Standard- and Micro-Dose rhBMP-2 for Implant Stability, Marginal Bone Loss, and Postoperative Sequelae: A Double-Blind Randomized Controlled Trial

N/ANot Yet RecruitingNCT07696299

University of Baghdad60 enrolled

Overview

This study will compare the effect of standard-dose and micro-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) with a placebo control on dental implant stability in the posterior mandible. Sixty patients requiring a single dental implant will be randomly assigned to one of three groups: standard-dose rhBMP-2, micro-dose rhBMP-2, or sterile saline only. Implant stability will be measured using Resonance Frequency Analysis at baseline, 2 weeks, 4 weeks, and 12 weeks. Marginal bone loss, peri-implant bone density, ectopic bone formation, and postoperative sequelae including swelling, pain, trismus, and soft tissue healing will also be evaluated during follow-up. The aim is to determine whether micro-dose rhBMP-2 can improve implant stability while reducing postoperative complications compared with the standard dose.

This prospective, double-blind, randomized controlled clinical trial is designed to evaluate the effect of locally applied recombinant human bone morphogenetic protein-2 (rhBMP-2) on peri-implant stability, marginal bone loss, peri-implant bone density, postoperative sequelae, and ectopic bone formation following dental implant placement in the posterior mandible. Sixty systemically healthy adult patients requiring a single implant-supported restoration in the posterior mandible will be enrolled and randomly allocated in a 1:1:1 ratio into three parallel groups (20 participants per group). Group A will receive the standard dose of rhBMP-2 (0.1 mg), Group B will receive a micro-dose of rhBMP-2 (0.02 mg), and Group C will receive sterile saline as the placebo control. Randomization will be computer-generated, and an independent assistant will prepare identical coded syringes to maintain allocation concealment. Patients, the operating surgeon, the clinical outcome assessor, and the statistician will remain blinded until completion of the final statistical analysis. All implants will be placed by the same surgeon using the MegaGen AnyRidge implant system following a standardized surgical protocol. The allocated solution will be delivered into the prepared implant osteotomy immediately before implant insertion. Healing abutments will be connected at the time of surgery to allow non-invasive longitudinal resonance frequency analysis without disturbing the peri-implant tissues. The primary outcome is peri-implant stability measured using Resonance Frequency Analysis (Osstell Beacon) at baseline, 2 weeks, 4 weeks, and 12 weeks after implant placement. Secondary outcomes include marginal bone loss and peri-implant bone density assessed using standardized CBCT at baseline, 6 months, and 12 months. Postoperative sequelae (pain, facial swelling, trismus, and early soft tissue healing) will be evaluated on postoperative days 1, 3, and 7. Ectopic bone formation will be assessed radiographically during follow-up. Statistical analyses will follow the intention-to-treat principle using repeated-measures and between-group analyses with statistical significance set at P \< 0.05.

Interventions

Standard-dose rhBMP-2BIOLOGICAL

Standard-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) is locally applied into the implant osteotomy immediately before implant placement at the manufacturer's recommended dose to enhance osseointegration and implant stability.

Micro-dose rhBMP-2BIOLOGICAL

Micro-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) is locally applied into the implant osteotomy immediately before implant placement at a reduced dose to evaluate whether comparable implant stability can be achieved with fewer dose-related adverse effects.

Sterile Normal SalineDRUG

Sterile normal saline is locally applied into the implant osteotomy immediately before implant placement as the placebo control.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients aged 20 to 55 years requiring a single dental implant for a single tooth missing in the posterior mandible (strictly limited to one implant per patient to prevent clustering effects and intra-subject correlation). Patients must be systemically healthy or medically well-controlled, categorized as ASA I or ASA II according to the American Society of Anesthesiologists classification. Surgical sites must exhibit D2 or D3 bone quality with adequate residual alveolar bone volume (minimum 6 mm width and 10 mm height). Patients must maintain optimal oral hygiene, suitable for a prosthetically driven implant treatment workflow. Exclusion Criteria: * Patients presenting with uncontrolled systemic conditions (e.g., unmanaged diabetes mellitus, active osteoporosis). A history of radiotherapy or chemotherapy in the maxillofacial region. Current heavy smoking habits (\>10 cigarettes per day). Active and untreated periodontal disease. Pregnancy or lactation.

Outcomes

Primary Outcomes

Peri-Implant Stability (Implant Stability Quotient [ISQ])

Peri-implant stability will be quantitatively assessed using Resonance Frequency Analysis (RFA) with the Osstell Beacon device. ISQ values will be recorded from two orthogonal directions (buccolingual and mesiodistal), and the mean value will be used for analysis to compare implant stability among the three study groups.

Time frame: Baseline (immediately after implant placement), 2 weeks, 4 weeks, and 12 weeks after implant placement

Secondary Outcomes

Marginal Bone Loss

Marginal bone loss will be evaluated using standardized CBCT images. Linear measurements from the implant-abutment junction to the highest crestal bone level will be recorded at the mesial and distal aspects of each implant and compared among the three study groups.

Time frame: Baseline (immediately after implant placement), 6 months, and 12 months after implant placement

Peri-Implant Bone Density

Peri-implant bone density will be evaluated using standardized CBCT scans. Bone density around the implant threads will be measured using Hounsfield Units (HU) or voxel gray values and compared among the three study groups to assess peri-implant bone remodeling.

Time frame: Baseline (immediately after implant placement), 6 months, and 12 months after implant placement

Soft Tissue Swelling

Postoperative soft tissue swelling will be assessed using standardized linear facial measurements between predetermined anatomical landmarks. Measurements will be obtained preoperatively and postoperatively to compare the degree of swelling among the three study groups.

Time frame: Baseline, postoperative days 1, 3, and 7

Pain Intensity (Visual Analog Scale [VAS])

Postoperative pain intensity will be assessed using a 10-cm Visual Analog Scale (VAS), where 0 indicates no pain and 10 indicates the worst imaginable pain. Participants will record their pain scores at each assessment time point, and the results will be compared among the three study groups.

Time frame: Daily during the first postoperative week

Trismus (Maximum Interincisal Distance)

Trismus will be assessed by measuring the maximum interincisal distance (MID) between the incisal edges of the upper and lower central incisors using a calibrated digital caliper. Measurements will be obtained at each assessment time point and compared among the three study groups.

Time frame: Baseline, postoperative days 1, 3, and 7

Soft Tissue Healing Index (Landry Index)

Early soft tissue wound healing will be assessed using the validated Landry, Turnbull and Howley Healing Index. The index evaluates tissue color, bleeding on palpation, granulation tissue, epithelialization of the incision margin, and suppuration, with scores ranging from 1 (very poor healing) to 5 (excellent healing).

Time frame: Postoperative days 1, 3, and 7

Ectopic Bone Formation

Ectopic bone formation will be assessed radiographically using standardized CBCT images. The presence, location, and extent of ectopic bone formation around the implant healing abutment will be evaluated and compared among the three study groups.

Time frame: 6 months and 12 months after implant placement