A histomorphometric meta-analysis of sinus elevation with various grafting materials.

ral
ssBioMed CentHead & Face Medicine
Open AcceReview
A histomorphometric meta-analysis of sinus elevation with various
grafting materials
Jörg Handschel*1, Melani Simonowska1, Christian Naujoks1,
Rita A Depprich1, Michelle A Ommerborn2, Ulrich Meyer1 and
Norbert R Kübler2
Address: 1Department for Cranio- and Maxillofacial Surgery, Heinrich-Heine-Universität, Moorenstr. 5, D-40225 Düsseldorf, Germany and
2Department for Operative and Preventive Dentistry and Endodontics, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf,
Germany
Email: Jörg Handschel* - handschel@med.uni-duesseldorf.de; Melani Simonowska - handschel@med.uni-duesseldorf.de;
Christian Naujoks - christian.naujoks@med.uni-duesseldorf.de; Rita A Depprich - depprich@med.uni-duesseldorf.de;
Michelle A Ommerborn - ommerborn@med.uni-duesseldorf.de; Ulrich Meyer - handschel@med.uni-duesseldorf.de;
Norbert R Kübler - norbert.kuebler@med.uni-duesseldorf.de
* Corresponding author
Abstract
: Several grafting materials have been used in sinus augmentation procedures including autogenous
bone, demineralized freeze-dried bone (DFDBA), hydroxyapatite, β-tricalcium phosphate (β-TCP),
anorganic deproteinized bovine bone and combination of these and others. Up to now a subject of
controversy in maxillofacial surgery and dentistry is, what is the most appropriate graft material for
sinus floor augmentation.
Purpose: The aim of this study is to provide a body of evidence-based data regarding grafting
materials in external sinus floor elevation concerning the fate of the augmented material at the
histomorphological level, through a meta-analysis of the available literature.
Materials and methods: The literature searches were performed using the National Library of
Medicine. The search covered all English and German literature from 1995 until 2006. For analyzing
the amount of bone the parameter "Total Bone Volume" (TBV) was assessed. TBV is determined
as the percentage of the section consisting of bone tissue.
Results: In a relatively early phase after implantation the autogenous bone shows the highest TBV
values. Interestingly, the different TBV levels approximate during the time. After 9 months no
statistically significant differences can be detected between the various grafting materials.
Conclusion: From a clinical point of view, the use of autogenous bone is advantageous if a
prosthetic rehabilitation (with functional loading) is expected within 9 months. In other cases the
use of anorganic deproteinized bovine bone in combination with autogenous bone seems to be
preferable. Donor side morbidity is ignored in this conclusion.
Published: 11 June 2009
Head & Face Medicine 2009, 5:12 doi:10.1186/1746-160X-5-12
Received: 25 February 2009
Accepted: 11 June 2009
This article is available from: http://www.head-face-med.com/content/5/1/12
© 2009 Handschel et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 10
(page number not for citation purposes)

Head & Face Medicine 2009, 5:12 http://www.head-face-med.com/content/5/1/12
Introduction
Since the external sinus floor elevation technique was first
introduced by Boyne [1] and Tatum [2] several grafting
materials have been used in sinus augmentation proce-
dures including autogenous bone [1-3], demineralized
freeze-dried bone (DFDBA)[4,5], hydroxyapatite [6], β-
tricalcium phosphate (β-TCP) [7], anorganic deprotein-
ized bovine bone [8] and combination of these and others
[9]. Up to now a subject of controversy in maxillofacial
surgery and dentistry exist, what is the most appropriate
graft material for sinus floor augmentation. The consen-
sus conference on sinus grafting held in 1996 showed that
in the light of little data which are evidence-based many
participants believed that autografts were the most effica-
cious [10]. However, the collection of autogeneous bone
requires an extra donor site surgery and carries with it
extra risks for morbidity and complaints, particularly
when bone from the iliac crest is harvested [11]. Accord-
ing to Kent and Block [3] an ideal grafting material should
fulfil the following criteria amongst other things:
Osteoinduction
Osteoconduction
Volume stability
These criteria are best analysed by histological examina-
tions. To the best of our knowledge, only a very small
number of randomized controlled clinical trials have
been conducted to compare various grafting materials
with regard to these histological criteria. The available evi-
dence therefore consists either of case reports, case series
or retrospective studies. The aim of this study is to provide
a body of evidence-based data regarding grafting materials
in external sinus floor elevation to assist surgeons to make
an informed choice between those materials, through a
meta-analysis of the available literature.
Methods
The literature searches were performed using the National
Library of Medicine (Internet: http://www.pubmed.com).
The search covered all English and German literature from
1995 until 2006. Keywords used in the search were:
"sinus" and "augmentation" and "bone substitute". The
search was confined to studies or reports in humans. No
animal studies were included. Moreover, review articles
and in vitro studies were excluded. In all, 120 articles were
identified and all abstracts were evaluated. After first eval-
uation the following inclusion criteria were added: The
surgical procedure has to be an external sinus floor eleva-
tion and because of the presence of only single reports of
some grafting materials – which does not allow a meta-
papers using autogenous bone, demineralized freeze-
dried bone (DFDBA), hydroxyapatite, β-tricalcium phos-
phate (β-TCP), anorganic deproteinized bovine bone (Bio
Oss®, Geistlich Biomaterials, Wolhusen, Switzerland) [8]
and combination of these materials were included. To
standardize the multiple combinations of Bio Oss® with
autogenous bone all mixing ratios higher than 80% Bio
Oss® to 20% bone were pooled in the Bio Oss® group. Mix-
ing ratios below (e.g. 50% Bio Oss® to 50% bone) were
subsumed under the Bio Oss® + autogeneous bone group.
Regarding the β-TCP group in almost all studies β-TCP
was used without autogenous bone. In addition to review
articles, interviews and editorials were excluded.
For analyzing the amount of bone the parameter "Total
Bone Volume" (TBV) was assessed. TBV is determined as
the percentage of the section consisting of bone tissue
[12]. This parameter was either directly taken from the
paper or calculated where possible. In studies reporting
woven and lamellar bone separately, the sum of both val-
ues was calculated whereas in studies determing lateral
and central bone biopsies the mean was calculated.
For statistical analysis the data were weighted according to
the number of observations in each study and the inverse
variance. Moreover, to detect any statistical significant dif-
ferences a weighted ANOVA with Random effect model
and alpha-adjustment according to Tukey-Kramer for post
hoc tests was used [13]. Differences were considered sta-
tistically significant if p < 0.05.
Results
After the initial literature search 120 articles were identi-
fied. Four of these articles were not written in English or
german and another four were animal studies. Six articles
were interviews or editorials and were excluded too. Of
the remaining 106 articles 25 were not related to the exter-
nal sinus floor elevation and another 16 articles gave an
account on rare grafting material. Of the remaining 65
articles only in 30 studies the histomorphological param-
eter TBV was evaluable. That means that this parameter
was explicitly noted in the article or could easily been cal-
culated. Finally, only 30 articles remain for data analysis
(table 1).
In many of these 30 articles various grafting materials
were described. In total 53 observations regarding grafting
materials could be found. The vast majority were prospec-
tive studies, followed by some case reports or case series
and finally one retrospective study (table 2).
A prerequisite for statistical analysis is that the mean val-
ues and the standard deviation is noted in the paper (cri-Page 2 of 10
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analysis for those materials- the focus was on materials
which are used in several studies/reports. Thus only
teria I) [13]. This is not the case in single case reports
(criteria II). That is why those papers meeting one of these

Head & Face Medicine 2009, 5:12 http://www.head-face-med.com/content/5/1/12
two criteria have to be excluded from further analysis
(table 3). If a meta-analysis for one specific grafting mate-
rial would be based on only one or two studies, the result
would almost echo the findings of the single study. There-
fore, it is rational to exclude materials with only one or
two reports (criteria III). Table 3 shows the number of
remaining studies/observations after application of these
three criteria (Tab. 3). Finally, 30 articles remain for eval-
uation [7,8,12,14-41]. The studies are listed in table 4
(table 4). In no studies any allergic reactions to grafting
materials or infections related to graft implantation were
described.
The weighted regression of TBV against the time point of
sampling shows the development of the bone volume
during time (Fig. 1). Interestingly, while Bio Oss®, Bio
Oss® with autogenous bone and β-TCP show a steep
increase the TBV of autogenous bone (without any addi-
tional grafting material) is decreasing. The increase of TBV
during time in the Bio Oss® group can be considered as sta-
tistically significant.
Regarding Fig. 1 it is striking that there are two clusters of
sampling. The first cluster comprise four until nine
months after initial surgery and the second cluster span
the time from nine months onwards. To compare the TBV
depending on the grafting material the mean values were
calculated for these two clusters. Because it is reasonable
to weight the study results regarding the number of obser-
vations and the standard deviation both the "normal" and
the adjusted mean values were calculated. In a relatively
early phase after implantation the autogenous bone
shows the highest TBV values. This was statistically signif-
icant (Fig. 2). Interestingly, the different TBV levels
approximate during the time. After 9 months no statisti-
cally significant differences can be detected between the
various grafting materials (Fig. 3). However, there was a
strong tendency that Bio Oss® with autogenous bone
shows the highest TBV values.
Discussion
External sinus floor augmentation has proven to be very
effective in increasing bone volume in edentulous maxil-
lary areas. Due to the significant resorption in the poste-
rior maxilla following teeth extraction [42] there is often
not enough bone volume to ensure the stability of dental
implants [43]. Elevation and augmentation of the maxil-
lary sinus can increase the bone height in the posterior
area of the maxilla [1,2]. Autogenous bone grafts obtained
from the patient himself is very successful in bone regen-
eration and serves as a gold standard [10]. However, the
explant of autogeneous bone requires an extra donor site
surgery and is associated with an extra risks for morbidity
and complaints, particularly when bone from the iliac
crest is harvested [11]. Various bone grafting materials
have been used as alternatives or supplements to autoge-
nous bone such as demineralized freeze-dried bone
(DFDBA), hydroxyapatite, β-tricalcium phosphate (β-
Table 1: Selection of evaluable articles by in- and exclusion criteria
Criteria Studies which do not meet the criteria Remaining studies
After initial literature search 120
English or german 4 116
Only human (no animal studies) 4 112
No interviews/editorials 6 106
Only external sinus floor elevation 25 81
Only autogenous bone, demineralized freeze-dried bone (DFDBA),
hydroxyapatite, β-tricalcium phosphate (β-TCP), anorganic
deproteinized bovine bone [8] and combination of these materials
16 65
TBV evaluable 35 30
Table 2: Distribution of articles and material observations
Σ Case reports Retrospective studies Prospective studies
Studies 30 3 1 26Page 3 of 10
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Examined grafting materials (in these studies) 53 4 3 46

Head & Face Medicine 2009, 5:12 http://www.head-face-med.com/content/5/1/12
TCP), anorganic deproteinized bovine bone [8] or combi-
nation of these materials. Bone grafting materials may
produce bone formation by osteogenesis, osteoinduction
or osteoconduction. Whereas osteogenesis is obtained by
providing osteogenic cells and matrix directly in the graft
(e.g. autogenous bone, distraction osteogenesis [44]),
osteoinduction postulates that the grafted material is
chemotactic to undifferentiated progenitor cells inducing
them to differentiate into osteoblasts [31,45]. Osteocon-
duction permits outgrowth of osteogenic cells from exist-
ing bone surfaces into the graft material [31]. Although
these mechanisms have been described in detail, the ques-
tion remains which bone grafting material is most suita-
ble in external sinus floor augmentation at the
histological level.
One important finding of this study is that there is only
little evidence for most of the grafting materials. Only
anorganic deproteinized bovine bone (Bio Oss®) and
pure-phase β-TCP (in most cases Cerasorb®, Curasan
Pharma GmbH, Kleinostheim, Germany, was used) as
well as autogenous bone (and combinations of these
materials) were found to present evaluable data for meta-
analysis. Interestingly, no reports regarding allergic reac-
tion or infections caused by implantation of grafting
material were described in the articles.
With regard to the TBV autogenous bone reaches the high-
est values during the first 9 months. This difference to the
other materials was statistically significant. That's means
that the percentage of mineralized bone was the highest.
That is not surprisingly, because in the specimens of the
other groups there are of course particles of the heterolo-
gous or alloplastic grafting material diminishing the per-
centage of the bone. Logically consistent the TBV shows
the lowest values in the Bio Oss® and β-TCP groups. In
contrast to this early phase there is no statistically signifi-
cant difference between the grafting materials in the later
phase anymore. Moreover, the values of the Bio Oss®
group and Bio Oss® with autogenous bone show higher
mean values than the pure autogenous bone, whereas the
mean value of β-TCP is almost equal to autogenous bone.
There could be two adverse effects after the initial grafting
procedure. On the one hand bone is resorbed because in
no case was any functional load on the grafting material
(The samples of the patients were taken before the
implant was in function). On the other hand the TBV in
the Bio Oss® and β-TCP groups increased during time.
That means that the grafting material is at least partially
resorbed and replaced by bone. (Reduction of soft tissue
volume hardly produce an increase of TBV because in
sinus lift procedures soft tissue is very rare in the grafted
material.) The first effect is well known and occurs in the
Table 3: Selection of evaluable material observations by three exclusion criteria
Total observation Criteria I: no mean
value or SD
Criteria II: single
case report
Criteria I or II Remaining material
observations
Algipore® 1 0 0 0 1
Bio Oss® 18 4 3 5 13*
Bio Oss® + autogen
(50:50 bis 80:20)
8 0 0 0 8*
DFDBA 1 1 0 1 0
HA 3 1 0 1 2
Autogen 13 3 5 4 9*
Autogen + DFDBA
50:50
1 0 0 0 1
Autogen + HA 50:50 1 0 0 0 1
β-TCP 7 1 1 1 6*
Σ 53 17 5 18 41 (36)
Note the numbers with * show the grafting materials with at least three reported observations (criteria III).Page 4 of 10
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alveolar bone usually after tooth extraction when the
functional load is reduced or absent [42]. Additionally,

Head & Face Medicine 2009, 5:12 http://www.head-face-med.com/content/5/1/12Table 4: List of reviewed publications. n = number of patients
Authors Year of publication Grafting material Mean healing time (months) n TBV (%) SD
Artzi Z. et al. 2001 BioOss 12.00 10 32.20 8.150
Artzi Z. et al. 2001 HA 12.00 10 42.10 10.010
Artzi Z. et al. 2002 BioOss 12.00 10 43.61 8.601
Artzi Z. et al. 2003 HA 12.00 10 32.95 7.991
Artzi Z. et al. 2005 BioOss 12.00 12 45.60 10.900
Artzi Z. et al. 2005 β-TCP 12.00 12 32.00 8.400
Boeck-Neto RJ. et al. 2002 autogen+DFDBA 10.00 5 50.46 16.290
Boeck-Neto RJ. et al. 2002 autogen+HA 10.00 5 46.79 8.560
Degidi M. et al. 2004 BioOss+autogen 6.00 12 38.80 3.200
Froum SJ. et al. 2002 BioOss 7.25 2 16.00 4.243
Froum SJ. et al. 2002 BioOss 11.00 1 32.00 .
Fugazotto PA. et al. 2003 BioOss 6.88 26 52.85 19.605
Fugazotto PA. et al. 2003 BioOss 12.50 5 68.80 7.400
Hallman M. et al. 2001 BioOss+autogen 7.00 16 24.70 16.901
Hallman M. et al. 2001 BioOss+autogen 30.00 12 50.70 22.800
Hallman M. et al. 2002 Autogen 12.50 11 37.70 31.300
Hallman M. et al. 2002 BioOss 14.75 10 39.90 8.000
Hallman M. et al. 2002 BioOss+autogen 12.50 11 41.70 26.600
John HD. et al. 2004 Autogen 5.50 4 53.50 2.520
John HD. et al. 2004 BioOss 5.50 21 29.52 7.430
John HD. et al. 2004 BioOss+autogen 5.50 13 32.23 6.860
Karabuda C. et al. 2001 BioOss 6.00 5 50.00 .
Karabuda C. et al. 2001 DFDBA 6.00 1 72.50 .
Karabuda C. et al. 2001 HA 6.00 3 27.50 8.660
Ozyuvaci H. et al. 2003 BioOss 7.00 44 47.50 0.945
Ozyuvaci H. et al. 2003 β-TCP 7.00 44 52.50 0.945
Proussaefs P. et al. 2003 BioOss 11.00 5 34.40 10.810Page 5 of 10
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