Cone Beam Computed Tomography and Histomorphometric Assessments on the Influence a Collagen Membrane Placed on the Antrostomy After Maxillary Sinus Floor Augmentation. A Randomized Clinical Trial.
Phase: NA
Conditions: Alveolar Bone Loss, Alveolar Bone Resorption
Sponsor: ARDEC Academy

Cone beam computed tomography and histomorphometric 
assessments on the influence a collagen membrane placed on the 
antrostomy after maxillary sinus floor augmentation. A 
randomized clinical trial.  
   
Authors   
Hideki Imai, DDS, Doctor, ARDEC Academy, Rimini, Italy  
Dr. Mauro Ferri, DDS, Doctor, Corporación Universitaria Rafael Núñez, Cartagena 
de Indias, Colombia  
Karol Alí Apaza Alccayhuaman, DDS, ARDEC Academy, Rimini, Italy  
Niklaus Peter Lang, DDS, PhD, Center for Dental Medicine, University of Zurich,  
Zurich, Switzerland   
Daniele Botticelli, BMBD, dentist, PhD, ARDEC Academy, Rimini, Italy  
  
Corresponding author:   
Dott. Karol Alí Apaza Alccayhuaman, DDS, ARDEC Academy, Viale Giovanni  
Pascoli 67 – 47923 RIMINI (ITALY) Tel.-Fax: +39 0541 393444   
E-mail: caroline7_k@hotmail.com  
  
May 18th 2015, Cartagena de Indias,  
           
  
Title   
Cone beam computed tomography and histomorphometric assessment on the 
influence a collagen membrane placed on the antrostomy after maxillary sinus floor 
augmentation. A randomized clinical trial.  
   
Authors   
Hideki Imai, DDS, Doctor, ARDEC Academy, Rimini, Italy  

Dr. Mauro Ferri, DDS, Doctor, Corporación Universitaria Rafael Núñez, Cartagena 
de Indias, Colombia  
Karol Alí Apaza Alccayhuaman, DDS, ARDEC Academy, Rimini, Italy  
Niklaus Peter Lang, DDS, PhD, Center for Dental Medicine, University of Zurich,  
Zurich, Switzerland   
Daniele Botticelli, BMBD, dentist, PhD, ARDEC Academy, Rimini, Italy  
  
Institution at which the work will be carried out:  
Corporación Universitaria Rafael Núñez, Cartagena de Indias, Colombia  
    
  
Corresponding author:   
Dott. Karol Alí Apaza Alccayhuaman, DDS, ARDEC Academy, Viale Giovanni  
Pascoli 67 – 47923 RIMINI (ITALY) Tel.-Fax: +39 0541 393444   
E-mail: caroline7_k@hotmail.com  
  
  
Conflict of Interest Statement  
The authors declare no conflict of interest regarding this study.  
Straumann, Basel, Switzerland will provide all biomaterials used for sinus floor 
elevation. Sweden & Martina SRL, Due Carrare, Padova, Italy, and ARDEC 
Academy, Ariminum Odontologica s.r.l., Rimini, Italy will cover the costs of the study.  
  
  
  
  
  
  
 

Abstract  
Aim: to evaluate the dimensional variation and osseointegration of mini-implants at 
augmented sinus with the antrostomy left unprotected or protected with a collagen 
membrane. 
Material and Methods: The Schneiderian mucosa will be elevated and the created 
space will be filled with a natural bovine bone grafting material (Cerabone® 1-2 mm, 
Botiss Biomaterials GmbH). In ten patients randomly selected (control sties), a native 
collagen membrane made of porcine dermis (Collprotect®, Botiss Biomaterials 
GmbH) will be placed on the antrostomy. In ten patients of the test group, the 
antrostomy will be left without the membrane. The flaps will be sutured and anti-
inflammatory drugs and antibiotics will be administrated to the patients. The sutures 
will be removed after 7 days. After 6 months, two mini-implants with different surface 
will be installed and retrieved after further 3 months for histomorphometric 
evaluations. 
CBCTs will be taken for all patients before surgery (T0), after 1 week from sinus floor 
augmentation (T1) and after 9 months of healing (T2) and evaluation of dimensional 
variations over time of soft and hard tissues will be performed.  
Introduction  
After sinus floor augmentation using a lateral access, it was suggested to protect the 
antrostomy with a membrane. In a systematic review on success of sinus floor 
elevation and implant survival with meta-analysis, it was shown that the best results 
were obtained using implant with a rough surface and placing a membrane to cover 
the antrostomy (Pjetursson et al. 2008). However, in a randomized clinical trial, 

similar results in new bone formation were observed histologically six months after 
sinus floor augmentation both with and without the use of a collagen membrane on 
the antrostomy (Barone et al. 2011). It has been further shown in an experiment in 
rabbits that, despite the use of a collagen membrane, the healing at the antrostomy 
was incomplete, as shown both at the histological and microtomographic analyses 
(Masuda et al. 2019). Moreover, in a clinical report, it was concluded that the use of 
collagen membrane does not protect from the migration of the biomaterial through 
the antrostomy (Nosaka et al. 2015). Aiming to improve the healing at the antrostomy 
and guarantee the closure during and after healing, the repositioning of the bone 
plate removed during the preparation of the osteotomy has been proposed 
(Lundgren et al. 2004, Cricchio 2011). In a study in rabbits (Moon et al. 2014), 
maxillary sinus augmentation was performed bilaterally. At the test sites, the bone 
window was repositioned while, at the control sites, a collagen membrane was used 
to cover the antrostomy. Higher and faster bone formation were seen at the test 
compared to the control sites. In another study in rabbits (Omori et al. 2018), a similar 
experiment was performed. However, at the test sites, a cyanoacrylate glue was 
applied to fix the bone window at the antrostomy after sinus floor augmentation. 
While the healing inside the augmented sinuses was similar in both groups, at the 
antrostomies the repositioned bone window was incorporated to the new bone 
formed within the elevated spaces while, at the collagen membrane sites, the healing 
incomplete, and the antrostomies presented residual defects.  
The biomaterial used may affect the healing. Autogenous bone has been shown to 
produce higher amounts of new bone compared to other biomaterials (Corbella et 

al. 2016). However, while autogenous bone is highly resorbed during healing, 
deproteinized bovine bone mineral is slowly resorbed and this allows its 
osteoconductive properties to be expressed (Caneva et al. 2017; De Santis et al 
2017). In a study on sinus floor augmentation in patients (Riachi et al. 2012), the 
dimensional variations of two biomaterial, a DBBM and a high temperature 
decalcified freeze-dried xenografts in granules, were evaluated. After 4 years from 
surgery, at the evaluation on panoramic x-rays, the DBBM presented a higher loss 
of vertical height (~33%) compared to the decalcified freeze-dried xenograft (~23%). 
In a systematic review (Shanbhag et al. 2014), the volume changes over time after 
maxillary sinus augmentations were evaluated on computed tomographies or cone 
beam computed tomographies (CBCTs). Volumetric changes from <20% to 45% 
were reported. It seems clinically relevant to study how the covering of the 
antrostomy with a collagen membrane may affect the dimensional variations within 
a sinus augmented with decalcified freeze-dried xenografts. Hence, the aim of the 
present study was to evaluate the dimensional variation and healing of the 
antrostomy left unprotected or protected with a collagen membrane.   
  
  
 

Material and methods   
The Declaration of Helsinki on medical protocols and ethics will be followed for the 
present study. The protocol was approved by the Ethical Committee of the  
University Corporation Rafael Núñez, Cartagena de Indias, Colombia (protocol  
#02-2015; 19 May 2015). This study will be submitted for registration to 
ClinicalTrials.gov PRS (https://clinicaltrials.gov) to obtain the NCT. The procedures 
and all possible complications will be thoroughly elucidated to each patient included 
in the study and signed informed consents will be collected. The Consort checklist 
will be followed for this report (http://www.consort-statement.org/).  
Study population   
For the present randomized clinical trial, all recruitments, surgeries and follow-ups 
will be carried out at the University Corporation Rafael Núñez, in Cartagena de Indias 
(Colombia). To calculate the sample size, the data from a radiographic evaluation on 
height variation over time of the augmented sinus were used and an n=10 was 
considered sufficient to show differences if they exist (Zijderveld et al. 2009). An 
author not involved in the surgery performed the randomization (MF). Sealed and 
opaque envelopes containing the assignments will be opened after the placement of 
the filler material within the elevated space.  
The following inclusion criteria have to be fulfilled:   
(i) 
presence of an edentulous atrophic zone in the posterior segment of the  
maxilla;  
(ii) 
height of the sinus floor ≤4 mm;   

(iii) 
desiring a prosthetic restoration of the zone using a fix prosthesis supported by 
implants;   
(iv) 
≥ 21 years of age;   
(v) 
good general health;   
(vi) 
no contraindication for oral surgical procedures;  (vii) not being pregnant.   
The patients will be excluded if they:   
(i) 
present a systemic disorder;   
(ii) 
had a chemotherapic or radiotherapeutic treatment;   
(iii) 
are smokers >10 cigarettes per day;   
(iv) 
have an acute or a chronic sinusitis;   
(v) 
had a previous bone augmentation procedures in the zone of interest.  
Biomaterial used  
The filler material will be Cerabone granulate 1.0-2.0 mm (Botiss Biomaterials 
GmbH, Zossen, Germany) composed of a ceramic consisting of hydroxyapatite 
(pentacalcium hydroxide trisphosphate) produced from bovine cancellous bone in a 
high-temperature process (>1200 ºC). The xenograft presents a macroporosity of 
dimension included within a range of 100-1500 µm.  
The membrane to be used to cover the antrostomy at the control sites is a Collprotect 
membrane (Botiss Biomaterials GmbH) made of porcine collagen obtained from the 
corium. Both biomaterials are distributed by Straumann, Basel, Switzerland.  
A machined and turned mini-implant of 2.4 mm of diameter and 8 mm of length 
(Sweden & Martina, Due Carrare, Padua, Italy), were installed.   

Clinical procedures  
After having exposed the lateral wall of the maxillary sinus, an antrostomy of about  
5 mm in height and 10 mm long will be prepared using a diamond insert (SFS 109 
029), Komet-Brasseler-GmbH, Germany) mounted on a sonic-air surgical instrument 
(Sonosurgery® TKD, Calenzano, Fi - Italy). The Schneiderian membrane will be 
elevated and clinical measurements will be performed using an UNC 15 probe (Hu-
Friedy, Chicago, IL, USA). The space obtained underneath the sinus mucosa will be 
filled with the xenograft and a resorbable collagen membrane will be placed to cover 
the antrostomy only at the randomly selected control sites. Single silk sutures will be 
used to secure the flaps. Amoxicillin 875 mg with clavulanic acid 125 mg twice a day 
for 6 days, non-steroidal anti-inflammatory drugs as needed, and mouth rinses with 
0.12% chlorhexidine three times a day for 10 days will be recommended. The sutures 
will be removed after 7 days, and the patients will be included in a maintenance 
follow-up system for the full extent of the study.  
After 6 months, two mini-implants with modified or turned surface were installed and 
retrieved after 3 months for histomorphometric evaluations. 
  
CBCT imaging procedures  
Cone bean computed tomographies (CBCTs) will be taken in a specialist radiological 
center at three different periods: (T0) before the first surgery, for diagnostic 
purposes, to identify bone widths, volumes, presence of septa and possible sinus 
pathologies; (T1) 1 week after the surgery, to evaluate dimensional variations 

compared to T0 and T2; (T2) 9 months after the surgery, to evaluated dimensional 
variations compared to T0 and T1.  
  
CBCT imaging analyses  
All radiographic evaluations will be performed with the software i-Dixel 2.0 (J. Morita 
Corporation, Kyoto, Japan). A line will be drawn following the floor of the nose, 
crossing the sinus cavity both in the coronal view (axis X) and in the lateral view (axis 
Z).   
Histomorphometric analyses 
Bone-to-implant contact and bone morphometry were evaluated along the mini-
implant surface. For both analyses, new bone formation, old pre-existing bone 
residuals, graft residuals, interpenetrating bone network (IBN, new bone formed 
inside the graft), and soft tissues were assessed. 
 
The Results Data Element Definitions  
The following parameters will be reported at the various period of tomographic 
evaluation: (MT) mucosa thickness, (C-F) bone crest height, (X-F) nasal floor height, 
(A-C) anastomosis height and (AD) its diameter, (XW) sinus width, (LM-F) balcony 
height, (LM-UM) window height, (ZW) sinus length, (ZE) the largest length of the 
xenograft/ hard tissue. The floor augmentation heights at the medial, middle and 
lateral aspects in the coronal view will be calculated using the axis X as reference at 
the various periods evaluated. The T0 X-area and T0 Z-area will be delimited by the 
sinus bone walls and the axis X and Z in the coronal and lateral views, respectively. 

In the coronal view, T1 X-area and T2 X-area will be obtained subtracting to T0 X-
area the areas below the X-axis not filled with biomaterial/ hard tissues (residual area 
and adding the area above the axis X filled with biomaterial/ hard tissues (exceeding 
area). The T1 and T2 Z-areas will be calculated similarly for the lateral view.  
 
Outcomes tomographic measures  
Primary outcome: Changing in height of the elevated zone.  
Description: Measurements will be assessed in the medial, middle and lateral 
regions of the elevated zone using the cone beam computerized tomographies 
(CBCTs) taken in various periods. Comparisons among the CBCTs of each 
participant will be performed.  
Timeframe: The CBCTs will be taken before surgery (T0) and 1-week (T1) and 9 
months (T2) after surgery.  
Secondary outcome: Changing in area of the elevated zone.  
Description: The area will be delineated by the sinus bone walls and the sinus 
mucosa. The changes will be evaluated on the cone beam computerized 
tomographies (CBCTs) taken in various periods. Comparisons among the CBCTs of 
each participant will be performed.  
Timeframe: The CBCTs will be taken before surgery (T0) and 1-week (T1) and 9 
months (T2) after surgery.  
Other pre-specified outcomes: MT) mucosa thickness, (C-F) bone crest height, (XF) 
nasal floor height, (A-C) anastomosis height and (AD) its diameter, (XW) sinus width, 

(LM-F) balcony height, (LM-UM) window height, (ZW) sinus length, (ZE) the largest 
length of the xenograft/ hard tissue.  
Description: Measurements will be assessed in the medial, middle and lateral 
regions of the elevated zone using the cone beam computerized tomographies 
(CBCTs) taken in various periods. Comparisons among the CBCTs of each  
participants will be performed.  
Timeframe: The CBCTs will be taken before surgery (T0) and 1-week (T1) and 9 
months (T2) after surgery.  
 
Outcomes histomorphometric measures  
Primary outcome: Bone-to-implant contact between the different surfaces and 
between membrane / no membrane groups 
Description: Measurements of new bone formation will be assessed on the 
histological images taken from the slides and performed between the most coronal 
bone contact to the surface and the apex of the mini-implant. Comparisons among 
test and control (without or with a collagen membrane of the access window) and 
between the two different surface conformations will be performed.  
Timeframe: three months of healing.  
Secondary outcome: Bone density  
Description: Measurements of new bone formation will be assessed on the 
histological images taken from the slides and performed between the most coronal 
bone contact to the surface and the apex of the mini-implant. Comparisons among 

test and control (without or with a collagen membrane of the access window) and 
between the two different surface conformations will be performed.  
 Timeframe: three months of healing.  
Data analysis  
The histomorphometric and radiographic measurements will be performed twice by 
a well-trained researcher (KAAA) that will be blinded about the differences in the 
protocols. Mean values will be obtained between the two measurements and used 
for analyses.  
Mean values and standard deviations (SD) will be calculated for each outcome 
variable. Differences between the test and control groups will be analyzed with the  
IBM SPSS Statistics software (IBM Inc., Chicago, IL, USA) using the Mann- 
Whitney test. The level of significance will be set at α=0.05.  
  
References  
1. Pjetursson BE, Tan WC, Zwahlen M, Lang NP. A systematic review of the 
success of sinus floor elevation and survival of implants inserted in 
combination with sinus floor elevation. J Clin Periodontol. 2008 Sep;35(8 
Suppl):216-40.  
2. Barone A, Ricci M, Grassi RF, Nannmark U, Quaranta A, Covani U. A 6month 
histological analysis on maxillary sinus augmentation with and without use of 
collagen membranes over the osteotomy window:  
randomized clinical trial. Clin Oral Implants Res. 2013 Jan;24(1):1-6.  

3. Masuda K, Silva ER, Botticelli D, Apaza Alccayhuaman KA, Xavier SP. 
Antrostomy Preparation for Maxillary Sinus Floor Augmentation Using Drills  
 
or  
a  
Sonic  
Instrument:  
A  
Microcomputed  
Tomography  
and  
Histomorphometric Study in Rabbits. Int J Oral Maxillofac Implants. 2019  
Feb 15. doi: 10.11607/jomi.7350. [Epub ahead of print]  
4. Nosaka, Y., Nosaka, H. & Arai, Y. (2015) Complications of postoperative 
swelling of the maxillary sinus membrane after sinus floor augmentation. 
Journal of Oral Science & Rehabilitation 1: 26-33.  
5. Lundgren S, Andersson S, Gualini F, Sennerby L. Bone reformation with sinus 
membrane elevation: a new surgical technique for maxillary sinus floor 
augmentation. Clin Implant Dent Relat Res. 2004;6(3):165-73.  
6. Cricchio G, Sennerby L, Lundgren S. Sinus bone formation and implant 
survival after sinus membrane elevation and implant placement: a 1- to 6year 
follow-up study. Clin Oral Implants Res. 2011 Oct;22(10):1200-1212.  
7. Moon YS, Sohn DS, Moon JW, Lee JH, Park IS, Lee JK. Comparative 
histomorphometric analysis of maxillary sinus augmentation with absorbable 
collagen membrane and osteoinductive replaceable bony window in rabbits. 
Implant Dent. 2014 Feb;23(1):29-36.  
8. Omori Y, Ricardo Silva E, Botticelli D, Apaza Alccayhuaman KA, Lang NP, 
Xavier SP. Reposition of the bone plate over the antrostomy in maxillary sinus 
augmentation: A histomorphometric study in rabbits. Clin Oral Implants Res. 
2018 Aug;29(8):821-834.  
9. Corbella S, Taschieri S, Weinstein R, Del Fabbro M. Histomorphometric 
outcomes after lateral sinus floor elevation procedure: a systematic review of 

the 
literature 
and 
meta-analysis. 
Clin 
Oral 
Implants 
Res. 
2016 
Sep;27(9):1106-22.  
10. Caneva M, Lang NP, Garcia Rangel IJ, Ferreira S, Caneva M, De Santis E,  
Botticelli D. Sinus mucosa elevation using Bio-Oss(®) or Gingistat(®) collagen 
sponge: an experimental study in rabbits. Clin Oral Implants Res. 2017 
Jul;28(7):e21-e30.  
11. De Santis E, Lang NP, Ferreira S, Rangel Garcia I Jr, Caneva M, Botticelli D. 
Healing at implants installed concurrently to maxillary sinus floor elevation 
with Bio-Oss(®) or autologous bone grafts. A histo-morphometric study in 
rabbits. Clin Oral Implants Res. 2017 May;28(5):503-511.  
12. Riachi F, Naaman N, Tabarani C, Aboelsaad N, Aboushelib MN, Berberi A, 
Salameh Z. Influence of material properties on rate of resorption of two bone 
graft materials after sinus lift using radiographic assessment. Int J Dent. 
2012;2012:737262.  
13. Shanbhag S, Shanbhag V, Stavropoulos A. Volume changes of maxillary 
sinus augmentations over time: a systematic review. Int J Oral Maxillofac 
Implants. 2014;29(4):881-892.  
14. Zijderveld SA, Schulten EA, Aartman IH, ten Bruggenkate CM. Long-term 
changes in graft height after maxillary sinus floor elevation with different 
grafting materials: radiographic evaluation with a minimum follow-up of 4.5 
years. Clin Oral Implants Res. 2009 Jul;20(7):691-700.