Periodontal regeneration compared with access flap surgery in human intra-bony defects 20-year follow-up of a randomized clinical trial: tooth retention, periodontitis recurrence and costs

TLDR: Regeneration provided better long-term benefits than Flap: no tooth loss, less periodontitis progression and less expense from re-intervention over a 20-year period.

Abstract: AIM: Compare the long-term outcomes and costs of three treatment modalities in intra-bony defects. MATERIALS AND METHODS: Forty-five intra-bony defects in 45 patients had been randomly allocated to receive: modified papilla preservation technique with titanium-reinforced expanded-polytetrafluoroethylene (ePTFE) membranes (MPPT Tit, N = 15); access flap with expanded-PTFE membranes (Flap-ePTFE, N = 15) and access flap alone (Flap, N = 15). Supportive periodontal care (SPC) was provided monthly for 1 year, then every 3 months for 20 years. Periodontal therapy was delivered to sites showing recurrences. RESULTS: Forty-one patients complied with SPC. Four subjects were lost to follow-up. Clinical attachment-level differences between 1 and 20 years were -0.1 ± 0.3 mm (p = 0.58) in the MPPT Tit; -0.5 ± 0.1 mm (p = 0.003) in the Flap-ePTFE and -1.7 ± 0.4 mm (p < 0.001) in the Flap. At 20 years, sites treated with Flap showed greater attachment loss compared to MPPT Tit (1.4 ± 0.4 mm; p = 0.008) and to Flap-ePTFE (1.1 ± 0.4 mm; p = 0.03). Flap group lost two treated teeth. Five episodes of recurrences occurred in the MPPT Tit, six in the Flap-ePTFE and fifteen in the Flap group. Residual pocket depth at 1-year was significantly correlated with the number of recurrences (p = 0.002). Sites treated with flap had greater OR for recurrences and higher costs of re-intervention than regenerated sites over a 20-year follow-up period with SPC. CONCLUSIONS: Regeneration provided better long-term benefits than Flap: no tooth loss, less periodontitis progression and less expense from re-intervention over a 20-year period. These benefits need to be interpreted in the context of higher immediate costs associated with regenerative treatment. These initial observations need to be extended to larger groups and broader clinical settings.

Figures

Table 1 Plaque control and gingival inflammation. Percentage of sites exhibiting detectable plaque or bleeding on probing at different time points

Table 3 Number of visits per patient req between 1 and 20 years over t between-group differences.

Table 2 Within-group changes in mm (paired t-test) between 1- and 20-years values for CAL and PPD and between-groups differences (analysis of variance).

Full text

Accepted Article
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/jcpe.12638
This article is protected by copyright. All rights reserved.
Received Date : 11-Feb-2016
Revised Date : 04-Oct-2016
Accepted Date : 05-Oct-2016
Article type : Randomized Clinical Trial
Periodontal Regeneration Compared with Access Flap Surgery in Human Intrabony
Defects 20-year Follow-up of a Randomized Clinical Trial: Tooth Retention,
Periodontitis Recurrence and Costs.
Running Title: 20-Year follow-up of regeneration
Pierpaolo Cortellini MD*§, Jacopo Buti**, Giovanpaolo Pini Prato MD*, Maurizio S.
Tonetti DMD*§#
* Accademia Toscana di Ricerca Odontostomatologica (ATRO), Florence, Italy
§ European Research Group on Periodontology (ERGOPERIO), Genova, Italy
** School of Dentistry, University of Manchester, Manchester, UK
#Dept. of Periodontology, Faculty of Dentistry, Hong Kong University, Hong Kong, PRC
SAR.
Corresponding Author: Pierpaolo Cortellini
Via Carlo Botta 16, 50136 Firenze
Phone +39 055 243950 – Fax +39 055 2478031
E-mail sandro@cortellini.org

Accepted Article
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Supported in part by: Accademia Toscana di Ricerca Odontostomatologica, Firenze, Italy;
European Research Group on Periodontology (ERGOPERIO), Genova, Italy
Key words: Intrabony defects, Periodontal Regeneration, Long term, Cost analysis
Conflict of Interest and Source of Funding Statement
The authors have stated explicitly that there are no conflicts of interest in connection with
this article.
Abstract
Aim: compare the long-term outcomes and costs of 3 treatment modalities in intrabony
defects.
Materials and Methods: 45 intrabony defects in 45 patients had been randomly allocated to
receive: modified papilla preservation technique with titanium reinforced e-
polytetrafluoroethylene (ePTFE) membranes (MPPT Tit, N=15); access flap with e-PTFE
membranes (Flap-ePTFE, N=15); access flap alone (Flap, N=15). Supportive periodontal
care (SPC) was provided monthly for 1 year, then every 3 months for 20 years. Periodontal
therapy was delivered to sites showing recurrences.
Results: 41 patients complied with SPC. 4 subjects were lost to follow-up. Clinical
attachment level differences between 1 and 20 years were -0.1±0.3mm (P=0.58) in the MPPT
Tit; -0.5±0.1mm (P=0.003) in the Flap-ePTFE; -1.7±0.4mm (P<0.001) in the Flap. At 20-

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years, sites treated with Flap showed greater attachment loss compared to MPPT-Tit (1.4 ±
0.4 mm; P=0.008) and to Flap-ePTFE (1.1 ± 0.4 mm; P=0.03). Flap group lost 2 treated
teeth. Five episodes of recurrences occurred in the MPPT-Tit, 6 in the Flap-ePTFE, 15 in the
Flap group. Residual pocket depth at 1-year was significantly correlated with the number of
recurrences (P=0.002). Sites treated with flap had greater OR for recurrences and higher
costs of re-intervention than regenerated sites over a 20-year follow-up period with SPC.
Conclusions: Regeneration provided better long-term benefits than Flap: no tooth loss, less
periodontitis progression, less expense from reintervention over a 20-year period. These
benefits need to be interpreted in the context of higher immediate costs associated with
regenerative treatment. These initial observations need to be extended to larger groups and
broader clinical settings.
Clinical Relevance
Scientific rationale for the study
Peristent deep pockets associated with intrabony defects entail high risk of recurrence and
progression of periodontitis over time. Intrabony defects can be treated either with
regenerative or flap surgery. This study evaluates the 20 year clinical stability of sites treated
with regeneration compared to flap sugery
Principal findings
Sites treated with regeneration are clinically more stable, show less recurrences, no tooth-loss
and lower costs associated with re-interventions than sites treated with access flap surgery
alone

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Practical implications
Clinicians should consider the long-term advantages of applying regenerative surgery when
treating deep intrabony defects. The higher initial cost of regeneration needs to be taken into
account.
Introduction
Teeth with deep periodontal pockets associated with deep intrabony defects have long been
considered a clinical challenge. Various approaches, including scaling and root planing, flap
surgery, osseous resective surgery, and periodontal regeneration have been proposed for the
treatment of intrabony defects (Pagliaro et al. 2008). Periodontal regeneration is effective in
the treatment of 1- 2- 3-wall intrabony defects or combination thereof, from very deep to
shallow, from wide to narrow (Cortellini & Tonetti 2015). In this context, the ability to
predictably obtain greater attachment level gains and shallower, maintainable pockets with
respect to standard flap procedures are key elements for the clinical decision to treat
intrabony defects with periodontal regeneration (Murphy & Gunsolley 2003, Needleman et
al. 2006, Esposito et al. 2009). The persistence of deep pockets following active periodontal
therapy has been associated with increased probability of tooth loss in patients attending
supportive periodontal care programs (Matuliene et al. 2008). A growing amount of evidence
indicates that results obtained with periodontal regeneration can be maintained over time
resulting in long-term retention of teeth presenting at baseline with deep pockets associated
with intrabony defects (Cortellini & Tonetti 2004, Sculean et al. 2008, Pretzl et al. 2009b,
Nygaard-Østby et al. 2010). Long-term studies after periodontal regeneration report
substantial stability of the outcomes over time in patients who do not smoke and comply with
a regular periodontal supportive care program (Cortellini et al. 1994, 1996, 1999, Cortellini
& Tonetti 2004, Eickholz et al 2007, Sculean et al. 2008, Pretzl et al. 2009, Nygaard-Østby et

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al. 2010). These observations are in agreement with clinical studies emphasizing the
importance of high oral hygiene standards to maintain teeth in healthy condition for long
periods of time (Axelsson et al 2004, Lindhe & Nyman 1984, Huynh-Ba et al. 2009,
Chambrone et al. 2010, Leininger et al. 2010, Bäumer et al. 2011, Ng et al. 2011). So far, no
prospective controlled studies with observation periods above 10 years have compared the
stability of outcomes obtained with regenerative and non-regenerative treatment modalities in
intrabony defects.
Aim of this follow-up study was to evaluate and compare the clinical stability of treatment
outcomes obtained with 2 different regenerative approaches and flap surgery in intrabony
defects and to perform a recurrence analysis to evaluate costs of re-interventions required
over a follow-up period of 20 years with regular supportive periodontal care.
Materials and Methods
Experimental Design
This 20-year follow-up of a randomized controlled clinical trial compares three treatment
modalities in deep intrabony defects: i) the test group was treated with titanium reinforced e-
PTFE membranes and the modified papilla preservation technique (MPPT Tit, Cortellini et al
1995a); ii) a barrier membrane group was treated with an access flap procedure and e-PTFE
membranes (Flap e-PTFE, Cortellini et al 1993); iii) a third group was treated with an access
flap procedure according to the Modified Widman Flap approach (Flap, Ramfjord & Nissle
1974). The design of the original trial has been reported along with the one year results
(Cortellini et al 1995b). Clinical outcomes of the three groups were longitudinally followed
for 20 years (Figure 1). The study protocol was approved in 1993 by the Ethic Committee of
the Accademia Toscana di Ricerca Odontostomatologica (ATRO, Firenze Italy). All patients
gave informed consent to participate into the clinical trial. Follow up data were recorded in

Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "Periodontal regeneration compared with access flap surgery in human intrabony defects 20year followup of a randomized clinical trial: tooth retention, periodontitis recurrence and costs" ?

At 20A cc ep te d A rt ic le This article is protected by copyright. 

Q2. What have the authors stated for future works in "Periodontal regeneration compared with access flap surgery in human intrabony defects 20year followup of a randomized clinical trial: tooth retention, periodontitis recurrence and costs" ?

This material does not allow further speculation into this aspect but allows better hypothesis generation for future studies. The data presented in this long-term RCT are pilot in nature and will have to be confirmed in larger trials but some consideration should be made as they provide insight into the design of future trials and analyses of ongoing ones. These initial data suggest that periodontal regeneration requires a higher initial cost but that as time passes the initial investment pays off in two ways: i ) higher tooth retention and less periodontitis progression ; and ii ) lower investment to manage periodontitis progression and tooth loss. Most of the cost for re-treatment was incurred in the second decade of observation and suggests that the added initial costs of regeneration may be even more justified for subjects with a long life expectancy. 

Q3. What is the effect of deep pockets on the patient?

The persistence of deep pockets following active periodontal therapy has been associated with increased probability of tooth loss in patients attending supportive periodontal care programs (Matuliene et al. 2008). 

Q4. What was the treatment of the defets?

Fifteen defets in 15 patients were treated with titanium reinforced membranes and the modified papilla preservation technique (Cortellini et al 1995a). 

Q5. What was the value of the unit of analysis?

The value of 0 indicated that the unit of analysis (patient) was no longer in the study (end of observational period, drop-out or tooth extraction). 

Q6. What is the purpose of this study?

Aim of this follow-up study was to evaluate and compare the clinical stability of treatment outcomes obtained with 2 different regenerative approaches and flap surgery in intrabony defects and to perform a recurrence analysis to evaluate costs of re-interventions required over a follow-up period of 20 years with regular supportive periodontal care. 

Q7. What are the key elements for the clinical decision to treat intrabony defects with periodontal?

In this context, the ability to predictably obtain greater attachment level gains and shallower, maintainable pockets with respect to standard flap procedures are key elements for the clinical decision to treat intrabony defects with periodontal regeneration (Murphy & Gunsolley 2003, Needleman et al. 2006, Esposito et al. 2009). 

Q8. What is the main driver of stability after access flap surgery?

All rights reserved.group (Cortellini et al 1996); in that study results indicated that patient - rather than treatment modality - factors are the major drivers of stability or recurrence after regenerative and conventional treatment in a given subject. 

Q9. How many practices were selected for this study?

The 9 selected practices was a convenience sample of representative practices with more then 10 years of experience in providing periodontal care in Italy. 

Q10. How was the recurrence of periodontitis diagnosed?

flagged by the attending hygienist during the routine SPC appointment (Lang et al 1986, Claffey et al 1990); ii) disease recurrence was then confirmed through the detection of a CAL loss ≥2mm by the calibrated examiner. 

Q11. What is the risk of recurrence of periodontitis?

Peristent deep pockets associated with intrabony defects entail high risk of recurrence and progression of periodontitis over time. 

Q12. What is the significance of the observation period of the present study?

The limited 3-year observation period of that study compared with the excellent outcomes noted in the present study during the first 10 years after access flap surgery question the significance of those observations: in subjects participating and compliant with the objectives of a good SPC program the choice of regenerative rather than access flap surgery does not seem to impact harder outcomes short to medium-term. 

Q13. What is the main difference between regenerative and conventional surgery?

On one side the nature of the histologic healing expected after access flap rather than regenerative surgery: repair with a long-junctional epithelium may be less stable. 

Q14. What is the significance of the association between residual PPD and re-treatment?

The association between residual PPD and progression/need for re-treatment observed in this study is consistent with the importance of this major ecological determinant on long-term stability, independent on other local and patient factors (Lang & Tonetti 1996, McGuire & Nunn 1996a, b, Kwok & Caton 2007).