The Influence of Mucosa Tissue Thickness on Marginal Bone Loss of Implants With Smooth Collars: A Prospective Controlled Trial
Phase: NA
Conditions: Gingival Tissue
Sponsor: University of Michigan

Official Title:  
The impact of mucosal phenotype on marginal bone levels around tissue level 
implants: A prospective controlled trial  
 
 
Study Protocol Amendment Approval Date:  
6/19/2019 
 
 
NCT Number:  
02925078 

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The Influence of Mucosa Tissue Thickness on Marginal Bone Loss of Implants 
with Smooth Collars: A Prospective Controlled Trial 
 
 
Principal Investigators: 
Hom-Lay Wang, DDS, MSD, PhD 
 
Co-Investigators: 
Hsun-Liang Chan, DDS, MS 
Gustavo Mendonça, DDS, MSc, PhD 
 
Study Coordinator: 
Alice Ou, RDH, MS 
 
Study Site: 
Graduate Periodontics 
Department of Periodontics and Oral Medicine 
University of Michigan School of Dentistry 
1011 N. University Ave., Ann Arbor, MI 48109-1078 
 
 
 
 
 
 
 
 

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Table of Contents 
 
Introductory Statement 
General Investigational Plan 
Study Protocol 
I. 
Introduction 
II. 
Objectives 
III. 
Treatment 
IV. 
Outcome analyses 
V. 
Statistical analyses 
VI. 
References 
 
 
 
 
 
 
 
 
 
 
 
 

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Introductory Statement 
 
The influence of mucosal thickness was shown to be related to marginal bone stability around 
implants. Several investigators suggested that a minimum of 2 mm peri-implant mucosa 
thickness was required to prevent peri-implant crestal bone loss on rough surface implants.1, 2 
However, other factors such as implant surfaces may also play a significant role on peri-implant 
crestal bone level. While previous studies showed the advantages of completely rough implants 
from machined surface implants (such as faster healing periods and lesser crestal bone loss), its 
comparable survival rate has been documented.3 Whether an initial two millimeters mucosal 
thickness is needed to obtain marginal bone stability around implants with different types of 
surfaces is still unknown.  
 
General Investigational Plan 
A single center, prospective controlled clinical trial is planned to investigate the effect of mucosa 
tissue thickness upon implant marginal bone changes on implant with smooth collar. Twenty 
eight adult patients who fulfill the inclusion criteria will be divided into 2 groups based upon the 
mucosa thickness (<2 mm and ≥2 mm). A signed written informed consent will be obtained from 
all subjects. Subjects will not be screened or treated until an informed consent has been 
obtained. Patient information will be protected according to the privacy regulations of the 
federal Health Insurance Portability and Accountability Act of 1996 (HIPAA). 

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The enrolled patients will receive implants with polished collar. Implants will be restored at 4 (±1) 
months after placement. Outcome analyses will be performed until 1 (±1 month) year after 
loading and clinical and radiographic parameters will be evaluated to compare clinical outcomes 
between groups. The primary outcome is implant marginal bone loss and probing depth from 
clinical and radiographic measurements.    
 
Study Protocol 
 
I.  Introduction 
 
The thickness of the gingiva (i.e. gingival biotype) varies between subjects. In 1969, Ochsenbein 
and Ross proposed two main types of gingival biotype (“pronounced scalloped” and “flat”) and 
their relationship with the contour of the osseous crest.4  Subjects belong to pronounced 
scalloped biotype have thinner soft buccal tissues and more advanced soft tissue recession than 
subjects who had the flat biotype.5 Claffey & Shanley (1986) defined thin tissue biotype as a 
gingival thickness < 1.5 mm and thick tissue biotype as tissue having thickness ≥ 2 mm.6 
 
Several pre-clinical studies have examined how mucosal thickness affects marginal bone loss 
around implants.1, 7 Abrahamsson et al. (1996) showed that sites with thin mucosa had an 
angulated pattern bone defects, whereas sites with an even pattern of the alveolar crest, the 
adjacent mucosa was consistently thick.7 Another study by Berglundh and Lindhe (1996) 
suggested that certain width of the peri-implant mucosa is required to protect osseointegration.1 

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They showed when ridge mucosa was thin (≤ 2 mm), more bone resorption and angular bony 
defect were noted.1  
 
A human prospective clinical trial reported that tissue/mucosa thickness may affect crestal bone 
stability around implants.2 Implants with a thick tissue biotype (>2 mm) had significantly less 
bone loss when compared to implants with thin tissue thickness (≤2 mm). Implants with initially 
thin tissue had bone loss up to 1.45 mm that occurred within the first year of function. Whereas 
thick tissues only had 0.2 mm bone loss that was noted.2 It was observed that thick mucosa 
formed an epithelial – connective tissue attachment to the titanium surface that protected and 
preserved the osseointegration. If this soft tissue dimension is not achieved, bone resorption 
might occur to establish a biological width of the epithelial – connective tissue attachment. Thus, 
it is suggested that a certain minimum width of peri-implant mucosa is required.7 
 
Recently, researches have shown implant surfaces may play a critical role for long-term implant 
success.8 Bacteria pathogens have been proposed as the main etiology factor of peri-implantitis 
leading to implant failure.9 Therefore, implant design that can help reduce plaque retention is 
important to facilitate good oral hygiene. Originally, smooth/polished collar implants were 
developed because it is easier to clean and harbors less plaque than rough surface implant.10 
Concurrently,  this has been changed to predominantly rough-coated surface to enhance 
osseointegration as well as a shortened waiting time.11 However, a study that compared the 
implant survival rate of smooth- and rough-surfaced implants showed similar survival rate (94%).3 
 

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To date, the influence of mucosa tissue thickness upon implant crestal bone loss on implant with 
smooth surface collar has not been determined yet. Hence, the aim of this study is to test the 
effect of mucosa tissue thickness upon implant marginal bone changes on implant with smooth 
collars. 
 
II. Objectives 
 
The primary objective of this study is to compare the amount of implant marginal bone loss 
radiographically and probing depth in between thin and thick mucosa group that will receive a 
machined collar implant. 
 
III. Treatment  
 
A. Patient selection 
 
The use of human subjects in this project will be submitted for approval by the Institutional 
Review Board (IRB) at the University of Michigan prior to conducting the study. Patients requiring 
an implant to replace a missing tooth in the premolar or 1st molar area will be recruited for this 
prospective controlled trial. A total of up to 40 subjects will be recruited with the goal of enrolling 
a minimum of 28 subjects divided into 2 groups (14 in each group) based upon the mucosa 
thickness (<2 mm and ≥2 mm).  A prospective design will be applied and implants with a polished 
collar will be placed.* 
                                                          
*  Biohorizons Tapered Internal Implant, Laser-Lok, RBT 

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Potential patients will be carefully screened according to the inclusion and exclusion criteria as 
follows:  
Inclusion Criteria 
 Male or Female  
 Aged ≥18  
 In need of one dental implant in the Maxillary or Mandibular area, premolar, or 1st 
molar  tooth  
 Natural adjacent teeth 
 Bone height of ≥10mm  
 Bone width of ≥5mm  
 Good oral hygiene  
 Stable periodontium  
 
Willingness to fulfill all study requirements 
Exclusion Criteria 
 
Need bone augmentation 
 
Need one dental implant that is anterior, a 2nd or 3rd molar tooth 
 
Current smoker or quit smoking less than one year 
 Pregnant or plan to get pregnant 
 Uncontrolled diabetes (HbA1C  > 7) 
 Medical conditions that may influence the outcome of the study (neurologic or 
psychiatric disorders, systemic infections ) 
 
Current use of oral bisphosphonates 
 
History of IV bisphosphonates 
 
History of radiation therapy in the head and neck area within 4 years 
 
Poor oral hygiene (plaque score more than 40% based on O’Leary plaque score) 
 
Once a group has been filled, subjects who meet the criteria of that group will be 
excluded 
 
 
 
B. Clinical assessments 
 

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Clinical measurements (probing depth, clinical attachment level and bleeding on probing) will be 
recorded using a UNC (University of North Carolina) manual probe. These measurements will be 
taken at two weeks post-operatory (V4), one month post-operatory (V5), crown impression (V6), 
crown restoration (V7), 6 months (V8), and 12 months (V9) after crown restoration. A tension-
free caliper will be used to measure mucosa thickness at the time of surgery. Clinical photographs 
will be taken at each appointment as well as standardized radiographs. In addition, bone 
sounding procedure under local anesthesia will be performed on the mid buccal and lingual side 
of the implant sites at 12 month follow-up to assess the level of the underlying bone. Subjects 
will also be receiving a cleaning at no charge to them at their 6 and 12 month visits.  
 
C. Radiographic assessment 
 
Intraoral radiographs will be taken using a paralleling technique with a Rinn-type film holder at 
the initial appointment  (V1), implant placement (V3), Crown impression (V6), crown delivery  
(V7), and at 6 (V8) and 12 (V9) months after crown restoration. The CBCT scan will be taken at 
the pre-implant surgery visit (V2) and the 12 month follow up (V9). Custom-made stents will be 
fabricated to ensure reproducibility and standardized radiographs. All assessments will be made 
by one examiner. Intra-examiner calibration will be performed. 
 
D. Surgical protocol 
 
Preliminary alginate impressions will be taken at the screening appointment for the purpose of 
making study models to then be able to fabricate a reference stent and surgical guide. On the 

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implant surgery visitvital signs will be taken. Local anesthesia will be performed by using local 
infiltration technique with 2% Lidocaine with 1:100k epinephrine or 1:50k epinephrine. 
Intrasulcular and crestal incision design will be made along the crest of the ridge, bisecting the 
existing zone of keratinized mucosa. Full-thickness flaps are raised on the buccal and 
lingual/palatal side up to or slightly beyond the level of the mucogingival junction, exposing the 
alveolar ridge of the implant surgical sites. Once the flaps are reflected and the bone is prepared, 
a surgical guide will be inserted and a series of drills are used to prepare the osteotomy site 
incrementally. All implants will be placed according to the manufacturer’s protocol (Biohorizons 
Tapered Internal Implant, Laser-Lok, RBT)  and the rough-smooth junction will be placed to the 
bone crest. The buccal mucosal thickness will be measured at different levels.  Implants with 9-
13 mm length and 3-5 mm width will be used. After implant placement a healing abutment will 
be connected and interrupted sutures will be placed to close the flaps. After suturing, 
standardized radiographs will be obtained. Other radiographs will be taken during the surgery to 
check implant angulation, these will not be standardized. The surgery is being done as part of 
standard of care. Subjects will be instructed to rinse with warm salt water once a day every day 
for two weeks. All subjects will be prescribed 500mg of amoxicillin to take 3 times a day for ten 
days.  If the subject is allergic to Amoxicillin, they will be prescribed 250 mg of Zithromax 6 tablets 
total /sig. 2 tablets the 1st day and Q.D. (1 x per day) until gone. In addition, the subject will be 
prescribed  600 mg of ibuprofen, taken as needed, for pain control. The sutures will be removed 
in 2 weeks.  
 
 

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E. Prosthodontic protocol 
 
All patients will have two (possibly more) visits to receive the permanent restoration. The crown 
impression will be performed 4(±1) months after implant placement and the final restoration 3+ 
weeks after that. Custom abutment and screw retained implant crown will be used. Proper 
occlusion, crown contours, and crown margins will be confirmed in the final restoration. The 
subject may have to return for more than one visit for the final restoration. This is to ensure the 
color, contours, and margins are correct. 
 
 
 
 
 
 
 
 

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F. Schedule of events 
Event
Screening
CBCT 
visit 
Implant 
Surgery 
2 weeks 
PO 
1 month 
PO 
Crown 
impression 
Crown
delivery 
6m
12m
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
Timeline 
Baseline 
(BL) 
2 (±1 day)
wks 
1 (± 1 wks) 
months 
4 (±1) M 
after BL 
3+ weeks 
after crown 
impression 
6(±1)M 
after crown 
delivery 
12(±1)M after 
crown 
delivery 
Informed consent
SIGN
X
X
X
X
X
X
X
Medical history
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
Vitals (BP and HR)
X
X
Dental Exam
X
Impressions 
X
Alginate 
 
X 
 
 
 
CBCT Scan
X
X
Implant 
placement 
 
X 
 
 
 
 
Clinical 
measurements 
 
 
X
X
X 
X 
X 
X 
Periapical 
Radiograph 
*S (standardized) 
X(S) 
 
X and X(S) 
X 
X(S) 
X(S) 
X(S) 
Clinical
photographs 
X 
X 
X
 
X 
X 
X 
Cleaning
X
X
Patient 
compensation 
payment 
 
 
 
 
 
X 

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IV. Outcome analysis 
The measurement variables and correspondent measurement time points are summarized in the 
Table. 
Measurement time 
Measurements 
Clinical outcomes
Baseline (V3) 
Mucosa thickness 
 
At two weeks post-operatory (V4), 
one month post-operatory (V5), 
crown impression (V6), and at crown 
delivery (V7), 
Probing depth, bleeding on probing, clinical 
attachment level 
6 (V8) and 12m (V9) after crown 
placement 
Probing depth, bleeding on probing, clinical 
attachment level 
Radiographic outcome 
 
At screening (V1), implant/surgery 
baseline (V3), crown impression 
(V6), crown delivery (V7), 6m (V8), 
and 12m (V9) after crown 
placement. 
Marginal bone level 
 
 
V. Statistical analyses 
 
Sample size 
In this present study, test significance level (α) that is used is 5% and the power analysis is 80%.  
Sample size for each group is calculated using a computer program with two sided equivalence 

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for difference of proportions in two group design.†  According to the previous study2  mean bone 
loss of implant placed in thin tissue biotype (µ1) was 1.450 mm and mean bone loss of implant 
placed in thick tissue biotype (µ2) was 0.170 mm. The difference in means in between two groups 
(µ1 - µ2) was 1.280 mm and common standard deviation was (σ) was 1.160 mm. Therefore, the 
sample (n) needed in each group in this present study is 14 patients.  
 
Hypothesis 
Null hypothesis is mucosa thickness does not affect implant marginal bone loss on implant with 
smooth collar. 
 
Statistical analysis 
One way ANOVA will be used to detect any differences in between groups and student t test 
analysis will be conducted to assess mean differences between the groups. 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                          
†nQuery Advisor®, version 7.0., Los Angeles; Statistical Solutions Inc., 2007 

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VI. Experimental flow chart: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig. 1 Schematic drawing of the study design 
 
 
Polished collar 
implant 
Polished collar 
implant 
X-rays follow-up at 6 
and 12 months after 
crown placement 
Subjects fulfilling the 
inclusion/exclusion criteria 
Thin tissue biotype (<2mm)
Thick tissue biotype (≥2mm)

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VII. References 
 
1. 
Berglundh T, Lindhe J. Dimension of the periimplant mucosa. Biological width revisited. Journal of 
clinical periodontology 1996;23:971-973. 
2. 
Linkevicius T, Apse P, Grybauskas S, Puisys A. The influence of soft tissue thickness on crestal bone 
changes around implants: a 1-year prospective controlled clinical trial. The International journal 
of oral & maxillofacial implants 2009;24:712-719. 
3. 
Balshe AA, Assad DA, Eckert SE, Koka S, Weaver AL. A retrospective study of the survival of 
smooth- and rough-surface dental implants. The International journal of oral & maxillofacial 
implants 2009;24:1113-1118. 
4. 
Ochsenbein C, Ross S. A reevaluation of osseous surgery. Dental clinics of North America 
1969;13:87-102. 
5. 
Anderegg CR, Metzler DG, Nicoll BK. Gingiva thickness in guided tissue regeneration and 
associated recession at facial furcation defects. Journal of periodontology 1995;66:397-402. 
6. 
Claffey N, Shanley D. Relationship of gingival thickness and bleeding to loss of probing attachment 
in shallow sites following nonsurgical periodontal therapy. Journal of clinical periodontology 
1986;13:654-657. 
7. 
Abrahamsson I, Berglundh T, Wennstrom J, Lindhe J. The peri-implant hard and soft tissues at 
different implant systems. A comparative study in the dog. Clinical oral implants research 
1996;7:212-219. 
8. 
Albrektsson T, Zarb G, Worthington P, Eriksson AR. The long-term efficacy of currently used dental 
implants: a review and proposed criteria of success. The International journal of oral & 
maxillofacial implants 1986;1:11-25. 
9. 
Peri-implant mucositis and peri-implantitis: a current understanding of their diagnoses and clinical 
implications. Journal of periodontology 2013;84:436-443. 
10. 
Aparna IN, Dhanasekar B, Lingeshwar D, Gupta L. Implant crest module: a review of biomechanical 
considerations. Indian journal of dental research : official publication of Indian Society for Dental 
Research 2012;23:257-263. 
11. 
Wennerberg A, Albrektsson T, Andersson B. Design and surface characteristics of 13 commercially 
available oral implant systems. The International journal of oral & maxillofacial implants 
1993;8:622-633.