Teriparatide on Maxillary Sinus Floor Osseointegration

Study Overview
=================
Brief Summary
-----------------
The aim of this triple blind randomized controlled trial will be to analyze the effect of a dose of teriparatide combined with a xenograft on bone augmentation of the maxillary sinus, to observe the microarchitecture of the newly formed bone and the primary and late stability of implants placed on these grafts. The sample is composed of 42 participants who have a clinical indication for maxillary sinus floor augmentation with bone grafting due to residual bone height less than or equal to 5mm for the installation of dental implants. Each side will be grafted with Bio-Oss® or Bio-Oss® combined with 1 dose (20 µg) of teriparatide (Forteo®). Three months after grafting, at the time of placement of dental implants, bone biopsies will be obtained using a short 2mm trephine bur. These bone cores will be submitted to histological and histomorphometric analysis. The stability of the implants will be measured, at the time of their installation, through the insertion torque, and through the use of resonance frequency equipment (Ostell®) in three moments: immediately and at 3 and 6 months after the installation of the dental implants.

Official Title
-----------------
Bone Microarchitecture and Implant Stabilization in Atrophic Jaws Reconstructed With Bone Grafts Treated With Teriparatide

Conditions
-----------------
Bone Regeneration

Intervention / Treatment
-----------------
* Drug: Teriparatide
* Procedure: Maxillary Sinus Augmentation
* Procedure: Dental Implant Installation
* Combination Product: Bone graft


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pneumatization of a maxillary sinus with a residual ridge ≤ 5 mm in height (according to baseline conebeam tomograph). Must sign an informed consent to participate in this study. Exclusion Criteria: Residual ridges less than 4 mm in height. Uncontrolled systemic disease (ASA 3, 4, 5, and 6) Presenting with osteoporosis or any disease of bone metabolism. Having received radiotherapy. Cancer. Any systemic condition that affects calcium absorption. Kidney disease. Coagulation disorders. History of sinusitis. Maxillary sinus pathology. Heavy smoking (> 1 pack per day). Drug or alcohol users. Pregnancy. Treatment with drugs that affect bone metabolism. Treatment with immunosuppressants. Allergies. Uncontrolled periodontal pathology. Tooth extractions in the last three months.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriparatide<br>Access to the maxillary sinus will be done through osteotomy, using a piezosurgery . Subsequently, the Schneider's membrane will be carefully lifted and, according to the randomization process, the graft material Bio-Oss® mixed with Forteo® will be delivered for placement on the sinus floor maxilla below Schneider's membrane. Next, the access window to the maxillary sinus and Schneider's membrane will be protected. The mucoperiosteal flap will be repositioned and closed | Drug: Teriparatide<br>* mixture of 20μg of teriparatide, 0.64ml of saline solution with 1g of Bio -Oss® or 1g of Bio-Oss® will be mixed with 0.72ml of saline solution.<br>* Other names: Teriparatide Pen Injector [Forteo];Procedure: Maxillary Sinus Augmentation<br>* Local anesthesia will be performed, mucoperiosteal flap will be raised to access the anterior wall of the maxillary sinus. Access to the maxillary sinus will be done through osteotomy, using a piezosurgery under irrigation with saline solution. Subsequently, the Schneider's membrane will be carefully lifted and, according to the randomization process, the graft material (Bio-Oss® mixed with saline solution or Bio-Oss® mixed with Forteo®) will be delivered for placement on the sinus floor maxilla below Schneider's membrane.Next, the access window to the maxillary sinus and Schneider's membrane will be protected. The mucoperiosteal flap will be repositioned and closed.<br>Procedure: Dental Implant Installation<br>* Local anesthesia will be performed a mucoperiosteal flap will be raised in the area for implant placement and a bone core 10 mm high and 2 mm in diameter will be removed with a 2 mm trephine bur. The bone biopsied through this nucleus is part of the region where the implant will be installed, and the height of the sample depends on the surgical planning carried out previously (3-month radiographic control). The sequence of drills to place the implant will continue, installation of the implant itself and, finally, verification of the insertion torque and measurement of the resonance frequency in the already installed implant. The mucoperiosteal flap must be repositioned and sutured.<br>Combination Product: Bone graft<br>* One arm:mixture of 20μg of teriparatide, 0.64ml of saline solution with 1g of Bio -Oss® In other arm: 1g of Bio-Oss® will be mixed with 0.72ml of saline solution.<br>* Other names: Bio-Oss®;|
| Placebo Comparator: Placebo<br>Access to the maxillary sinus will be done through osteotomy, using a piezosurgery . Subsequently, the Schneider's membrane will be carefully lifted and, according to the randomization process, the graft material, Bio-Oss® mixed with saline solution, will be delivered for placement on the sinus floor maxilla below Schneider's membrane. Next, the access window to the maxillary sinus and Schneider's membrane will be protected. The mucoperiosteal flap will be repositioned and closed | Procedure: Maxillary Sinus Augmentation<br>* Local anesthesia will be performed, mucoperiosteal flap will be raised to access the anterior wall of the maxillary sinus. Access to the maxillary sinus will be done through osteotomy, using a piezosurgery under irrigation with saline solution. Subsequently, the Schneider's membrane will be carefully lifted and, according to the randomization process, the graft material (Bio-Oss® mixed with saline solution or Bio-Oss® mixed with Forteo®) will be delivered for placement on the sinus floor maxilla below Schneider's membrane.Next, the access window to the maxillary sinus and Schneider's membrane will be protected. The mucoperiosteal flap will be repositioned and closed.<br>Procedure: Dental Implant Installation<br>* Local anesthesia will be performed a mucoperiosteal flap will be raised in the area for implant placement and a bone core 10 mm high and 2 mm in diameter will be removed with a 2 mm trephine bur. The bone biopsied through this nucleus is part of the region where the implant will be installed, and the height of the sample depends on the surgical planning carried out previously (3-month radiographic control). The sequence of drills to place the implant will continue, installation of the implant itself and, finally, verification of the insertion torque and measurement of the resonance frequency in the already installed implant. The mucoperiosteal flap must be repositioned and sutured.<br>Combination Product: Bone graft<br>* One arm:mixture of 20μg of teriparatide, 0.64ml of saline solution with 1g of Bio -Oss® In other arm: 1g of Bio-Oss® will be mixed with 0.72ml of saline solution.<br>* Other names: Bio-Oss®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histology | osteoblasts/mm2 | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histomorphometry | Describe de presence of following parameters: necrosis, inflammation, vascularization and angiogenesis, fibrosis, presence of medullary adipose tissue, new bone formation and foreign body reaction | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
teriparatide, Bio-Oss®, bone graft, dental implants, maxillary sinus augmentation, bone regeneration