Distance Between Dental Implants as a Risk Indicator for Peri-implant Disease. A Multi-center Cross-sectional Study
Conditions: Peri-implant Mucositis, Peri-Implantitis
Sponsor: Universitat Internacional de Catalunya

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RESEARCH PROTOCOL 
 
Study number (NCT): PER-ECL-2023-5 
Protocol versión: 1.0 
Version date: 20/09/2023 
Date presentation: 10/04/2024 
Main Reseacher: Cristina Vallés 
Secondary Researcher: Ioannis Terpou, Filipa Fernandes 
Tutor: Tiago Ribeiro-Amaral, 
Departament: Periodoncia 
Research Line: Diagnosis, prevention and treatment of periodontal and peri-implant diseases.  
Research Title: Distance between dental implants as a risk indicator for peri-implant disease. A 
multicentric cross-sectional study 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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In the last decades, replacement of teeth with dental implants became a very frequent procedure, 
and it is associated with high rates of implant survival (Albrektsson and Donos, 2012). However, the 
incidence of technical and biological complications seems to be frequent (Scwartz et al., 2018). Since 
the number of subjects receiving dental implants is growing continuously (Schimmel et al., 2017), 
preventing and effectively resolving peri-implant diseases on the long-term without compromising 
esthetic results have become one of the major endeavors of this field. 
In 2017, the World Workshop, jointly held by the European Federation of Periodontology and the 
American Academy of Periodontology on the classification of Periodontal and Peri-Implant Diseases, 
defined peri-implant disease as a pathological condition occurring in tissues around dental implants, 
characterized by inflammation in the peri-implant connective tissue [i.e., peri-implant mucositis (PM)], 
and progressive loss of supporting bone [i.e., peri-implantitis (PI)] (Schwarz et al., 2018). The onset 
of peri-implant diseases is characterized by the presence of etiological factors similar to those 
involved in the etiology of periodontal diseases and it might occur within the first three years of 
function in a non-linear and accelerating pattern (Derks et al., 2016). 
A systematic review and meta-analysis, performed by Jan Derks and colleagues in 2015, found a 
prevalence of 43% for PM and 22% of PI. Later on, in Spain, Rodrigo et al. (2018) observed a similar 
prevalence with 27% of subjects presenting PM and 24% of the subjects presenting bleeding on 
probing and radiographic bone loss ≥ 2mm after at least 5 years of function (PI).  
In order to prevent such diseases, addressing active periodontal diseases previous to implant 
surgery is mandatory; however, several factors associated with less prevalence of such diseases 
have been investigated pre-clinically and clinically. In this sense, a minimum of 1.5mm of bone 
surrounding the dental implant (Monje et al., 2019), a hygienic prosthesis (Serino et al., 2009, 
Katafuchi et al, 2018), a correct 3D prosthetically driven implant position (Herman et al., 2000, Buser 
et al., 2004) and enroll the patient in a tailored SPT program (Schwarz et al., 2018) are crucial in 
order to obtain long-term success and peri-implant health. 
Several of these factors focus on improving oral hygiene access and motivate the patient to be more 
effective. Thus, a relevant surgical aspect that clinicians must consider at the time of implant 
placement, in order to allow a correct prosthetic design, is the distance between adjacent tooth-
implant and inter-implant distances. For the horizontal space between adjacent tooth-implant, a 
distance of at least 1.5–2 mm from the adjacent teeth has been advocated especially for the anterior 
teeth (Van Oosterwyck et al., 1998). In addition, to prevent esthetic complications, it is advised to 
leave 3–4 mm of space between dental implants (Tarnow at al., 2000, Esposito et al., 1993). In this 
study, however, platform-matched implants were used. 

 
 
 
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In this sense, preclinical and clinical studies investigated the influence of inter-implant distance on 
marginal bone loss around platform-switched implants. In 2006, a preclinical study demonstrated 
that distances of 1, 2, and 3mm between implants did not result in statistically significant differences 
on marginal bone level around implants with a platform switch (Novaes et al., 2006). Likewise, 
Rodriguez-Ciurana et al. (2009) observed a minimal bone resorption (i.e., 0.62 mm) around platform-
switched implants placed less than 3 mm apart. 
Recently, a long-term retrospective study evaluated the biological complication rate of three types of 
implant-supported fixed dental prosthesis (non-splinted crowns, three splinted crowns and a 3-unit 
implant supported bridge) over two or three bone-level implants. The results of the investigation 
indicated that the prevalence of peri-implantitis was higher (16.7%) when three splinted crowns with 
three implants were used when compared with a 3-unit implant supported bridge over two implants 
(2.8%) (Ravidà et al., 2019).  
Nonetheless, to our knowledge, no study has yet evaluated the association between the inter-implant 
distance of contiguous dental implants and peri-implant diseases.  
Therefore, the aim of this study is to analyze contiguous dental implants and its peri-implant status 
depending on different inter-implant distances.  
1.BACKGROUND 
Implants have become a popular and widely used treatment option for treating partial and total 
edentulism. As the number of implants placed increases, so does the incidence of peri-implant 
mucositis and peri-implantitis. Several factors, such as a 3D correctly placed implant has been 
associated with better esthetic and overall outcomes on the long-term. Nevertheless, understanding 
a minimal threshold for inter-implant distance depending on type of implant might be critical to 
prevent such diseases.  
 
2. OBJECTIVES 
 
2.1 General objective 
To evaluate the association between the inter-implant distance of contiguous dental implants and 
the prevalence of peri-implant diseases. 
2.2 Specific objective 

 
 
 
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To evaluate the association between implant type (bone/tissue-level) and the prevalence of peri-
implant diseases according to the inter-implant distance of contiguous dental implants.  
3. HYPOTHESIS 
 
3.1 General Hypothesis 
A reduced inter-implant distance (i.e., < 3mm) of contiguous dental implants will result in a higher 
prevalence of peri-implant diseases. 
3.2 Specific Hypothesis 
Tissue level implants (i.e., one-piece implants) placed with an inter-implant distance < 3mm will result 
in a higher prevalence of peri-implant diseases than bone level implants. 
4. MATERIAL AND METHODS 
 
4.1 Study Design  
The present research project has been designed as a multicentric cross-sectional study. The 
STROBE guidelines have been followed in the design of this observational study.  
4.2 Ethical issues 
The study will be performed after the approval of the Ethics Committee of the Universitat 
Internacional de Catalunya (UIC) and Faculdade de Medicina Dentária da Universidade de Lisboa 
(FMDUL) and will be intended to be registered in clinicaltrials.gov. Also, this research will be 
conducted according to the principles outlined in the Declaration of Helsinki (revised, amended, and 
clarified in 2013). In addition, all study participants will provide written informed consent before 
participating in the study.  
4.3 Study population 
Subjects will be selected from an electronic database collected at the CUO (UIC) / CU (FMDUL) and 
composed of patients treated with at least two contiguous dental implants before 2021. This 
investigation will use a stratified random sampling based on year of implant placement to select a 
representative sample of subjects with implant-supported restorations conducted during the period 
2001–2020 at the CUO and CU. Then, two examiners (I.T. / F.F.) will contact patients by telephone 

 
 
 
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once every 2 days (with a maximum of 3 attempts) for an evaluation by the same investigators (I.T / 
F.F). 
Criteria for subject selection will be as follows:  
- The patient must be ≥18 years of age and systemically healthy; 
- Partially edentulous patients, rehabilitated until 2020 (i.e., a minimum of 3 years of function 
time) with at least two contiguous implant-supported restorations in the maxilla or mandible;  
- Screw or cemented-retained prosthesis; 
- Fixed dental prosthesis (i.e., single crowns and partial prosthesis);  
- No implant mobility. 
Moreover, the exclusion criteria will be the following: 
- Pregnant and lactating women; 
- Patients who have taken systemic antibiotics during the 3 months prior to the examination; 
- Patients being treated with drugs that may induce a gingival overgrowth; 
- Patients undergoing orthodontic treatment (since it can influence periodontal diagnosis); 
- Patients who have received mechanical debridement during the 3 months prior to the exam; 
- Patients who have received surgical treatment for peri-implantitis; 
- Psychophysical inability to carry out study procedures. 
 
4.4 Study Groups 
 
Patients who meet the selection criteria will be included in the study and will be classified based on 
the inter-implant distance: 
 
Group 1: Inter-implant distance ≤ 3mm 
 
Group 2: Inter-implant distance > 3 mm 
 
4.5 Sample Size Calculation 
 
Sample size calculation has been based on the primary outcome variable (prevalence of peri-implant 
diseases). Previous studies have observed a patient-level prevalence of peri-implant diseases of 
24%. Our hypothesis is that the prevalence of peri-implant diseases is higher when the inter-implant 
distance is reduced, around 44%. Accepting an alpha risk of 5% and a beta risk of 20% in a two-
sided test, a total of 180 patients with adjacent dental implants (90 patients in each group) are 
required. Therefore, 90 patients will be recruited at each center. A loss rate of 12% has been 

 
 
 
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estimated. 
 
4.6 Researchers training 
All participating researchers will attend two training and calibration online meetings. The main aims 
of these meetings will be to review the objectives of the study and the protocol, standardize case 
selection, and data collection process. 
4.7 Data collection 
Two calibrated investigators will consecutively call patients for an appointment and will be 
responsible of enrolling the patients.  
The study variables will be recorded in a case report form (CRF) specially designed for the study. 
Each study patient will be assigned a numerical code comprising a 3-digit patient code (assigned 
correlatively as they are included in the study). Only the study investigators will be able to identify 
the patient by their code.  
Medical history of the patients will be reviewed. Patients will also be advised of their role in this study 
and asked to sign an informed consent. After giving consent, patients will undergo a full-mouth 
manual probing using a periodontal probe PCP-UNC 15 (HuFriedy®, Rockwell St, Chicago, IL) to 
determine their periodontal and peri-implant status and, if necessary, a full-mouth periapical 
radiographic examination will be performed. 
4.11 Statistical analysis 
The Shapiro-Wilk test will be used to determine if the data follow a Gaussian distribution. Descriptive 
statistics will be expressed as mean ± standard deviations (SD), median or percentage for 
parametric, non-parametric and categorical data, respectively. 
Comparisons between study groups will be performed using Chi-square test (Fisher's exact test with 
observed frequencies <5) for categorical variables while continuous variables will be tested using 
Student's T test (Mann Whitney U test in variables that are not normally distributed). For ordinal 
variables, the linear relationship will be calculated using Kendall's tau coefficient. 
A final logistic regression model will be performed including the prevalence of peri-implant diseases 
as a dependent variable. The study group and other potential cofactors will be included as 
independent variables. 
Intra- and inter-examiner reproducibility will be calculated with the intraclass correlation coefficient. 

 
 
 
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A p-value <0.05 will be considered statistically significant. R Studio software will be used for all 
analyses.