Joint Degree Master Program of the International Medical College

and the Universities Dresden, Essen, Saarland, Leipzig, Szeged and Bangkok Scientific director: Univ.-Prof. Dr. med. Dr. med. dent. Dr. h.c. U. Joos

Outcome of dental implants in patients with a history of periodontitis

Master thesis

Master of Science in Implantology and Dental Surgery

International Medical College Gartenstraße 21

D-48147 Münster

from:

Dr. S. M. M. Bakush

2013

Dr. surname, street XX, postal code, city

Summary Objectives: the aim of the present study was to perform a systematic review of

prospective and retrospective studies regarding the long term (>5years) outcome of

dental implant placed in patients with previous tooth loss due to the history of

periodontitis and to assess how this impact on implant survival, peri-implantitis risk as

well as soft and hard tissue loss.

Methods: an electronic search of the literature was performed between March and June

2013 using MEDLINE (National Library of Medicine)-PubMed, a literature search for

articles published up to and including year 2012was performed.

Results: the initial database search yielded 1433 studies, 40 studies passed the first

review phase and 15 studies were finally selected with >5years observation period.

Because of considerable discrepancies among these studies, statistical analysis was not

performed.

Conclusions: the survival and success rate of dental implant in periodontally

compromised patients has to be not significant different than periodontally healthy

subjects. However, there was a tendency toward greater amount of marginal bone loss

and higher risk of peri-implant disease in patients with history of periodontitis.

Key words: dental implant, periodontitis, peri-implantitis, survival, bone loss.

2

Contents 1 Introduction ................................................................................................................ 3

2 Material and methods................................................................................................. 5

3 Results ........................................................................................................................ 6

3.1 Periodontitis and peri-implantitis ...................................................................... 7

3.1.1 Periodontal pocket depth (PPD) .................................................................. 7

3.1.2 Bleeding on probing (BoP) ....................................................................... 11

3.1.3 Marginal bone loss .................................................................................... 12

3.1.4 Implant survival ........................................................................................ 13

3.2 The prevalence of peri implantitis................................................................... 14

3.3 Effect of smoking ............................................................................................ 14

4 Discussion ................................................................................................................ 15

5 List of tables............................................................................................................. 22

6 List of abbreviations ................................................................................................ 23

7 Bibiliography ........................................................................................................... 24

3

1 Introduction

During the last decade, the use of dental implants has become an established and widely

used treatment modality for the rehabilitation of patients who have experienced loss of

teeth. Recent systematic reviews (1, 2) have provided evidences that support the suitable

long term prognosis of implant therapy in general population.

Although the general effect of implant therapy provide a high rate of success,

complications do occur which are associated with failure and loss of implant.

Bone quality, surgical trauma, bacterial contamination and overload are factors

associated with early implant failure, while a history of periodontal disease seems to

induce the patient to a higher risk of biological complications (peri-implant disease)

which is considered a late complication of implant therapy (3).

Several risk factors for peri-implant disease have been classified by many studies. It has

been reported that poor oral hygiene can increase the risk of peri-implant disease by 2.5

times as plaque initiated peri-implant mucositis (4) Therefore, patient compliance and

motivation are essential for long term peri-implant health.

A history of periodontal disease with deep pockets is considered another risk factor for

peri-implant disease; this may highlight the important role of undergoing an adequate

periodontal maintenance program (5, 6).

Smoking is associated with high peri-implant marginal bone loss compared with non-

smokers (4, 7). In addition, diabetes represents as a risk factor for periodontitis and

therefore may increase the risk of peri-implant disease (8).

However, there is no enough data available regarding the prognosis of dental implants

in periodontally compromised patients which represent a large proportion of those who

would be seeking implant therapy.

There are two stages of peri implant disease, namely, peri-mucositis and peri-

implantitis. While peri-implant mucositis is a reversible inflammation of the soft tissue

without any bone loss, peri-implantitis affects both the soft and hard tissue resulting in

loss of the supporting peri-implant bone (9).

The pathogenesis of peri-implantitis and periodontitis is very similar, both being

stimulated by a pathogen-containing biofilm. This plaque biofilm that develops at the

implant site has shown to resemble that at the neighboring teeth (10).

4

By placement of dental implant into partially edentulous dentition, the ecological

condition of the oral cavity impacting biofilm formation on implant may vary from that

of fully edentulous patients (11).

Therefore pocket may act as a reservoir for colonization of periodontal pathogens

around implants. This implies the important role of periodontal maintenance programs

which may affect on the prognosis of osseointegrated implants in periodontally

compromised patients which was indicated by several studies (12-15).

In the previously published literature reviews the outcome of dental implant therapy in

individuals with and without history of periodontal disease-associated tooth loss has

been analysed (16,17).In addition the prevalence of peri-implantitis and the amount of

peri-implant marginal bone loss was investigated.

Reviews of short and long terms studies (18,19) evaluated the marginal bone loss

around implants in generalized aggressive and chronic periodontitis patients .The

controversy was whether the previous history of aggressive periodontitis had more

impact on amount of marginal bone loss than a history of chronic periodontitis,and if

there is a difference in the amount of marginal bone loss between short and long term

studies.

In order to achieve suitable results, it is thus important that the included studies in the

present review have long term observation periods, as peri-implantitis disease is

considered to be one of the late complications of implant therapy.

Basically, information regarding the susceptibility of patients with a history of

periodontitis to peri-implantitis is still controversial in the literature, as is the long-term

performance of implants in these patients.

Thesis objective

Therefore, the aim of this review was to evaluate the long term survival rate of dental

implants placed in patients with previous tooth loss due to periodontitis and to assess its

impact on the implant success rate.

In this context the following questions have to be answered:

5

Research questions

1 Do patients susceptible to periodontal disease demonstrate an elevated risk for peri-

implantitis and loss of hard and soft tissue?

2. What are the success and survival rates of implants placed in such patients after a

minimal observation period of 5 years?

2 Material and methods

An electronic search of the literature was performed between March and June 2013 to

identify all articles investigating the above addressed questions. Information about the

survival rate of implants placed in patients with a history of periodontitis was retrieved.

This was evaluated by several parameters such as periodontal pocket depth, bleeding on

probing and marginal bone loss. In the present review, the search was also extended to

evaluate the incidence of peri-implantitis in periodontally-susceptible patients. The

search was conducted using MEDLINE (National Library of Medicine)-PubMed

without restrictions concerning the date of publication. Multiple keywords, including

dental implant, periodontitis, periodontal pocket, bone loss,were used (connecting

different keywords with AND, OR). This was followed by a manual search, and

references were used to identify relevant articles. A second electronic search was

performed using additional keywords such as: bleeding, survival rate and peri-

implantitis. The titles and abstracts of all articles identified from the electronic and

manual search were screened to eliminate articles that clearly failed to meet the

following inclusion and exclusion criteria:

Inclusion criteria:

• Randomized controlled clinical trials, prospective and retrospective clinical

studies.

• The mean follow up time should be at least 5 years.

Exclusion criteria:

• In vitro and animal studies, as well as case reports or case studies.

• Studies in a language other than English or without an English abstract.

6

• When multiple reports of the same study were identified, only the most recent

report was included.

The parameters were investigated based on the following definitions:

Periodontal pocket depth: is measured from the floor of the gingival sulcus to the

gingival margin and measured with the aid of periodontal probe.

Bleeding on probing: the susceptibility of peri-implant tissue to bleed indicate the

presence of inflammation.

Marginal bone loss: was measured as a distance from marginal bone level to the

shoulder of the implant.

Survival rate of implant: preservation of osseointegrated and no need to be removed at

time of examination.

Incidence of peri-implantitis: defined as signs of inflammation and bleeding around

the implant associated with progressive bone loss.

3 Results

The initial database search yielded 1433 studies, 40 studies passed the first review

phase, and 15 studies were finally selected after screening on the basis of the inclusion

and exclusion criteria. The included studies were either prospective or retrospective in

nature and with observation period of at least 5 years.

Two of the included studies reported long-term data about patients with generalized

aggressive periodontitis (20, 21), three studies reported long term data for chronic

periodontitis patients (22-24). In the study of De.Boever 2009, data about both chronic

and aggressive periodontitis was reported (25). A comparison was made in the three of

the included studies between severely, moderately periodontally compromised and

periodontally healthy patients (26-28). By the study of Costa et al .2012, the sample of

the study was divided into two groups: one group with preventive maintenance

(GTPgroup) and other group without preventive maintenance during the study period

(GNTP). In this context, .several procedures during the preventive maintenance visit

were performed, such as assessment of the periodontal and peri-implant status ,oral

hygiene instructions ,the application of disclosing agents and when necessary

mechanical debridement (29). Another study divided the total sample according to the

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age-related bone loss score (ArB-score) into two groups, subjects with ArB-score <25

were defined as the non-perio group, whereas those with a score >55 was considered as

the perio group (30).

Two studies reported data for periodontally healthy and periodontally-compromised

patients (5, 31). However, one of these studies divided the PHP and PCP patients into 4

groups of 20 patients using different types of implants (31). Therefore, the groups were

further subdivided into PHP-N (patients treated with Nobel Biocare implants) and PHP

–S (patients treated with Straumann dental implants), PCP-N and PCP-S.

The publication date of the studies were no older than 2002. Reasons for exclusion

were: articles written in a language other than English, non-clinical studies (case reports

and reviews) and observation periods less than 5 years.

Due to the heterogeneity of the studies (different observation periods, different sample

size ...etc), it was not possible to perform a statistical analysis of the data.

3.1 Periodontitis and peri-implantitis

The 15 studies were categorized with respect to the parameters being observed into

periodontal pocket depth (PPD), bleeding on probing (BoP), marginal bone loss (MBL),

survival rate of implants and the prevalence of peri-implantitis (Table 1).

A detailed description of the studies related to each parameter is provided below:

3.1.1 Periodontal pocket depth (PPD)

The periodontal pocket is defined as a pathologically deepened gingival sulcus. The

depth of the periodontal pocket is measured from the floor of the gingival sulcus to the

gingival margin and is measured with the aid of a periodontal probe.

The literature search yielded 9 studies evaluating the periodontal pocket depth (PPD). In

four studies, a comparison was undergone between teeth and implants. Two studies

reported deeper pockets around implants than teeth after an observation period of 5

years. A significant difference was reported especially in case of pockets with a depth of

4 mm, with an incidence of 16.9% and 26.6% around teeth and implants, respectively.

Although patients undergoing a preventive maintenance program showed better results

in terms of periodontal pocket depth, however, the PPD around implants was deeper

also under such maintenance. (29, 32) One long term study (10 years observation

period) showed no significant difference between both teeth and implants, with a PPD

8

Study Study design Observation period

No. of patients

No. of implants

PPD BoP MBL Survival rate Prevalence of peri-implantitis

Tooth Implant Tooth Implant Agerbaek et al.2006

Prospective <4 years 56 127 16.9% > 4mm

26.6% > 4mm 31.5% 44.1 % NR NR +++

3.7% > 5mm

3.9% > 5mm

3.3% > 6mm

3.9% > 6mm

Lee et al. 2012

Retrospective 5 years 60 30 PHP 30 PCP

117 61 PHP 56 PCP

NR PHP 2.81mm PCP 2.83mm

NR PHP 17.2% PCP 29.6%

PHP 0.26mm PCP 0.45mm

NR PHP 16.7% PCP without RP 36.7% PCP with RP 53.8%

Costa et al. 2012

Retrospective 5 years 80 80 GNTP >4mm 8.2 ± 12.8 % GTP >4mm 4.8 ± 8.7%

GNTP >5mm 16.7± 27% GTP >5mm 5.9 ± 13.6%

GNTP 40.4 ± 20.7% GTP 26 ± 19.6%

GNTP 62.7 ± 20.9% GTP 33.3 ± 25%

GNTP 41.5% GTP 17.9%

NR GNTP 43.9% GTP 18%

9

Study Study design Observation period

No. of patients

No. of implants

PPD BoP MBL Survival rate Prevalence of peri-implantitis

Roos-Jansaker et al. 2006

Prospective 9-14 years 218 1057 NR NR NR 46.6 ± 27%

NR 95.7% +++

Karoussis et al. 2003

Prospective 10 years 53 Group A 8 Group B 45

112 NR GroupA3.03mm GroupB2.52mm

NR GroupA O.40 GroupB 0.26

GroupA (m=0.48mm,d=0.50mm) GroupB (m=1mm, d=0.94m)

GroupA90.5% GroupB96.5%

GroupA 28.6% GroupB 5.8%

Karoussis et al. 2004

Prospective 10 years 89 179 2.02 mm

2.78 mm 30.20 42.20 m= 0.68mm d= 0.72mm

NR +++

Wennström et al.2004

Prospective 5years 51 149 NR 3.1mm(o.8) NR 5%(10.6) 0.41mm 97.3% NR

Mengel et al.2007

Prospective 10years 10 43 3.0-3.6 mm

<4mm NR NR GAgp 1.3mm PHP 100% PCP 83.3%

NR

De.Boever et al.2009

Prospective 11 years 221 513 NR m 3.18±1 d 3.15 ±1

NR 38.4% m 0.28 ±0.7 d 0.24 ±0.6

NSP98% CAP96% GAP80%

12.7%

Gianserra et al.2010

Retrospective 5years 1477 5843 NR NR NR NR S P 2.6mm M P 2.7mm N P 1.2 mm

NR NR

Hardt et al.2002

Retrospective 5years 97 NPG 25 PG 25

346 NR NR NR NR NPG 1.7mm PG 2.2mm

NPG97% PG 92%

NR

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Study Study design Observation period

No. of patients

No. of implants

PPD BoP MBL Survival rate Prevalence of peri-implantitis

Swierkot et al.2012

Prospective 5-16years 53

179 NR NR NR NR NR PHP 100% GAgp96%

PHP 10% GAgP 26%

Matarasso et al.2010

Retrospective 10years 80 PHP 40 PCP 40

80 PHP-N 20 PHP-S 20 PCP-N 20 PCP-S 20

NR NR NR

PHP-N 15.9±2.3 PHP-S 16.3±1.3 PCP-N 16.2±1.6 PCP-S 14.4±2.3

PHP-N 1.95±0.42 PHP-S 1.43±0.38 PCP-N 2.78±0.48 PCP-S 2.32±0.41

PHP-N 95% PHP-S 95% PCP-N 95% PCP-S 85%

NR

Roccuzzo et al.2010 part 1

Prospective

10years

101

246

NR NR NR NR

PHP0.75(±0.88) Mpcp1.14(±1.11 Spcp0.98(±1.22)

PHP 96.6% M pcp 92.8% S pcp 90%

+++

Roccuzzo et al.2011 part 2

Prospective 10years 101 246 NR PHP 3.1±0.5 M PCP 3.5±0.9 S PCP 3.9±0.7

NR PHP 12.3±2.1 M PCP 31±2.5 S PCP 30.9±2.6

NR NR PHP 10.7% M PCP 27% S PCP 47.2%

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Table 1: Studies included in the review. PPD = Periodontal pocket depth, BoP = Bleeding on probing, MBL = Marginal bone loss, PHP = Periodontal-healthy patient, PCP = Periodontal-compromised patient, RP = Residual pocket, GNTP = Group with no periodontal maintenance, GTP = Group with periodontal maintenance, m = mesial, d = distal , GAgp, GAP = Generalized aggressive periodontitis, PH = Periodontally healthy, NSP =Periodontally non-susceptible patients, CAP = Chronic adult periodontitis, SP = Patients with severe periodontitis, MP = Patients with moderate periodontitis, NP = Patients with no periodontitis, NPG = Non-periodontal group, PG = Periodontal group, GroupA=patients with history of chronic periodontitis, GroupB=patients with no history of periodontitis, +++ = high prevalence of peri-implantitis,NR=non relevant.

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of 2.02 and 2.78mm respectively (22). In contrast, another study with the same

observation period reported deeper PPD around implants than around teeth (20).

Two studies measured the PPD in periodontally-healthy and periodontally-compromised

patients. Both studies reported statistically no significant differences in PPD (5, 23).

However, in one study significant difference was reported between patients with

residual periodontitis and healthy subjects if the criterion of PPD was ≥ 5 mm. and BoP

were used. In this study, different implant designs and surfaces were used; however,

these factors did not seem to affect the clinical parameters (5).

The two studies evaluated the periodontal pocket depth in periodontitis-susceptible

patients. Here, a PPD of ≤ 3mm in almost 80% of the cases was reported (24, 25).

In the study by Roccuzzo et al.2011, the periodontal pocket depth was compared

between three groups after 10 years observation period. Here, the mean PD was 3.1 ±

0.5 in periodontally healthy individuals (PHP), 3.5 ± 0.9 in moderately periodontally-

compromised patients (PCP) and 3.9 ± 0.7 in severely periodontally-compromised

patients. Here, the difference was considered significant between the PHP and severely

PCP patients (28).

In the same study there was also a periodontal pocket measurement of 6mm or more

around the implants in a percentage of 1.7%, 15.9% and 27.2% in PHP, moderately PCP

and severely PCP respectively (28).

3.1.2 Bleeding on probing (BoP)

Most of the studies showed bleeding on probing with different percentages. In three

studies bleeding on probing was observed around teeth and implants. Implants showed

more susceptibility to bleeding on probing after 5 and 10 years, even if periodontal

maintenance programs were followed (22, 29, 32).

Other studies compared peri-implant bleeding on probing in periodontally-compromised

subjects with periodontally healthy subjects and reported higher percentages in patients

susceptible to periodontitis with a range between 32-40% (5, 23, 25, 33).This was

controversial with another study which reported only 5% of bleeding on probing in

patients susceptible to periodontitis. Here, it is important to mention that all patients

included in this study underwent an individual periodontal maintenance program

throughout the follow-up period (24).

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There was also a significant difference in BOP between three groups in the study by

Roccuzzo et al 2010 which was 12.3+2.1% in PHP, 31.0+2.5 in moderately PCP and

30.9+2.6 in severely PCP (28).

3.1.3 Marginal bone loss

The marginal bone loss was measured as the distance from the marginal bone level to

the shoulder of the implant.

Marginal bone loss was observed in most of the included studies. In two studies, a

comparison between periodontally healthy and periodontally-compromised subjects

showed higher mean bone loss after observation periods of 10 years (22, 23). In another

study, there was no significant difference in the amount of bone loss between NPG

(1.7mm) and PG (2.2mm) patients (30). However, 64% of the PG patients had a mean

peri-implant loss of >2mm compared with 24% for the NPG patients, and the

percentage of implants showing 2mm of bone loss from baseline (abutment connection)

and after 5years was 62% in the perio group and 44% in the non-perio groups.

Four studies measured bone loss around implants in periodontitis-susceptible patients.

Three of which reported a mean bone loss of less than 1mm (22, 24, 25). One study

showed a mean marginal bone loss of 1.3mm after 10 years in patients with generalized

aggressive periodontitis (20).

In a study, after 10 years observation period, significantly higher amount of bone loss in

periodontally-compromised patients compared to periodontally healthy patients was

reported independent of the implant type used (31). In contrast, the study by Roccuzzo

et al 2010 reported no significant difference between three groups (PHP, moderately

and severely PCP) (28, 31). Both studies reported 3mm or more of bone loss(pathologic

bone resorption due to peri-implantitis) which was four time higher in PCP compared

with PHP (31). .In the other study, the percentage of sites with bone loss 3mm or more

was significant between PHP (4.7%) and severe PCP (15.1%) (28) .

There was a difference in the amount of bone loss between group with preventive

maintenance (GNTP) and group without preventive maintenance (GTP) 41.5% and

17.9% respectively after 5years observation period (29).

In the study by Gianserra et al.2010, the difference was significant in severe

periodontitis (2.6mm) compared to non periodontitis (1.2mm) (26).

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3.1.4 Implant survival

Survival rate is defined as preservation of osseointegrated implant and not need to be

removed at time of observation. Nine of the included studies was reported the survival

rate of implants in patients with a history of peridontitis. One long term study (more

than 10 years) reported a survival rate of 97.5% in periodontally-susceptible patients

(33).An almost similar high survival rate of implants was reported in another study after

an observation period of 5years (24). In contrast, one 10 year comparative study

reported a lower survival rate of 83.3% in comparison to 100% in the periodontally-

healthy patients. Here, it is noteworthy to mention that the patients included in this

study were treated for generalized aggressive periodontitis (20).This was confirmed by

two studies after more than 10 years observation period which was reported that implant

in generalized aggressive periodontitis had a five time greater risk of failure than

periodontally healthy individuals with 100% survival rate in GAgP and 96% in PHP,

which compared patients with a healthy periodontium, chronic periodontitis and

generalized aggressive periodontitis and reported a survival rate of 98%, 96% and 80%,

respectively (21, 25) .

In two studies, no significant difference was reported after an observation period of 5

years (23, 30). However, one of these studies continued the follow up period to 10 years

and reported a statistically significant difference with a survival rate of 96.5% and

90.5% for the healthy patients and patient with history of chronic periodontitis,

respectively (23) which was in accordance with the survival rate in study by Matarasso

et al.2010 was reported a survival rate between 85%-95% in periodontally compromised

individuals in dependent of the type of implant used (31). However in the same study

there was a trend toward increase loss of implant in periodontally compromised

compared to periodontally healthy subjects.

In the study by Roccuzzo et al.2010, the survival rate for solid- screw implants and all

other types of implants was reported separately (28). These solid screw implants have

not been in use for a long time. However, there was no significant difference

demonstrated between periodontally healthy, moderately-compromised and severely-

compromised subjects (96.6%, 92.8%, and 90%) for all implants and (98%, 94.2%,

90%) for the solid-screw implants.

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In the same study, there was a high incidence of implant loss in both moderate PCP and

severe PCP who did not adhere to the Supportive periodontal therapy program (SPT)

(28):

3.2 The prevalence of peri implantitis The incidence of peri-implantitis is defined as signs of inflammation and bleeding

around the implants associated with progressive marginal bone loss.

The prevalence of peri implantitis was reported in 10 studies .A correlation between

periodontitis and prevalence of peri implantitis was reported in most of the included

studies. It was reported in several studies with different observation periods, a

significantly greater incidence of peri-implantitis in patients with history of chronic

periodontitis (5, 22, 32, 33).

The use of a preventive maintenance program during the study showed to affect in the

prevalence of peri-implantitis with a percentage of 43.9% and 18% in the GNTP and

GTP, respectively (29). Another study also reported the effect of undergoing a

maintenance program for implant after insertion with 12.7% prevalence of peri-

implantitis (25).

The incidence of peri implantitis was also significantly 14 times higher in patients with

generalized aggressive periodontitis than periodontally healthy patients (21).These

results were in accordance with the study of Karousis et al.2003 which reported 28.6%

of peri-implantitis in chronic periodontitis compared to 5.8% in the non-periodontitis

group (23).

The difference was also significant in the incidence of peri-implantitis between

periodontally healthy (10.7%) and severely periodontally compromised patients (47.2%)

(27).

3.3 Effect of smoking Smoking was reported in five of the included studies. A correlation between peri-

implant marginal bone loss and smoking was reported in two of the included studies

(22, 24)..Marginal bone loss in smokers was approximately 1mm greater compared to

non-smokers (22), and 0.76mm in smokers and 0.22mm in non smokers (24).

In the study by Karoussis et al. 2003, there was no significant difference in incidence

rate of peri-implantitis, success rate, and survival rate between smokers and non-

15

smokers in both groups of patients with and without history of chronic periodontitis

(23). However , there was a tendency for a lower survival rate in smokers (80%) than

non smokers (100%) in patients with a history of periodontitis .This finding suggests

that smokers susceptible to chronic periodontitis yield a higher risk for implant loss than

non-smokers periodontal patients or patients without history of periodontal disease.

In another study, former smokers passed through an extensive period of smoking

cessation (6.3 - 9.2years) which was associated with insignificant occurrence of peri-

implantitis (29).

On the other hand, the study by Agerbaek et al .2006 reported that smoking had no

effect on BOP and on the microflora at implant site (32).

There was also three times higher risk of peri-implantitis in smokers in the study by

Roos-Jansaker et al.2006 (7).

4 Discussion The purpose of this systematic review was to evaluate the long term (>5years) survival

rate of dental implants placed in patients with previous tooth loss due to periodontitis,

and to assess how this impacts on implant survival, peri-implantitis risk as well as soft

and hard tissue loss.

Due to the heterogeneity of the studies (different observation periods, different types of

studies), it was not possible to perform a statistical analysis of the data. The gold

standard for systematic reviews is to study randomized clinical trials (RCT), which are

the studies with the most robust design. Prospective studies were classified in category

B according to the strength of evidence and clearly indicate a higher quality of data

compared to retrospective studies. However, most of the studies included in this review

were prospective in nature.

There is a debate on whether the outcome of dental implants in patients with a history of

periodontitis is as successful as has been observed in patients without periodontitis and

if these patients are prone to an increased incidence of peri-implantitis .

This present review analyzed studies up to 2012 with at least 5 years follow-up period.

One study included a relatively limited number of patients (10 patients) (20), while all

other included studies evaluated larger sample sizes (up to 1000 patients)

16

Periodontally-compromised patients have been defined by patients that have had a

history of periodontitis (chronic or aggressive), but with no active disease at the time of

implant placement. The patients are usually subjected to “successful” periodontal

therapy (nonsurgical and/or surgical) before implant placement. It has been stressed that

neglected or poorly treated periodontitis might increase the risk for peri-implantitis

(34)..However; till now there is no accepted definition for ‘successful’ periodontal

therapy. In this review, the selected studies have not clearly defined the periodontal

status of the patients at the time of implant placement. In addition, certain studies

included a control group comprising periodontally healthy individuals, whereas other

studies included only periodontally compromised patients.

Typical 5-year survival estimates reported in the literature range from 90% to 98% (35-

41), while 10-year survival estimates are in the range of 89% to 95% (34, 42-44).

However, the exact success criteria used vary considerably, but if progressive bone loss

is interpreted as the loss of >1.5 mm bone around the implant, it can be inferred that the

10-year success rate of the implants inserted in the present population of periodontally

compromised patients may be in the range of 60% to 70%. This is considerably lower

than the 10-year success estimates of 90% to 93% that have been reported for implants

inserted in healthier subjects (43). Clearly, the high bone loss rate for implants inserted

in the present periodontal patients may be indicative of a further decrease in the future

of the implant survival. Implant overload was also implicated as one of the possible

factors associated with implant failure (45). No studies considered details on

overloading of implant-supported prostheses, but some studies reported the type of

prostheses provided. Unfortunately, the types of prostheses and potential loading

situations varied widely.

The prevalence of peri-implantitis can vary depending on the criteria used to define it,

and criteria that include both radiographic bone loss and pocket depth result in a more

conservative outcome than the criteria that include pocket depth alone (46). In this

review, the criteria used to identify peri-implantitis included mainly marginal bone loss

and periodontal pocket depth.

Data reported in the literature suggest that PPD around implants placed in patients with

a history of chronic periodontitis tends to increase throughout a long-term period.

Moreover, the proportion of deep pockets seems to be higher in patients with a history

of chronic periodontitis than in periodontally healthy subjects. In one study, 80% of

17

peri-implant sites presented PPD ≤ 3mm, while only 5.3% had a value of ≥ 6mm after a

5 year observation period, resulting in a mean peri-implant PPD of 3.1mm (24). In a 10-

year study (23), demonstrated that implants placed in patients with a history of chronic

periodontitis had statistically significantly greater proportion of PPD > 5mm without

bleeding on probing, as well as of PPD = 5mm with bleeding on probing, compared

with patients without a history of periodontitis. Baelum et al. found a continuous

increase of the percentages of implants exhibiting PPD ≥ 4mm and ≥ 6mm from 1 to 5

years and subsequently from 5 to 10 years (47). Similar results were reported by

Ellegaard et al. (2006) for implants placed in patients with a history of chronic

periodontitis, following a sinus membrane elevation procedure (48). However, these

studies were not included in this review since they were non-clinical studies.

Lee et al 2012 assumed that the maintenance of periodontal health rather than the

previous history of periodontitis is the critical determinant of increased risk of peri-

implant disease (5). In this study, it was reported that patients with at least one residual

periodontal pocket ≥ 6 mm had significantly more implants with PPD ≥ 5 mm with

BOP and radiographic bone loss than both the PHP and the PCP with no residual

periodontal pockets ≥ 6 mm. On the other hand, PCP who did not have any recurrence

of periodontal pockets ≥ 6 mm had similar outcomes to the PHP, Here, the recurrence of

periodontitis, or the presence of new areas of periodontal disease progression was

indicated by the presence of at least one periodontal pocket ≥ 6 mm at the follow-up

examination. In addition, it is important to mention that all patients examined in this

study were suffering from generalized moderate-to-advanced chronic periodontitis.

The results of this study highlight the importance of supportive periodontal therapy

where clinical and radiographic parameters should be re-assessed at every follow-up

visit to detect peri-implant problems as early as possible and to find adequate therapy to

intercept the problems (49). In addition, the SPT program permits monitoring and

maintenance of periodontal stability, as this appears to be a key factor for the success of

implant therapy. This was confirmed by other studies, which also reported a significant

decrease in the incidence of peri-implantitis and implant loss due to the protective effect

of preventive maintenance (16, 29, 50). In the study by Roccuzzo et al.2010 there was a

correlation between implant failure and lack of full adhesion to SPT during the follow-

up in both PCP groups (28). On the other hand,, correctly performed SPT can maintain

high chance of implant survival even in PCP. However, it remains unclear whether

more aggressive treatment, including more surgical intervention, systemic antibiotic

18

therapy would decrease the incidence of peri-implantitis, or whether presence of

residual pocketing at the follow up visit is a marker of inherent patient susceptibility

that would not be affected by additional periodontal therapy. This was seen in the study

by Roccuzzo et al.2011 where antibiotic and /or surgical therapy was performed in 10%

of the cases in the PHP group, 27% of cases in moderate PCP and in 47.2% of cases in

the severe PCP and showed a significant differences between the PHP and severe PCP

group (27).

The second parameter evaluated in this review was the marginal bone loss. Included

studies that had a control group comprising periodontally healthy individuals indicated

that the long-term mean peri-implant marginal bone loss for patients with a history of

chronic periodontitis may be considered comparable to what has been presented for the

general population (5, 26, 30): On the other hand, one controlled study has found a

statistically significant difference in mean peri-implant marginal bone loss between

patients with a history of chronic periodontitis and periodontally healthy subjects (23).

Similar results were reported by De Boever et al. 2009, here PH patients and patients

with CP showed no difference in peri-implant variables, but patients with GAP had

more marginal bone loss, and more peri-implantitis (25)..These long term studies

suggest increased susceptibility to progressive marginal bone loss around implants in

patients with GAP. Therefore, marginal bone loss at implants in patients with GAP as

compared with implants in PH patients or CP patients was not significantly greater.

However, peri-implantitis does not seem to be system-dependent, but rather a condition

associated with several risk factors and host susceptibility. These factors include:

smoking, medical conditions such as diabetes, and the edentulous situation of the patient

(partially or completely edentulous)

It has been suggested that implants placed in partially edentulous patients are more at

risk for bacterial colonization with a perio-pathogenic micro-flora emerging from the

periodontal pockets around diseased teeth in the same mouth (13, 51, 52). They

proposed that partially edentulous patients with titanium implants will easily be

colonized by putative periodontal pathogens in contrast to fully edentulous patients.

However, if a destruction of the marginal bone around the implants occurs, this does not

seem to be solely related to the presence of a perio-pathogenic microflora. It is rather

the result of a complex interaction between the microorganisms and host factors, similar

to what has been seen around natural teeth affected with destructive periodontitis.

19

Accordingly a past history of periodontitis may represent a significant risk factor for

complications around implants in patients that have been treated for advanced

periodontitis. Untreated periodontal disease and refractory periodontitis patients are at

risk for complications and a regular maintenance program is essential to keep the

periodontal and peri-implant tissues healthy

One study demonstrated that bacterial colonization of the implant surface may cause

peri-implant mucositis (13). Consequently, it has been suggested that patients should

not be subjected to dental implant therapy if they present with inflammation or

inadequate oral hygiene (53). Therefore, infection control including extraction of non-

retainable teeth, oral hygiene instruction, scaling, root planning, and periodontal

surgery, if indicated, was performed before implant treatment. The importance of pre-

implant infection control is supported by experimental studies in humans (54-58).

Smoking is considered another factor, as it has been identified as a strong risk factor

associated with periimplant diseases (59-61). Several studies found an increased risk for

implant failure by a factor of almost 2.5 among smokers (62, 63). Smoking status was

however not always reported in the selected studies. Karoussis et al. divided both

periodontitis and non-periodontitis patients in a smoker and non-smoker group. In

patients in the periodontitis group, 47.6% of the implants were installed in smokers.

This was 19.8% of the implants in the patients without a history of periodontitis.

However, owing to the limited number of subjects followed over 10 years, the

differences in survival, incidence rates of peri-implantitis or success rates between

smokers and nonsmokers in both groups of patients, with and without a history of

chronic periodontitis, did not reach statistical significance (23). Nevertheless, there was

a trend for a lower survival rate of implants in smokers vs. non-smokers (80% vs.

100%) in patients with a history of chronic periodontitis. This finding indicates that

smokers susceptible to chronic periodontitis yield a higher risk for implant loss than

non-smoking periodontal patients (23).

Moreover, one study with a 5-year follow-up period reported that smokers exhibited

statistically significantly higher mean peri-implant marginal bone loss than non-smokers

(0.76mm vs. 0.22mm, respectively) (24).. In addition a long period of smoking

cessation reduces the harmful effects of previous tobacco history on periodontal clinical

parameters (64-67). It should be emphasized that, in the present study (29), former

20

smokers passed through an extensive period of smoking cessation (9.2 ± 6.3 years) and

were not significantly associated with the occurrence of peri-implantitis.

Conflicting results have been published about the influence of diabetes associated with a

higher risk of peri-implant disease. Some studies report a positive association (68, 69),

whereas others found no association (64, 70).Thus, diabetes was not associated with the

occurrence of peri-implant disease in subjects with pre-existing peri-implant mucositis.

This finding may well be related to the small number of diabetics in the initial sample.

Some studies mentioned other factors that may affect the survival rate of implants, such

as the type of implant placed and the type of surgery for implant placement, whether it

was a one stage or a two stage surgery. One study reported a significant drop in one

stage implant survival after 10 years, with a survival rate of 78%, although higher

results were observed after 5 years follow up (47). Here, it was assumed that the

relatively decreased survival rate of these one-stage implants could be related to the

type of implant, since all implants placed using this approach were hollow-screwed,

which are impossible to treat once peri-implantitis has developed. These results were

confirmed by another study which observed that hollow screw implants had a lower

survival rate than solid screw implants (37). However, in this study no indication was

found that the difference between the two types of implants should be attributed to the

implant type. Rather, it was indicated that other factors such as implant length and the

type of implant placement (one-stage or two-stage) might be the explanatory factor.

Implant surface could also affect the outcome of dental implants. A high incidence of

implant loss was reported for implants with very rough surfaces (23, 30). This was

confirmed by two other studies, which reported a positive relationship between implants

with minimal rough surfaces with the presence of SPT and the incidence of peri-

implantitis (50, 71). Here, the incidences of peri-implantitis did not vary between

patients with or without a history of periodontitis .An experimental study on dogs with

different surface roughness of implants reported that rougher surface had a high rate of

progression of an already established peri-implantitis (72, 73).

In the study by Rosenberg et al.2004 reported increase the implant survival rate for

periodontally compromised patients (from 81% to 90.6%) and for periodontally healthy

individuals (from 92.6% to 93.7%) in the exclusion of hydroxyapatite-coated implant

from the overall number of implants (74).

21

However, there was no significant difference in peri-implant bone loss between

machined and rough surface designs was reported in the study by Wennström et al.2004

(24).

Microbiology:

In one study, a comparison between the the microbiota presented in teeth and implants

was performed, according to the periodontal pocket depth and bleeding on probing.

Periodontal pocket depths of >4mm and >5mm at tooth site harbored more bacteria than

implant sites, although all subjects were incorporated into a designed maintenance care

program (32),

It was reported by another study that the higher proportion of Gram-negative species

colonizing implants in the subjects with history of periodontal disease compared with

non periodontally subjects. This indicated the transmission of species from previously

extracted periodontally involved teeth (49) .

Therefore, it was concluded that a history of periodontitis had a greater influence on the

peri-implant microbiota than implant loading time (75)

Conclusion

The survival and success rate of dental implant in periodontally compromised patients

has shown to be not significantly different from periodontally healthy subjects.

However, there is a tendency toward a greater amount of marginal bone loss and higher

risk of peri-implant disease in patients with a history of periodontitis and especially

generalized aggressive periodontitis.

Furthermore, patients with a history of periodontitis should be strongly motivated to

adhere to adequate and correct periodontal maintenance program as it has proven to be a

key factor in enhancing the long term outcome of implant therapy by controlling re-

infection.

22

5 List of tables

Table 1 Studies included in the review 8-11

23

6 List of abbreviations

PPD periodontal pocket depth

BOP Bleeding on probing

MBL Marginal bone loss

PH Periodontal-healthy patients

PCP Periodontal-compromised patients

RP Residual pocket

GNTP Group with no periodontal maintenance

GTP Group with periodontal maintenance

m mesial

d distal

GAgp , GAP Generalized aggressive periodontitis

PH Periodontally healthy

NSP periodontally non-susceptible patients

CAP Chronic adult periodontitis

SP patients with sever periodontitis

MP patients with moderate periodontitis

NP patients with no periodontitis

NPG Non- periodontal group

PG periodontal group

Group A Patients with a history of chronic periodontitis

Group B Patients with no history of periodontitis

+++ High prevalence of peri-implantitis

M PCP Moderately-periodontally compromised patients

S PCP Severely-periodontally compromised patients

NR Non relevant

24

7 Bibiliography

1. Berglundh T, Persson L, Klinge B. A systematic review of the incidence of biological and technical complications in implant dentistry reported in prospective longitudinal studies of at least 5 years. J Clin Periodontol 2002;29 Suppl 3:197-212; discussion 232-193.

2. Pjetursson BE, Tan K, Lang NP, Bragger U, Egger M, Zwahlen M. A systematic review of the survival and complication rates of fixed partial dentures (FPDs) after an observation period of at least 5 years. Clin Oral Implants Res 2004;15:667-676.

3. Esposito M, Hirsch JM, Lekholm U, Thomsen P. Biological factors contributing to failures of osseointegrated oral implants. (II). Etiopathogenesis. Eur J Oral Sci 1998;106:721-764.

4. Heitz-Mayfield LJ. Peri-implant diseases: diagnosis and risk indicators. J Clin Periodontol 2008;35:292-304.

5. Cho-Yan Lee J, Mattheos N, Nixon KC, Ivanovski S. Residual periodontal pockets are a risk indicator for peri-implantitis in patients treated for periodontitis. Clin Oral Implants Res 2012;23:325-333.

6. Renvert S, Persson GR. Periodontitis as a potential risk factor for peri-implantitis. J Clin Periodontol 2009;36 Suppl 10:9-14.

7. Roos-Jansaker AM, Lindahl C, Renvert H, Renvert S. Nine- to fourteen-year follow-up of implant treatment. Part II: presence of peri-implant lesions. J Clin Periodontol 2006;33:290-295.

8. Ferreira SD, Silva GL, Cortelli JR, Costa JE, Costa FO. Prevalence and risk variables for peri-implant disease in Brazilian subjects. J Clin Periodontol 2006;33:929-935.

9. Albrektsson T IF. Consensus report of session IV. In: Proceedings of the First European Workshop on Periodontology. Quintessence 1994:365-369.

10. De Boever AL, De Boever JA. Early colonization of non-submerged dental implants in patients with a history of advanced aggressive periodontitis. Clin Oral Implants Res 2006;17:8-17.

11. Mombelli A, van Oosten MA, Schurch E, Jr., Land NP. The microbiota associated with successful or failing osseointegrated titanium implants. Oral Microbiol Immunol 1987;2:145-151.

12. Koka S, Razzoog ME, Bloem TJ, Syed S. Microbial colonization of dental implants in partially edentulous subjects. J Prosthet Dent 1993;70:141-144.

13. Leonhardt A, Adolfsson B, Lekholm U, Wikstrom M, Dahlen G. A longitudinal microbiological study on osseointegrated titanium implants in partially edentulous patients. Clin Oral Implants Res 1993;4:113-120.

14. Leonhardt A, Berglundh T, Ericsson I, Dahlen G. Putative periodontal pathogens on titanium implants and teeth in experimental gingivitis and periodontitis in beagle dogs. Clin Oral Implants Res 1992;3:112-119.

15. Mombelli A, Marxer M, Gaberthuel T, Grunder U, Lang NP. The microbiota of osseointegrated implants in patients with a history of periodontal disease. J Clin Periodontol 1995;22:124-130.

25

16. Schou S, Holmstrup P, Worthington HV, Esposito M. Outcome of implant therapy in patients with previous tooth loss due to periodontitis. Clin Oral Implants Res 2006;17 Suppl 2:104-123.

17. Van der Weijden GA, van Bemmel KM, Renvert S. Implant therapy in partially edentulous, periodontally compromised patients: a review. J Clin Periodontol 2005;32:506-511.

18. Karoussis IK, Kotsovilis S, Fourmousis I. A comprehensive and critical review of dental implant prognosis in periodontally compromised partially edentulous patients. Clin Oral Implants Res 2007;18:669-679.

19. Kim KK, Sung HM. Outcomes of dental implant treatment in patients with generalized aggressive periodontitis: a systematic review. J Adv Prosthodont 2012;4:210-217.

20. Mengel R, Behle M, Flores-de-Jacoby L. Osseointegrated implants in subjects treated for generalized aggressive periodontitis: 10-year results of a prospective, long-term cohort study. J Periodontol 2007;78:2229-2237.

21. Swierkot K, Lottholz P, Flores-de-Jacoby L, Mengel R. Mucositis, peri-implantitis, implant success, and survival of implants in patients with treated generalized aggressive periodontitis: 3- to 16-year results of a prospective long-term cohort study. J Periodontol 2012;83:1213-1225.

22. Karoussis IK, Muller S, Salvi GE, Heitz-Mayfield LJ, Bragger U, Lang NP. Association between periodontal and peri-implant conditions: a 10-year prospective study. Clin Oral Implants Res 2004;15:1-7.

23. Karoussis IK, Salvi GE, Heitz-Mayfield LJ, Bragger U, Hammerle CH, Lang NP. Long-term implant prognosis in patients with and without a history of chronic periodontitis: a 10-year prospective cohort study of the ITI Dental Implant System. Clin Oral Implants Res 2003;14:329-339.

24. Wennstrom JL, Ekestubbe A, Grondahl K, Karlsson S, Lindhe J. Oral rehabilitation with implant-supported fixed partial dentures in periodontitis-susceptible subjects. A 5-year prospective study. J Clin Periodontol 2004;31:713-724.

25. De Boever AL, Quirynen M, Coucke W, Theuniers G, De Boever JA. Clinical and radiographic study of implant treatment outcome in periodontally susceptible and non-susceptible patients: a prospective long-term study. Clin Oral Implants Res 2009;20:1341-1350.

26. Gianserra R, Cavalcanti R, Oreglia F, Manfredonia MF, Esposito M. Outcome of dental implants in patients with and without a history of periodontitis: a 5-year pragmatic multicentre retrospective cohort study of 1727 patients. Eur J Oral Implantol 2010;3:307-314.

27. Roccuzzo M, Bonino F, Aglietta M, Dalmasso P. Ten-year results of a three arms prospective cohort study on implants in periodontally compromised patients. Part 2: clinical results. Clin Oral Implants Res 2012;23:389-395.

28. Roccuzzo M, De Angelis N, Bonino L, Aglietta M. Ten-year results of a three-arm prospective cohort study on implants in periodontally compromised patients. Part 1: implant loss and radiographic bone loss. Clin Oral Implants Res 2010;21:490-496.

29. Costa FO, Takenaka-Martinez S, Cota LO, Ferreira SD, Silva GL, Costa JE. Peri-implant disease in subjects with and without preventive maintenance: a 5-year follow-up. J Clin Periodontol 2012;39:173-181.

26

30. Hardt CR, Grondahl K, Lekholm U, Wennstrom JL. Outcome of implant therapy in relation to experienced loss of periodontal bone support: a retrospective 5- year study. Clin Oral Implants Res 2002;13:488-494.

31. Matarasso S, Rasperini G, Iorio Siciliano V, Salvi GE, Lang NP, Aglietta M. A 10-year retrospective analysis of radiographic bone-level changes of implants supporting single-unit crowns in periodontally compromised vs. periodontally healthy patients. Clin Oral Implants Res 2010;21:898-903.

32. Agerbaek MR, Lang NP, Persson GR. Comparisons of bacterial patterns present at implant and tooth sites in subjects on supportive periodontal therapy. I. Impact of clinical variables, gender and smoking. Clin Oral Implants Res 2006;17:18-24.

33. Roos-Jansaker AM, Lindahl C, Renvert H, Renvert S. Nine- to fourteen-year follow-up of implant treatment. Part I: implant loss and associations to various factors. J Clin Periodontol 2006;33:283-289.

34. Leonhardt A, Grondahl K, Bergstrom C, Lekholm U. Long-term follow-up of osseointegrated titanium implants using clinical, radiographic and microbiological parameters. Clin Oral Implants Res 2002;13:127-132.

35. Behneke A, Behneke N, d'Hoedt B. The longitudinal clinical effectiveness of ITI solid-screw implants in partially edentulous patients: a 5-year follow-up report. Int J Oral Maxillofac Implants 2000;15:633-645.

36. Brocard D, Barthet P, Baysse E, Duffort JF, Eller P, Justumus P, et al. A multicenter report on 1,022 consecutively placed ITI implants: a 7-year longitudinal study. Int J Oral Maxillofac Implants 2000;15:691-700.

37. Buser D, Mericske-Stern R, Bernard JP, Behneke A, Behneke N, Hirt HP, et al. Long-term evaluation of non-submerged ITI implants. Part 1: 8-year life table analysis of a prospective multi-center study with 2359 implants. Clin Oral Implants Res 1997;8:161-172.

38. Chuang SK, Tian L, Wei LJ, Dodson TB. Kaplan-Meier analysis of dental implant survival: a strategy for estimating survival with clustered observations. J Dent Res 2001;80:2016-2020.

39. Lindh T, Gunne J, Tillberg A, Molin M. A meta-analysis of implants in partial edentulism. Clin Oral Implants Res 1998;9:80-90.

40. Naert I, Koutsikakis G, Duyck J, Quirynen M, Jacobs R, van Steenberghe D. Biologic outcome of implant-supported restorations in the treatment of partial edentulism. part I: a longitudinal clinical evaluation. Clin Oral Implants Res 2002;13:381-389. 41. Vehemente VA, Chuang SK, Daher S, Muftu A, Dodson TB. Risk factors affecting dental implant survival. J Oral Implantol 2002;28:74-81.

42. Boioli LT, Penaud J, Miller N. A meta-analytic, quantitative assessment of osseointegration establishment and evolution of submerged and non-submerged endosseous titanium oral implants. Clin Oral Implants Res 2001;12:579-588.

43. Ferrigno N, Laureti M, Fanali S, Grippaudo G. A long-term follow-up study of non-submerged ITI implants in the treatment of totally edentulous jaws. Part I: Ten-year life table analysis of a prospective multicenter study with 1286 implants. Clin Oral Implants Res 2002;13:260-273.

27

44. Lekholm U, Gunne J, Henry P, Higuchi K, Linden U, Bergstrom C, et al. Survival of the Branemark implant in partially edentulous jaws: a 10-year prospective multicenter study. Int J Oral Maxillofac Implants 1999;14:639-645.

45. Tonetti MS, Schmid J. Pathogenesis of implant failures. Periodontol 2000 1994;4:127-138.

46. Ong CT, Ivanovski S, Needleman IG, Retzepi M, Moles DR, Tonetti MS, et al. Systematic review of implant outcomes in treated periodontitis subjects. J Clin Periodontol 2008;35:438-462.

47. Baelum V, Ellegaard B. Implant survival in periodontally compromised patients. J Periodontol 2004;75:1404-1412.

48. Ellegaard B, Baelum V, Kolsen-Petersen J. Non-grafted sinus implants in periodontally compromised patients: a time-to-event analysis. Clin Oral Implants Res 2006;17:156-164.

49. Mombelli A, Lang NP. The diagnosis and treatment of peri-implantitis. Periodontol 2000 1998;17:63-76.

50. Quirynen M, Abarca M, Van Assche N, Nevins M, van Steenberghe D. Impact of supportive periodontal therapy and implant surface roughness on implant outcome in patients with a history of periodontitis. J Clin Periodontol 2007;34:805-815.

51. Meffert RM. Periodontitis and periimplantitis: one and the same? Pract Periodontics Aesthet Dent 1993;5:79-80, 82.

52. Nevins M. Will implants survive well in patients with a history of inflammatory periodontal disease? J Periodontol 2001;72:113-117.

53. Buser D, Weber HP, Bragger U. The treatment of partially edentulous patients with ITI hollow-screw implants: presurgical evaluation and surgical procedures. Int J Oral Maxillofac Implants 1990;5:165-175.

54. Abrahamsson I, Berglundh T, Lindhe J. Soft tissue response to plaque formation at different implant systems. A comparative study in the dog. Clin Oral Implants Res 1998;9:73-79.

55. Berglundh T, Lindhe J, Marinello C, Ericsson I, Liljenberg B. Soft tissue reaction to de novo plaque formation on implants and teeth. An experimental study in the dog. Clin Oral Implants Res 1992;3:1-8.

56. Ericsson I, Berglundh T, Marinello C, Liljenberg B, Lindhe J. Long-standing plaque and gingivitis at implants and teeth in the dog. Clin Oral Implants Res 1992;3:99-103.

57. Pontoriero R, Tonelli MP, Carnevale G, Mombelli A, Nyman SR, Lang NP. Experimentally induced peri-implant mucositis. A clinical study in humans. Clin Oral Implants Res 1994;5:254-259.

58. Zitzmann NU, Berglundh T, Marinello CP, Lindhe J. Experimental peri-implant mucositis in man. J Clin Periodontol 2001;28:517-523.

59. Aglietta M, Siciliano VI, Rasperini G, Cafiero C, Lang NP, Salvi GE. A 10-year retrospective analysis of marginal bone-level changes around implants in periodontally healthy and periodontally compromised tobacco smokers. Clin Oral Implants Res 2011;22:47-53.

28

60. Heitz-Mayfield LJ, Huynh-Ba G. History of treated periodontitis and smoking as risks for implant therapy. Int J Oral Maxillofac Implants 2009;24 Suppl:39-68.

61. Karbach J, Callaway A, Kwon YD, d'Hoedt B, Al-Nawas B. Comparison of five parameters as risk factors for peri-mucositis. Int J Oral Maxillofac Implants 2009;24:491-496.

62. Leonhardt A, Dahlen G, Renvert S. Five-year clinical, microbiological, and radiological outcome following treatment of peri-implantitis in man. J Periodontol 2003;74:1415-1422.

63. Wilson TG, Jr., Nunn M. The relationship between the interleukin-1 periodontal genotype and implant loss. Initial data. J Periodontol 1999;70:724-729.

64. Anner R, Grossmann Y, Anner Y, Levin L. Smoking, diabetes mellitus, periodontitis, and supportive periodontal treatment as factors associated with dental implant survival: a long-term retrospective evaluation of patients followed for up to 10 years. Implant Dent 2010;19:57-64.

65. Bain CA. Smoking and implant failure--benefits of a smoking cessation protocol. Int J Oral Maxillofac Implants 1996;11:756-759.

66. Lambert PM, Morris HF, Ochi S. The influence of smoking on 3-year clinical success of osseointegrated dental implants. Ann Periodontol 2000;5:79-89.

67. Rosa EF, Corraini P, de Carvalho VF, Inoue G, Gomes EF, Lotufo JP, et al. A prospective 12-month study of the effect of smoking cessation on periodontal clinical parameters. J Clin Periodontol 2011;38:562-571.

68. Moy PK, Medina D, Shetty V, Aghaloo TL. Dental implant failure rates and associated risk factors. Int J Oral Maxillofac Implants 2005;20:569-577.

69. Zupnik J, Kim SW, Ravens D, Karimbux N, Guze K. Factors associated with dental implant survival: a 4-year retrospective analysis. J Periodontol 2011;82:1390-1395.

70. Abdulwassie H, Dhanrajani PJ. Diabetes mellitus and dental implants: a clinical study. Implant Dent 2002;11:83-86.

71. Evian CI, Emling R, Rosenberg ES, Waasdorp JA, Halpern W, Shah S, et al. Retrospective analysis of implant survival and the influence of periodontal disease and immediate placement on long-term results. Int J Oral Maxillofac Implants 2004;19:393-398.

72. Albouy JP, Abrahamsson I, Persson LG, Berglundh T. Spontaneous progression of peri-implantitis at different types of implants. An experimental study in dogs. I: clinical and radiographic observations. Clin Oral Implants Res 2008;19:997-1002. 73. Berglundh T, Gotfredsen K, Zitzmann NU, Lang NP, Lindhe J. Spontaneous progression of ligature induced peri-implantitis at implants with different surface roughness: an experimental study in dogs. Clin Oral Implants Res 2007;18:655-661.

74. Rosenberg ES, Cho SC, Elian N, Jalbout ZN, Froum S, Evian CI. A comparison of characteristics of implant failure and survival in periodontally compromised and periodontally healthy patients: a clinical report. Int J Oral Maxillofac Implants 2004;19:873-879.

75. Lee KH, Maiden MF, Tanner AC, Weber HP. Microbiota of successful osseointegrated dental implants. J Periodontol 1999;70:131-138.

29

Declaration of academic integrity

I declare that I independently completed this thesis and this thesis was not previously

submitted to another academic institution. I also confirm that no other sources have

been used than those indicated in this thesis and the thoughts taken directly or indirectly

from external sources are properly marked as such.

Oldenburg, and 25/07/2013

Dr. S. M. M. Bakush