Effect of Healing Time on New Bone Formation Following Tooth Extraction and Ridge Preservation With Demineralized Freeze-Dried Bone Allograft

• Sponsor: The University of Texas Health Science Center at San Antonio (Other)
• Overall Status: Completed
• CT.gov ID: NCT02154386
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Duration (Months): 19
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

Bone grafting following tooth extraction is commonly performed to preserve bony ridge dimensions adequate to support subsequent implant placement. Alveolar ridge resorption commonly occurs following tooth extraction, and the decrease in bone volume has the potential to make dental implant therapy impossible without surgery to reconstruct the ridge. The aim of ridge preservation grafting is to prevent or minimize this resorptive process, thereby preserving an adequate volume of bone for implant placement. Ridge preservation generally involves placement of a particulate bone graft material in the tooth socket, followed by use of a membrane or similar substance over the socket entrance to contain the bone graft. Various grafting materials have been recommended for these ridge preservation procedures, including demineralized freeze-dried bone allograft (DFDBA). The timing of dental implant placement following ridge preservation procedures is controversial, and few studies have examined the effects of different healing time intervals between ridge preservation and implant placement. The purpose of this project is to evaluate the formation of new bone at a site where tooth extraction has been performed followed by grafting using DFDBA. Two different study groups are included, one having the dental implant placed 8-10 weeks after tooth extraction and ridge grafting, the other having the dental implant placed 18-20 weeks after extraction and grafting.

Condition or Disease	Intervention/Treatment	Phase
Bone Augmentation	Device: Ridge preservation using DFDBA	N/A

Detailed Description

The purpose of this study is to compare healing following tooth extraction and ridge preservation with DFDBA at a healing time point 8-10 weeks after treatment compared to a healing time point 18-20 weeks after treatment. There have been no studies to determine differences in new bone formation using DFDBA for this purpose at various healing time points post-grafting. The primary objective is to histologically determine the amount of new bone formation and residual graft material present at the two healing time points after grafting with DFDBA. Histologic healing will be compared based on three criteria: % of new vital bone formation, % of residual graft material, and % of nonmineralized connective tissue/bone marrow. The null hypothesis is that there will be no difference between the % new bone formation at 8-10 weeks after grafting compared to 18-20 weeks after grafting.

This entire protocol involves procedures that are standard care. There will be two subject groups in this study. All subjects will require extraction of a non-molar tooth, followed by replacement of the missing tooth with a dental implant. In order to ensure that the bone core removed during implant osteotomy preparation is taken totally within the confines of the former tooth socket, the tooth to be extracted will have a position and angulation that is the same as the implant that will replace the tooth. Each group will have 22 subjects. Only one tooth will be evaluated in any given subject.

Both groups will consist of subjects who will have cortical DFDBA grafted into the extraction socket for ridge preservation following tooth extraction. Group 1 will have a biopsy core taken at the time of implant placement 8-10 weeks after socket grafting. Group 2 will have a biopsy core taken at the time of implant placement 18-20 weeks after socket grafting. Allocation of subjects into group 1 or 2 will based on randomization once enrolled into the study. Subjects will be asked to draw a sealed envelope out of a stack of envelopes, each containing a single slip of paper coded with #1 or a #2. This will determine the treatment group.

All of the bone graft materials used in this study will come from the same donor (LifeNet Health). The materials will be procured and processed in the same manner and will have the same particle size and percent residual calcium. This greatly decreases potential variability inherent in bone taken from different donors or processed in different manners.

At the time of subject enrollment, the following standard care procedures will be performed:

Impressions will be made for fabrication of diagnostic casts and radiographs will be taken of the tooth to be extracted. A clear measurement stent will be made on the cast for vertical and horizontal ridge dimensions.

Following local anesthesia, the tooth will be extracted, and the number of bony walls in each socket will be recorded, along with the presence of any bony dehiscences or fenestrations. After extraction, the measurement stent will be placed and a hole will be made in the occlusal surface directly over the buccal bony wall and the lingual bony wall. Holes will be made in the buccal and lingual flanges of the measurement stent at a level approximately 3mm from the bony crests and ridge calipers will be used to make a horizontal ridge width measurement. These measurements will be recorded. The socket will be thoroughly debrided, a 1.0cc bottle of cortical DFDBA will be hydrated with sterile saline and the DFDBA will be placed in the socket to restore the ridge to appropriate contour. A collagen barrier (Collatape or Collaplug) will then be placed over the socket orifice and secured with sutures. Flaps will not be reflected to obtain primary closure. If a large dehiscence exists following extraction, which would most likely affect the facial socket wall, a collagen barrier with a longer resorption time, such as the Zimmer collagen socket repair membrane or BioGide collagen membrane will be used instead of Collatape or Collaplug. As part of standard care, patients will be prescribed systemic doxycycline 100mg twice a day for 7 days after surgery (if patient has sensitivity to doxycycline, alternate will be amoxicillin 500mg three times a day for 7 days). The patient will be seen 7-10 days after extraction/ridge preservation to assess healing, and again 1 month after the procedure.

The implant will be placed 8-10 weeks after ridge preservation in Group 1 and 18-20 weeks after ridge preservation in Group 2. At the time of implant placement, the first osteotomy will be prepared using a hollow trephine drill instead of a solid drill. Use of a hollow trephine allows retention of the bony core; whereas, use of solid drills results in removal of the bone in very small particles that cannot be examined histologically. Drilling of the pilot implant osteotomy has historically been done both ways (trephine drill or solid drill). The bone core in the trephine will be removed from the trephine, placed in 10% formalin, and prepared for histologic examination. The study will end immediately after removal of the trephined bone core.

Following initial preparation of the implant site with the trephine, the osteotomy will be completed and an implant of the appropriate length and diameter will be placed. The size of the implant will be such that it will engage not only newly formed bone in the socket itself, but at least 2-3mm of bone apical to the former socket site. A healing abutment will then be placed.

All subjects will be examined at 7-10 days and 1 month following implant placement. The patient will then be referred to their restorative dentist for final restoration.

The histologic cores will be processed for demineralized sections and will be stained. The following histologic parameters will be measured: percent new bone formation, percent residual graft material, and percent connective tissue/other.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Healing Time on New Bone Formation Following Tooth Extraction and Ridge Preservation With Demineralized Freeze-Dried Bone Allograft
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 8-10 week healing group dental implant placed (and bone core biopsy harvested) 8-10 weeks after tooth extraction/grafting	Device: Ridge preservation using DFDBA; tooth extraction followed by ridge preservation grafting using DFDBA
Active Comparator: 18-20 week healing group dental implant placed (and bone core biopsy harvested) 18-20 weeks after tooth extraction/grafting	Device: Ridge preservation using DFDBA; tooth extraction followed by ridge preservation grafting using DFDBA

Outcome Measures

Primary Outcome Measures

1. Percent New Vital Bone Formation [after removal of bone core from site of dental implant placement at 18-20 weeks following tooth extraction and grafting]

   Bone core biopsy will be evaluated histologically for percent new vital bone formation

Secondary Outcome Measures

1. Change in Ridge Width [at time of implant placement at 8-10 or 18-20 weeks following tooth extraction and grafting]

   Ridge width measured at time of tooth extraction and grafting and again at time of implant placement. Changes in ridge width are determined (negative number signifies loss of ridge width)

2. Change in Buccal Ridge Height [at time of implant placement at 8-10 or 18-20 weeks following tooth extraction and grafting]

   Ridge height measured at time of tooth extraction and grafting and again at time of implant placement. Changes in ridge height are determined (negative number signifies loss of ridge height)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Patient currently a patient at dental school or eligible for treatment at dental school

• Patient resides within 50 mile radius of dental school

• A single rooted tooth that has been identified by dental faculty as requiring extraction

• Have adequate restorative space for a dental implant-retained restoration

• Have at least 10mm of alveolar bone height, without impinging on the maxillary sinus or inferior alveolar canal.

• Have a dehiscence of the buccal or lingual bony plate of the tooth socket extending no more than 50% of the total depth of the socket.

• Female patients who have undergone a hysterectomy, tubal ligation, or menopause, and non-pregnant women of child-bearing potential.

Exclusion Criteria:

• not meeting inclusion criteria above

• Active localized or systemic infection other than periodontitis.

• Inadequate bone dimensions or restorative space dimensions to place a dental implant

• Presence of a disease entity, medical condition or therapeutic regimen which decreases probability of soft tissue and bony healing, e.g., poorly controlled diabetes, chemotherapeutic and immunosuppressive agents, autoimmune diseases, history of bisphosphonate use or long-term steroid therapy.

• Positive medical history of endocarditis following oral or dental surgery.

• Sensitivity or allergy to Bacitracin, Gentamicin, Polymyxin B Sulfate, alcohol and/or surfactants (per package insert)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT Health Science Center School of Dentistry	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• The University of Texas Health Science Center at San Antonio

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Brian L Mealey, Graduate Program Director, Periodontics, The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT02154386
• Other Study ID Numbers: HSC20130440H
• First Posted: Jun 3, 2014
• Last Update Posted: Dec 3, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Brian L Mealey, Graduate Program Director, Periodontics, The University of Texas Health Science Center at San Antonio: bone augmentation; tooth extraction; dental implant

Study Results

Participant Flow

Arm/Group Title	8-10 Week Healing Group	18-20 Week Healing Group
Arm/Group Description	dental implant placed (and bone core biopsy harvested) 8-10 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA	dental implant placed (and bone core biopsy harvested) 18-20 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA
Period Title: Overall Study
STARTED	23	23
COMPLETED	22	21
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	8-10 Week Healing Group	18-20 Week Healing Group	Total
Arm/Group Description	dental implant placed (and bone core biopsy harvested) 8-10 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA	dental implant placed (and bone core biopsy harvested) 18-20 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA	Total of all reporting groups
Overall Participants	23	23	46
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56.1	55.4	55.7
Sex: Female, Male (Count of Participants)
Female	13 56.5%	12 52.2%	25 54.3%
Male	10 43.5%	11 47.8%	21 45.7%

Outcome Measures

1. Primary Outcome

Title	Percent New Vital Bone Formation
Description	Bone core biopsy will be evaluated histologically for percent new vital bone formation
Time Frame	after removal of bone core from site of dental implant placement at 18-20 weeks following tooth extraction and grafting

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	8-10 Week Healing Group	18-20 Week Healing Group
Arm/Group Description	dental implant placed (and bone core biopsy harvested) 8-10 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA	dental implant placed (and bone core biopsy harvested) 18-20 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA
Measure Participants	20	19
Mean (Standard Deviation) [percentage of vital bone]	32.63 (21.45)	47.41 (11.66)

2. Secondary Outcome

Title	Change in Ridge Width
Description	Ridge width measured at time of tooth extraction and grafting and again at time of implant placement. Changes in ridge width are determined (negative number signifies loss of ridge width)
Time Frame	at time of implant placement at 8-10 or 18-20 weeks following tooth extraction and grafting

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	8-10 Week Healing Group	18-20 Week Healing Group
Arm/Group Description	dental implant placed (and bone core biopsy harvested) 8-10 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA	dental implant placed (and bone core biopsy harvested) 18-20 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA
Measure Participants	22	19
Mean (Standard Deviation) [ridge width change (mm)]	-1.41 (2.11)	-0.66 (1.55)

3. Secondary Outcome

Title	Change in Buccal Ridge Height
Description	Ridge height measured at time of tooth extraction and grafting and again at time of implant placement. Changes in ridge height are determined (negative number signifies loss of ridge height)
Time Frame	at time of implant placement at 8-10 or 18-20 weeks following tooth extraction and grafting

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	8-10 Week Healing Group	18-20 Week Healing Group
Arm/Group Description	dental implant placed (and bone core biopsy harvested) 8-10 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA	dental implant placed (and bone core biopsy harvested) 18-20 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA
Measure Participants	22	19
Mean (Standard Deviation) [change in bone height (mm)]	-1.82 (2.23)	-1.18 (1.31)

Adverse Events

Arm/Group Title	8-10 Week Healing Group		18-20 Week Healing Group
Arm/Group Description	dental implant placed (and bone core biopsy harvested) 8-10 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA		dental implant placed (and bone core biopsy harvested) 18-20 weeks after tooth extraction/grafting Ridge preservation using DFDBA: tooth extraction followed by ridge preservation grafting using DFDBA
All Cause Mortality
	8-10 Week Healing Group		18-20 Week Healing Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	8-10 Week Healing Group		18-20 Week Healing Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	8-10 Week Healing Group		18-20 Week Healing Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		0/21 (0%)
Surgical and medical procedures
poor healing of extraction site	1/22 (4.5%)	1	0/21 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.