Ridge Preservation Following Tooth Extraction Using Porcine and Bovine Xenograft Materials
Phase: NA
Conditions: Alveolar Bone Loss
Sponsor: The University of Texas Health Science Center at San Antonio

 
16-0285H, Mealey, Form BC, 06-08-16, NS 
 
 
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COVER PAGE FOR PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 
 
 
 
 
 
Official Study Title: Ridge Preservation Following Tooth Extraction Using Porcine and Bovine 
Xenograft Materials 
 
 
NCT number: NCT02802319 
 
IRB Approval Date: 06/08/16 
 
Unique Protocol ID: HSC20160285H 
 
 
 
 

 
16-0285H, Mealey, Form BC, 06-08-16, NS 
 
 
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Protocol Template Form 
 
Item 1 UTHSCSA 
Tracking Number 
HSC20160285H 
TITLE: Ridge Preservation Following Tooth Extraction Using Porcine and Bovine Xenograft Materials 
 
Item 2 Abstract / Project Summary 
Provide a succinct and accurate description of the proposed 
research. State the purpose/aims. Describe concisely the research 
design and methods for achieving the stated goals. This section 
should be understandable to all members of the IRB, scientific and 
non-scientific.   
DO NOT EXCEED THE SPACE PROVIDED. 
Purpose/Objectives:  The purpose of the proposed study is to examine histologic wound healing following tooth extraction 
and ridge preservation using bovine versus porcine xenograft material.  
Research Design/Plan: The study is a two-arm, parallel-design, randomized, prospective clinical trial. This entire protocol 
involves procedures that are standard care. The protocol is similar in design to the protocol our study group has used 
repeatedly and published in multiple papers.4-6,9  
Methods: Subjects will have a non-molar tooth extracted and the socket grafted with one of two different bone graft 
materials (bovine-derived xenograft [Bio-Oss] or porcine-derived xenograft [Zcore]). At the time of implant placement 
18-20 weeks after tooth extraction a small core biopsy specimen will be removed from the implant site. The core biopsy 
will then be evaluated for the primary outcomes: % vital bone formation, % residual graft material, and % “CT/other” 
(fibrous tissue and marrow space).  We will also be evaluating the following secondary outcomes using a custom 
measuring stent for each subject: change in ridge width; change in buccal ridge height, and change in lingual ridge height. 
Clinical Relevance: Having a high percentage of new vital bone after tooth extraction and ridge preservation may be 
beneficial in maintaining ridge dimensions for implant placement. This study will examine differences in vital bone 
formation with bovine vs porcine xenografts after tooth extraction and ridge preservation. 
 
 
 
Item 3 
Background 
 
Describe past experimental 
and/or clinical findings 
leading to the formulation 
of your study.   
For research involving 
unapproved drugs, describe 
animal and human studies.   
For research that involves 
approved drugs or devices, 
describe the FDA approved 
uses of this drug/device in 
relation to your protocol. 
Insert background: Bone grafting following tooth extraction is commonly performed to preserve 
bony ridge dimensions adequate to support subsequent implant placement. Alveolar ridge 
resorption often 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.1  
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 
cortical and cancellous freeze-dried bone allograft (FDBA), demineralized freeze-dried bone 
allograft (DFDBA), allografts processed without freeze-drying, various xenografts, alloplasts 
and autografts.  
 
Our research group has published numerous studies evaluating a variety of materials for ridge 
preservation.2-10  Beck & Mealey examined healing using a non-freeze-dried bone allograft 
prepared using the proprietary Tutoplast process (PUROS) and found similar new vital bone 
formation following a healing period of 3 months versus 6 months after ridge preservation.2 In 
both groups, newly formed vital bone constituted approximately 45% of the total volume of the 
histologic specimens.  In Wood & Mealey the use of cortical DFDBA provided a higher 
percentage of new vital bone formation (38.4%) than did cortical mineralized FDBA (24.6%).4 
A major strength of this study was that the comparison graft materials for both study groups 

 
16-0285H, Mealey, Form BC, 06-08-16, NS 
 
 
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came from the same tissue donor, eliminating any issues that might arise from using different 
donor sources. Similarly, three additional studies done by our research group used a single 
source of donor bone for both study treatment groups.6,9,10   
 
Our research group examined the effect on new bone formation of ridge preservation procedures 
performed using either cortical or cancellous FDBA.6 There was no significant difference in new 
vital bone formation between the cortical (median 16.1%) and cancellous (median 13.0%) 
FDBA groups. A significantly greater percentage of residual graft material was detected in the 
cortical FDBA group as compared to the cancellous FDBA group, and a significantly greater 
percentage of nonmineralized CT/other material was found in the cancellous FDBA group as 
compared to the cortical FDBA group. We recently published a study comparing 100% 
mineralized cortical FDBA to a combination of 70% mineralized/30% demineralized cortical 
FDBA.9 The combination mineralized/demineralized allograft resulted in increased vital bone 
percentage, (36.2%) compared to the 100% mineralized allograft group (24.7%). 
 
Until recently, the primary animal source for xenografts use in oral surgical procedures has been 
the cow.  Bovine bone xenografts have been used widely for treatment of periodontal  bony 
defects and for alveolar bone defects. In one of our previous studies5, we used a bovine-derived 
xenograft material for ridge preservation and found a vital bone percentage of 32.8% following 
an 18-20 week healing period.  Other animal sources of xenograft have become popular in the 
past 10 years, including equine and porcine sources.  A porcine bone xenograft (pig source) has 
been introduced to the American dental market (Zcore; distributed by Osteogenics, Inc.). While 
this material is in clinical use for oral surgical procedures, there are to date no published data on 
its osteoconductive potential following tooth extraction and ridge preservation. The purpose of 
this study is to evaluate clinical and histologic wound healing following tooth extraction and 
ridge preservation using bovine and porcine xenografts.   
 
References: 
 
1. Avila-Ortiz G, Elangovan S, Kramer KWO, Blanchette D, Dawson DV. Effect of 
alveolar ridge preservation after tooth extraction: a systematic review and meta-analysis. 
J Dent Res 2014; 93: 950-958. 
2. Beck TM, Mealey BL.  Histological Analysis of Healing After Tooth Extraction with 
Ridge Preservation Using Mineralized Human Bone Allograft. Journal of 
Periodontology 2010; 81: 1765-1772. 
3. Hoang TN, Mealey BL. Histological comparison of healing following ridge preservation 
using human demineralized bone matrix putty with one versus two different sized bone 
particles. Journal of Periodontology 2012; 83: 174-181. 
4. Wood RA, Mealey BL. Histological comparison of healing following tooth extraction 
with ridge preservation using mineralized vs. demineralized freeze dried bone allograft. 
Journal of Periodontology 2012; 83: 329-336. 
5. Cook DC, Mealey BL. Histological comparison of healing following tooth extraction 
with ridge preservation using two xenograft products. Journal of Periodontology 2013; 
84: 585-594. 
6. Eskow AJ, Mealey BL. Histological evaluation of healing following tooth extraction 
with ridge preservation using cortical versus cancellous freeze dried bone allograft. 
Journal of Periodontology 2014; 85: 514-524. 
7. Coomes AM, Mealey BL, Huynh-Ba G, Barboza-Arguello C, Moore WJ, Cochran DL. 
Buccal bone formation after flapless extraction: A randomized controlled clinical trial 
comparing recombinant human bone morphogenetic protein-2/absorbable collagen 
carrier and collagen sponge alone.  Journal of Periodontology 2014; 85: 525-535. 
8. Frost NA, Banjar AA, Galloway PB, Huynh-Ba G, Mealey BL. The decision-making 
process for ridge preservation procedures following tooth extraction. Clin Adv 
Periodont 2014; 4:56-63. 

 
16-0285H, Mealey, Form BC, 06-08-16, NS 
 
 
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9. Borg T, Mealey BL. Histological comparison of healing following tooth extraction with 
ridge preservation using mineralized freeze dried bone allograft alone versus a 
combined mineralized-demineralized freeze dried bone allograft. J Periodontology 
2015; 86: 348-355. 
10. Whetman J, Mealey BL. Effect of healing time on new bone formation following tooth 
extraction and ridge preservation with demineralized freeze-dried bone allograft. A 
randomized controlled clinical trial. Submitted to Journal of Periodontology March 
2016. 
 
Item 4 
Purpose and rationale 
Insert purpose, objectives 
and research 
questions/hypotheses here. 
 If you cut and paste from 
another document, make 
sure the excerpted material 
answers the question 
Insert purpose: The study is designed to examine histologic wound healing following ridge 
preservation using bovine xenograft and porcine xenograft materials. 
This entire protocol involves procedures that are standard care. The study is a 2-arm, parallel-
design, randomized, prospective clinical trial. The test group subjects will have extraction 
sockets grafted with porcine xenograft (Zcore). This test group will be compared to an active 
control group using bovine xenograft (Bio-Oss).  The null hypothesis is that there will be no 
significant difference in formation of new vital bone between treatment groups (primary 
outcome).  
In keeping with the protocol our study group has used several times before, the plan will be to 
extract non-molar teeth and graft with the test/control materials. Each subject will provide a 
single non-molar tooth site for study treatment.  The graft material will be covered with a non-
resorbable dense polytetrafluoroethylene (d-PTFE) membrane (TXT-200 singles, Osteogenics 
Inc). This d-PTFE membrane will be removed 4 weeks after placement during the 4-week post-
op visit. Following 18-20 weeks of healing, we will place the dental implant.  To place a dental 
implant, an osteotomy (hole in the bone) is prepared into which the implant is placed. This 
osteotomy can be prepared with either a solid drill, in which case the bone that is removed is 
suctioned into the suction system, or with a hollow trephine drill into which a core of bone can 
be collected. The only "research procedure" being done in the current study is the collection of 
this bone core biopsy for histologic evaluation. The core biopsy will then be evaluated for the 
primary outcomes: % vital bone formation, % residual graft material, and % “CT/other” (fibrous 
tissue and marrow space).  We will also be evaluating the following secondary outcomes using 
a custom measuring stent for each subject: change in ridge width; change in buccal ridge 
height, and change in lingual ridge height. 
 
 
Item 5 
Study Population(s) Being Recruited 
 
In your recruitment plan, how many 
different populations of prospective 
subjects do you plan to target? 
Provide number: 1  
 
 
 
Identify the criteria for inclusion:  
Identify the criteria for exclusion:  

 
16-0285H, Mealey, Form BC, 06-08-16, NS 
 
 
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e.g., a population can be individuals 
with type 2 diabetes controlled with diet 
and/or a population of healthy controls.  
Or a population can be individuals 
attending an education program, etc. 
 
List each different population on a 
separate row and provide a short 
descriptive label:   
(e.g., normal-healthy, diabetics, 
parents, children, etc.) 
 
To add rows use copy & paste 
Patients seen in Periodontics 
• 
A single rooted tooth that has 
been identified as requiring extraction 
• 
Patient desires a dental implant 
to replace the missing tooth 
• 
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. 
• 
Are nonsmokers or former 
smokers. Current smokers may be 
included if they smoke <10 cigarettes per 
day 
 
 
• 
who will not cooperate with the 
follow-up schedule.   
• 
Patients will are mentally 
incompetent, prisoners, or pregnant. 
• 
Pregnant women or women 
intending to become pregnant during the 
study period. Prior to dental surgery, 
females of child-bearing age are asked 
verbally if there is any possibility that 
they are pregnant.  If not, we proceed 
with surgery and no pregnancy test is 
done.  If the woman states that there is a 
possibility that she is pregnant, we do a 
urine pregnancy test to rule pregnancy in 
or out. So use of the urine pregnancy test 
is only done if she says she may be 
pregnant.  [If needed: An over-the-
counter urine pregnancy test will be 
provided to female subjects in the 
graduate periodontics clinic of UTHSCSA.  
Subjects will be allowed access to a 
private restroom and the results of the 
tests will be read by one of the named 
investigators.  Only those with a negative 
pre-operative pregnancy test will 
continue in the study.] Grafted patients 
who become pregnant during the study 
will be withdrawn, but will be followed 
until completion of pregnancy.   
• 
Smokers who smoke >10 
cigarettes per day 
• 
Clinical and/or radiographic 
determinations which will preclude 
inclusion in this study are: Active 
infection other than periodontitis; 
Inadequate bone dimensions or 
restorative space for a dental implant; 
Presence of a disease entity, condition or 
therapeutic regimen which decreases 

 
16-0285H, Mealey, Form BC, 06-08-16, NS 
 
 
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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. 
Insert response here 
Insert response here 
Insert response here 
 
 
Item 6 
Research Plan / Description of the Research Methods a.  Provide a comprehensive narrative describing the research methods.   
Provide the plan for data analysis (include as applicable the sample size calculation). 
 
Step-by-Step Methods: The purpose of the proposed study is to examine histologic wound healing following ridge 
preservation using bovine xenograft compared to porcine xenograft. The study is a two-arm, parallel-design, 
randomized, prospective clinical trial. This entire protocol involves procedures that are standard care. The 
protocol is similar in design to the protocol our study group has used repeatedly and published in multiple 
papers.4-6,9,10  
 
There will be two subject groups in this study.  All subjects will require extraction of at least one non-molar 
tooth, followed by replacement of the missing tooth with a dental implant. If a given subject requires more than 
one tooth extraction, only one tooth site will be included in the study (the site with the best bony walls present 
after extraction; if two or more sites have equally good bony walls, the study site will be selected randomly by 
coin toss if there are two teeth to be extracted, or by drawing a number from a hat if more than 2 teeth require 
extraction). Based on power analysis and drop-out experience from previous studies, a total of 22 subjects will 
be recruited per group, with a maximum enrollment of 44 subjects for the 2 groups combined.  
 
Test group subjects will have extraction sockets grafted with cancellous porcine-derived xenograft (Zcore; 
Osteogenics Inc.). This test group will be compared to an active control group in which extraction sockets are 
grafted using cancellous bovine-derived xenograft (Bio-Oss; Geistlich, Inc.).  Allocation of subjects into test or 
control group will based on numbers drawn from a stack of sealed envelopes. At the beginning of the study there 
will be 22 envelopes containing a piece of paper inscribed with “Group 1” and 22 envelopes with “Group 2” 
(Group 1=  porcine Zcore; Group 2 = bovine Bio-Oss). The subjects will not be randomized until after the tooth 
to be extracted has been removed (see below). 
 
At the time of subject enrollment, the following standard procedures will be performed: impressions will be 
made for fabrication of diagnostic casts.  The tooth or teeth to be extracted will be noted on the casts.  
Radiographs will be taken of the tooth or teeth to be extracted. A clear resin measuring stent will be fabricated in 
the laboratory to allow standardization of the location of clinical measurements of ridge width and height. A 
small flap will be reflected to an extent about 3mm beyond the bony walls of the socket, with transection of the 
mesial and distal papillae as needed.  The measuring stent will be placed and measurements of ridge width and 
ridge height will be taken and recorded to the nearest 0.5mm.  Ridge width will be measured using a ridge 
caliper at a point approximately 4mm apical to the facial and lingual bony crest through small holes created in 
the stent at those locations.  Ridge height will be measured through two holes in the occlusal aspect of the stent – 
one hole directly above the facial bony crest and another hole directly above the lingual bony crest.  This stent 
will be retained for use during the subsequent implant placement surgery.  
 
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. Buccal and lingual flap elevation will be minimized and will 
extend only approximately 3mm beyond the bony crest on the facial and lingual surfaces. The buccal plate 
thickness will be measured using an Iwanson gauge positioned perpendicular to the inner wall of the extraction 
socket. One beak of the gauge will be placed within the extraction socket 1.0mm below the alveolar bone crest. 

 
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The other beak will be placed on the external bone surface. This buccal plate thickness measurement will be 
recorded to the nearest tenth of a millimeter. The socket will be thoroughly debrided. The subject will then be 
randomized by drawing a sealed envelope from the stack, and either porcine or bovine xenograft will be 
placed in the socket to restore the ridge to appropriate contour. A non-resorbable dense polytetrafluoroethylene 
(d-PTFE) membrane (TXT-200 singles, Osteogenics Inc) will then be placed over the socket orifice extending 
about 3mm beyond the bony socket walls. Sutures will be placed over the membrane to secure it in place. 
Primary closure will not be attempted. Patients will be placed on systemic antibiotics for one week after surgery, 
a standard care practice. Amoxicillin 500mg three times daily will be the primary antibiotic selected.  If the 
patient is penicillin-allergic, clindamycin or doxycycline will be substituted. The d-PTFE membrane will be 
removed 4 weeks after placement during the 4-week post-op visit.  
Dehiscences of the bony walls of the socket may be found during the extraction procedure, as they are relatively 
common.  If the dehiscence is deeper than 50% of the total socket depth, the subject will be withdrawn 
from the study.  If the dehiscence is less than 50% of the depth of the socket, a larger flap will be reflected so 
that the d-PTFE membrane can extend 3mm beyond the bony walls of the dehiscence.  The patient will be seen 
7-10 days after extraction/ridge preservation to assess healing, and again 4 weeks after the procedure.  The d-
PTFE membrane will be removed at this 4-week post op visit. 
 
At the time of implant placement approximately 18-20 weeks after extraction and ridge preservation, the 
individual subject’s measuring stent and caliper will be used to determine the ridge width and ridge height at the 
same locations as done in the tooth extraction/grafting surgery visit. The first osteotomy will be prepared using a 
hollow trephine with internal diameter of 2.0mm instead of a solid drill. The trephine drill will be used to a depth 
of approximately 8mm, ensuring that the bone within the trephine comes from the former socket area and not 
from surrounding native bone. The bone removed from the osteotomy site remaining in the trephine will be 
prepared for histologic examination and analyzed for new bone growth. 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.  A surgical guide stent 
will be fabricated on the diagnostic casts and will be used to ensure proper positioning of the trephine at the site 
of the grafted ridge preservation procedure.  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. The study itself will end at the 
time of the bone core removal. All subjects will be examined at 7-10 days following implant placement and at 
several visits between implant placement and final determination of implant stability for restoration, usually 
about 3-5 months after implant placement. The patient will then be referred to his/her restorative dentist for final 
restoration.  
 
At the 18-20 week post-extraction/ridge preservation visit, in cases where the bone width or bone density is 
insufficient for implant placement at the time of osteotomy preparation with the trephine drill and subsequent 
implant drills, the implant will not be placed.  Instead, guided bone regeneration will be performed in the usual 
manner and the site will be allowed to heal for 4-5 months before implant placement. As for all subjects, the 
study itself will end at the time of bone core removal. 
 
 
Data Analysis Plan: The primary hypothesis to be tested is whether the mean percentage of new bone observed 
histologically for patients receiving a porcine xenograft for ridge preservation in an extraction site prior to 
implant placement is different than those receiving a bovine xenograft at a time point approximately 18-20 
weeks after grafting. The distribution of new bone percentages is expected to be positively skewed, conforming 
to a double exponential distribution.  The hypothesis will be tested using a Mann-Whitney U test.  A total of 44 
patients will receive treatment in a non-molar tooth site, with a minimum of 70% of patients expected to be fully 
compliant under the study protocol, so that the sample size available for histologic examination will be at least 
14 patients per treatment group.  This proposed sample size is sufficient to detect a mean difference of one 
standard deviation or more by Mann-Whitney U test at the 0.05 level with power of 88.5%.  For example, if the 
population standard deviation of new bone percentage within patients is 10% or less, then the proposed sample is 
sufficient to detect a clinically significant mean difference of 10% or more new bone for patients receiving 

 
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porcine xenograft compared to bovine xenograft.   
 
 
 
Item 7 Risks Section: 
Complete the following table to describe the risks of all research procedures listed in Step 2, Institutional Form (items 28-34).  Do not list risks of Routine care 
procedures here.  
 ☐ N/A, Risks are described in the informed consent document – do not complete this table. 
Research procedures 
 
example: 
• 
History and physical 
• 
Questionnaire 
• 
Laboratory tests 
 
Add or delete rows as needed 
Risks 
 
List the reasonably expected risks 
under the following categories as appropriate: 
Randomization - Ridge 
preservation following 
tooth extraction using one 
of 2 graft materials in 
preparation for dental 
implant placement 
Serious and likely; 
o None 
Serious and less likely; 
o None 
Serious and rare; 
The two xenograft products used in this study both have the organic components of bone 
removed during processing, leaving only the inorganic components of bone.  It is hypothetically 
possible for a person to have an allergic reaction to bovine or porcine implanted products, but 
such reactions have not been reported with the materials used in this study. 
Not serious and likely; 
o None 
Not serious and less likely 
o There is no additional research related risk involved in the use of the bovine or porcine 
xenografts for ridge preservation, as there is no alteration to the clinical course or standard care 
treatment for this study. While we may indeed find that there is more new vital bone formation 
in one group vs. another, there is no reason to think that will impact the success of the implant 
that is placed. Thus, the study is definitely minimal risk.   There is, of course, a hypothetical risk 
that disease transmission could occur with the bone graft materials but it is not quantifiable, as 
it has not occurred. Both materials are terminally sterilized with gamma radiation.  
Obtain bone core sample at 
site of implant placement 
Serious and likely; 
o None 
Serious and less likely; 
o None 
Serious and rare; 
o None 
Not serious and likely; 
o None 
Not serious and less likely 
o Perforation of the drilling instrument (called a trephine) outside the bone while taking  the bone 
core. There is no difference in risk for perforation of the instrument when taking a bone core 
with a trephine compared to using a solid bone drill for preparing the “hole” for the implant. 
The only difference between a trephine and a solid drill is that the trephine is hollow so the 
bone removed from the “hole” remains inside the trephine, while the bone removed from the 
“hole” with a solid drill turns to small particles that are suctioned out of the mouth during  
preparation of the implant site.