardo LH, Pallos D. Longitudinal clinical evaluation of adjunct minocycline in the treatment of chronic periodontitis. J Periodontol 2006; 77(2): 161–6. 5. Giuliani F, Hader W, Wee Yong VW. Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction. Journal of Leucocyte Biology 2005; 78: 135–43. 6. Perno M. Pharmacotherapy in periodontal therapy. 2007. p. 6–13. 7. Oringer RJ, Al-Shammari KF, Aldredge WA, Iacono VJ, Eber RM, Wang HL, Berwald B, Nejat R, Giannobile WV. Effect of locally delivered minocycline microspheres on markers of bone resorption. J Periodontol 2002; 73(8): 101–8. 8. Paquette D, Oringer R, Lessem J, Offenbacher S, Genco R . L o c a l l y d e l i v e r e d m i n o c y c l i n e m i c r o s p h e r e s f o r t h e treatment of periodontitis in smokers. J Clin Periodontol 2003; 30(9): 787–94. 9. Meinberg AT, Barnes CM, Dunning DG, Reinhardt RA. Comparison of conventional periodontal maintenance versus scaling and root planning with subgingival minocycline. J Periodontol 2002; 73(2): 167–73. 10. Yaffe A., Herman A, Bahar H, Binderman L. Combined local application of tetracycline and biophosphonate reduces alveolar bone resorption in rats. J Periodontol 2003; 74: 1038–42. 11. Gorsky M, Epstein J, Rabenstein S, Elishoov H, Yarem N. Topical minocycline and tetracycline rinses in treatment of recurrent aphthous stomatitis: A randomized cross over study. Dermatology Online Journal 2007; 2. 12. Mc Coll E, Patel K, Dahlen G, Tonneti M, Graziani F. Supportive periodontal therapy using mechanical instrumentation or 2% minocycline gel: A 12 month randomized, controlled, single masked pilot study. J Clin Periodontol 2006; 33(2): 141–50. 13. Grenier D, Huot MP, Mayrand D. Ion-chelating activity of tetracycline and its impact on the susceptibility of Actinobacillus actinomycetemcomitans to these antibiotics. American Society for Microbiology 2000; 44(3): 763–6. 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