Evaluation of Fluid Biomarkers Around Implants Exhibiting Early Stage Periimplant Bone Loss

Evaluation of Biomarkers Involved In Bone Metabolism (Remodeling) In Periimplanter Crevicular Fluid of Implants With Early Marginal Bone Loss: A Retrospective Clinical Study

This study aimed to compare biological mediators known to be important in peri-implant diseases in implants with and without early stage marginal bone loss. A total of 118 implants in 59 patients were designated as test and control groups. The radiographic and periodontal data of the included implants, along with peri-implant sulcus fluid samples, were evaluated.

Study Overview

• Status: Completed
• Conditions: Marginal Bone Loss; Peri-implant Marginal Bone Loss; Peri-implant Bone Loss; Peri-Implant Health
• Intervention / Treatment: Other: Collecting of peri-implant sulcus fluid; Diagnostic test: Periapical radiography

Detailed Description

This study included clinical and radiographic records of patients who received implant treatment in the maxilla and/or mandible between 11/2021 and 9/2024. Patients were divided into test and control groups based on the presence/absence of EMBL after prosthetic loading. Periodontal clinical measurements were recorded and peri-implant sulcus fluid (PISF) samples were collected. Sclerostin, calprotectin, type I collagen cross-linked N-telopeptide (NTx), matrix metalloproteinase (MMP)-8, and MMP-9 levels were analyzed using ELISA. Group comparisons were performed with the statistical analyses.

• Study Type: Observational
• Enrollment (Actual): 59

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Denizli, Turkey (Türkiye), 20160
    • Pamukkale University, Faculty of Dentistry, Periodontology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients who received implant treatment at the Department of Periodontology, Pamukkale University Faculty of Dentistry.

Description

Inclusion Criteria:

• Presence of 1 mm or more of radiographic marginal bone loss within the first 3 months after implant placement
• Availability of radiographic documentation
• Availability of demographic data, surgical records, and data related to the implant used
• Physical condition classified as Class I and II according to the American Society of Anesthesiologists (ASA) classification
• Patients with no smoking history in the last 10 years
• Fixed implant-supported restorations
• Screw-retained implants

Exclusion Criteria:

• Patients receiving and/or maintaining implant treatment at centers other than the Department of Periodontology, Pamukkale University Faculty of Dentistry
• Patients with incomplete or unreachable files or radiographic documentation
• Patients with a known systemic disease/condition that alters their physical condition or bone metabolism
• Severe bruxism cases
• Pregnant and breastfeeding patients
• Patients with incomplete implant-supported prosthesis
• Areas grafted during or before implant surgery
• Removable implant-supported restorations
• Cement-retained implants
• Patients undergoing peri-implantitis treatment

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Test; Presence of marginal bone loss of 1 mm or more within the first 3 months after implant placement	Other: Collecting of peri-implant sulcus fluid; To evaluate biomarkers associated with peri-implant bone loss, periopaper was placed in the peri-implant pocket and absorbed with sulcus fluid.; Diagnostic test: Periapical radiography; Parallel cone technique was used during periapical imaging to accurately measure peri-implant bone loss.
Control; Presence of less than 1 mm of marginal bone loss within the first 3 months after implant placement	Other: Collecting of peri-implant sulcus fluid; To evaluate biomarkers associated with peri-implant bone loss, periopaper was placed in the peri-implant pocket and absorbed with sulcus fluid.; Diagnostic test: Periapical radiography; Parallel cone technique was used during periapical imaging to accurately measure peri-implant bone loss.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calprotectin levels in peri-implant crevicular fluid	After collecting peri-implant sulcus fluid using the paper strip method, calprotectin levels in the peri-implant sulcus region were determined using the ELISA method and recorded in ng/ml.	6-8 week after prosthetic treatment
Sclerostin levels in peri-implant crevicular fluid	After collecting peri-implant sulcus fluid using the paper strip method, sclerostin levels in the peri-implant sulcus region were determined using the ELISA method and recorded in pg/ml.	6-8 week after prosthetic treatment
NTx levels in peri-implant crevicular fluid	After collecting peri-implant sulcus fluid using the paper strip method, NTx levels in the peri-implant sulcus region were determined using the ELISA method and recorded in ng/ml.	6-8 week after prosthetic treatment
MMP-8 levels in peri-implant crevicular fluid	After collecting peri-implant sulcus fluid using the paper strip method, MMP-8 levels in the peri-implant sulcus region were determined using the ELISA method and recorded in ng/ml.	6-8 week after prosthetic treatment
MMP-9 levels in peri-implant crevicular fluid	After collecting peri-implant sulcus fluid using the paper strip method, MMP-9 levels in the peri-implant sulcus region were determined using the ELISA method and recorded in ng/ml.	6-8 week after prosthetic treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic detecting of Peri-implant marginal bone loss	The amount of marginal bone loss was determined by comparing the periapical radiograph taken on the day the implants were placed with the radiograph taken at 3 months. Measurements of digital radiographic images were performed using computer software. Then, study groups were determined according to the presence or absence of peri-implant marginal bone loss.	Baseline, 3 months
Modified Bleeding İndex	This assessment was performed based on the bleeding response following gentle probing with a plastic probe in the four regions of each implant (mesial, distal, palatal/lingual, and buccal). The severity of bleeding observed within approximately 10-30 seconds after probing was scored and recorded. The scoring system was graded as follows: 0: no bleeding, 1: bleeding at a single point, 2: bleeding at several points or in a linear pattern, 3: heavy bleeding following probing.	During the same session as the peri-implant fluid collection procedure
Peri-implant pocket depth	A plastic periodontal probe was used to determine peri-implant pocket depth. Measurements were taken by using the probe, supported by its own weight, parallel to the long axis of the tooth. Pocket depth was measured at 6 sites (mesio-buccal, buccal, disto-buccal, mesio-palatal/lingual, palatal/lingual, disto-palatal/lingual) for each implant included in the study and recorded in millimeters (mm). The pocket depth value for each dental implant was obtained by calculating the average of the 6 measured values.	During the same session as the peri-implant fluid collection procedure
Gingival İndex	The mesial, distal, buccal, and lingual/palatal surfaces of each tooth/implant were evaluated separately, and the average of the scores obtained was recorded as the gingival index value for that tooth/implant. Scoring during the evaluation was performed as follows: 0 = normal gingiva, 1 = mild inflammation (color change, mild edema, no bleeding on probing), 2 = moderate inflammation (redness, edema, bleeding on probing), 3 = severe inflammation (marked redness, edema, ulceration, spontaneous bleeding). Subsequently, all values were summed and divided by the total number of teeth and implants to record the gingival index score.	During the same session as the peri-implant fluid collection procedure
Modified Plaque İndex	The mesial, distal, buccal, and lingual/palatal surfaces around the teeth/implants were examined, and the average of the scores obtained for each surface was recorded as the plaque index for that tooth/implant. The scoring criteria were as follows: 0 = no plaque, 1 = plaque detectable only with a probe, 2 = soft plaque accumulation visible to the naked eye, 3 = the tooth surface covered with a distinct plaque layer. Subsequently, all values were summed and divided by the total number of teeth and implants to record the modified plaque index score.	During the same session as the peri-implant fluid collection procedure
Peri-implant mucosal recession	The abutment-implant interface was designated as the reference point for determining the extent of peri-implant mucosal recession, and the distance between the reference point and the free gingival margin was measured using a periodontal probe. Mucosal recession was recorded in four regions (mesio-buccal, mid-buccal, disto-buccal, mid-lingual/palatal) for each implant included in the study. The recession value for each implant was obtained by calculating the average of the four measured values.	During the same session as the peri-implant fluid collection procedure

Collaborators and Investigators

• Sponsor: Pamukkale University
• Collaborators: Pamukkale University scientific research project department
• Investigators: Principal Investigator: Raziye Tugce Can Keles, R.A., Pamukkale University Faculty of Dentistry, Department of Periodontology; Study Director: Gizem Torumtay Cin, Assoc. Prof., Pamukkale University Faculty of Dentistry, Department of Periodontology

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2025
• Primary Completion (Actual): September 6, 2025
• Study Completion (Actual): September 6, 2025

Study Registration Dates

• First Submitted: May 3, 2026
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: implant; sclerostin; marginal bone loss; matrix metalloproteinases; calprotectin; peri-implant sulcular fluid; n-terminal type I collagen telopeptide
• Additional Relevant MeSH Terms: Sclerosteosis
• Other Study ID Numbers: E-60116787-020-604271; 2025DİŞF001 (Other Identifier: Office of Scientific Research Projects of Pamukkale University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No