Mauro Donati Effect of immediate functional loading

Daniele Botticelli
Vincenzo La Scala
on osseointegration of implants used
Cristiano Tomasi for single tooth replacement. A human
Tord Berglundh
histological study

Authors’ affiliations: Key words: dental implants, human histology, immediate loading, osteotome, single tooth
Mauro Donati, Department of Periodontology, The
Sahlgrenska Academy at University of Gothenburg,
Private practice, Perugia, Italy Abstract
Daniele Botticelli, Ariminum Odontologica, Oral Objective: To analyze hard tissue reactions to immediate functionally loaded single implants that
Surgery Division, Rimini, Italy
were installed either with a conventional drill preparation procedure or with an osteotome
Vincenzo La Scala, Private practice, Pistoia, Italy
Cristiano Tomasi, Department of Periodontology, preparation technique.
The Sahlgrenska Academy at University of Materials and methods: Thirteen subjects with two sites requiring single tooth rehabilitation by
Gothenburg, Private practice, Trento, Italy
means of implants volunteered for the study. Each subject received one test (immediate
Tord Berglundh, Department of Periodontology,
The Sahlgrenska Academy at University of functionally loaded) and one control (non-loaded) implant. In six subjects (group 1) the implants
Gothenburg were placed using a conventional drilling procedure, whereas in the remaining seven subjects
Corresponding author: (group 2) an osteotome preparation procedure was performed. Block biopsies containing test and
Mauro Donati control implants and peri-implant bone tissues were collected at 1 month in four of the subjects in
Department of Periodontology group 1 and in five subjects of group 2. The remaining implant sites were sampled at 3 months
The Sahlgrenska Academy at University of
Gothenburg after implant placement. The biopsies were prepared for histological examination.
Box 450 Results: Two implants of the test-2 group (osteotome preparation) representing 1 month of
SE 405 30 Göteborg healing and another test-2 implant representing 3 months of healing failed to integrate. A
Sweden
Tel.: +46 31 786 3124 multilevel multivariate statistical analysis demonstrated that no differences in bone-to-implant
Fax: +46 31 786 37 91 contact (BIC)% were found in between test and control implants, the density of newly formed
e-mail: mauro.donati@odontologi.gu.se
peri-implant bone was significantly higher around test than control implants at 1 and 3 months of
healing. Sections representing osteotome technique sites showed fractured trabeculae and large
amounts of bone particles.
Conclusions: It is suggested that immediate loading of implants does not influence the
osseointegration process, whereas the density of newly formed peri-implant bone at such sites
appears to be increased in relation to unloaded control implants. The use of an osteotome
preparation technique during installation results in damage of peri-implant bone and enhances the
risk for failure in osseointegration.

Date:
Accepted 2 March 2012
To cite this article:
Donati M, Botticelli D, La Scala V, Tomasi C, Berglundh T.
Effect of immediate functional loading on osseointegration of
implants used for single tooth replacement. A human
histological study.
Clin. Oral Impl. Res. 24, 2013, 738–745
doi: 10.1111/j.1600-0501.2012.02479.x
An increasing concern regarding the possibil-
ity to shorten the healing period of time in
the implant-prosthetic rehabilitation has
become evident and numerous clinical stud-
ies have reported on the outcome of immedi-
ate loading of implants in various clinical
situations (Esposito et al. 2009; Romanos
et al. 2010). Clinical studies (Calandriello
et al. 2003; Glauser et al. 2005; Lindeboom
et al. 2006; Donati et al. 2008) demonstrated
that immediate functional loading implants
placed with conventional installation tech-
nique and with sufficient primary stability
may be considered a valid treatment alterna-
tive in single tooth replacement.
Human histological studies on retrieved
immediately loaded implants have conflict-
ing results regarding the degree of bone-to-
implant contact (BIC) in relation to conven-
tional loaded implants (Degidi et al. 2003b,
2009; Rocci et al. 2003; Romanos 2009). Such
studies were, in addition, based on few sam-
ples retrieved from different subjects and the
question whether immediate functional load-
ing is beneficial or detrimental to the osseo-
integration process remains to be elucidated.
The most commonly applied method for
osteotomy preparation of the recipient site
for dental implants is the use of a series of
drills with increasing diameter. In specific
situations where the bone density was
considered as compromised an alternative
technique by means of an osteotome was
introduced. The purpose of such an osteo-
tome technique was to increase the primary
stability of dental implant by laterally

738 © 2012 John Wiley & Sons A/S


condensing the trabecular bone (Summers
1994). In a large clinical multicenter study
on immediate loading to implants in single
tooth replacement (Donati et al. 2008) it was
observed that implant loss was more com-
mon in sites where implants were installed
according to an osteotome technique than in
sites where implants were installed using
conventional drill preparation technique.
The aim of the present study was to ana-
lyze hard tissue reactions to immediate func-
tionally loaded single implants that were
installed either with a conventional drill
preparation procedure or with a modified os-
teotome preparation technique.
Materials and methods
This study was designed as clinical-histologi-
cal, intra-individually controlled, single
masked trial and was conducted at four clinical
centers in Italy and at the Department of Peri-
odontology, University of Gothenburg. The
study protocol was approved by the human
review board at the University of Perugia.
Thirteen non-smoking subjects (11 men
and 2 women, mean age 53.8; range 37–70)
with two sites requiring single tooth rehabili-
tation by means of implants volunteered for
the study. All subjects received detailed
information on the study and signed a writ-
ten consent before the start of the treatment.
The subjects had to fulfill the following
inclusion criteria; good general health,
absence of oral and dental disorders, missing
of two teeth distally to the canines in the
upper or lower jaw, normal occlusion in reci-
pient sites for implants,  3 months of heal-
ing following tooth extraction, alveolar bone
crest in recipient sites wider than 6 mm and
higher than 11 mm and an attainment of the
insertion torque at the implant installation of
at least 20 Ncm (to allow the screw-retention
of the abutment). The study was designed to
provide each subject with one test (immedi-
ate functionally loaded) and one control (non-
loaded) implant.
Allocation of subjects to groups and surgical
procedures
The surgical procedure was carried out as
reported by Donati et al. (2008). Briefly, each
subject received an antibiotic prophylaxis 1 g
of Augmentin (Amoxicillin 875 mg + Clavul-
anate potassium 125 mg; Glaxo Smith Kline,
Brentford, UK) 1 h prior to surgery. Following
local anesthesia full thickness flaps were ele-
vated to expose the bone ridge. The prepara-
tion of the recipient sites in each subject was
carried out either by a conventional drilling
© 2012 John Wiley & Sons A/S
Donati et al
Human histology of immediate functional loading of implants
technique or by a modified osteotome prepa-
ration technique as described in Donati
et al.(2008). A stratified randomization proto-
col was applied to allocate subjects to the dif-
ferent preparation technique groups
(conventional drill vs. osteotome) and accord-
ing to healing time (1 or 3 months). The allo-
cation of subjects to groups is described in
Table 1.
In six subjects (group 1) the implants were
placed using a conventional drilling proce-
dure according to the standards described in
the manual for surgical procedures of the
implant system (Astra Tech Dental, Mölndal,
Sweden), In the remaining seven subjects
(group 2) a modified osteotome preparation
procedure was performed (Table 1). Following
an initial preparation with a twist drill (∅
2.5 mm), osteotomes (Astra Tech Dental)
were used to widen the prepared canal to a
diameter of 3.2 mm. The implants used were
OsseoSpeedTM (Astra Tech Dental), ∅ 3.5
with lengths of 8 mm. All implants in both
subject groups had an insertion torque of
 20 NCm and no bone dehiscence or fenes-
tration defects occurred after implant place-
ment. Cover screws were connected to the
implants in the control sites and the flaps
were replaced and secured with interrupted
sutures to cover the implants.
Prosthetic procedures
The prosthetic procedure of the test implants
was initiated following the completion of the
surgical procedure. The position of the
implant was transferred by means of an
impression-implant pick up, which was fixed
to the surgical stent with an autopolymeriz-
ing resin as described in Donati et al. (2008).
The implant was provided a healing abut-
ment and the flaps were adjusted and secured
Table 1. Distribution of subjects according
treatment procedures and healing time
Number Healing
of subjects Procedures time
4 subjects Test 1 1 month
Control 1
5 subjects Test 2 1 month
Control 2
2 subjects Test 1 3 months
Control 1
2 subjects Test 2 3 months
Control 2
Test 1 = conventional drill preparation +
immediate functional loading.
Test 2 = modified osteotome preparation +
Immediate functional loading.
Control 1 = conventional drill preparation +
no load.
Control 2 = modified osteotome preparation
+ no load.
around the healing abutments with inter-
rupted sutures. A custom-made abutment
(preparable abutment; Astra Tech Dental)
and a temporary crown were produced.
Between 12 and 24 h after implant installa-
tion the healing abutment was removed and
the custom-made abutment was connected to
the test implant and tightened to 20 Ncm.
The temporary acrylic crown was placed with
a temporary cement (Temp Bond; Kerr Co.,
Orange, CA, USA). The crowns were in full
contact in centric occlusion. Suture removal
was performed at 10–14 days after implant
surgery. The control implants were allowed
to heal in a submerged position.
Retrieval of the implants
Block biopsies containing test and control
implants and peri-implant bone tissues were
collected at 1 month in four of the subjects in
group 1 and in five subjects of group 2. The
remaining implant sites were sampled at
3 months after implant placement (Table I).
The temporary crowns and the custom-made
abutments were removed and, following local
anesthesia, flaps were elevated. Healing abut-
ments ZebraTM (∅ 4 mm; Astra Tech AB,
Mölndal, Sweden) were connected to both
implants and used as guides for the biopsy pro-
cedure. A trephine burr, ∅ 5 mm, was used to
remove the implants together with a 0.8 mm
wide zone of the surrounding bone tissue
(Fig. 1). The biopsies were placed in 4% forma-
lin.
Following the biopsy procedure each site
was further prepared with drills and Osseo-
SpeedTM implants (Astra Tech AB) ∅ 5.0 mm
and 11 mm in length were placed. Cover
screws were connected and the flaps were
replaced and closed to cover all implants.
After 3 months abutment connection and
prosthetic therapy was performed with single
crowns. In four sites, it was not possible to
place implants immediately after biopsy. In
such sites flaps were replaced and closed to
cover the prepared canal and implant therapy
Fig. 1. Block biopsy containing the implant and the
peri-implant bone.
739 | Clin. Oral Impl. Res. 24, 2013 / 738–745
Donati et al
Human histology of immediate functional loading of implants
was performed after an additional 3-month
period of healing.
Histological preparation and analysis
The biopsies were processed for ground sec-
tioning according to Donath & Breuner
(1982). The specimens were dehydrated in
increasing grade of ethanol and embedded in
methacrylate (Technovit® 7200 VLC-resin;
Kulzer, Friedrichsdorf, Germany) and subse-
quently divided into two parts (Exakt®, Appa-
ratebau, Norderstedt, Germany). Two central
sections were prepared and reduced to a
thickness of about 25 lm using a cutting-
grinding device (Exakt®, Apparatebau). The
remaining portions of the biopsies were
remounted and cut in a perpendicular direc-
tion and two central sections (25 lm) were
prepared from each unit. Two sections were
stained in toluidine blue and two with fibrin
stain of Ladewig (Donath & Breuner 1982).
The histological examination was per-
formed using a Leitz DM-RBE® microscope
(Leica, Heidelberg, Germany) equipped with
an image system (Q-500 MC®; Leica). In each
section the degree of BIC%, i.e. the length
fraction of the implant surface that was in
direct contact with mineralized bone (newly
formed/immature bone and old/mature bone)
observed within the macro-threaded and the
micro-threaded portions of the implants was
assessed. The densities (%) of newly formed/
immature bone tissue and old/mature bone
within the area between the peaks of the
macro-thread (“chamber area”) and in a
500 lm-wide zone of the peri-implant bone
were determined using a point-counting pro-
cedure. Thus, a lattice comprising 100 light
points (Schroeder & Munzel-Pedrazzoli 1973)
was superimposed over the tissue at a magni-
fication of 9200 and the percentage area
occupied by newly formed/immature bone,
old/mature bone, and residual tissue (e.g.
non-mineralized tissue, bone remnants, and
unidentified structures) were determined
(Berglundh et al. 2003, 2005, 2007; Abra-
hamsson et al. 2004).
Data analysis
Regression multivariate multilevel models
were built to account for the variability
between histological sections from the same
implant and to estimate the correlation
between outcome variables (i.e. BIC %, bone
density %) within implant sites and the
residual variance between subjects. Differ-
ences between implants according to (i) treat-
ment procedures (i.e. immediate functional
loading vs. non-loading), (ii) healing time
(1 month vs. 3 months), and (iii) site prepara-
740 | Clin. Oral Impl. Res. 24, 2013 / 738–745
tion techniques (i.e. conventional drill prepa-
(a)
ration vs. modified osteotome technique)
were analyzed. A statistical package specifi-
cally designed for multilevel modeling
(MLwiN 2.11©; Center for Multilevel Model-
ling, University of Bristol, Bristol, UK) was
applied. The significance for each variable
was evaluated by the Wald test. Data
obtained from each section were collapsed
and weighted mean values and 95% confi-
dence intervals (CI) were used to analyze dif-
ferences. The lower level unit in the model
was the section and the upper level unit was
the subject. P-values <0.05 were considered
as significant in all analyses.
Results
All patients were eventually restored with
implant-supported single-crown restorations
in accordance with the treatment plan. Two
implants of the test-2 group (modified osteo-
tome preparation) representing 1 month of (b)
healing and another test-2 implant represent-
ing 3 months of healing failed to integrate.
All implants that failed to integrate were
removed between the second and the fourth
week of healing.
Histological observations
Ground sections from biopsies containing
implants and the surrounding bone tissue are
illustrated in Figs 2–5. At 1 month of healing
in both test and control units representing
“conventional preparation” sites newly
formed bone containing immature, woven
bone was found in contact with the implant
surface (Figs 2 and 3). In the tissue compart-
ments between the peaks of the macro-thread
a distinct border separated the old-mature
bone from the newly formed tissue. Woven
bone extended from the old parent lamellar Fig. 2. Ground section of a test implant representing
bone into the central and inner portion of the group 1 (conventional drill preparation) and 1 month of
area between the macro-threads and in the healing. Original magnification 916, toluidine blue (a).
Detail of (a) the left side of the central portion of the
area lateral to the micro- and macro-threads.
implant. Original magnification 950 (b).
In the sections representing 3 months heal-
ing of both test and control units at the con-
implants installed according to (i) treatment
ventional installation technique sites (Figs 4
procedure (i.e. immediate functional loading
and 5) the area between the macro-threads
vs. non-loading), (ii) site preparation tech-
and lateral to the macro and micro-threads
nique (i.e. conventional drill preparation vs.
was occupied with parallel-fibered bone and
modified osteotome technique), and (iii) heal-
lamellar bone. The corresponding specimens
ing time (1 month vs. 3 months) using the
representing the osteotome technique showed
BIC% and of bone density as dependent vari-
in the majority of sites fractured trabeculae
ables.
and gross amounts of bone particles (Fig. 6).
Table 2 describes the results from the anal-
ysis of the multilevel multivariate model
Multivariate analysis of data from the
histological measurements that was built using the total BIC% as the
Four regression multivariate multilevel mod- dependant variable. Treatment procedure
els were built to analyze differences between (immediate functional loading vs. not load-
© 2012 John Wiley & Sons A/S

(a)
(b)
Fig. 3. Ground section of a control implant represent-
ing group 1 (conventional drill preparation) and
1 month of healing. Original magnification 916, tolui-
dine blue (a). Detail of (a) the right side of the central
portion of the implant. Original magnification 950 (b).
ing) and healing time (1 month vs. 3 months)
were introduced as explanatory variables.
Although a significant increase regarding BIC
% was observed for both the entire portion of
mineralized tissue (total) and for the newly
formed bone adjacent to the micro-threaded
portion of the implant between 1 and 3-
month healing, no significant difference was
detected between 1 and 3-months for the
macro-threaded portion area. No significant
© 2012 John Wiley & Sons A/S
Donati et al
Human histology of immediate functional loading of implants
(a)
(b)
Fig. 4. Ground section of a test implant representing
group 1 (conventional drill preparation) and 3 months of
healing. Original magnification 916, toluidine blue (a).
Detail of (a) the right side of the marginal, micro-
threaded portion of the implant. Original magnification
950, interference contrast (b).
differences in BIC% were observed between
test (immediate functional loading) and con-
trol (not loading) implants at 1 and 3 months
of healing. The residual variance at the
patient level was for all variables signifi-
cantly different from 0 (P < 0.05). The corre-
lation between data from sections
representing the same implant unit was 0.46
(a)
(b)
Fig. 5. Ground section of a control implant represent-
ing group 1 (conventional drill preparation) and
3 months of healing. Original magnification 916, tolui-
dine blue (a). Detail of (a) the right side of the marginal,
micro-threaded portion of the implant. Original magni-
fication 950, interference contrast (b).
(46%) between the micro- and macro-
threaded portion of the implants regarding
newly formed bone and 0.49 (49%) for all
mineralized tissue (i.e. total).
A second multivariate multilevel model
was built with the percentage of bone density
at the micro- and macro-threaded portions of
the implant and in the area between macro-
threads (chamber) as the dependant variable.
Treatment procedure and healing time were
introduced as explanatory variables (Table 3).
741 | Clin. Oral Impl. Res. 24, 2013 / 738–745
Donati et al
Human histology of immediate functional loading of implants

Table 2. Results from the analysis of the bone-to-implant contact% using the multivariate multi-
(a) level statistical model. Treatment procedures and healing times are explanatory variables. Total
refers to all types of bone; newly formed and old bone
Test Control

BIC% 1 3 1 3
Micro-threaded part total 26.3 ± 7.2 45.1 ± 10.9 30.8 ± 7.4 49.6 ± 10.6
Micro-threaded part new bone 25.6 ± 8.3 41.5 ± 12.4 24.7 ± 8.6 40.6 ± 12.3
Macro-threaded part total 32.0 ± 9.4 51.2 ± 15 29.9 ± 9.1 49.0 ± 14.3
Macro-threaded part new bone 30.0 ± 10.4 47.9 ± 16.1 25.3 ± 10.2 42.9 ± 15.4

Lower level unit: section.

Weighted mean values and 95% CI.

Table 3. Results from the analysis of the bone density% using the multivariate multilevel statisti-
cal model. Treatment procedures and healing times are explanatory variables
Test Control

Bone density% 1 3 1 3
Micro-threaded part new bone 16.7 ± 4.4 25.3 ± 6.4 11.4 ± 4.3 20 ± 6.3
Micro-threaded part old bone 25.3 ± 4.6 17.7 ± 6.9 25.3 ± 4.4 17.8 ± 6.9
Macro-threaded part new bone 17.8 ± 3.3 19.5 ± 4.8 12.1 ± 3 13.8 ± 4.9
Macro-threaded part old bone 30.2 ± 6.4 20.5 ± 9.4 27.9 ± 6.0 18.2 ± 9.2
Chamber area new bone 22.8 ± 5.2 29.3 ± 7.4 13.9 ± 5.2 20.5 ± 7.2
Chamber area old bone 6.9 ± 2.9 3.1 ± 3.7 9.5 ± 2.7 5.7 ± 3.8

Lower level unit: section.

Weighted mean values and 95% CI.

(b)

Table 4. Results from the analysis of the bone-to-implant contact% using the multivariate multi-
level statistical model. Site preparation techniques and healing times are explanatory variables.
Total refers to all types of bone; newly formed and old bone
Drill Osteotome

BIC% 1 3 1 3
Micro-threaded part total 32.3 ± 8.9 50.8 ± 10.9 25.5 ± 7.8 43.9 ± 11.3
Micro-threaded part new bone 29.2 ± 10.1 44.8 ± 13.4 20.9 ± 9.8 36.6 ± 13.3
Macro-threaded part total 28.2 ± 12.2 48.2 ± 13.8 33.2 ± 11.6 53.1 ± 15.5
Macro-threaded part new bone 23.4 ± 12.7 42.7 ± 16.7 30.4 ± 12.5 49.3 ± 18.1

Lower level unit: section.

Weighted mean values and 95% CI.

Fig. 6. Ground section of a control implant represent-
ing group 2 (osteotome preparation) and 1 month of
healing. Original magnification 916, toluidine blue (a).
Detail of (a) the left side of the central portion of the
implant. Original magnification 950 (b).
The density of newly formed bone was
significantly larger at test than at control
specimens at micro-, macro-threaded and
chamber areas after 1 and 3 months of heal-
ing. On the other hand, no significant differ-
ences were detected between test and control
sites regarding the density of old-mature bone
in any of the micro-, macro-threaded or
chamber areas. The residual variance at the
patient level was significantly different from
0 for the dependent variables (micro-, macro-
thread portion and chamber area) regarding
the density of newly formed bone (P < 0.05).
The correlation between data from sections
representing the same implant unit on the
bone density (%) at different areas varied
between 30% and 40%.
Table 4 describes the multilevel multivari-
ate model that was built using the BIC% for
the entire portion of the mineralized tissue
as the dependent variable. Site preparation
technique (i.e. conventional drill preparation
vs. modified osteotome technique) and heal-
ing time (1 month vs. 3 months) were intro-
duced as explanatory variables. A significant
increase regarding the total BIC% and the
BIC% of the newly formed bone between1
and 3-month healing was observed. No sig-
nificant differences in BIC% were observed
between conventional drill preparation and
modified osteotome technique at 1 and
3 months of healing. The residual variance at
the patient level was significantly different
from 0 for all variables (P < 0.05). The corre-
lation between data from sections represent-
ing the same implant unit was 0.46 (46%)
between the micro- and macro-threaded por-
tion of the implant regarding newly formed
bone and 0.48 (48%) for all mineralized tis-
sues (total).
A fourth multivariate multilevel model
was constructed with the percentage (%) of
bone density at the micro- and macro-
threaded portions of the implant and the area
between macro-threads (chamber) as the
dependent variable. Site preparation tech-
nique and healing time were introduced as
explanatory variables (Table 5). Significant
differences were observed between site prepa-
ration techniques for the macro-thread por-

742 | Clin. Oral Impl. Res. 24, 2013 / 738–745 © 2012 John Wiley & Sons A/S
 Donati et al
Human histology of immediate functional loading of implants
Table 5. Results from the analysis of the bone density% using the multivariate multilevel statisti-
cal model. Site preparation techniques and healing times are explanatory variables
Drill Osteotome
Bone density% 1 3 1 3
Micro-threaded part new bone 15.5 ± 5.7 23.7 ± 7.0 12.4 ± 5.3 20.5
Micro-threaded part old bone 26.3 ± 5.3 18.7 ± 6.8 24.2 ± 5.2 16.6
Macro-threaded part new bone 14.1 ± 4.1 16.4 ± 5.2 14.9 ± 4.0 17.1
Macro-threaded part old bone 34.5 ± 5.8 24 ± 7.6 23.5 ± 5.8 13.1
Chamber area new bone 16.6 ± 6.7 23.1 ± 8.7 18.5 ± 5.9 25.1
Chamber area old bone 10.4 ± 2.5 6.5 ± 3.3 6.2 ± 2.5 2.3
Lower level unit: section.
Weighted mean values and 95% CI.
tion and the chamber area regarding the old- received the intended implant-supported
mature bone. No significant differences were restorative therapy.
detected between conventional drill prepara- Healing around immediately loaded
tion and modified osteotome preparation implants has been examined in several ani-
techniques regarding newly formed bone for mal experiments. Romanos et al. (2002)
any of the variables (micro-, macro-threaded placed three implants on each side of the
and chamber area). The residual variance at mandible in six monkeys. Test implants
the patient level was significantly different were immediately loaded after installation,
from 0 for the dependent variables (micro-, whereas control implants were allowed to
macro-thread portion, and chamber area) heal in a submerged position for 3 months.
related to density of newly formed bone Test and control implants were exposed to
(P < 0.05). The correlation between data from functional load for 3 months. It was reported
sections representing the same implant unit that BIC% did not differ between test and
on the bone density (%) at different areas var- control sites, while bone density in the area
ied between 30% and 47%. between threads was significantly larger
around test than control implants. Bousdras
et al. (2007) analyzed bone reactions adjacent
Discussion to single implants exposed to immediate
loading for 10 weeks in a porcine model.
The present study was carried out to analyze Nine of the 12 implants exposed to func-
bone healing around immediately and func- tional load failed to integrate. In the remain-
tionally loaded single implants installed ing sites, the histological analysis showed
according to two different surgical procedures. that there was no difference in BIC% and in
It was observed that immediate functional bone density between test and control
loading to single implants does not influence implants. Lee et al. (2009) evaluated the
the osseointegration process, whereas the den- effect of immediate loading on BIC% in three
sity of newly formed peri-implant bone at dogs. Biopsies were obtained at 2 months
such sites increased in relation to unloaded after implant placement. A single section for
control implants. Furthermore, the use of a each implant was taken into account for the
modified osteotome preparation technique histological analysis. No difference was
during installation results in damage of peri- observed between test and control implants
implant bone and enhances the risk for failure in terms of BIC%. Although there are meth-
in osseointegration. odological differences between the experi-
Human biopsies have often been used to mental studies referred to and the present
study hard and soft tissue reactions around histological study in humans, the findings
experimental implants with smaller dimen- regarding BIC% and bone density are in
sions than those of regular dental implants agreement.
(Lang et al. 2011; Cecchinato et al. 2012). In Although consistency was found regarding
such studies the experimental implants were results on BIC% and bone density in the
retrieved using a technique similar to that present study and in the pre-clinical models,
applied in the present study. Although the there is less agreement with claims made in
implants in the present study were regular- human histology reports. First, there is lim-
sized dental implants, the biopsy procedure ited information in the literature regarding
was carried out in such a way that the result- histological evaluation of bone healing
ing prepared canal in bone could be used for around immediately loaded implants in
dental implants with a larger diameter. All humans. In a study by Rocci et al. (2003) five
patients in the present study eventually subjects received implant-supported prosthe-
© 2012 John Wiley & Sons A/S
sis in the posterior mandible. Two implants
in one subject were exposed to immediate
loading, while seven implants in four sub-
jects were loaded after 2 months of undis-
turbed healing. The two immediately loaded
± 7.7
± 7.2 implants were retrieved with the adjacent
± 5.7 peri-implant bone after 9 months of function,
± 8.6 whereas biopsies from the remaining seven
± 8.1
± 3.5
implant sites were obtained after a period of
5–7 months. The histological examination
showed a larger BIC% for the immediate
loading implants than sites for the implants
exposed to “delayed load”. Degidi et al.
(2003a) collected biopsies from two implant
sites exposed to immediate loading in one
subject and from one non-loaded implant site
in a second patient. 6 months after implant
placement, immediately loaded and the
unloaded implants were removed for the his-
tological analysis. The results indicated that
the immediately loaded implants had a larger
BIC% than the control implant. Romanos
et al. (2005) reported on a case series on
immediate loading and human biopsies. Of
the 29 implant biopsies obtained for histolog-
ical analysis one site represented a “control”
unit that was not exposed to immediate load-
ing. Biopsies were collected after 2–
10 months of healing/loading. It was reported
that the BIC% varied between 54% and 80%.
In a single section from one test and one con-
trol implant retrieved from one subject, the
BIC% was found to be larger for the test than
for the control site. Degidi et al. (2009) col-
lected biopsies from one immediately loaded
implant in each of two patients and from one
control implant in each of two other subjects.
The results from the histological examina-
tion indicated a larger BIC% in test than in
control sites.
The study design of the current trial pre-
sented with an intra-individual comparison
between single immediately loaded implants
and single submerged un-loaded implants.
The decision to evaluate test and control pro-
cedures in an intra-subject comparison was
taken to overcome an anticipated variability
between individuals. In fact, the statistical
analysis in the present study revealed a sig-
nificant variability between subjects regard-
ing BIC% and bone density. The absence of
differences in BIC% between immediately
loaded and un-loaded implants in the present
study thus indicates that immediate loading
does not influence the process of formation
of new bone in contact with implant during
healing.
Several authors (Summers 1994; Nkenke
et al. 2002) reported that an osteotome prepa-
ration technique may improve the bone den-
743 | Clin. Oral Impl. Res. 24, 2013 / 738–745
Donati et al
Human histology of immediate functional loading of implants
sity of the implant site leading to an
enhanced primary stability. In a previous
study on immediate loading to implants used
for single tooth rehabilitation from our group
(Donati et al. 2008), 54 of the implants
exposed to immediate loading were installed
in 51 subjects with a modified osteotome
preparation technique and 50 immediately
loaded implants were placed using a conven-
tional drill procedure in 50 subjects. While 3
(5.5%) implants failed to integrate in osteo-
tome preparation group, one implant (2%) in
the conventional drill preparation group did
not integrate. Similar results were reported
by Koutouzis et al. (2011). They installed 20
implants in 18 subjects. One implant (5%)
that was inserted with an osteotome tech-
nique failed to integrate. In the study by Kou-
touzis et al. (2011) it was further
demonstrated that implants installed with an
osteotome technique did not demonstrate a
high insertion torque that is in contrast to
the concept that osteotome preparation tech-
nique enhances the primary stability.
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