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Basic and Clinical Research

Influence of Systemic Conditions on the Incidence of Periimplant Pathology

A Case-Control Study

de Araújo Nobre, Miguel RDH, MSc*; Maló, Paulo DDS, PhD; Antune, Elsa RDH

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doi: 10.1097/ID.0000000000000071
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Periimplant pathology (PIP) is defined as “the term for inflammatory reactions with loss of supporting bone tissue surrounding the implant in function.”1 The number of clinical studies focusing on the topic of risks for PIP is low because the majority of studies usually focuses on the implant outcome success/failure and not on the possible reasons for failure.2–21

There are several factors that may play an important role in the etiology of PIP. The influence of a history of periodontitis on the risk of incidence of PIP was first indicated in clinical studies that identified this factor as a risk indicator20–28 and later confirmed through a systematic review that registered a higher incidence of PIP in periodontal disease susceptible patients,29 making periodontitis a factor to be considered to play a major role in the PIP process.

Smoking constitutes one of the most common discussed factors about its adverse effect on implant rehabilitations. There are reports on a 2-fold higher incidence of implant failures in patients who are smokers (daily consumption of cigarettes) compared with nonsmokers.30 Relatively to PIP, several revision studies identified tobacco consumption as a risk factor22,31–33 as well as comparative and cohort studies that registered tobacco's deleterious effect on bone loss.7,12,34,35

Systemic factors play an important role in the balance between the host, the agent, and the environment. Despite previous consensus statements suggesting a negative effect of systemic conditions on implant survival,36 that trend may not be so clear in the situations of late implant failures: On one hand, radiotherapy was considered to influence significantly the implant failure in the period between abutment connection surgery and 2 years of follow-up,37 and nevertheless, there are significant associations between implant failure and the patient's medical status (evaluated through the American Society of Anesthesiology physical status classification system)38; on the other hand, systemic health factors do not seem to be absolute contraindications in the etiology of late implant loss,39,40 suggesting that the degree of systemic disease control may be far more important than the nature of the disorder itself.41 Although there are several reports in the literature relating to implant failure and systemic compromising, the same is not found in PIP; concerning osteoporosis, a recent study did not find any significant relation between this condition and PIP.42 The aim of this study was to determine the influence of systemic conditions identified as possible factors associated indirectly with increased risk for the incidence of PIP and consequent failure of the implant.

Materials and Methods

This article was written after the Strobe (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.43 This study was approved by the National Commission of Data Protection (Portugal) and the Faculty of Medicine, University of Lisbon Ethical Board.

The study population consisted of patients over 18 years, of both genders, rehabilitated with dental implants at the Center for Implantology and Fixed Oral Rehabilitation, Malo Clinic Lisbon, Portugal. Cases were defined as patients rehabilitated with dental implants at the Center for Implantology and Fixed Oral Rehabilitation, Malo Clinic Lisbon diagnosed with PIP. Controls were defined as patients rehabilitated with dental implants at the same center without diagnosis of PIP after implant treatments.

PIP was diagnosed through presence of periimplant pockets ≥5 mm44 diagnosed through probing of the periimplant sulcus/pocket using a probe calibrated to 0.25 N (Click-Probe; Kerrhawe S.A., Bioggio Svizzera, Switzerland)45; bleeding on probing45; vertical bone loss visible to x-ray46; attachment loss equal to, or greater than, 2 mm.47

Inclusion criteria were: (1) patients who underwent surgery to insert dental implants and followed at the clinical center, (2) patients rehabilitated with implant-supported prostheses with a minimum follow-up of 1 year after surgery, and (3) patients who gave their informed consent to have their charts reviewed in this retrospective study.

Exclusion criteria were (1) patients who had undergone surgery for placement of dental implants for less than 1 year; (2) patients who refused, or were unable, to give informed consent; prevalent cases of PIP; (3) patients whose medical records were incomplete or missing; (4) patients who underwent immunosuppressive therapy; and (5) patients under 18 years of age.

This study was conducted between January and July 2009. The matching between cases and controls was carried for the demographic variables: age (2 years ≤ case age ≤ 2 years) and gender, due to high probability of association of these variables with implant failure: more prevalent in men,16 and ages over 40 years48 and follow-up time of implantation (2 months ≤ case follow-up ≤ 2 months), due to a possible correlation between the increase in follow-up time (exposure time) and the occurrence of PIP.49 A 1:4 relation between cases and controls was established to optimize the number of cases needed.

The sample was obtained from a list of patients underwent implant surgery. There were initially 1763 eligible patients (346 cases and 1417 controls). Of these, 383 patients (66 cases and 317 controls) were excluded from the study; 181 patients had incomplete diagnosis (12 cases and 169 controls); and 202 patients refused to participate (54 cases and 148 controls). From the 1380 patients (280 cases and 1100 controls), 30 patients (10 cases and 20 controls) were randomly selected to be included in the pilot study and consequently excluded from the study, reaching the final 1350 patients (270 cases and 1080 controls).

The sample consisted of 1350 individuals of both genders, divided by 2 groups: cases and controls. The average age of our sample was 55.8 years (SD = 10.2 years), with a minimum of 28 years and a maximum of 88 years. Regarding gender, most of the individuals were female with 62.7% of the sample. The implants were inserted between February 1998 and November 2006, consisting of implants from the Nobel Biocare (Gothenburg, Sweden) system; 296 with machined surface and 1054 with moderately rough surface (TiUnite). Data collection consisted in indirect documentation and filling in the data on a digital form, by consulting the patient's clinical file (record sheets, radiographs, medical questionnaire, and clinical diary).

The independent variables were comorbidities according to the American Society of Anesthesiology physical status classification system (ASA I—a normal healthy patient, ASA II—a patient with mild systemic disease, and ASA III—a patient with severe systemic disease)50 collected from the patients records and classified accordingly; history of irradiation of the head and neck in the previous 6 months, collected from the patients records and registered as present or absent; history of chemotherapy in the previous 6 months, collected from the patients records and registered as present or absent; smoking habits (SH) collected from patients records and classified as current smoker, former smoker for at least 1 year, or nonsmoker; history of periodontitis (HP) collected from patients records and radiographs and registered as present or absent; postmenopausal hormone replacement therapy, collected from patient records and registered as present or absent.

Statistical Analysis

We performed univariate analysis for characterization of cases and controls in relation to the independent variables. Bivariate analysis was conducted to evaluate the difference between the groups of cases and controls in relation to the independent variables. In nominal independent variables, the comparison between cases and controls was performed using the χ2 test (on presence of applicability conditions, otherwise the Fisher exact test was applied, with supplemental measures of Cramer V or the contingency coefficient). Crude odds ratios (OR) with 95% confidence intervals (CIs) were calculated for the variables significantly different in the bivariate analysis. Estimation of the attributable fraction (AF) of PIP for the cases exposed to the risk factors identified in the bivariate analysis was calculated through an equation,51 according to the OR of exposure:

where AF = attributable fraction; A1+ = prevalence of the disease in the exposed; M1+ = prevalence of the disease; and OR = odds ratio. In this study, the AF represents the decline in PIP that could be achieved by eliminating the exposure to the risk factor.


The univariate analysis is described in Table 1. Overall, there were low frequencies for some variables, namely ASA III status, history of chemotherapy in the previous 6 months, and postmenopausal hormone replacement therapy. There were no patients with the history of head and neck irradiation in the previous 6 months. The patients with ASA II and III status presented with different comorbidities: The majority of patients presented a (1) cardiovascular condition (62.2%), followed by (2) rheumatologic condition (10.7%), and (3) diabetes (9.7%), with 119 patients presenting more than 1 comorbidity (Table 2). The bivariate analysis resulted in significant differences between cases and controls for the variables HP (P = 0.000) and SH (P = 0.000) (Table 3). Crude OR with 95% CI is described in Table 4. Patients with HP had a 25-fold increase in the probability of incidence of PIP. Patients who were smokers had a 2-fold increase in the probability of experiencing the disease. Applying the attributable risk fraction, it was observed that if patients exposure to HP and SH could be suppressed, it would have resulted in a 96% and a 51% decrease in the incidence of PIP, respectively (Table 4).

Table 1:
Frequencies and Percentages of the Independent Variables
Table 2:
Distribution of the Type and Frequency of Comorbidities in the Sample Per Cases and Controls
Table 3:
Results From Bivariate Analysis for the Independent Variables With Significant Differences Between Cases and Controls
Table 4:
Crude OR With Corresponding 95% CIs and Attributable Risk Fraction Calculations for the Variables Significantly Associated With the Incidence of PIP


In this study, there was a difference between cases and controls in variable HP, with a higher frequency in cases compared with controls (79% vs 30%), which was significant (P = 0.000). This variable proved to be a risk factor for the occurrence of the disease (OR = 25). These findings are supported by Schou,29 Heitz-Mayfield,22 and Hammerle and Glauser23 who identified HP as a risk factor for PIP. Likewise, Brocard et al26 in a multicenter study with 7 years of follow-up in 1022 implants, reported that individuals who have lost their teeth due to periodontal disease have a higher susceptibility to the development of PIP. Because of commonalities in etiology between the periimplant disease and periodontal disease,52 one would expect that a HP disease could exert a strong influence as a risk factor for the incidence of PIP. Carrying the concept for the clinical rationale, it means that if a patient loses teeth due to periodontal disease and replaces them with implants without altering significantly the modifiable factors (such as oral hygiene habits), this patient will be more at risk of the infection process to take place again, this time at the implant level.

Patients with SH had a different distribution between cases and controls, with a higher frequency of smokers in cases (39%), relatively to controls (24%), and further confirmed in the crude OR calculation (OR = 2). This result is confirmed by several revision studies that attested the relation between tobacco consumption and the incidence of PIP.22,31–33 Tobacco is effectively a risk factor for PIP, acting at the host defense level32 and increasing the likelihood of disease occurrence. There were no significant differences between cases and controls for some of the variables investigated. History of irradiation of the head and neck in the previous 6 months, history of chemotherapy in the previous 6 months, and postmenopausal hormone replacement therapy were not representative in the sample, making it difficult to draw any conclusion. ASA II and ASA III patients represented about 42% of the global sample but similarly distributed between cases (37.8%) and controls (43%). The nonsignificant difference between cases and controls meant that these patients were not more at risk of the incidence of PIP, reaching similar results reported earlier but for implant failure, suggesting that the mere presence of systemic health factors were not a contraindication for late implant loss to occur.39,40 A recent systematic review highlighted this fact when investigating the success and survival rates of dental implants in the medically compromised patient, reporting that the degree of systemic disease control by the patient could be of higher importance compared with the nature of the disorder itself.41

The importance of controlling risk factors for the incidence of PIP were illustrated through the estimation of the AF for PIP of the cases exposed. The risk factor HP, possessing an AF related to PIP of 96%, is likely to be modified only theoretically given that completely removing the exposure to the HP, for example, it would not meet the assumptions for rehabilitation with dental implants because natural teeth would still be present and in function. However, the exposure to the risk factor SH, with an AF related to PIP of 51%, is likely to be modified with good prognosis for the number of cases. In both situations, this would mean a consequent reduction in the population at risk, potentially reducing the number of cases.51

The limitations of this study are the retrospective design and the lack of control for the possible effects that the variable smoking may exert on the incidence of PIP, both the amount of smoking or the possible confounder effect,53 as this variable could be correlated with both the dependent variable (PIP) and independent variables (systemic conditions and HP). The generalization of the results should be performed with caution as the data were derived from a single clinical center and a single implant system. The effect of these variables should be tested using prospective study designs, controlling for the presence of other variables of interest in the etiopathogenesis of the PIP and also for confounders, through multivariable analysis.


In an era where there is a change of focus of the clinical research community from the simple report of implant failures to the study of factors that could influence those failures, this study investigated risk factors for the incidence of the main cause of late implant failure, PIP. Patients presenting a HP or SH had a higher probability of having PIP (25-fold and 2-fold, respectively), whereas no significant differences were found between cases and controls for the presence of comorbidities (such as cardiovascular disease or diabetes) or history of chemotherapy and irradiation of the head and neck. Through the AF, it was estimated that the theoretical removal of the exposure to HP and SH would result in a potential decline of at least half of the patients with PIP, which translated to a potential reduction in late implant failure represents an important benefit in the outcome of implant-supported rehabilitations.


Professor P. Maló is currently a consultant for Nobel Biocare. M. de Araújo Nobre and E. Antunes received grants from Nobel Biocare Services AG.


This study was funded by a grant from Nobel Biocare Services AG (grant no. 2012–1126).


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dental implants; periodontitis; smoking

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