Histologic Comparison of Healing After Tooth Extraction With Ridge Preservation Using Two Different Xenografts
Phase: NA
Conditions: Partial Edentulism
Sponsor: University of Colorado, Denver

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COMIRB Protocol 
COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD 
CAMPUS BOX F-490    TELEPHONE:  303-724-1055  Fax:  303-724-0990 
 
 
 
Protocol #: 18-1722 
Project Title: 
Histologic Comparison of Healing After Tooth Extraction with Ridge 
Preservation Using Two Different Xenografts  
 
 
Principal Investigator:  Kerri Font 
Version Date: 9.15.21  
 
 
 
  
 
I. 
Hypotheses and Specific Aims:   
 
1) There will be additional vital bone at 16-20 weeks with Salvin-Oss®. 
2) To compare the clinical and histological outcome of using   
Bio-Oss® or Salvin-Oss® in a tooth extraction ridge preservation model.  
 
II. 
Background and Significance:  
 
 
Dental implants have become a predictable and reliable therapy in the 
replacement of missing teeth. (1-3) Extraction sites that are not grafted for ridge 
preservation may lose up to 50% of their ridge width the first year after extraction. 
(4-6) Ridge preservation is a simple procedure that has proven to decrease the loss 
of ridge width during healing. (7-9) Multiple graft products are on the market, such as 
allografts, xenografts, and alloplasts.  All have been used in ridge preservation 
techniques in an attempt to maintain the ridge width after the tooth was extracted. 
For this study we focus on xenografts to preserve alveolar bone after tooth 
extraction prior to placement of a dental implant. 
 
Xenografts are commonly used materials for bone growth and bone contour 
augmentation techniques. Xenografts have been shown to have osteoconductive 
potential, (10) similar to that of the allografts (11), in addition to providing a scaffold 
for space maintenance. (12) The turnover of the xenograft particles has been shown 
to be longer than that of allografts(13) which may be beneficial in maintaining the 
volume of tissue in the area. Prior studies have compared demineralized freeze-
dried bone allograft (DFDBA) and freeze-dried bone allograft (FDBA) for 

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percentage of vital bone(14), however currently there is no study comparing the two 
most common used xenografts on the market, Bio-Oss® and Salvin-Oss®. The 
use of xenografts is routine care, and the selection of the specific product is 
currently based on the cost to obtain the material and provider preference (e.g. 
personal handling preference). The purpose of the current study is to compareBio-
Oss® and Salvin-Oss® in the preservation of alveolar bone after extraction of non-
molar teeth.  Bio-Oss® is a bovine product while Salvin-Oss® is porcine. Both  
products that have similar manufacturer stated outcomes. Bio-Oss® has been on 
the market longer than Salvin-Oss® and is more costly. Both are FDA approved for 
bone grafting techniques in humans. 
The primary objective is to histologically evaluate and compare the percentage of 
new bone formation in healing extraction sockets of non-molar teeth grafted with 
Bio-Oss® versus Salvin-Oss®. 
The secondary aim is to observe clinical changes in ridge height and ridge width 
after grafting with these two materials. 
 
III. Preliminary Studies/Progress Report:  none 
 
IV. Research Methods 
This is a single site, open label, randomized study, comparing two FDA-
approved xenografts, Bio-Oss® and Salvin-Oss®. 
 
A. Outcome Measure(s):   
 
1) Histologically measure % vital bone, % residual graft, % of connective 
tissue  
2) Clinically measure:  
a. the change of ridge height on the buccal and lingual  
b. change of ridge width 
c. % change of ridge width 

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B. Description of Population to be Enrolled:   
 
40 patients, who must be active, non-emergency patients at the University of 
Colorado School of Dental Medicine Graduate Periodontics Department will be 
enrolled in this study. Subjects will be included if they are at least 18 years of age, 
consent to be in the study, planned for non-emergent dental treatment, and ASA 
Class I or II. 
Patients who qualify must require extraction of a single-rooted non-molar 
tooth and are interested in receiving a dental implant at the site of tooth extraction. 
Patients must be committed to have the dental implant placed 16-20 weeks after 
extraction and ridge preservation 
Inclusion criteria: 1) adequate restorative space for implant-retained 
restoration; 2) >10mm alveolar bone height without impingement on the maxillary 
sinus or inferior alveolar canal; 3) root location and angulation that would be 
consistent with the subsequent implant placement.  To ensure an adequate depth 
of socket for harvesting a bone core biopsy without inclusion of native bone all 
roots should have a minimum of 10mm of radiographic bone support, and have 
angulation similar to the angulation of the implant to be placed at the site. 
 
Subjects will be excluded if <18 years old, currently pregnant or require antibiotic 
prophylaxis prior to dental procedures as outlined by the 2017 American Heart 
Association guidelines, decisional challenged adults, are a current smoker or ASA 
Class III or IV. 
 
Study Design and Research Methods   
 
Patients will be randomly assigned (1:1) to one of two treatment groups (Bio-
Oss® or Salvin-Oss®) at the time of surgery through random selection of sealed 
envelopes.  

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The xenograft materials to be studied, Bio-Oss® and Salvin-Oss®, will each be 
obtained from a single batch. This request for single batch materials will be given 
to the manufacturer prior to shipment of the bone material.  
 
All bone material will be ground to a particle size ranging from 250-1000um per 
the manufacturer.  
 
3) Measuring of clinical endpoints (as described below):  
a. the change of ridge height on the buccal and lingual  
b. change of ridge width 
c. % change of ridge width 
 
 
Surgical procedure (Routine Care, except where indicated as research only): 
 
The identified tooth will be extracted per standard of care in a minimally traumatic 
manner with either no flap or minimal flap reflection no more than 2mm beyond the 
alveolar crest, followed by curettage and irrigation of the socket. The socket will be 
thoroughly examined for defects, such as dehiscences or fenestrations. As 
previously described by Beck and Mealey(15) a University of North Carolina (UNC) 
periodontal probe will be used to make the following clinical measurements: the 
height of the buccal and lingual crest will be measured by using a UNC periodontal 
probe to connect the midfacial cemento-enamel junctions of the adjacent teeth, 
and then the vertical distance from that reference line to the crest of bone on the 
midfacial and midlingual will be measured. Calipers will be used to measure the 
ridge width as well as buccal plate thickness 2mm from the crest of the ridge at the 
midfacial aspect to the nearest 0.5mm. All measurements will be performed by 
one of two examiners that will be calibrated. All surgeries will be performed by 
periodontal residents under the direct supervision of board-certified attending 
faculty. The faculty will then select the xenograft product to be used based on the 

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product identified in the sealed envelope. While the measurements are being 
completed, the randomly selected graft material (Bio-Oss® or Salvin-Oss®) will be 
hydrated with sterile water. The socket will be filled to or slightly coronal to the 
crest of the bone. A resorbable collagen membrane material will be placed over 
the graft material and will be secured over the socket orifice with non-resorbable 
sutures (this is the standard of care for site preservation techniques). Flaps will not 
be reflected unless a minor dehiscence is detected. In cases in which there is a 
bony dehiscence, small flaps will be reflected just beyond the extend of the 
dehiscence and a collagen membrane material will be used to cover dehiscence 
(per standard of care). Only minor dehiscences will be accepted; if the depth of the 
dehiscence is 50% or greater the depth of the socket, the participant will be 
excluded from the study. Post-operative instructions will be given to the patient 
along with post-operative analgesics and antibiotics. Sutures will be removed 2 
weeks after ridge preservation procedure (per standard of care). 
 
Patients will return approximately 3 months after the extraction for a cone-
beam computerized tomographic scan (CBCT), which is the standard of care for 
implant placement work up. At the time of implant placement 16-20 weeks after 
extraction, there will be minimal buccal and lingual flap reflection, and ridge width 
as well as buccal and lingual height measurements will be made as previously 
described.  
 
In routine care, the first step in implant placement is creating an osteotomy site 
with a 2.0mm diameter twist drill and suctioning away the removed bone. 
For this study, we will not use a twisted drill, but rather a  trephine drill with a 
2.0mm internal diameter and a hollow center. This will allow us to save a core 
biopsy approximately 8mm in length, rather than discarding the drilled-out bone. 
The core biopsywill then be placed in 10% neutral-buffered formalin. This use of 
the hollow trephine drill is the only research procedure in this study, and will allow 
us to obtain bone for histological analysis.  
 

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Following collection of the core biopsy material, the osteotomy is enlarged to 
slightly smaller dimension than the actual implant being placed. The smallest 
implant diameter on the market is 2.9mm.  
 
 
Histological samples will be stained with Harris’s hematoxylin and 
counterstained with treosin. Each section will be examined at 20X magnification, 
with the entire area of the section evaluated.  Similar to Wood and Mealey(14), 
image manipulation software will be used to create individual layers of vital bone, 
residual graft particles, and CBCT/other.  These layers will be converted to a 
binary (black and white) form, and area by percentage of each of the three layers 
will be digitally calculated based on number of pixels using image analysis 
software. 
 
C. Description, Risks and Justification of Procedures and Data Collection 
Tools: 
 
The UNC periodontal probe and caliper are used routinely in clinical practice to 
chart periodontal values. 
CBCT are used since they deliver lower radiation than medical grade CT scans 
and are routinely taken as standard of care for implant placement.  
The risk of using the hollow drill to obtain a core biopsy is no greater than the risk 
of using a twisted drill and discarding the drilled our bone material. 
    
D. Potential Scientific Problems:   
 
A potential dropout rate of 30% was anticipated with the number of patients 
needed for statistical significance. 
 
E.   Data Analysis Plan:   
 

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Unpaired Student t tests will be used for between-group comparison of ridge 
dimensions and of percentages of newly formed vital bone, residual bone graft 
particles, and CT/other. Mann-Whitney U tests will be performed to confirm 
significant findings based on t tests. Discrete measure comparisons for treatments 
will be performed using Fisher exact tests. For all tests, P<0.05 will be considered 
significant. Pearson correlations will be used to assess the relationships between 
the histologic bone core percentages for the three tissue groups. Spearman 
correlations will be used to evaluate relationships between the histologic 
percentages and the clinical ridge dimension changes in each group.  
 
G.  Summarize Knowledge to be Gained:  
  
If there is more vital bone at an earlier time point in Salvin-Oss® than Bio-Oss® 
then a clinician may re-enter the site at an earlier time point for implant placement. 
 
 H. References: 
 
1) Berglundh T, Persson L, Klinge B. A systematic review of the incidence of 
biological and technical complications in implant dentistry reported in 
prospective longitudinal studies of at least 5 years. J Clin Periodontol 
2002;29(Suppl. 3):197-212;discussion 232-233. 
2) Buser D, Ingimarsson S, Dula K, Lussi A, Hirt HP, Belser UC. Long-term 
stability of osseointegrated implants in augmented bone: A 5-year prospective 
study in partially edentulous patients. Int J Periodontics Restorative Dent 
2002;22:109-117. 
3) Lekholm U, Grondahl K, Jemt T. Outcome of oral implant treatment in partially 
edentulous jaws followed 20 years in clinical function. Clin Implant Dent Relat 
Res 2006;8:178-186. 
4) Van der Weijden F, Dell’Acqua F, Slot DE. Alveolar bone dimensional changes 
of post-extraction sockets in humans: A systematic review. J Clin Periodontol 
2009;36:1048-1058. 
5) Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue 
contour changes following single-tooth extraction: A clinical and radiographic 
12-month prospective study. Int J Periodontics Restorative Dent 2003;23:313-
323. 

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6) Araujo M, Linder E, Wennstrom J, Lindhe J. The influence of Bio-Oss Collagen 
on healing of an extraction socket: An experimental study in the dog. Int J 
Peridodontics Restorative Dent 2008;28:123-135. 
7) Iasella JM, Greenwell H, Miller RL, et al. Ridge preservation with freeze-dried 
bone allograft and a collagen membrane compared to extraction alone for 
implant site development: A clinical and histologic study in humans. J 
Periodontol 2003;74:990-999. 
8) Nevins M, Camelo M, De Paoli S, et al. A study of the fate of the buccal wall of 
extraction sockets of teeth with prominent roots. Int J Periodontics Restorative 
Dent 2006;26:19-29. 
9) Darby I, Chen ST, Buser D. Ridge preservation techniques for implant therapy. 
Int J Oral Maxillofac Implants 2009;24(suppl.):260-271. 
10) Schwartz Z, Weesner T, van Dijk S et al. Ability of deproteinized cancellous 
bovine bone to induce new bone formation. J Periodontol 2000;71:1258-1269. 
11) Piattelli A, Scarano A, Corigliano M, Piatteli M. Comparison of bone 
regeneration with the use of mineralized and demineralized freeze-dried bone 
allografts: A histological and histochemical study in man. Biomaterials 
1996;17:1127-1131. 
12) Richardson CR, Mellonig JT, Brunsvold MA, McDonnell HT, Cochran DL. 
Clinical evaluation of BioOss: a bovine xenograft for the treatment of 
periodontal osseous defects in humans. J Clin Periodontol 1999;26:421-428. 
13) Carmagnola D, Adrianens P, Berglundh T. Healing of human extraction 
sockets filled with Bio-Oss. Clin Oral Implant Res 2003;14:137-143. 
14) Wood R, Mealey BL. Histologic comparison of healing after tooth extraction 
with ridge preservation using mineralized versus demineralized freeze-dried 
bone allograft. J Periodontol 2012;83:329-336. 
15) Beck TM, Mealey BL. Histologic analysis of healing after tooth extraction with 
ridge preservation using mineralized human bone allograft. J Periodontol 
2010;81:1765-1772.