Local and Systemic Inflammatory Bone Alterations Related to Dental Implant Survival.

STUDY DESIGN This is a retrospective cohort study.

PATIENTS AND SAMPLE The sample will be selected from patients who have undergone implant placement at the University of Barcelona Dental Hospital (HOUB).

Inclusion criteria

• Patients over 18 years of age
• Patients with implants placed within the last 10 years
• Patients with accessible complete medical and dental records
• Patients with documented implant follow-up via periapical radiographs and/or OPG
• Patients with documented pre-implant tooth status
• Patients with blood test results available from the 6 months prior to or following implant placement
• Implants lost due to peri-implant pathology causing bone resorption

Exclusion criteria

for the study group:

• Failure to meet inclusion criteria

Sample size calculation:

Based on a total of 3,500 implants placed over 10 years and an expected proportion of 0.05, the calculated sample size is 192 implants. Although this is a retrospective study, we will aim to obtain the maximum number of cases, with a minimum of 50. Considering that the rate of peri-implantitis in implants adjacent to a tooth with periapical pathology can be 31%, compared to 2.8% for those that are not(18),The minimum sample size for implants with peri-implantitis (Yes/No) would be 36, with a confidence interval of 0.05.

METHODS, TECHNIQUES, TESTS, INTERVENTIONS

• Initially, a list of implants that failed over the last 10 years will be obtained; medical records will be reviewed to assess for the presence of osteoporosis or vitamin D deficiency. Regarding vitamin D deficiency, laboratory test results will be used for confirmation. For osteoporosis, the assessment will consider whether the patient reports a history of the condition and/or if there is a medical report and/or bone densitometry results available.
• Additionally, laboratory tests will be evaluated for the presence of calcium-phosphate metabolism disorders. The number of failed implants per patient will be recorded; patients will be included if at least one failure occurred.
• In cases of systemic disorders, any medication taken for the condition in question will be noted.
• Patient-related data, such as sex and age, will be collected.
• Data regarding the day of surgery-such as whether regeneration was performed, the occurrence of complications, etc.-will also be collected.
• For patients who experienced a failure, the study will assess whether the failed implants were adjacent to an endodontically treated tooth or located at a site of a previous endodontic failure. Patient radiographic records will be reviewed to assess bone loss on the mesial and distal aspects of the remaining implants; this loss will be quantified in millimeters (mesially and distally) based on the radiograph taken on the day of implantation and the implant length.
• In cases of systemic disorders affecting bone, results will be reported both per implant and per patient to minimize bias.
• For implants near an adjacent tooth with pathology or placed in a previously affected site, the case will be considered positive if the tooth extraction occurred less than 3 months prior(19). - On the other hand, we will analyze endodontic failure in terms of the presence of signs and symptoms: the presence of pain and the appearance or persistence of inflammation and fistulas.Radiographically, it is defined as the persistence of a periapical radiolucent lesion over a period of 6 to 24 months. Histologically, a lack of repair or destruction of periapical structures is observed, accompanied by the presence of inflammatory cells. (20,21) Teeth will be evaluated using the Periapical Index (PAI) (22), which categorizes periapical status as follows: 1. Periapical bone destruction almost certainly absent, 2. Periapical bone destruction probably absent, 3. Uncertain, 4. Periapical bone destruction probably present, 5. Periapical bone destruction definitely present. Additionally, the size of the periapical lesion will be measured on periapical radiographs (mesio-distal x corono-apical).

Peri-implantitis will be categorized based on the degree of mesial and distal bone loss around the implants, using the index employed by Monje et al. (23): Mild: 3-4 mm or < 25% of implant length. Moderate: 4-5 mm or ≥ 25%-50% of implant length. Advanced: > 6 mm or > 50% of implant length.

The following primary variables will be analyzed:

ITEMS VARIABLES Sex Categorical-dichotomous Age Numerical-continuous

The variables studied regarding the implant analysis will be:

MEASUREMENT VARIABLE TYPE Analyzed implant Categorical-polychotomous Type of regeneration Categorical-polychotomous Dimensions of achieved regeneration (in mm) Numerical-continuous Type of material used for regeneration Categorical-polychotomous Measurements of the implant platform-to-bone crest relationship (in mm) Numerical-continuous Measurement of mesial-distal bone loss (in mm) Numerical-continuousTime from implant placement to the radiograph taken to assess bone loss (in months) Continuous numerical Implant failure Dichotomous categorical Time from implant placement to implant failure (in months) Continuous numerical Implant type Polychotomous categorical Prosthesis type Polychotomous categorical

The variables studied regarding the relationship with an endodontically treated tooth will be:

MEASUREMENT VARIABLE TYPE Implant analyzed Polychotomous categorical Distance to the tooth (in mm) Continuous numerical Periapical Index (PAI) Polychotomous categorical Implant site in relation to endodontic failure Dichotomous categorical Periapical lesion dimensions (in mm) Continuous numerical Signs and symptoms of endodontic failure Polychotomous categorical Time since extraction Continuous numerical

The parameters analyzed from blood tests and medical history will be:

VARIABLE VARIABLE TYPE Creatinine Continuous numerical BUN Continuous numerical Glomerular filtration rate Continuous numerical Urea Continuous numerical Calcium Continuous numerical Phosphorus Continuous numericalVitamina D 25 Vitamin D 25 Numerical-continuous PTH Numerical-continuous C-reactive protein Numerical-continuous ESR Numerical-continuous Osteoporosis Categorical-dichotomous

In summary, the methodology to be used is as follows:

• Failed implants will constitute Cohort 1.
• For each failed implant, a non-failed implant will be selected from a patient with matching characteristics regarding sex, age, implant type, surgical/complication data, regeneration, etc., and prosthesis type. This will allow for the homogenization of results; however, as previously mentioned, for cases involving systemic disorders, results will be reported both per implant and per patient.
• Given that the survival rate of dental implants is approximately 95% (4%-8% failure rate, depending on the techniques used) over a 1-10 year period, non-failed implants placed in or before April 2024 will be sought. (24)
• These non-failed implants may fall into one of two categories: 1. Mesial and/or distal bone loss (Cohort 2); 2. Implant without bone loss (success) (Cohort 3).
• In each case, the previously described systemic and local characteristics and medical history will be recorded.

DATA INTERPRETATION AND STATISTICAL METHODS Variable data will be entered into Microsoft Excel (Microsoft Office 2019 suite; Microsoft Corporation, Washington, USA, 2013) and analyzed using SPSS 26.0 for Windows (SPSS, Illinois, USA, 2019).

Logic, range, and result consistency tests will be used for data management. For categorical variables, a descriptive analysis will be conducted using tables of absolute and relative frequencies (frequency and percentage), along with a bivariate analysis using a chi-square test when the conditions for... are not met....application. For scale variables, normality will be assessed using the Shapiro-Wilk test (p > 0.1) and visual analysis of normal P-P plots and box plots. If the conditions for application are met, a descriptive analysis based on the mean and standard deviation will be performed, along with a bivariate analysis using parametric ANOVA tests for independent samples. If the conditions for application are not met, a descriptive analysis based on the median and interquartile range will be conducted, along with a bivariate analysis using non-parametric tests (Kruskal-Wallis test).

The principal investigator will collect patient data from the computerized database of the University of Barcelona Dental Hospital (HOUB).

Likewise, the principal investigator will conduct the data analysis and interpret the results.

The principal investigator's intra-operator agreement (Cohen's Kappa coefficient) is 0.82.

Inclusion criteria

• Patients over 18 years of age
• Patients with implants placed within the last 10 years
• Patients with access to complete medical and dental records
• Patients with documented implant progression via periapical radiographs and/or OPG
• Patients with documented pre-implant tooth status
• Patients with blood test results from the 6 months prior to or following implant placement
• Implants lost due to peri-implant pathology causing bone resorption

Exclusion criteria

• Those patients who does not meet inclusion criteria