GCF MMP-8 Levels in Smokersand Non-Smokers With ChronicPeriodontitis Following Scalingand Root Planing Accompanied bySystemic Use of FlurbiprofenBulent Kurtis,* Gulay Tuter,* Muhittin Serdar,† Selin Pinar,* Ilkim Demirel,* and Utku Toyman*

Background: Cigarette smoking has been identified as an importantrisk factor for the initiation and progression of chronic periodontitis(CP). The aim of this study was to investigate the effects of phase I peri-odontal therapy and adjunctive flurbiprofen administration on matrixmetalloproteinase (MMP)-8 levels in gingival crevicular fluid (GCF)samples from smoking and non-smoking patients with CP.

Methods: Twenty-nine non-smoking and 29 smoking patients withCP were divided into four groups according to periodontal treatmentmodalities. Group 1 (non-smokers with CP) and group 3 (smokerswith CP) patients received daily 100-mg flurbiprofen tablets in a 2 ·1 regimen for 10 days together with scaling and root planing (SRP). Pa-tients in group 2 (non-smokers with CP) and group 4 (smokers with CP)received placebo tablets in a 2 · 1 regimen for 10 days together withSRP. Plaque index (PI), gingival index (GI), probing depth (PD), andclinical attachment level (CAL) measurements were recorded; GCFsamples were collected from each sampling area at baseline and afterthe 10-day period of drug intake by a single examiner who was unawareof the treatment modality. Assays for GCF MMP-8 were carried out byan enzyme-linked immunosorbent assay.

Results: All groups showed statistically significant reductions in PIand GI scores following the phase I periodontal treatment (P <0.05),but no statistical differences were observed in PD and CAL scores aftertherapy. In all groups, the reduction of GCF MMP-8 levels after therapywas statistically significant compared to baseline levels (P <0.001).When groups 1 and 3 and 2 and 4 were compared according to GCFMMP-8 levels after the therapy, no statistically significant differenceswere observed (P = 0.117 and P = 0.485, respectively).

Conclusion: Flurbiprofen administration had no additional inhibitoryeffect over SRP alone on GCF levels of MMP-8 in smokers compared tonon-smokers with CP. J Periodontol 2007;78:1954-1961.

KEY WORDS

Chronic periodontitis; flurbiprofen/therapeutic use;gingival crevicular fluid; matrix metalloproteinase-8; smoking.

Periodontitis is character-ized by chronic infectionand inflammation in sup-

porting periodontal tissues,causing destruction of peri-odontal connective tissues, lossof periodontal attachment, andresorption of alveolar bone.The matrix metalloproteinases(MMPs) are a group of impor-tant enzymes that cause theremodeling and degradation ofconnective tissue in pathologictissue turnover, and imbalancebetween activated MMPs andtheir endogenous inhibitorslead to breakdown of extracel-lular matrix in periodontitis.1,2

On the vascular level, duringperiodontal inflammation un-der the stimulation of bacterialpathogens and their products,polymorphonuclear leukocytes(PMNs) and macrophages syn-thesize a broad spectrum ofmatrix-degrading proteases,called MMPs.2,3 MMPs also areproduced by fibroblasts,4 kera-tinocytes,5 and endothelial cells.6

Elevated levels of MMPs ingingival tissue and gingivalcrevicular fluid (GCF) during

* Department of Periodontology, Faculty of Dentistry, Gazi University, Ankara, Turkey.† Department of Biochemistry, Gulhane Military Medical Academy, Ankara, Turkey.

doi: 10.1902/jop.2007.070149

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inflammation reflect the degree of collagen fiber andconnective tissue destruction, and PMNs play animportant role in MMP-mediated periodontal tissuebreakdown.7,8 MMP-8 is a PMN-type collagenaseinvolved in periodontal tissue degradation in subjectswith periodontal disease.9 PMN-type collagenase isstored in specific granules of PMNs and is releasedrapidly when PMNs are triggered. MMP-8 has beendetected in GCF samples from sites of periodontitis,and researchers10,11 found that MMP-8 plays a keyrole in destroying periodontal supporting tissues dur-ing chronic periodontal disease. In addition, Golubet al.12 reported that MMP-8 accounted for 94% to96% of the total collagenase in GCF collected frompatients with chronic periodontitis (CP).

Non-steroidal anti-inflammatory drugs (NSAIDs)are selective inhibitors of the cyclooxygenase path-way and, thereby, prevent the synthesis of prostaglan-dins, thromboxanes, and prostacycline.13 Numerousresearchers have investigated the ability of NSAIDsto modify the host response in animal and humantrials;13,14 NSAIDs given as an adjunct to non-surgicalperiodontal therapy reduced the gingival inflamma-tion, rate of attachment loss, and alveolar bone loss.Pelletier and Pelletier15 examined the effects of NSAIDs(nimesulide and naproxen) on the proteoglycan ma-trix breakdown and metalloprotease synthesis of hu-man osteoarthritic cartilage; under in vitro conditions,these NSAIDs significantly reduced the degradationof proteoglycan and stromelysin synthesis. Addition-ally, Barracchini et al.16 reported that meloxicam andindomethacin can inhibit the activities of human ar-thritic synovial fluid MMPs in vitro. Flurbiprofen isone of the NSAIDs, and previous studies identified thatit has an inhibiting effect on alveolar bone resorptionand attachment loss by reducing the numbers of oste-oclasts; significantly positive clinical and therapeuticeffects of flurbiprofen were observed as an adjunct toperiodontal treatment.17 Salmon et al.18 reported thatleukocyte accumulation was inhibited by the NSAIDsindomethacin and flurbiprofen. Investigators also re-ported that the concentrations of prostaglandin E2

(PGE2) and thromboxane B2 in exudate could be re-duced by these drugs; however, the concentrationof leukotriene B4 was unchanged. In addition, it wasreported that flurbiprofen had high relative potencyas an inhibitor of interleukin-1.19

Previous studies20,21 indicated that cigarettesmoking is a major risk factor for the developmentof periodontal diseases, and the role of smoking inthe pathogenesis of periodontal disease has beenstudied extensively. However, there is no clear con-sensus about the microbial composition of subgingi-val plaque obtained from smokers and non-smokersor about changes in the mechanisms of biologic hostresponse as a major risk factor in periodontal break-

down.22-24 Smoking impairs the chemotaxis andphagocytosis of neutrophils, and harmful effects of to-bacco products have been detected on cell movementand the oxidative burst.25,26 In addition, harmful com-ponents of smoking may contribute to the productionof cytokines and inflammatory mediators.27 It was ob-served that immunofluorescence intensity, represent-ing MMP-8 expression, in the periodontal tissues ofsmokers is significantly higher than in the periodontaltissues of non-smokers.28 However, Liede et al.29 re-ported that smokers had significantly lower salivaryMMP-8 levels and proteolytic enzyme activity thannon-smokers. In addition, Soder et al.30 found nostatistically significant differences between smokersand non-smokers with regard to GCF MMP-8 levels.Although it is well known that smoking is the majorenvironmental risk factor for the initiation and pro-gression of chronic periodontal disease, there areconflicting results about the mechanisms of smokingon periodontal destruction. Previous studies31,32 indi-cated that smokers do not respond to periodontaltherapy as well as non-smokers. Therefore, research-ers have focused on the use of adjunctive topical orsystemic antimicrobial or anti-inflammatory thera-pies in addition to scaling and root planing (SRP) toobtain better results in smokers with CP.33,34 In arecent study, Tomasi and Wennstrom35 reported ad-ditional benefits with the use of adjunctive local dox-ycycline in the treatment of smokers. Also, we shouldmention our previous investigation of the effects ofSRP and the adjunctive use of flurbiprofen on theGCF PGE2 and thiobarbituric acid reactive substance(TBARS) levels in smokers and non-smokers withCP.36 SRP plus flurbiprofen had more inhibitory ef-fects on GCF levels of PGE2 and TBARS in smokerscompared to non-smokers with CP. However, the po-tential efficiency of adjunctive systemic flurbiprofenon GCF levels of MMPs in the treatment of smokerswith CP remained unclear.

Therefore, the purpose of the present study was toinvestigate the efficiency of systemic flurbiprofen ad-ministration as an adjunct to SRP on clinical parame-ters and MMP-8 levels in GCF samples from smokersand non-smokers with CP.

MATERIALS AND METHODS

Patient Selection and Clinical ProceduresFifty-eight subjects were involved in the presentstudy. The study groups were divided as follows:

Group 1: Fourteen non-smokers with CP (two fe-males and 12 males; mean age, 46.61 years; range,39 to 55 years). Periodontal treatment: SRP + sys-temic NSAID (flurbiprofen tablet, 100 mg; 2 · 1 regi-men daily [two tablets once a day] for 10 days).

Group 2: Fifteen non-smokers with CP (seven fe-males and eight males; mean age, 47.76 years; range,

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43 to 54 years). Periodontal treatment: SRP + placebotablets (2 · 1 regimen daily for 10 days).

Group 3: Fourteen smokers with CP (four femalesand 10 males; mean age, 48.55 years; range, 42 to55 years). Periodontal treatment: SRP + systemicNSAID (flurbiprofen tablet, 100 mg, 2 · 1 regimendaily for 10 days).

Group 4: Fifteen smokers with CP (six females andnine males; mean age, 50.40 years; range, 46 to 56years). Periodontal treatment: SRP + placebo tablets(2 · 1 regimen daily for 10 days).

Patients were selected between March 2004 andMay 2006 from those newly referred to the Depart-ment of Periodontology, Faculty of Dentistry, GaziUniversity. Informed consent was obtained from allsubjects, and GCF sampling and clinical procedureswere explained fully before the study. The protocolwas approved by the Ethical Committee, Faculty ofDentistry, Gazi University.

Periodontal disease status was determined by clin-ical examination and radiographs. CP group patientswere selected as having at least six sites with >4 mmprobing depth and showing radiographic evidence ofbone and attachment loss in their single rooted-teeth.All subjects were in good general health and none hadreceived periodontal therapy or medication during thepast 6 months; no participant had a history of sys-temic conditions, such as heart disease, diabetes mel-litus, stomach or duodenal ulcer, or other types ofdisorders. All subjects were not on any medicationthat could affect the manifestations of periodontaldisease, such as chronic antibiotic use, phenytoin, cy-closporin, anti-inflammatory drugs, systemic cortico-steroids, or calcium channel blockers. None of thewomen were postmenopausal. Information regardingsmoking habits was obtained through a questionnaire.Smokers were defined as those who had smoked ‡10cigarettes daily for >5 years. Non-smokers were se-lected from the patients who had never smoked.

The clinical evaluations of patients were based onthe following parameters: plaque index (PI),37 gingi-val index (GI),38 probing depth (PD), and clinical at-tachment loss (CAL). All clinical parameters weremeasured with a Goldman/Fox Williams probe cali-brated in millimeters. Clinical measurements wereperformed on six sites per tooth (mesio-buccal, mid-buccal, disto-buccal, mesio-palatal or -lingual, mid-palatal or -lingual, and disto-palatal or -lingual) fromthe study sites. At the first appointment, single-rootedteeth (anterior teeth or premolars) with PD >4 mmwere selected as study sites to ensure standardizationof SRP. The following day, GCF samples were ob-tained, and baseline clinical scores were recordedfrom the previously selected sites. The same groupof teeth was chosen for clinical recording and GCFsampling for all groups to keep the standardization.

The patients were instructed on daily plaque control.The flurbiprofen groups received 100-mg tablets, andthe placebo groups received placebo tablets (all 2 ·1 for 10 days). All patients were instructed to takethe drugs at the same time each day, and they didnot take any other drugs during flurbiprofen intake.On day 3 of drug intake, SRP was performed by sharpsickles and Gracey and universal curets in the studysites under local anesthesia (40 mg/ml articaineHCl with 0.006 mg/ml epinephrine) for 10 to 12minutes per tooth. Oral hygiene instructions were re-inforced after the therapy. On the tenth day of flurbi-profen intake, clinical measurements and GCFsamples were obtained again from the study sites.Also, the required periodontal therapies were per-formed on other teeth.

GCF Sampling and ProcessingGCF samples were collected using periopaper‡ strips.The sample sites were gently air-dried, and all supra-gingival plaque was removed. The area was isolatedcarefully to prevent saliva contamination. The paperstrip was inserted into the crevice £1 mm and left inplace for 30 seconds. Care was taken to avoid me-chanical injury of the gingival tissues. Strips contam-inated by bleeding or exudate were discarded. Theamount of GCF on the strips was measured by weigh-ing the accumulated fluid. The paper strips wereplaced into coded, sealed plastic microcentrifugetubes and weighing was repeated immediately aftercollection to account for any evaporation. Tubes con-taining the strips were covered with paraffin andstored at -70�C until further enzyme processing.

The mass of the fluid on each strip was convertedto a volume in milliliters by assuming that the densityof GCF was 1, and mass (milligrams) was convertedto the volume (milliliters).

GCF Analysis of MMP-8The levels of MMP-8 in GCF samples were assayed byusing a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit.§ All assayprocedures were carried out according to the manu-facturer’s instructions using human recombinantstandards. GCF samples were eluted from the stripsby a centrifugal method.39 Elution was carried outwith the addition of 200 ml ELISA test buffer includedin the kit contents. Then, the microcentrifuge tubescontaining the strips and the buffer were centrifugedfor 20 minutes at 3,000 · g. After centrifugation, thestrips were removed, and the fluid remaining in thetubes was analyzed for MMP-8 using the above-mentioned commercial ELISA kit. The amount of

‡ Oraflow, Plainview, NY.§ Quantikine, R&D Systems, Minneapolis, MN.

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crevicular MMP-8 in each sample was determined bystandard calibration curves. The peroxidase-sub-strate color reaction was assessed using a readerset to a wavelength of 490 nm. Results were calcu-lated based on ELISA concentration values and re-ported as total enzyme amounts (pg – SD) persample.

Statistical AnalysisData analysis was performed using a statistical soft-ware package.i All results were analyzed by applyingthe Shapiro-Wilk test for determination of normal andabnormal data distribution. The statistical signifi-cance of the differences in the MMP-8 levels and clin-ical parameters between pre- and post-treatmentwere analyzed using the Wilcoxon signed-rank test.Mann-Whitney U tests also were used to determinethe significance of the differences among the studygroups according to pre- and post-treatment valuesfor all clinical parameters and MMP-8 levels. A P value<0.05 was considered statistically significant.

RESULTS

Statistical baseline and after-therapy values, includ-ing the clinical parameters and GCF volumes for allgroups, are given in Table 1.

No statistically significant differences were ob-served in clinical parameters and GCF MMP-8 levelsbetween smoking and non-smoking groups (betweengroups 1 and 3 and between groups 2 and 4) at base-line (P >0.05).

PI and GI scores decreased after periodontal ther-apy for all groups (P <0.05) compared to baselinevalues. No statistically significant differences in PDand CAL scores were found between baseline and af-ter-therapy results for any group (P >0.05). Althougha statistically significant reduction in GCF volume wasobserved after therapy for groups 3 and 4, no statisti-cally significant differences were found between base-line and after-therapy results for groups 1 and 2.

Statistically significant differences were found be-tween baseline and after-therapy values in GCF levelsof MMP-8 for all groups (P = 0.001; Fig. 1). When theMMP-8 levels in GCF of smokers and non-smokerswere compared after therapy, no statistically signifi-cant differences were observed between groups1 and 3 and between groups 2 and 4 (P = 0.117 andP = 0.485, respectively; Fig. 1).

DISCUSSION

Because of the established relationship betweensmoking and periodontal disease progression andreports that smokers have a poorer response tonon-surgical periodontal therapy than non-smokers,GCF levels of MMP-8 were analyzed at baseline andafter systemic flurbiprofen intake for 10 days in smok-ing and non-smoking patients with CP. SRP pro-cedures were performed on the third day of drugintake because our aim was to evaluate the efficiency

Table 1.

Comparison of Clinical Parameters and GCF Volumes at Baseline and After Therapy inStudy Groups (median and 25% to 75% quartiles)

Non-Smokers Smokers

SRP + Flurbiprofen (group 1)(N = 14)

SRP + Placebo (group 2)(N = 15)

SRP + Flurbiprofen (group 3)(N = 14)

SRP + Placebo (group 4)(N = 15)

Baseline

Median

(quartiles)

Post

Therapy

Median

(quartiles)

P

Value

Baseline

Median

(quartiles)

Post

Therapy

Median

(quartiles)

P

Value

Baseline

Median

(quartiles)

Post

Therapy

Median

(quartiles)

P

Value

Baseline

Median

(quartiles)

Post

Therapy

Median

(quartiles)

P

Value

PD (mm) 4.23

(3.75 to 4.90)

4.24

(3.76 to 4.92)

0.348 4.31

(4.05 to 4.65)

4.30

(4.09 to 4.68)

0.671 4.52

(3.81 to 5.26)

4.53

(3.83 to 5.27)

0.430 4.41

(4.22 to 4.70)

4.40

(4.21 to 4.69)

0.639

PI 1.70

(1.53 to 1.91)

0.40

(0.00 to 0.60)

0.001 1.87

(1.75 to 1.89)

0.39

(0.12 to 0.50)

0.001 1.92

(1.67 to 2.14)

0.29

(0.00 to 0.50)

0.001 1.96

(1.75 to 2.13)

0.34

(0.01 to 0.54)

0.001

GI 1.86

(1.77 to 1.99)

0.58

(0.00 to 0.91)

0.001 1.97

(1.81 to 1.99)

0.37

(0.10 to 0.21)

0.001 1.93

(1.74 to 2.07)

0.61

(0.39 to 0.82)

0.001 2.03

(1.88 to 2.13)

0.53

(0.19 to 0.68)

0.001

CAL (mm) 4.89

(4.23 to 5.47)

4.88

(4.22 to 5.49)

0.905 4.18

(3.70 to 4.81)

4.19

(3.73 to 4.83)

0.16 4.58

(3.81 to 5.25)

4.59

(3.80 to 5.27)

0.073 4.17

(4.00 to 4.43)

3.88

(3.34 to 3.87)

0.229

GCF (ml) 2.48

(1.97 to 3.19)

2.31

(1.70 to 2.54)

0.541 2.23

(1.83 to 2.50)

2.46

(1.99 to 3.07)

0.24 3.11

(2.14 to 4.10)

1.99

(1.84 to 2.18)

0.005 2.60

(2.07 to 2.70)

2.29

(1.50 to 3.20)

0.022

i SPSS, Chicago, IL.

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of flurbiprofen, combined with phase I periodontaltherapy, in the light of the knowledge that the anti-inflammatory effects of NSAIDs required ;48 hoursafter the medication.40 Conversely, a short time inter-val was chosen to examine the initial effects of flurbi-profen as an adjunct to phase I periodontal treatmenton the GCF MMP-8 levels to eliminate the adverse ef-fects of flurbiprofen over a longer period and to avoidthe influence of later wound healing on the GCF profile.

Although some investigators suggested that non-smokers had higher GI and bleeding on probing(BOP) values than smokers and, conversely, smokershad deeper PD and more loss of attachment thannon-smokers, van der Weijden et al.41 reported nostatistically significant differences between smokersand non-smokers regarding the mean percentageof sites that bled upon probing (smokers = 76%,non-smokers = 72%). Apatzidou et al.21 also foundno significant differences for the initial PD measure-ments between smokers and non-smokers (meanPD = 5.9 – 0.6 mm for smokers and 6.2 – 0.8 mmfor non-smokers). In addition, Bostrom et al.42 re-ported the same clinical characteristics in terms ofPD, frequency of diseased sites, and supragingivalplaque in smokers and non-smokers. Similar to theprevious reports, no significant differences were foundin the baseline clinical scores between smoking andnon-smoking groups in the present study. In earlierstudies, elevated MMP levels in GCF were detectedin periodontitis sites compared to healthy sites, andthe amounts of MMP in GCF correlated with the degree

of periodontal breakdown.9,10 In addition, treatmentof periodontitis resulted in a local decrease in MMPlevels in GCF, suggesting the MMPs are importantmolecules in periodontal tissue destruction.11

As a relevant study investigating the relationshipbetween smoking and GCF levels of MMP-8, Soder43

investigated the elastase activity, levels of PGE2, andMMP-8 in GCF from smokers and non-smokers withrefractory periodontitis; no statistically significant dif-ferences were found between smokers and non-smokers concerning the GCF levels of MMP-8. Inaddition, Soder et al.30 found no statistically signifi-cant differences in the GCF levels of MMP-8 betweensmokers and non-smokers. We also found no statisti-cally significant differences in the baseline GCF levelsof MMP-8 between smokers and non-smokers; there-fore, our findings are in line with the previous studies.

Liede et al.29 compared the periodontal status andsalivary collagenase-2 (MMP-8) levels in smokersand ex-smokers. Salivary general proteolytic activityand MMP-8 levels were significantly lower in currentsmokers than in ex-smokers. In a recent study, Liuet al.28 investigated MMP-8 expression by immunoflu-orescence staining in periodontal tissue samples ofsmokers and non-smokers. They reported signifi-cantly higher MMP-8 expression in smokers (1,154– 124 units) than in non-smokers (817 – 60 units).There seem to be conflicting results about the possiblemarkers in GCF and saliva for periodontal breakdownin smokers and non-smokers with CP. To the best ofour knowledge, the present study is the first reportto assess the adjunctive effect of systemic flurbiprofenon GCF levels of MMP-8 in the treatment of smokersand non-smokers with CP. Although most investiga-tors reported greater reductions in PD in non-smokerscompared to smokers after non-surgical periodontaltherapy,44 Pucher et al.45 reported a similar responseto non-surgical periodontal therapy in smokers andnon-smokers with reference to reduction in PD, at-tachment gain, and reduction in BOP. Zuabi et al.46

reported no difference in PD and CAL scores betweensmokers and non-smokers after non-surgical peri-odontal treatment. Palmer et al.34 investigated the re-sponse of SRP with and without adjunctive systemicmetronidazole or locally applied 25% metronidazolegel in smokers and non-smokers with previously un-treated moderate to advanced periodontitis. Therewere no differences in any clinical measurement in re-sponse to treatment regimens for 2 or 6 months forsmokers or non-smokers. In agreement with the pre-vious studies, smoking and non-smoking treatmentgroups showed the same healing response to SRP inour study. However, the reduction of GCF volume wasstatistically significant only in the smoking groups.This result might be related to the effect of smoking onthe periodontal tissues, resulting in vasoconstriction in

Figure 1.Comparisons of GCF levels of MMP-8 between baseline and aftertherapy within study groups and comparisons of the after-therapylevels between smokers and non-smokers (between groups 1 and 3and between groups 2 and 4). Special symbols identify the position ofoutliers (o) and extreme values (*).

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peripheral blood vessels that may affect the immune-inflammatory host response, and the reducing effectsof flurbiprofen on the vascular permeability.

In a meta-analysis,47 Preshaw et al. examined therole of subantimicrobial-dose doxycycline (SDD) asan adjunct to SRP in the treatment of smokers andnon-smokers with CP. The results of this meta-analy-sis demonstrated the benefits of adjunctive SDD for 9months in smokers and non-smokers; the outcomesof the treatment were intermediate and broadly simi-lar in smokers who received SDD and non-smokerswho received placebo. In the present study, similarclinical outcomes and GCF MMP-8 levels were de-tected in smokers and non-smokers who receivedflurbiprofen or placebo as an adjunct to SRP. It is diffi-cult to make a sharp comparison between the previousstudies and the present study because of differences inthe time intervals between baseline and after treat-ment, the adjunctive medication procedures, and thedifferent pharmacokinetic effects of the different drugs.

Machion et al.33 investigated the clinical effects oflocally delivered doxycycline combined with SRPcompared to SRP alone in the treatment of smokerswith CP. They reported superior benefits of the adjunc-tive local doxycycline therapy on PD reduction insmokers with deep periodontal pockets. In a recentstudy,36 we investigated the GCF levels of PGE2 andTBARS levels in smokers and non-smokers with CPafter phase I periodontal therapy plus the systemicuse of flurbiprofen. Additional flurbiprofen intakehad more inhibitory effects on GCF PGE2 and TBARSin the groups of smokers compared to non-smokers.However, in the present study, similar reductions inclinical and GCF parameters occurred in smokersand non-smokers with CP. The results of the presentstudy could not justify the systemic administrationof flurbiprofen for the reduction of GCF MMP-8 levelsin smokers and non-smokers with CP. The inconsis-tencies between the previous and present studiescould be explained by the different pathways in theanti-inflammatory effects of systemically adminis-trated flurbiprofen on certain biochemical inflamma-tory mediators in CP. In addition, no significantdifferences were found between groups that were ad-ministered placebo and flurbiprofen with regard toGCF MMP-8 levels in the present study. For that rea-son, regardless of smoking, future studies investigat-ing the relationship of NSAIDs-PMNs-MMPs to themechanisms of connective tissue breakdown in pa-tients with CP would be worthwhile because this axishas not been studied well.

Greenwald et al.48 investigated the suppression ofMMP activities by oral flurbiprofen, tetracycline, orcombined flurbiprofen plus tetracycline in extractsof inflamed paw tissue from rats with adjuvant arthri-tis. The combination of the two agents administrated

orally completely inhibited collagenase activity andproduced substantial normalization of radiographicjoint damage, far greater than either drug alone. In arecent study, Lee et al.49 reported that a combinationregimen of SDD and low-dose NSAID flurbiprofen(50 mg) synergistically suppressed MMPs and otherneutral proteinases in the gingiva of CP patients aftera 3-week regimen ofmedication.Further studies wouldbe valuable to investigate the longer-term and lower-dose effects of flurbiprofen or combination flurbipro-fen and SDD therapy on GCF MMP profile in smokersand non-smokers with CP. In addition, future studiesinvestigating the GCF levels of MMPs and tissue inhib-itor of matrix metalloproteinases (TIMPs) may haveimportance because the balance between MMPs andTIMPs is believed to be of central significance in thedestruction of connective tissue matrices.

CONCLUSIONS

The present study demonstrated the clinical benefitsof SRP with or without an NSAID (flurbiprofen) insmokers and non-smokers shortly after the initialphase of periodontal therapy. No additional inhibitionof GCF MMP-8 levels was caused by adjunctive flurbi-profen.

ACKNOWLEDGMENTS

This study was financially supported by the scientificresearch foundation of Gazi University (grant 03/2004-24). The authors express their thanks and grat-itude to Prof. Guler Ulku, Faculty of Education, GaziUniversity, for her effort in proofreading.

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Correspondence: Dr. Bulent Kurtis, Department of Peri-odontology, Faculty of Dentistry, Gazi University, BiskekCad. 82. sok, 06510 Emek, Ankara, Turkey. Fax: 90-312-223-92-26; e-mail: bulkurtis@yahoo.com.

Submitted March 20, 2007; accepted for publication April19, 2007.

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