Ridge Preservation Following Tooth Extraction Using Mineralized Freeze-Dried Bone Allograft Compared to PUROS Mineralized Bone Allograft
Phase: NA
Conditions: Alveolar Bone Loss
Sponsor: The University of Texas Health Science Center at San Antonio

COVER PAGE FOR PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 
 
 
 
 
 
Official Study Title: Ridge Preservation Following Tooth Extraction 
Using Mineralized Freeze-Dried Bone Allograft Compared to PUROS 
Mineralized Bone Allograft   
 
NCT number: NCT02515058 
 
IRB Approval Date: June 30, 2015 
 
Unique Protocol ID: 15-0552H 
 

 
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Protocol Template Form 
 
Item 1 UTHSCSA 
Tracking Number 
HSC20150552H 
 
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 ridge 
preservation using FDBA compared to PUROS bone allograft.  
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 (FDBA or PUROS). At the time of implant placement 12 weeks after tooth extraction a small core biopsy 
specimen will be removed from the implant site. Clinical measurements of the ridge dimensions will be taken at the time 
of tooth extraction and again at the time of implant placement. 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 FDBA VS. PUROS 
 
 
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 several studies evaluating a variety of materials for ridge 
preservation.2-9  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 

 
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came from the same tissue donor, eliminating any issues that might arise from using different 
donor sources. Similarly, two additional studies done by our research group used a single source 
of donor bone for both study treatment groups.6,9   
 
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. Finally, we have recently completed a study comparing 
100% cortical FDBA to a combination of 70% cortical/30% cancellous FDBA.9 The 
combination allograft resulted in increased vital bone percentage, (36.2%) compared to the 
100% FDBA group (24.7%). 
 
In reviewing the vital bone formation we have seen across multiple studies when FDBA was 
used in one or more study arms4,6,9, it is noteworthy that the amount of new bone formation seen 
with the mineralized non-freeze-dried PUROS allograft used in Beck & Mealey2 (approximately 
45% new bone) was higher than that seen when mineralized freeze-dried bone allograft was 
used (approximately 13-25%).  However, there are no published direct comparison data 
evaluating FDBA versus bone allograft processed via the Tutoplast process (PUROS) when used 
for ridge preservation after tooth extraction. 
 
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. 
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. 

 
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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 with mineralized freeze-dried bone allograft (FDBA) or mineralized bone 
allograft prepared via the Tutoplast process which does not involved freeze-drying. 
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 a PUROSE. This test group will be compared to an active control group 
using FDBA as the graft material.  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 
resorbable bovine pericardium membrane (called CopiOs). Following 12 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:  
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 
• 
who will not cooperate with the 

 
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been identified by dental faculty as 
requiring extraction 
• 
Desire 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 
 
 
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 
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) 
Insert response here 
Insert response here 
Insert response here 
 

 
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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 FDBA compared to PUROS bone allograft. 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  
 
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 PUROS mineralized bone allograft 
(prepared using the Tutoplast process). This test group will be compared to an active control group in which 
extraction sockets are grafted using cancellous mineralized freeze-dried bone allograft (FDBA).  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=  cancellous PUROS; Group 2 = cancellous mineralized FDBA). 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.  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. 
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 subject will then be randomized by drawing a sealed 
envelope from the stack. The socket will be thoroughly debrided, and either cancellous PUROS or cancellous 
FDBA will be placed in the socket to restore the ridge to appropriate contour.  A CopiOs bovine pericardium 
resorbable collagen membrane 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.   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 CopiOs membrane can extend 3mm beyond the bony walls of the dehiscence.  The patient 

 
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will be seen 7-10 days after extraction/ridge preservation to assess healing, and again 1 month after the 
procedure.   
 
At the time of implant placement approximately 12 weeks after extraction and ridge preservation2, 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 12 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 mineralized cancellous PUROS graft for ridge preservation in an extraction 
site prior to implant placement is different than those receiving a mineralized cancellous FDBA graft at a time 
point approximately 12 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 PUROS compared to FDBA.   
 
 
 

 
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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 12 weeks post-
grafting 
Serious and likely; 
o Npne 
Serious and less likely; 
o None 
Serious and rare; This is a standard of care risk 
FDBA may contain traces of the processing reagents Bacitracin, Gentamicin, Polymyxin B 
Sulfate, alcohol, and/or surfactants. Caution should be exercised if the patient has a 
known sensitivity or allergy to any of these antibiotics or reagents. PUROS may contain 
trace amounts of residual chemicals used in processing: acetic acid, acetone, hydrogen 
peroxide and sodium hydroxide. 
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 FDBA or PUROS 
materials for ridge preservation, as there is no alteration to the clinical course or 
standard care treatment for this study. Each of these materials is commonly used in 
clinical practice.  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 to achieve a sterility assurance level (SAL) of 
10-6.  
Insert procedure here 
Serious and likely; 
o Insert risk here or enter "none" 
Serious and less likely; 
o Insert risk here or enter "none" 
Serious and rare; 
o Insert risk here or enter "none" 
Not serious and likely; 
o Insert risk here or enter "none" 
Not serious and less likely 
o Insert risk here or enter "none" 
Insert procedure here 
Serious and likely; 
o Insert risk here or enter "none" 
Serious and less likely; 
o Insert risk here or enter "none" 
Serious and rare; 
o Insert risk here or enter "none" 
Not serious and likely; 
o Insert risk here or enter "none" 
Not serious and less likely 
o Insert risk here or enter "none" 
 
 
 

 
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