Journal of Periodontology; Copyright 2016
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A Randomized, Double-masked Clinical Trial Comparing Four Periodontitis Treatment Strategies: 5-year Tooth Loss Results Hans R Preus, PhD*, Per Gjermo, PhD*, and Vibeke Baelum, PhD† *Department of Periodontology, Institute of Clinical Odontology, Faculty of Dentistry, University of Oslo, Norway. †Department of Dentistry Health, Aarhus University, Denmark. Background: Tooth loss is the ultimate negative consequence of periodontitis, and reports of the extent to which different treatment strategies may influence the loss of teeth in the long run are hard to find. Aim: To test the hypothesis that there is no difference in the 5-year clinical outcome of therapy in terms of tooth mortality between groups of patients treated with conventional over-weeks scaling and root planing (SRP) or same-day full-mouth disinfection (FDIS), with or without adjunctive metronidazole. Materials and Methods: 184 patients with moderate to severe periodontitis were randomly allocated to one of four treatment groups 1) FDIS+metronidazole, 2) FDIS+placebo, 3) SRP+metronidazole, 4) SRP+placebo. A total of 161 patients (88%) completed the five-year follow-up examination, and data on the number and timing of tooth extractions as well as the pre-extraction diagnoses and reasons for extractions, were analysed. Results: No differences were observed between groups in the number of -, reasons for - or time of extractions in the four groups at baseline, 1-, 3 - or 5 years post-treatment. Conclusion: If regarding extractions, or retention of teeth, as a measure for failure or success 5 years following completion of periodontal therapy, none of the 4 strategies produced a better end result than the other.
KEY WORDS: Dental Scaling, Periodontal debridement, Antibiotics, Metronidazol, Tooth loss, Tooth extraction.
Tooth loss is the probable negative consequence of untreated periodontitis or of failed or incorrect therapy.1 On the basis of the existing literature, it is difficult to assess the extent to which teeth are extracted as part of the periodontal treatment plan, e.g., removal of ‘hopeless’ teeth prior to treatment commencement, and to what extent the periodontal treatment has been unable to ensure their preservation. Lindhe & Nyman2 reported extracting average 3.3 teeth per patient during the pre-surgical phase in a 5-year prospective study of periodontal therapy among 75 patients, but these extractions comprised teeth ‘which from endodontic and cariologic viewpoints could not be successfully treated, teeth with periodontal pockets extending down to the apex, and teeth which on prosthodontic indications should not be maintained’. Pihlstrom et al.3 reported on tooth loss during and up to 6.5 years after therapy among (initially) 17 patients, and found that a total of 19 teeth were extracted. However, 7 of the patients were lost to the study at different (and unknown) times after therapy, rendering the denominator for calculations of tooth loss rates somewhat uncertain. Even so, Pihlstrom et al.3 reported that 8 teeth were extracted during therapy (≈ 8/17 = 0.5 tooth/patient), and that of the remaining 11 teeth extracted, three were within the first year, two were extracted between 1 and 5 year, and the remaining four were extracted between 5 and 6,5 year. Carnevale et al.,4 in a retrospective study, found that an average of 1.9 teeth/patient were extracted during active periodontal treatment, whereas 16% of the patients experienced extractions of an average of 1.3 teeth/patient during the supportive periodontal treatment phase, which had a mean duration of 7.8 years. Moreover, to the best of our knowledge tooth loss has not been studied as an outcome in randomized clinical trials of periodontal treatment. A systematic review of the effect of full-mouth treatment modalities for chronic periodontitis, which stated tooth loss as the primary outcome, found no studies reporting results to this end,5 and a 1
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systematic review of clinical trials on the effect of periodontitis treatments typically reported only on surrogate outcomes such as clinical attachment level and probing pocket depth changes.6 As pointed out by Hujoel7 trials using true endpoints such as tooth loss are challenging, in part because tooth loss is a long-term outcome while periodontal trials tend to be short-term, thereby rendering the number of tooth loss events too low for statistical evaluation. Additional arguments against tooth loss as an outcome include claims regarding the subjective nature of decisions to extract teeth, as well as the argument that teeth may be extracted for reasons unrelated to periodontitis or periodontal therapy. However, attempts to distinguish periodontal from non-periodontal tooth loss are fraught with problems, and it is unlikely that such distinctions can be accurately made. Hence, the answer to the question ‘periodontal or nonperiodontal’ may well be ‘both’. This situation is well known from many other research areas, and in cancer screening it has been shown that results may differ profoundly, whether diseasespecific or all-cause mortality end points are used to assess the outcomes of screening programs.8 As all-cause mortality, in contrast to disease-specific mortality, is known to be an unbiased outcome, all-cause mortality is therefore generally preferred for evaluation of cancer screening programs. The same argument can be made for tooth loss and this would therefore suggest that all-cause tooth loss, rather than disease-specific tooth loss, should be used as the preferred tooth loss outcome in periodontal trials. Recently, we completed a 5-year randomized clinical trial of four periodontal treatment modalities, the one-year results of which have previously been published.9,10 Even though this trial was not planned with tooth loss as the primary endpoint, the scarcity of such data make it of interest to analyze and report the loss of teeth over the entire 5-year trial period with a view to assess if the long-term benefit of the four treatment modalities differ in terms of tooth retention.
MATERIALS AND METHODS The data originate in the above mentioned intervention trial carried out among 184 patients with severe chronic periodontitis.9 Participants were enrolled following informed consent among periodontal patients referred by local dentists to a periodontal specialist clinic in Telemark County in the southern part of Norway. Candidate participants, aged 35 - 75 years, underwent a three-month pre-study hygiene phase with a view to obtain excellent oral hygiene,10 subsequent to which eligibility for the trial was assessed on the basis at least five sites remaining with pockets ≥ 5 mm. Moreover, since the treatment involved the use of metronidazole (MET), absence of bacterial species with known low sensitivity to MET (e.g. Aggregatibacter actinomycetemcomitans, Pseudomonas, Echerichia coli, Serratia, Shigella, or Acinetobacter spp) was required; just as there should be no known allergies or adverse reactions to this antibiotic.9 The eligibility was further contingent upon showing a high standard of oral hygiene during the pre-study hygiene phase, i.e. having less than 15% of the sites with plaque.10 Towards the end of the pre-study hygiene phase, and prior to randomization and commencement of therapy, participants who had teeth that were deemed ‘problematic’ or ‘hopeless’ were referred to their own local dentist with a written request for treatment or extractions, as deemed appropriate by the patient and dentist. For the purpose of consent, the participant was given a copy of the referral, which explained why it was deemed necessary to have the tooth/teeth treated or extracted. When the problems leading to the referral were fractures, endodontic lesions or other tractable conditions, the written request was for therapy or extraction, leaving the final decision to the local dentist and the patient together. The
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reasons stated in these referral letters were subsequently used to categorize the reasons for tooth loss, in the event of tooth extraction being the outcome of the referral. Obviously, many of the teeth referred for treatment or extraction had more than one problem, and overall twenty different problems were observed, each of which could be combined for any given tooth. Therefore, the attempt made in the present study to categorize these problems as reasons for extractions is for purely descriptive purposes, and all statistical analysis of tooth loss is based on all-cause tooth loss. Supplementary Table 1 in online Journal of Periodontology describes the five extraction categories employed in the present study; total periodontitis, < 25% attachment, fracture, endodontic/pulpal problems, and miscellaneous, and their contents in terms of the main reasons given for the extractions. Following the baseline clinical examination, which was carried out after completion of the pre-study hygiene phase, eligible participants were assigned to one of four treatment arms using a random allocation table.11 The four treatment modalities comprised full mouth disinfection+metronidazole (FDIS + MET); full mouth disinfection+placebo (FDIS); scaling and root planing+metronidazole (SRP+MET); and scaling and root planing+placebo (SRP), the details of which have been described previously.9,10 Full clinical follow-up examinations were carried out at 3 months, and at 1, 3 and 5 years after treatment. The parameters recorded at each clinical examination comprised plaque (yes/no), bleeding on probing (yes/no), probing pocket depth as well as clinical attachment level in mm at the mesial, buccal, distal and lingual/palatal aspect of each tooth present. A codebook manager (PG) kept all patient and allocation data throughout the study, thereby securing blinding of the clinical research staff at all times.9 Following completion of the active treatment, all patients were enrolled in a maintenance scheme, according to which supportive therapy was provided at 3, 6 and 12 months following therapy, and every 6 months after that. During the first year and at year 2, 3, 4 and 5 the supportive care was provided at the periodontal specialist clinic, while the intervening maintenance care sessions at year 1½, 2½, 3½ and 4½ were carried out by the participants’ own dentist. The 55 dentists, who provided supportive therapy to the participants in the study, were given annual courses in periodontal maintenance starting with a 3 h seminar prior to the participant enrollment period.9 Supportive care comprised a light scaling of all surfaces of all teeth, combined with a more focused scaling of sites presenting with deepened pockets and gingival bleeding on probing. The oral hygiene was checked, without disclosing solution procedures, and oral hygiene reinstructions and adjustments of interdental brush size were carried out as necessary. The local dentists involved in carrying out supportive therapy for the trial participants were instructed to avoid extracting teeth for the full length of the study unless they had been asked in writing to do so by the principal investigator (HP). In case tooth extractions were nonetheless deemed necessary, the dentists were asked to send their extraction diagnoses as well as immediate pre-extraction x-rays of the extracted tooth/teeth to the PI. In case of missing information, HP requested both diagnoses and X-rays in formal letters to the dentists upon recording tooth loss at the next follow-up examination. In case such requests were not honored, HP visited the clinic in question to obtain the clinical records and x-rays pertaining to the particular tooth extractions. Thereby, information for all but six of the extracted teeth were obtained (for these, the only medical record was “extracted”, and no record of extraction diagnoses or radiographs were found) on the clinical reasons given for the extractions. During the maintenance phase, the discovery of teeth with questionable diagnoses, such as probable “endo-perio” lesions or/and vertical cracks extending into the root, led to referrals to a specialist in endodontics that could give a distinct diagnosis using endodontic microscope.
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Such elaborate diagnostic service was paid for by the research grant, whereas the ensuing therapy was paid by the patient, leaving the decision of extraction or endodontic therapy to the patients themselves. Statistical testing of the null-hypothesis of identical participation rates at year 1, - 3 and 5 among the four treatment groups was carried out using Fisher’s exact test. Statistical testing of the null-hypothesis of no differences between treatment groups in the per person mean number of teeth present at baseline, and at years 1, 3 and 5 were carried out using ANOVA with Bonferroni corrections. These analyses were undertaken for the different subsets of participants participating at baseline (n=184) and at year 1 (AVO1yr; n=180), year 3 (AVO3yr; n=167), and year 5 (AVO5yr; n=161). Statistical testing of the null-hypothesis that the prevalence of any tooth loss (frequency of persons with any tooth loss) over the 5-year trial period would be the same in all treatment groups was carried out using a Chi-square test, and the null-hypothesis that the per person mean number of teeth extracted among those with extractions would be the same across treatment groups was tested using ANOVA with Bonferroni corrections. A 5% significance level was used. Additional details regarding patient recruitment, eligibility assessment, in- and exclusion criteria, randomization procedures, patient flow and clinical assessments have been published elsewhere.9,10 The project protocol was approved by the Privacy Ombudsman for the Norwegian Universities (#15768) and Regional Committee for Medical Research Ethics, (Oslo, Norway) (REC South East 2.2006.3573/S-06458b). U.S. National Institutes of Health Clinical Trials Registry number is NCT01318928.
RESULTS A total of 161 (88%) of the 184 participants originally enrolled in the trial completed the 5year trial (supplementary Table 2 in online Journal of Periodontology). A flow diagram is shown in supplementary Figure 1 in online Journal of Periodontology. The larger part of the dropout occurred between the follow-up consultations at year 1 and year 3. The reasons for dropout included death (n=3), critical illness (n=6), relocation to remoter areas of the country or abroad (n=2), while 12 participants chose to discontinue participation due to inconvenience or for other personal reasons. No statistically significant differences were observed between treatment groups in the participant retention rates, whether at 1, 3 or 5 years (supplementary Table 2 in online Journal of Periodontology). No statistically significant differences were found among the four treatment groups regarding the number of teeth retained at the 1, 3 or 5 year follow-up examinations (Table 1). Overall, 45% of the participants who completed the 5th year follow-up (AVO5yr) did not experience tooth loss during the 5-year trial period, ranging from 36% in the FDIS treatment group to 56% in the FDIS+MET treatment group (Table 2). However, regarding the prevalence of tooth loss over 5 years, no statistically significant differences between the treatment groups were observed. When considering only those participants who had tooth extractions, it was observed that participants in the SRP+MET group had statistically significantly more teeth extracted over the 5-year period (mean number of teeth extracted = 3.0) than participants in the FDIS group (mean number of teeth extracted = 1.8, p=0.031) or in the SRP group (mean number of teeth extracted = 1.7, p=0.019). During the first year of the trial, no statistically significant differences were observed between treatment groups in the mean number of teeth extracted among patients with tooth extractions, but the difference arose between year 1 and year 5 (Table 2) to produce the statistically significant difference between the SRP+MET group and the FDIS or the SRP group.
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A tabulation of the extraction diagnoses provided for the teeth extracted over the 5-year period revealed that 58% (23/40), 49% (22/45), 40% (28/70) and 34% (12/36) of the extractions carried out in the FDIS+MET, FDIS, SRP+MET or SRP treatment groups, respectively, were reported to be fully or partly related to the periodontal conditions (‘total periodontitis’ or ‘< 25% attachment’) of the teeth (Table 3). Most of these periodontal extractions were carried out prior to treatment commencement (Table 3), and forty-four (54%) of the 81 teeth extracted prior to treatment commencement had no occlusion contacts. Extractions after year 1 were more likely to be related to endodontic problems or fractures/cracks extending into the root. The highest clinical attachment loss recording observed in the extracted teeth at the last clinical examination prior to the extraction (Table 4) confirmed the relatively larger contribution of periodontal problems among teeth extracted prior to therapy than for teeth extracted during the subsequent five years of follow-up. This pattern was further augmented when considering the deepest probing pocket depth observed at the last clinical examination prior to extraction of the teeth (Table 5). Figure 1 shows the intraoral distribution of the teeth missing at baseline and the extractions carried out during the study. Second molars, closely followed by first molars and maxillary premolars were the tooth types most commonly missing at baseline. The teeth extracted before commencement of treatment also essentially belonged to these tooth types, particularly second molars, while teeth extracted after year 1 were more uniformly distributed across the dentition.
DISCUSSION As far as we are aware, the present study is the first randomized controlled clinical intervention trial providing results on total tooth loss for up to 5 years following different periodontitis treatment modalities. The results indicate that the mechanical (FDIS vs. SRP) and antibiotic regimen (MET vs. placebo) used in the active treatment phase made no difference in terms of total tooth loss over a 5-year period, or in terms of the occurrence (prevalence of tooth loss) over the 5-year period, whereas the statistically significantly higher number of teeth extracted among patients in the SRP+MET group is noteworthy. Although no randomized clinical trials of periodontal therapy have employed tooth loss as the primary outcome variable, retrospective studies on periodontal treatment that report on tooth mortality and its risk factors are numerous.2-4,12-31 Basically, they all agree that tooth mortality is low long after therapy in well-maintained patients with good oral hygiene. Although most (95%) of the patients included in the present study could be classified as having Severe Periodontitis according to the AAP/CDC case definition system32 and 72% were diagnosed with Extensive Periodontitis according to the EWP5 case definition system proposed33 the loss of teeth following therapy in this population of patients appears either lower than or similar to that observed in previous studies of tooth loss in relation to periodontal therapy2-4,12-31 However, there are a number of reasons why this contention should be cautiously evaluated. Many studies are retrospective, or small, and few studies have reported on pre-therapy extractions and the reasons for these. Among those few that have reported on pre-therapy (here meaning pre-surgical) extractions, Lindhe and Nyman2 reported an extraction rate of 3.3 teeth/patient among 75 patients, later followed for 5 years, whereas Pihlstrom et al.3 reported 0 extractions before therapy. However, it must be emphasized that Pihlstrom and coworkers3 made an active decision not to extract any teeth, regardless of condition, before therapy, and this decision resulted in 8 extractions in their 17 patients (0.5 teeth/patient) during therapy instead. In the present study an average of 0.5 (81/161) teeth per 5
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patient were extracted prior to treatment commencement9 and 0.68 (110/161) teeth/patient were extracted during therapy and maintenance in the 161 patients completing the study. Hence, 1.2 (191/161=1.19) teeth per patient were extracted alltogether from screening to finishing the 5 year follow-up in those 161 patients who completed the study. However, comparisons are difficult to make since most studies on retention of teeth are retrospective and mostly report on teeth lost during maintenance.34 Besides Chambrone and Chambrone27 (0.9 teeth/patient) the present study reports lower extraction rates than most other studies.2,4,12—26,28-31 Among the patients who actually had teeth extracted (n=88) in the present study, the average number was 2.2 teeth lost per patient (191/88). The 18 (99-81) teeth lost between commencement of therapy and 1 year beyond (Table 3) were all extracted due to endodontic problems and/or fractures, and none were extracted periodontal reasons only. These extractions represented both pre-therapy misjudgments on the part of the PI, as well as acute situations arising during these 12 months. Patients in the SRP + MET group showed a statistically significantly higher number of extractions than patients in the placebo groups. However, already at baseline this group had the lowest number of teeth present (Table 1), the highest frequency of smokers (63% vs. an average of 53% in the other groups)8 and also the highest average age among the four groups compared (56.8 vs an average of 54.6 yrs in the other groups),9 all of which might be part of the explanation for the higher tooth loss over the 5 years in this group. When considering only those patients who had extractions, it is noteworthy that not only did the SRP+MET group patients with extractions experience the highest number of extractions (3.0, Table 2) but even the FDIS+MET group also tended to have a higher number of extractions (2.2, Table 2) than was seen in the two placebo groups. While it would be prudent to consider if this might represent an untoward effect of the metronidazole treatment, it is also clear from the relatively low occurrence of tooth loss observed in the present study that much larger samples are needed to provide a valid answer. When analyzing why patients consent to, or request for tooth extractions, one has to consider the sociodemographic characteristics of the patient population, the dentists’ willingness/readiness to extract and the cost of dental therapy in the country where the study is conducted. In Norway, approximately 40% of the costs of periodontal therapy, including replacement of teeth mesial to the first molars when lost due to periodontal diseases, are covered by the social system (HELFO), so this kind of treatment is not very costly. In contrast, the cost of endodontic therapy of the first or second molars is quite expensive, and is not covered by HELFO. This means that treating a second molar, including both endodontic and crown therapy, may not be within the economical reach for a patient, and the tooth may therefore be sacrificed for economic reasons. Most patients in the present study live outside the general urban areas of Norway, and one may anticipate that many of the extracted teeth in this study would never have been extracted if the patient worked and lived in or around the bigger cities, where average income is higher and esthetics probably more important. Vatne et al.35 reported on a “quality of life” study from this patient population 1 year following therapy, and these data suggest that the present study population represent a less dentally aware group, as many of the patients did not place too much value on losing teeth, having their ability to chew reduced or having some esthetic flaws in their smiles. These factors may explain the patients’ preference for tooth extractions over more expensive procedures necessary to retain teeth. Corroborating this interpretation we observed that the most frequently extracted tooth type was the second molar, and that more than 50% of the pretreatment extractions (37% of all extractions, results not shown) concerned teeth that did not occlude with other teeth.
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CONCLUSION The results of the present study indicate that if regarding extractions, or tooth as the measure of failure or success 5 years following the completion of periodontal therapy, none of the 4 treatment strategies tested would produce a better end result than the other. Neither tooth retention, nor the occurrence of tooth loss differed between treatment groups, although a trend was noted for more tooth extractions among those who had teeth extracted in the SRP+MET group relative to the FDIS or the SRP groups. The reasons for extractions and the extraction pattern in the years following therapy are in accordance with the results of previous studies. ACKNOWLEDGEMENTS: There is no conflict of interest associated with this report, which was financed by the Norwegian Research Council, Oslo, Norway; grants # 185120 and 229029.
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Corresponding Author; Hans R Preus, Dept of Periodontology, IKO, Faculty of Dentistry, PO 1109 Blindern, 0317 Oslo, Norway, +47 22 85 21 63 (tel.), [email protected]. (May be published) Submitted May 25, 2016; accepted for publication August 11, 2016. Figure 1 Intraoral distribution of teeth missing at baseline (miss. BL), extracted before treatment commencement (Bef. Tx), during the first year after treatment commencement (Tx-1yr) and between the year 1 and year 5 follow-up examinations among the 161 participants who completed the trial. Table 1. Mean number of teeth (standard deviation) retained at various time points during the study, according to treatment modality. All valid observations (AVO) at 1 year (AVO1yr) refers to participants retained in study at the one-year follow-up examination, while AVO3yr and AVO5yr refer to participants retained in study at the three- and five-year follow-up examinations, respectively. Time of Participant subset Treatment group assessment FDIS+MET FDIS SRP+MET SRP Total Baseline All enrolled (n=184) 23.9 (4.3) 24.0 (3.9) 22.9 (3.8) 24.7 (3.6) 23.9 (3.9) AVO1yr (n=180) 24.0 (4.3) 24.0 (3.9) 22.8 (3.8) 24.7 (3.7) 23.9 (3.9) AVO3yr (n=167) 23.9 (4.4) 24.2 (4.0) 23.0 (3.8) 24.7 (3.8) 23.9 (4.0) AVO5yr (n=161) 24.0 (4.4) 24.1 (4.0) 22.8 (3.8) 24.6 (3.9) 23.9 (4.1) 1-yr follow-up AVO1yr (n=180) 23.2 (4.6) 23.3 (3.9) 22.1 (4.2) 24.1 (4.0) 23.2 (4.2) AVO3yr (n=167) 23.3 (4.6) 23.5 (4.0) 22.2 (4.2) 24.2 (4.0) 23.3 (4.2) AVO5yr (n=161) 23.4 (4.6) 23.5 (4.0) 22.0 (4.2) 24.1 (4.0) 23.2 (4.0) 3-yr follow-up AVO3yr (n=167) 23.0 (5.0) 23.2 (4.1) 21.8 (4.5) 24.0 (3.9) 23.0 (4.4) AVO5yr (n=161) 23.1 (5.0) 23.2 (3.9) 21.7 (4.5) 23.9 (3.9) 23.0 (4.5) 5-yr follow-up AVO5yr (n=161) 23.0 (5.0) 23.0 (4.3) 21.1 (5.0) 23.6 (4.1) 22.7 (4.7) Table 2. Distribution of the 161 participants, who completed the 5-yr study, according to the number of teeth lost, by study period and treatment group. Time period Number of Treatment group Total teeth lost FDIS+MET FDIS SRP+MET SRP BL - 1 yr No tooth loss 28 (68%) 24 (62%) 28 (67%) 29 (74%) 109 (68%) 1 tooth 5 (12%) 10 (26%) 4 (10%) 5 (13%) 24 (15%) 2 teeth 6 (15%) 1 (3%) 5 (12%) 3 (8%) 15 (9%) 3 teeth 1 (2%) 2 (5%) 3 (7%) 1 (3%) 7 (4%) 4+ teeth 1 (2%) 2 (5%) 2 (4%) 1 (3%) 6 (4%) Mean # (sd) of teeth lost among 1.8 (0.9) 1.7 (1.2) 2.3 (1.2) 1.8 (1.0) 1.9 (1.1) those patients who lost teeth 13 15 14 10 52 1 yr – 5 yr No tooth loss 32 (78%) 24 (62%) 26 (62%) 24 (62%) 106 (66%) 1 tooth 4 (10%) 12 (31%) 6 (14%) 12 (31%) 34 (21%) 2 teeth 3 (7%) 2 (5%) 5 (12%) 2 (5%) 12 (7%) 3 teeth 2 (5%) 1 (3%) 2 (5%) 1 (3%) 6 (4%) 4+ teeth 3 (7%) 3 (2%) Mean # (sd) of teeth lost among 1.8 (0.8) 1.3 (0.6) 2.4 (1.6)* 1.3 (0.6) 1.7 (1.1) those patients who lost teeth 9 15 16 15 55 BL - 5 yr No tooth loss 23 (56%) 14 (36%) 19 (45%) 17 (44%) 73 (45%) 1 tooth 8 (20%) 14 (36%) 5 (12%) 12 (31%) 39 (24%) 2 teeth 4 (10%) 5 (13%) 6 (14%) 7 (18%) 22 (14%) 3 teeth 2 (5%) 4 (10%) 7 (17%) 1 (3%) 14 (9%) 4+ teeth 4 (10%) 2 (5%) 5 (12%) 2 (5%) 13 (8%) Mean # (sd) of teeth lost among 2.2 (1.5) 1.8 (1.6) 3.0 (2.2) † 1.7 (0.9) 2.2 (1.6) those patients who lost teeth 18 25 23 22 88 * Statistically significantly higher than for group FDIS (p=0.031, ANOVA with Bonferroni correction) 9
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† Statistically significantly higher than for group SRP (p=0.019, ANOVA with Bonferroni correction)
‡ Percentages may not add up to 100% due to rounding. Table 3. Reasons for tooth extractions among the 161 participants, who completed the 5-yr study, by study period and treatment group Period Reason for extraction FDIS+MET FDIS SRP+MET SRP Total n of teeth n of teeth n of teeth n of teeth n of teeth (%) (%) (%) (%) (%) * Total periodontitis 8 (33%) 6 (23%) 7 (22%) 5 (29%) 26 (26%) BL – 1 yr < 25% attachment† Fracture Endodontic/pulpal problems Miscellaneous‡ Total number of teeth extracted Extracted before Tx commencement 1 yr – 5 yr Total periodontitis < 25% attachment† Fracture Endodontic/pulpal problems Miscellaneous‡ Total number of teeth extracted BL – 5 yr Total periodontitis < 25% attachment† Fracture Endodontic/pulpal problems Miscellaneous‡ Total number of teeth extracted *
9 (38%) 2 (8%) 4 (17%) 1 (4%) 24 17 (71%) 6 (38%) 5 (31%) 4 (25%) 1 (6%) 16 8 (20%) 15 (38%) 7 (18%) 8 (20%) 2 (5%) 40
12 (46%) 2 (8%) 6 (23%) 26 21 (81%) 2 (11%) 2 (11%) 6 (32%) 8 (42%) 1 (5%) 19 8 (18%) 14 (32%) 8 (18%) 14 (32%) 1 (2%) 45
17 (53%) 1 (3%) 5 (16%) 2 (6%) 32 28 (88%) 2 (5%) 2 (5%) 10 (26%) 12 (32%) 12 (32%) 38 9 (13%) 19 (27%) 11 (16%) 17 (24%) 14 (20%) 70
6 (35%) 2 (12%) 2 (12%) 2 (12%) 17 15 (88%) 1 (5%) 4 (21%) 10 (53%) 4 (21%) 19 6 (17%) 6 (17%) 6 (17%) 12 (33%) 6 (17%) 36
Most (81 of 99) of the teeth extracted in this period were extracted before treatment commencement.
†includes hypermobility ‡includes deep caries, root resorption, accident, wrong tooth, unstated reasons Table 4. The mean value of the highest clinical attachment level (mm) recorded in each extracted tooth at the last clinical examination before the extraction. Given according to treatment group and time of extraction. Based on the 161 participants who completed the 5-year trial. n refers to the number of teeth extracted. Period of extraction Treatment group Total FDIS+MET FDIS SRP+MET SRP Mean (sd) n Mean (sd) n Mean (sd) n Mean (sd) n Before treatment 8.8 (1.8) 10.0 (1.7) 9.4 (1.7) 8.7 (1.9) 9.3 (1.8) commencement 17 21 28 15 81 From active treatment 6.6 (4.2) 7.8 (2.9) 5.0 (4.2) 7.5 (4.9) 6.7 (3.7) commencement to year 1 7 5 4 2 18 Between year 1 and year 3 5.5 (4.2) 6.5 (3.2) 4.8 (2.9) 4.2 (2.6) 5.3 (3.3) 10 12 16 6 44 Between year 3 and year 5 5.2 (3.0) 5.3 (2.5) 4.7 (3.2) 5.2 (3.4) 5.0 (3.1) 6 7 22 13 48
10
44 (44%) 7 (7%) 17 (17%) 5 (5%) 99 81 (82%) 5 (5%) 10 (11%) 25 (27%) 34 (37%) 18 (20% 92 31 (16%) 54 (28%) 32 (17%) 51 (27%) 23 (12%) 191
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Table 5. The mean value of the highest probing pocket depth (mm) recorded in each extracted tooth at the last clinical examination before the extraction. Given according to treatment group and time of extraction. Based on the 161 participants who completed the 5-year trial. Treatment group FDIS+MET FDIS SRP+MET SRP Total Period of extraction Mean (sd) Mean (sd) Mean (sd) Mean (sd) Before treatment 8.7 (1.8) 10.0 (1.9)* 8.2 (2.3) 8.5 (1.9) 8.8 (2.1) commencement From active treatment 5.4 (3.2) 5.2 (2.6) 5.0 (2.4) 5.5 (3.5) 5.3 (2.7) commencement to year 1 Between year 1 and year 3 3.9 (2.4) 4.1 (1.2) 3.3 (1.1) 3.2 (0.8) 3.6 (1.5 ) Between year 3 and year 5 3.5 (1.4) 4.6 (1.7) 3.3 (1.4) 3.9 (1.6) 3.7 (1.5) * Statistically significantly higher than for group SRP+MET (p=0.014, ANOVA with Bonferroni correction)
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A Randomized, Double-masked Clinical Trial Comparing Four Periodontitis Treatment Strategies: 5-year Tooth Loss Results Hans R Preus, PhD*, Per Gjermo, PhD*, and Vibeke Baelum, PhD† *Department of Periodontology, Institute of Clinical Odontology, Faculty of Dentistry, University of Oslo, Norway. †Department of Dentistry Health, Aarhus University, Denmark. Background: Tooth loss is the ultimate negative consequence of periodontitis, and reports of the extent to which different treatment strategies may influence the loss of teeth in the long run are hard to find. Aim: To test the hypothesis that there is no difference in the 5-year clinical outcome of therapy in terms of tooth mortality between groups of patients treated with conventional over-weeks scaling and root planing (SRP) or same-day full-mouth disinfection (FDIS), with or without adjunctive metronidazole. Materials and Methods: 184 patients with moderate to severe periodontitis were randomly allocated to one of four treatment groups 1) FDIS+metronidazole, 2) FDIS+placebo, 3) SRP+metronidazole, 4) SRP+placebo. A total of 161 patients (88%) completed the five-year follow-up examination, and data on the number and timing of tooth extractions as well as the pre-extraction diagnoses and reasons for extractions, were analysed. Results: No differences were observed between groups in the number of -, reasons for - or time of extractions in the four groups at baseline, 1-, 3 - or 5 years post-treatment. Conclusion: If regarding extractions, or retention of teeth, as a measure for failure or success 5 years following completion of periodontal therapy, none of the 4 strategies produced a better end result than the other.
KEY WORDS: Dental Scaling, Periodontal debridement, Antibiotics, Metronidazol, Tooth loss, Tooth extraction.
Tooth loss is the probable negative consequence of untreated periodontitis or of failed or incorrect therapy.1 On the basis of the existing literature, it is difficult to assess the extent to which teeth are extracted as part of the periodontal treatment plan, e.g., removal of ‘hopeless’ teeth prior to treatment commencement, and to what extent the periodontal treatment has been unable to ensure their preservation. Lindhe & Nyman2 reported extracting average 3.3 teeth per patient during the pre-surgical phase in a 5-year prospective study of periodontal therapy among 75 patients, but these extractions comprised teeth ‘which from endodontic and cariologic viewpoints could not be successfully treated, teeth with periodontal pockets extending down to the apex, and teeth which on prosthodontic indications should not be maintained’. Pihlstrom et al.3 reported on tooth loss during and up to 6.5 years after therapy among (initially) 17 patients, and found that a total of 19 teeth were extracted. However, 7 of the patients were lost to the study at different (and unknown) times after therapy, rendering the denominator for calculations of tooth loss rates somewhat uncertain. Even so, Pihlstrom et al.3 reported that 8 teeth were extracted during therapy (≈ 8/17 = 0.5 tooth/patient), and that of the remaining 11 teeth extracted, three were within the first year, two were extracted between 1 and 5 year, and the remaining four were extracted between 5 and 6,5 year. Carnevale et al.,4 in a retrospective study, found that an average of 1.9 teeth/patient were extracted during active periodontal treatment, whereas 16% of the patients experienced extractions of an average of 1.3 teeth/patient during the supportive periodontal treatment phase, which had a mean duration of 7.8 years. Moreover, to the best of our knowledge tooth loss has not been studied as an outcome in randomized clinical trials of periodontal treatment. A systematic review of the effect of full-mouth treatment modalities for chronic periodontitis, which stated tooth loss as the primary outcome, found no studies reporting results to this end,5 and a 1
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systematic review of clinical trials on the effect of periodontitis treatments typically reported only on surrogate outcomes such as clinical attachment level and probing pocket depth changes.6 As pointed out by Hujoel7 trials using true endpoints such as tooth loss are challenging, in part because tooth loss is a long-term outcome while periodontal trials tend to be short-term, thereby rendering the number of tooth loss events too low for statistical evaluation. Additional arguments against tooth loss as an outcome include claims regarding the subjective nature of decisions to extract teeth, as well as the argument that teeth may be extracted for reasons unrelated to periodontitis or periodontal therapy. However, attempts to distinguish periodontal from non-periodontal tooth loss are fraught with problems, and it is unlikely that such distinctions can be accurately made. Hence, the answer to the question ‘periodontal or nonperiodontal’ may well be ‘both’. This situation is well known from many other research areas, and in cancer screening it has been shown that results may differ profoundly, whether diseasespecific or all-cause mortality end points are used to assess the outcomes of screening programs.8 As all-cause mortality, in contrast to disease-specific mortality, is known to be an unbiased outcome, all-cause mortality is therefore generally preferred for evaluation of cancer screening programs. The same argument can be made for tooth loss and this would therefore suggest that all-cause tooth loss, rather than disease-specific tooth loss, should be used as the preferred tooth loss outcome in periodontal trials. Recently, we completed a 5-year randomized clinical trial of four periodontal treatment modalities, the one-year results of which have previously been published.9,10 Even though this trial was not planned with tooth loss as the primary endpoint, the scarcity of such data make it of interest to analyze and report the loss of teeth over the entire 5-year trial period with a view to assess if the long-term benefit of the four treatment modalities differ in terms of tooth retention.
MATERIALS AND METHODS The data originate in the above mentioned intervention trial carried out among 184 patients with severe chronic periodontitis.9 Participants were enrolled following informed consent among periodontal patients referred by local dentists to a periodontal specialist clinic in Telemark County in the southern part of Norway. Candidate participants, aged 35 - 75 years, underwent a three-month pre-study hygiene phase with a view to obtain excellent oral hygiene,10 subsequent to which eligibility for the trial was assessed on the basis at least five sites remaining with pockets ≥ 5 mm. Moreover, since the treatment involved the use of metronidazole (MET), absence of bacterial species with known low sensitivity to MET (e.g. Aggregatibacter actinomycetemcomitans, Pseudomonas, Echerichia coli, Serratia, Shigella, or Acinetobacter spp) was required; just as there should be no known allergies or adverse reactions to this antibiotic.9 The eligibility was further contingent upon showing a high standard of oral hygiene during the pre-study hygiene phase, i.e. having less than 15% of the sites with plaque.10 Towards the end of the pre-study hygiene phase, and prior to randomization and commencement of therapy, participants who had teeth that were deemed ‘problematic’ or ‘hopeless’ were referred to their own local dentist with a written request for treatment or extractions, as deemed appropriate by the patient and dentist. For the purpose of consent, the participant was given a copy of the referral, which explained why it was deemed necessary to have the tooth/teeth treated or extracted. When the problems leading to the referral were fractures, endodontic lesions or other tractable conditions, the written request was for therapy or extraction, leaving the final decision to the local dentist and the patient together. The
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reasons stated in these referral letters were subsequently used to categorize the reasons for tooth loss, in the event of tooth extraction being the outcome of the referral. Obviously, many of the teeth referred for treatment or extraction had more than one problem, and overall twenty different problems were observed, each of which could be combined for any given tooth. Therefore, the attempt made in the present study to categorize these problems as reasons for extractions is for purely descriptive purposes, and all statistical analysis of tooth loss is based on all-cause tooth loss. Supplementary Table 1 in online Journal of Periodontology describes the five extraction categories employed in the present study; total periodontitis, < 25% attachment, fracture, endodontic/pulpal problems, and miscellaneous, and their contents in terms of the main reasons given for the extractions. Following the baseline clinical examination, which was carried out after completion of the pre-study hygiene phase, eligible participants were assigned to one of four treatment arms using a random allocation table.11 The four treatment modalities comprised full mouth disinfection+metronidazole (FDIS + MET); full mouth disinfection+placebo (FDIS); scaling and root planing+metronidazole (SRP+MET); and scaling and root planing+placebo (SRP), the details of which have been described previously.9,10 Full clinical follow-up examinations were carried out at 3 months, and at 1, 3 and 5 years after treatment. The parameters recorded at each clinical examination comprised plaque (yes/no), bleeding on probing (yes/no), probing pocket depth as well as clinical attachment level in mm at the mesial, buccal, distal and lingual/palatal aspect of each tooth present. A codebook manager (PG) kept all patient and allocation data throughout the study, thereby securing blinding of the clinical research staff at all times.9 Following completion of the active treatment, all patients were enrolled in a maintenance scheme, according to which supportive therapy was provided at 3, 6 and 12 months following therapy, and every 6 months after that. During the first year and at year 2, 3, 4 and 5 the supportive care was provided at the periodontal specialist clinic, while the intervening maintenance care sessions at year 1½, 2½, 3½ and 4½ were carried out by the participants’ own dentist. The 55 dentists, who provided supportive therapy to the participants in the study, were given annual courses in periodontal maintenance starting with a 3 h seminar prior to the participant enrollment period.9 Supportive care comprised a light scaling of all surfaces of all teeth, combined with a more focused scaling of sites presenting with deepened pockets and gingival bleeding on probing. The oral hygiene was checked, without disclosing solution procedures, and oral hygiene reinstructions and adjustments of interdental brush size were carried out as necessary. The local dentists involved in carrying out supportive therapy for the trial participants were instructed to avoid extracting teeth for the full length of the study unless they had been asked in writing to do so by the principal investigator (HP). In case tooth extractions were nonetheless deemed necessary, the dentists were asked to send their extraction diagnoses as well as immediate pre-extraction x-rays of the extracted tooth/teeth to the PI. In case of missing information, HP requested both diagnoses and X-rays in formal letters to the dentists upon recording tooth loss at the next follow-up examination. In case such requests were not honored, HP visited the clinic in question to obtain the clinical records and x-rays pertaining to the particular tooth extractions. Thereby, information for all but six of the extracted teeth were obtained (for these, the only medical record was “extracted”, and no record of extraction diagnoses or radiographs were found) on the clinical reasons given for the extractions. During the maintenance phase, the discovery of teeth with questionable diagnoses, such as probable “endo-perio” lesions or/and vertical cracks extending into the root, led to referrals to a specialist in endodontics that could give a distinct diagnosis using endodontic microscope.
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Such elaborate diagnostic service was paid for by the research grant, whereas the ensuing therapy was paid by the patient, leaving the decision of extraction or endodontic therapy to the patients themselves. Statistical testing of the null-hypothesis of identical participation rates at year 1, - 3 and 5 among the four treatment groups was carried out using Fisher’s exact test. Statistical testing of the null-hypothesis of no differences between treatment groups in the per person mean number of teeth present at baseline, and at years 1, 3 and 5 were carried out using ANOVA with Bonferroni corrections. These analyses were undertaken for the different subsets of participants participating at baseline (n=184) and at year 1 (AVO1yr; n=180), year 3 (AVO3yr; n=167), and year 5 (AVO5yr; n=161). Statistical testing of the null-hypothesis that the prevalence of any tooth loss (frequency of persons with any tooth loss) over the 5-year trial period would be the same in all treatment groups was carried out using a Chi-square test, and the null-hypothesis that the per person mean number of teeth extracted among those with extractions would be the same across treatment groups was tested using ANOVA with Bonferroni corrections. A 5% significance level was used. Additional details regarding patient recruitment, eligibility assessment, in- and exclusion criteria, randomization procedures, patient flow and clinical assessments have been published elsewhere.9,10 The project protocol was approved by the Privacy Ombudsman for the Norwegian Universities (#15768) and Regional Committee for Medical Research Ethics, (Oslo, Norway) (REC South East 2.2006.3573/S-06458b). U.S. National Institutes of Health Clinical Trials Registry number is NCT01318928.
RESULTS A total of 161 (88%) of the 184 participants originally enrolled in the trial completed the 5year trial (supplementary Table 2 in online Journal of Periodontology). A flow diagram is shown in supplementary Figure 1 in online Journal of Periodontology. The larger part of the dropout occurred between the follow-up consultations at year 1 and year 3. The reasons for dropout included death (n=3), critical illness (n=6), relocation to remoter areas of the country or abroad (n=2), while 12 participants chose to discontinue participation due to inconvenience or for other personal reasons. No statistically significant differences were observed between treatment groups in the participant retention rates, whether at 1, 3 or 5 years (supplementary Table 2 in online Journal of Periodontology). No statistically significant differences were found among the four treatment groups regarding the number of teeth retained at the 1, 3 or 5 year follow-up examinations (Table 1). Overall, 45% of the participants who completed the 5th year follow-up (AVO5yr) did not experience tooth loss during the 5-year trial period, ranging from 36% in the FDIS treatment group to 56% in the FDIS+MET treatment group (Table 2). However, regarding the prevalence of tooth loss over 5 years, no statistically significant differences between the treatment groups were observed. When considering only those participants who had tooth extractions, it was observed that participants in the SRP+MET group had statistically significantly more teeth extracted over the 5-year period (mean number of teeth extracted = 3.0) than participants in the FDIS group (mean number of teeth extracted = 1.8, p=0.031) or in the SRP group (mean number of teeth extracted = 1.7, p=0.019). During the first year of the trial, no statistically significant differences were observed between treatment groups in the mean number of teeth extracted among patients with tooth extractions, but the difference arose between year 1 and year 5 (Table 2) to produce the statistically significant difference between the SRP+MET group and the FDIS or the SRP group.
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A tabulation of the extraction diagnoses provided for the teeth extracted over the 5-year period revealed that 58% (23/40), 49% (22/45), 40% (28/70) and 34% (12/36) of the extractions carried out in the FDIS+MET, FDIS, SRP+MET or SRP treatment groups, respectively, were reported to be fully or partly related to the periodontal conditions (‘total periodontitis’ or ‘< 25% attachment’) of the teeth (Table 3). Most of these periodontal extractions were carried out prior to treatment commencement (Table 3), and forty-four (54%) of the 81 teeth extracted prior to treatment commencement had no occlusion contacts. Extractions after year 1 were more likely to be related to endodontic problems or fractures/cracks extending into the root. The highest clinical attachment loss recording observed in the extracted teeth at the last clinical examination prior to the extraction (Table 4) confirmed the relatively larger contribution of periodontal problems among teeth extracted prior to therapy than for teeth extracted during the subsequent five years of follow-up. This pattern was further augmented when considering the deepest probing pocket depth observed at the last clinical examination prior to extraction of the teeth (Table 5). Figure 1 shows the intraoral distribution of the teeth missing at baseline and the extractions carried out during the study. Second molars, closely followed by first molars and maxillary premolars were the tooth types most commonly missing at baseline. The teeth extracted before commencement of treatment also essentially belonged to these tooth types, particularly second molars, while teeth extracted after year 1 were more uniformly distributed across the dentition.
DISCUSSION As far as we are aware, the present study is the first randomized controlled clinical intervention trial providing results on total tooth loss for up to 5 years following different periodontitis treatment modalities. The results indicate that the mechanical (FDIS vs. SRP) and antibiotic regimen (MET vs. placebo) used in the active treatment phase made no difference in terms of total tooth loss over a 5-year period, or in terms of the occurrence (prevalence of tooth loss) over the 5-year period, whereas the statistically significantly higher number of teeth extracted among patients in the SRP+MET group is noteworthy. Although no randomized clinical trials of periodontal therapy have employed tooth loss as the primary outcome variable, retrospective studies on periodontal treatment that report on tooth mortality and its risk factors are numerous.2-4,12-31 Basically, they all agree that tooth mortality is low long after therapy in well-maintained patients with good oral hygiene. Although most (95%) of the patients included in the present study could be classified as having Severe Periodontitis according to the AAP/CDC case definition system32 and 72% were diagnosed with Extensive Periodontitis according to the EWP5 case definition system proposed33 the loss of teeth following therapy in this population of patients appears either lower than or similar to that observed in previous studies of tooth loss in relation to periodontal therapy2-4,12-31 However, there are a number of reasons why this contention should be cautiously evaluated. Many studies are retrospective, or small, and few studies have reported on pre-therapy extractions and the reasons for these. Among those few that have reported on pre-therapy (here meaning pre-surgical) extractions, Lindhe and Nyman2 reported an extraction rate of 3.3 teeth/patient among 75 patients, later followed for 5 years, whereas Pihlstrom et al.3 reported 0 extractions before therapy. However, it must be emphasized that Pihlstrom and coworkers3 made an active decision not to extract any teeth, regardless of condition, before therapy, and this decision resulted in 8 extractions in their 17 patients (0.5 teeth/patient) during therapy instead. In the present study an average of 0.5 (81/161) teeth per 5
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patient were extracted prior to treatment commencement9 and 0.68 (110/161) teeth/patient were extracted during therapy and maintenance in the 161 patients completing the study. Hence, 1.2 (191/161=1.19) teeth per patient were extracted alltogether from screening to finishing the 5 year follow-up in those 161 patients who completed the study. However, comparisons are difficult to make since most studies on retention of teeth are retrospective and mostly report on teeth lost during maintenance.34 Besides Chambrone and Chambrone27 (0.9 teeth/patient) the present study reports lower extraction rates than most other studies.2,4,12—26,28-31 Among the patients who actually had teeth extracted (n=88) in the present study, the average number was 2.2 teeth lost per patient (191/88). The 18 (99-81) teeth lost between commencement of therapy and 1 year beyond (Table 3) were all extracted due to endodontic problems and/or fractures, and none were extracted periodontal reasons only. These extractions represented both pre-therapy misjudgments on the part of the PI, as well as acute situations arising during these 12 months. Patients in the SRP + MET group showed a statistically significantly higher number of extractions than patients in the placebo groups. However, already at baseline this group had the lowest number of teeth present (Table 1), the highest frequency of smokers (63% vs. an average of 53% in the other groups)8 and also the highest average age among the four groups compared (56.8 vs an average of 54.6 yrs in the other groups),9 all of which might be part of the explanation for the higher tooth loss over the 5 years in this group. When considering only those patients who had extractions, it is noteworthy that not only did the SRP+MET group patients with extractions experience the highest number of extractions (3.0, Table 2) but even the FDIS+MET group also tended to have a higher number of extractions (2.2, Table 2) than was seen in the two placebo groups. While it would be prudent to consider if this might represent an untoward effect of the metronidazole treatment, it is also clear from the relatively low occurrence of tooth loss observed in the present study that much larger samples are needed to provide a valid answer. When analyzing why patients consent to, or request for tooth extractions, one has to consider the sociodemographic characteristics of the patient population, the dentists’ willingness/readiness to extract and the cost of dental therapy in the country where the study is conducted. In Norway, approximately 40% of the costs of periodontal therapy, including replacement of teeth mesial to the first molars when lost due to periodontal diseases, are covered by the social system (HELFO), so this kind of treatment is not very costly. In contrast, the cost of endodontic therapy of the first or second molars is quite expensive, and is not covered by HELFO. This means that treating a second molar, including both endodontic and crown therapy, may not be within the economical reach for a patient, and the tooth may therefore be sacrificed for economic reasons. Most patients in the present study live outside the general urban areas of Norway, and one may anticipate that many of the extracted teeth in this study would never have been extracted if the patient worked and lived in or around the bigger cities, where average income is higher and esthetics probably more important. Vatne et al.35 reported on a “quality of life” study from this patient population 1 year following therapy, and these data suggest that the present study population represent a less dentally aware group, as many of the patients did not place too much value on losing teeth, having their ability to chew reduced or having some esthetic flaws in their smiles. These factors may explain the patients’ preference for tooth extractions over more expensive procedures necessary to retain teeth. Corroborating this interpretation we observed that the most frequently extracted tooth type was the second molar, and that more than 50% of the pretreatment extractions (37% of all extractions, results not shown) concerned teeth that did not occlude with other teeth.
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CONCLUSION The results of the present study indicate that if regarding extractions, or tooth as the measure of failure or success 5 years following the completion of periodontal therapy, none of the 4 treatment strategies tested would produce a better end result than the other. Neither tooth retention, nor the occurrence of tooth loss differed between treatment groups, although a trend was noted for more tooth extractions among those who had teeth extracted in the SRP+MET group relative to the FDIS or the SRP groups. The reasons for extractions and the extraction pattern in the years following therapy are in accordance with the results of previous studies. ACKNOWLEDGEMENTS: There is no conflict of interest associated with this report, which was financed by the Norwegian Research Council, Oslo, Norway; grants # 185120 and 229029.
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Pihlstrom BL, Oliphant TH, McHugh RB. Molar and nonmolar teeth compared over 6 1/2 years following two methods of periodontal therapy. J Periodontol 1984;55:499-504.
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10. Preus HR, Dahlen G, Gjermo P, Baelum V. Microbiological observations following four treatment strategies among periodontitis patients maintaining a high standard of oral hygiene. A secondary analysis of a randomized controlled clinical trial. J Periodontol 2015; 86:856-865. 11. Altman DG. Clinical trials. In: Altman DG, ed. Practical statistics for medical research. London: Chapman & Hall/CRC; 1991:p456. 12. Hirschfeld L, Wasserman B. A long-term survey of tooth loss in 600 treated periodontal patients. J Periodontol 1978;49:225-237. 13. McFall WT. Tooth Loss in 100 Treated Patients With Periodontal Disease: A Long-Term Study. J Periodontol 1982; 53: 539-549. 14. Lindhe J, Nyman S. Long-term maintenance of patients treated for advanced periodontal disease. J Clin Periodontol 1984; 11:504–514.
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15. Goldman MJ, Ross IF, Goteiner D. Effect of periodontal therapy on patients maintained for 15 years or longer. A retrospective study. J Periodontol 1986;57:347-353. 16. Wood W, Greco G, McFall WTJr. Tooth loss in patients with moderate periodontitis after treatment and long-term maintenenance care. J Periodontol 1989;60:516-520. 17. Mcguire MK, Nunn ME. Prognosis versus actual outcome. III. The effectiveness of clinical parameters in accurately predicting tooth survival. J Periodontol 1996; 67:666-674. 18. McLeod DE, Laison PA, Spivey JD. The predictability of periodontal treatment as measured by tooth loss; a retrospective study. Quintessence Int 1998;29:631-635. 19. Kocher T, König J, Dzierzon U, Sawaf H, Plagmann HC. Disease progression in periodontally treated and untreated patients - a retrospective study. J Clin Periodontol 2000;27:866-872. 20. Tonetti MS, Steffen P, Muller-Campanile V, Suvan J, Lang NP. Initial extractions and tooth loss during supportive care in a periodontal population seeking comprehensive care. J Clin Periodontol 2000; 27: 824831. 21. Matthews DC, Smith CG, Hanscom SL. Tooth loss in periodontal patients. J Can Dent Assoc 2001;67: 207210. 22. König J, Plagmann HC, Rühling A, Kocher T. Tooth loss and pocket probing depths in compliant periodontally treated patients: a retrospective analysis. J Clin Periodontol 2002;29:1092-1100. 23. Axelsson P, Nyström B, Lindhe L. The long-term effect of a plaque control program on tooth mortality, caries and periodontal disease in adults. Results after 30 years of maintenance. J Clin Periodontol 2004; 31: 749–757. 24. Paulander J, Axelsson P, Lindhe J, Wennström JL. Intra-oral pattern of tooth and periodontal bone loss between the age of 50 and 60 years. A longitudinal prospective study. Acta Odont Scand 2004;62: 214-222. 25. Schatzle M, Loe H, Lang NP, Burgin W, Anerud A, Boysen H. The clinical course of chronic periodontitis. J Clin Periodontol 2004; 31:1122-1127. 26. Al-Shammari KF, Al-Khabbaz AK, Al-Ansari JM, Neiva R, Wang H-L. Risk indicators for tooth loss due to periodontal disease. J Periodontol 2005; 76:1910-1918. 27. Chambrone LA, Chambrone L. Tooth loss in well maintained patients with chronic periodontitis during long-term supportive therapy in Brazil. J Clin Periodontol 2006; 33:759-764. 28. Eickholz P, Kaltschmitt J, Berbig J, Reitmer P, Pretzl B. Tooth loss after active periodontal therapy. I: Patient-related factors for risk, prognosis, and quality of outcome. J Clin Periodontol 2008;35:165-174. 29. Jansson L, Lagervall M. Periodontitis progression in patients subjected to supportive maintenance care. Swed Dent J 2008;32:105-114. 30. Tsami A, Pepelassi E, Kodovazenitis G, Komboli M. Parameters affecting tooth loss during supportive care in a periodontal population seeking comprehensive care. J Clin Periodontol 2009; 27:824-831. 31. Dannewitz B, Zeidler A, Hüsing J, et al. Loss of molars in periodontally treated patients: results 10 years and more after active periodontal therapy. J Clin Periodontol 2016; 43: 53–62. 32. Page RC, Eke PI. Case definitions for use in population based surveillance of periodontitis. J Periodontol 2007; 78: 1387 – 1399. 33. Tonetti MS, Claffey N. Advances in the progression of periodontitis and proposal of definitions of a periodontitis case and disease progression for use in risk factor research. Group C consensus report of the 5th European workshop in periodontology. J Clin Periodontol 2005; 32 (suppl 6): 210 – 213. 34. Chambrone L, Chambrone D, Lima LA, Chambrone LA. Predictors of tooth loss during long-term periodontal maintenance: a systematic review of observational studies. J Clin Periodontol 2010;37:675-684. 35. Vatne JF, Mehlum Gunleiksrud T, Gjermo P, Sandvik L, Preus HR. Perception of own efforts; Patient centered - vs. clinically observed outcomes of non-surgical periodontal therapy in a Norwegian population. BMC Oral Health 2015; 15:61. doi: 10.1186/s12903-015-0037-3
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Corresponding Author; Hans R Preus, Dept of Periodontology, IKO, Faculty of Dentistry, PO 1109 Blindern, 0317 Oslo, Norway, +47 22 85 21 63 (tel.), [email protected]. (May be published) Submitted May 25, 2016; accepted for publication August 11, 2016. Figure 1 Intraoral distribution of teeth missing at baseline (miss. BL), extracted before treatment commencement (Bef. Tx), during the first year after treatment commencement (Tx-1yr) and between the year 1 and year 5 follow-up examinations among the 161 participants who completed the trial. Table 1. Mean number of teeth (standard deviation) retained at various time points during the study, according to treatment modality. All valid observations (AVO) at 1 year (AVO1yr) refers to participants retained in study at the one-year follow-up examination, while AVO3yr and AVO5yr refer to participants retained in study at the three- and five-year follow-up examinations, respectively. Time of Participant subset Treatment group assessment FDIS+MET FDIS SRP+MET SRP Total Baseline All enrolled (n=184) 23.9 (4.3) 24.0 (3.9) 22.9 (3.8) 24.7 (3.6) 23.9 (3.9) AVO1yr (n=180) 24.0 (4.3) 24.0 (3.9) 22.8 (3.8) 24.7 (3.7) 23.9 (3.9) AVO3yr (n=167) 23.9 (4.4) 24.2 (4.0) 23.0 (3.8) 24.7 (3.8) 23.9 (4.0) AVO5yr (n=161) 24.0 (4.4) 24.1 (4.0) 22.8 (3.8) 24.6 (3.9) 23.9 (4.1) 1-yr follow-up AVO1yr (n=180) 23.2 (4.6) 23.3 (3.9) 22.1 (4.2) 24.1 (4.0) 23.2 (4.2) AVO3yr (n=167) 23.3 (4.6) 23.5 (4.0) 22.2 (4.2) 24.2 (4.0) 23.3 (4.2) AVO5yr (n=161) 23.4 (4.6) 23.5 (4.0) 22.0 (4.2) 24.1 (4.0) 23.2 (4.0) 3-yr follow-up AVO3yr (n=167) 23.0 (5.0) 23.2 (4.1) 21.8 (4.5) 24.0 (3.9) 23.0 (4.4) AVO5yr (n=161) 23.1 (5.0) 23.2 (3.9) 21.7 (4.5) 23.9 (3.9) 23.0 (4.5) 5-yr follow-up AVO5yr (n=161) 23.0 (5.0) 23.0 (4.3) 21.1 (5.0) 23.6 (4.1) 22.7 (4.7) Table 2. Distribution of the 161 participants, who completed the 5-yr study, according to the number of teeth lost, by study period and treatment group. Time period Number of Treatment group Total teeth lost FDIS+MET FDIS SRP+MET SRP BL - 1 yr No tooth loss 28 (68%) 24 (62%) 28 (67%) 29 (74%) 109 (68%) 1 tooth 5 (12%) 10 (26%) 4 (10%) 5 (13%) 24 (15%) 2 teeth 6 (15%) 1 (3%) 5 (12%) 3 (8%) 15 (9%) 3 teeth 1 (2%) 2 (5%) 3 (7%) 1 (3%) 7 (4%) 4+ teeth 1 (2%) 2 (5%) 2 (4%) 1 (3%) 6 (4%) Mean # (sd) of teeth lost among 1.8 (0.9) 1.7 (1.2) 2.3 (1.2) 1.8 (1.0) 1.9 (1.1) those patients who lost teeth 13 15 14 10 52 1 yr – 5 yr No tooth loss 32 (78%) 24 (62%) 26 (62%) 24 (62%) 106 (66%) 1 tooth 4 (10%) 12 (31%) 6 (14%) 12 (31%) 34 (21%) 2 teeth 3 (7%) 2 (5%) 5 (12%) 2 (5%) 12 (7%) 3 teeth 2 (5%) 1 (3%) 2 (5%) 1 (3%) 6 (4%) 4+ teeth 3 (7%) 3 (2%) Mean # (sd) of teeth lost among 1.8 (0.8) 1.3 (0.6) 2.4 (1.6)* 1.3 (0.6) 1.7 (1.1) those patients who lost teeth 9 15 16 15 55 BL - 5 yr No tooth loss 23 (56%) 14 (36%) 19 (45%) 17 (44%) 73 (45%) 1 tooth 8 (20%) 14 (36%) 5 (12%) 12 (31%) 39 (24%) 2 teeth 4 (10%) 5 (13%) 6 (14%) 7 (18%) 22 (14%) 3 teeth 2 (5%) 4 (10%) 7 (17%) 1 (3%) 14 (9%) 4+ teeth 4 (10%) 2 (5%) 5 (12%) 2 (5%) 13 (8%) Mean # (sd) of teeth lost among 2.2 (1.5) 1.8 (1.6) 3.0 (2.2) † 1.7 (0.9) 2.2 (1.6) those patients who lost teeth 18 25 23 22 88 * Statistically significantly higher than for group FDIS (p=0.031, ANOVA with Bonferroni correction) 9
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† Statistically significantly higher than for group SRP (p=0.019, ANOVA with Bonferroni correction)
‡ Percentages may not add up to 100% due to rounding. Table 3. Reasons for tooth extractions among the 161 participants, who completed the 5-yr study, by study period and treatment group Period Reason for extraction FDIS+MET FDIS SRP+MET SRP Total n of teeth n of teeth n of teeth n of teeth n of teeth (%) (%) (%) (%) (%) * Total periodontitis 8 (33%) 6 (23%) 7 (22%) 5 (29%) 26 (26%) BL – 1 yr < 25% attachment† Fracture Endodontic/pulpal problems Miscellaneous‡ Total number of teeth extracted Extracted before Tx commencement 1 yr – 5 yr Total periodontitis < 25% attachment† Fracture Endodontic/pulpal problems Miscellaneous‡ Total number of teeth extracted BL – 5 yr Total periodontitis < 25% attachment† Fracture Endodontic/pulpal problems Miscellaneous‡ Total number of teeth extracted *
9 (38%) 2 (8%) 4 (17%) 1 (4%) 24 17 (71%) 6 (38%) 5 (31%) 4 (25%) 1 (6%) 16 8 (20%) 15 (38%) 7 (18%) 8 (20%) 2 (5%) 40
12 (46%) 2 (8%) 6 (23%) 26 21 (81%) 2 (11%) 2 (11%) 6 (32%) 8 (42%) 1 (5%) 19 8 (18%) 14 (32%) 8 (18%) 14 (32%) 1 (2%) 45
17 (53%) 1 (3%) 5 (16%) 2 (6%) 32 28 (88%) 2 (5%) 2 (5%) 10 (26%) 12 (32%) 12 (32%) 38 9 (13%) 19 (27%) 11 (16%) 17 (24%) 14 (20%) 70
6 (35%) 2 (12%) 2 (12%) 2 (12%) 17 15 (88%) 1 (5%) 4 (21%) 10 (53%) 4 (21%) 19 6 (17%) 6 (17%) 6 (17%) 12 (33%) 6 (17%) 36
Most (81 of 99) of the teeth extracted in this period were extracted before treatment commencement.
†includes hypermobility ‡includes deep caries, root resorption, accident, wrong tooth, unstated reasons Table 4. The mean value of the highest clinical attachment level (mm) recorded in each extracted tooth at the last clinical examination before the extraction. Given according to treatment group and time of extraction. Based on the 161 participants who completed the 5-year trial. n refers to the number of teeth extracted. Period of extraction Treatment group Total FDIS+MET FDIS SRP+MET SRP Mean (sd) n Mean (sd) n Mean (sd) n Mean (sd) n Before treatment 8.8 (1.8) 10.0 (1.7) 9.4 (1.7) 8.7 (1.9) 9.3 (1.8) commencement 17 21 28 15 81 From active treatment 6.6 (4.2) 7.8 (2.9) 5.0 (4.2) 7.5 (4.9) 6.7 (3.7) commencement to year 1 7 5 4 2 18 Between year 1 and year 3 5.5 (4.2) 6.5 (3.2) 4.8 (2.9) 4.2 (2.6) 5.3 (3.3) 10 12 16 6 44 Between year 3 and year 5 5.2 (3.0) 5.3 (2.5) 4.7 (3.2) 5.2 (3.4) 5.0 (3.1) 6 7 22 13 48
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44 (44%) 7 (7%) 17 (17%) 5 (5%) 99 81 (82%) 5 (5%) 10 (11%) 25 (27%) 34 (37%) 18 (20% 92 31 (16%) 54 (28%) 32 (17%) 51 (27%) 23 (12%) 191
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Table 5. The mean value of the highest probing pocket depth (mm) recorded in each extracted tooth at the last clinical examination before the extraction. Given according to treatment group and time of extraction. Based on the 161 participants who completed the 5-year trial. Treatment group FDIS+MET FDIS SRP+MET SRP Total Period of extraction Mean (sd) Mean (sd) Mean (sd) Mean (sd) Before treatment 8.7 (1.8) 10.0 (1.9)* 8.2 (2.3) 8.5 (1.9) 8.8 (2.1) commencement From active treatment 5.4 (3.2) 5.2 (2.6) 5.0 (2.4) 5.5 (3.5) 5.3 (2.7) commencement to year 1 Between year 1 and year 3 3.9 (2.4) 4.1 (1.2) 3.3 (1.1) 3.2 (0.8) 3.6 (1.5 ) Between year 3 and year 5 3.5 (1.4) 4.6 (1.7) 3.3 (1.4) 3.9 (1.6) 3.7 (1.5) * Statistically significantly higher than for group SRP+MET (p=0.014, ANOVA with Bonferroni correction)
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