Natalia Lioubavina-Hack

Niklaus P. Lang
Thorkild Karring

Authors affiliations:
Natalia Lioubavina-Hack, Thorkild Karring,
Department of Periodontology and Oral
Gerontology, Royal Dental College, University of
Aarhus, Aarhus, Denmark
Niklaus P. Lang, Department of Periodontology and
Fixed Prosthodontics, University of Berne School of
Dental Medicine, Berne, Switzerland
Correspondence to:
Prof. Dr odont. Thorkild Karring
Department of Periodontology and Oral
Gerontology
Faculty of Health Sciences
Royal Dental College
University of Aarhus
Vennelyst Boulevard 9
DK-8000 Aarhus C
Denmark
Tel.: 45 8942 4135
Fax: 45 4619 4122
e-mail: odonhs@adm.au.dk

Significance of primary stability for

osseointegration of dental implants

Key words: bone formation, dental implants, guided tissue regeneration, ITI system,
osseointegration, primary stability
Abstract
Aim: To investigate the significance of the initial stability of dental implants for the
establishment of osseointegration in an experimental capsule model for bone
augmentation.
Material and methods: Sixteen male rats were used in the study. In each rat, muscleperiosteal flaps were elevated on the lateral aspect of the mandibular ramus on both sides,
resulting in exposure of the bone surface. Small perforations were then produced in the
s

ramus. A rigid, hemispherical Teflon capsule with a diameter of 6 mm and a height of 4 mm

s

and with a hole in its middle portion, prepared to fit the circumference of an ITI HC
titanium implant of 2.8 mm in diameter, was fixed to the ramus using 4 mini-screws. On one
side of the jaw, the implant was placed through the hole in such a way that its apex did not
make contact with the mandibular ramus (test). This placement of the implant did not
ensure primary stability. On the other side of the jaw, a similar implant was placed through
the hole of the capsule in such a way that contact was made between the implant and the
surface of the ramus (control). This provided primary stability of the implant. After
placement of the implants, the soft tissues were repositioned over the capsules and sutured.
After 1, 3, 6 and 9 months, four animals were sacrificed and subjected to histometric analysis.
Results: The mean height of direct bone-to-implant contact of implants with primary
stability was 38.8%, 52.9%, 64.6% and 81.3% of the implant length at 1, 3, 6 and 9 months,
respectively. Of the bone adjacent to the implant surface, 28.1%, 28.9%, 52.6% and 69.6%,
respectively, consisted of mineralized bone. At the test implants, no bone-to-implant
contact was observed at any observation time or in any of these non-stabilized specimens.
Conclusion: The findings of the present study indicate that primary implant stability is a
prerequisite for successful osseointegration, and that implant instability results in fibrous
encapsulation, thus confirming previously made clinical observations.

Date:
Accepted 15 April 2005
To cite this article:
Lioubavina-Hack N, Lang NP, Karring T. Significance
of primary stability for osseointegration of dental
implants.
Clin. Oral Impl. Res. 17, 2006; 244250.
doi: 10.1111/j.1600-0501.2005.01201.x

Copyright r Blackwell Munksgaard 2006

244

A sufficient quantity of bone is required for

the installation of oral implants and their
successful long-term prognosis (Adell et al.
1990; Nyman & Lang 1994). However,
severe resorption of the alveolar ridge in
vertical and/or horizontal dimensions after
tooth loss often occurs, thus jeopardizing
the subsequent placement of oral implants.

The biological principle of guided tissue

regeneration (GTR) (Karring et al. 1993)
has been used successfully in several studies in experimental animals and in humans for alveolar ridge augmentation
(Seibert & Nyman 1990; Buser et al.
1991; Cortellini et al. 1993; Lang et al.
1994b; Donos et al. 2002), and for the

Lioubavina-Hack et al . Primary implant stability and osseointegration

treatment of bone defects associated with

implants (Dahlin et al. 1989, 1991; Becker
& Becker 1990; Nyman et al. 1990; Jovanovic et al. 1992; Lehmann et al. 1992;
Andersson et al. 1993; Lang et al. 1994a;
Hurzeler et al. 1995). It has also been
demonstrated that the formation of considerable amounts of new bone beyond the
skeletal envelope can be attained predictably in experimental animals and in humans
by applying the GTR principle (Kostopoulos et al. 1994; Schmid et al. 1994; Lundgren et al. 1995; Hammerle et al. 1996;
Lioubavina et al. 1999). It was shown
that such newly generated bone formed
by the GTR principle on the rabbit calvaria
has the potential to osseointegrate a titanium implant placed on the bone surface,
although the amount of osseointegration
varied widely from one specimen to the
other (Schmid et al. 1991).
Several factors such as the primary stability of the implant, the morphology of the
bony bed, control of infection and an adequate healing period without loading are
critical for the long-term success of dental
implants (for a review, see Lang & Nyman
1994). Lack of primary implant stability, as
well as mechanical and physical stress of
osseointegrated implants resulted in loss of
osseointegration, leading to implant failures (Adell et al. 1986; Sanz et al. 1991;
Quirynen et al. 1992; Becker et al. 1994;
Isidor 1996, 1997). However, the influence
of primary implant instability on the establishment of osseointegration during bone
augmentation by GTR has not yet been
investigated histologically. Therefore, the
purpose of the present study was to examine histologically the significance of the
primary stability of titanium dental implants for the establishment of osseointegration, using an experimental capsule
model for bone augmentation.

muscle-periosteal flap was elevated from

the mandibular ramus with a periosteal
elevator leaving the bone denuded. Small
perforations in the ramus were produced by
means of a round bur. A rigid, non-porous
s
hemispherical Teflon capsule with an
internal diameter of 6 mm, a height of
4 mm and a peripheral collar was fixed to
the ramus with 4 mini-screws (Leibinger
GmbH, Freiburg, Germany). Prior to fixation, a hole was prepared in the mid-portion of the capsule to fit the circumference
s
of an ITI HC (Institute Straumann, Basel,
Switzerland) titanium implant with a diameter of 2.8 mm and a length of 4 mm. On
one side of the jaw, chosen at random, the
(test) implant was placed through the hole
in such a way that its apex did not make
contact with the mandibular ramus. This
placement of the implant did not ensure
primary stability, and the implant could be
moved by small forces.
On the other side of the jaw, a similar
(control) implant was placed in the hole of
the capsule in such a way that contact was
made between the implant and the surface
of the ramus (Fig. 1). This provided primary
stability of the control implant. After placement of the implants, the soft tissues
were repositioned over the capsules and
sutured with 4.0 Vicryl sutures (Ethicon
Inc. 2000, Norderstedt, Germany). At the
end of the surgical session, the anesthesia
s
was terminated by injection of Revivon
(Pherrovet, Malmo, Sweden).
After 1, 3, 6 and 9 months, four animals
were killed, and the mandibles were dissected free. They were fixed in 10%
neutral-buffered formalin, dehydrated in
alcohol and subsequently embedded in

Stable implant

methylmethacrylate. Undecalcified sections were cut through the capsule and

the inserted implant perpendicular to the
lateral surface of the mandibular ramus.
When the mid-portion of the implant was
reached, the blocks were rotated 901, and
several sections of the implant were obtained in a plane that was perpendicular to
the first cutting plane. In total, four sections per block with a thickness of 100
125 mm representing the mid-portion of the
implants in the two perpendicular planes
were stained with toluidine blue and subjected to histometric analysis.

Histometric analysis

In the prepared sections, the following

parameters were assessed:
(1)

(2)

(3)

(4)

The implant height (IH), i.e., the

length of the implant surface available
for osseointegration, defined as the
distance from the contact of the implant with the inner surface of the
capsule to the apex of the implant.
The height of the peri-implant bone
(PIB) was recorded from the apex of the
implant to the most coronal level of
new bone formed in the capsule. This
was expressed as a percentage of IH.
The extent of direct boneimplant
contact (osseointegration)(OB) was recorded from the apex of the implant
and again, was expressed as a percentage of IH.
The amount of mineralized bone in
contact with the implant (MOB) was
recorded as the length of mineralized
bone-to-implant contact. This also
was expressed as a percentage of IH.

Non-stable implant

Material and methods

Sixteen, 6-month-old male albino rats of
the Wistar strain were used in the study.
During operative procedures, the animals
were anesthetized with a subcutaneous ins
jection of Immobilon (Pherrovet, Malmo,
Sweden). In each rat, percutaneous incisions were made at both sides of the mandible, 5 mm coronal to its inferior border.
The masseter muscle was exposed, and a

Fig. 1. Schematic drawing illustrating the site with a primary stable (control) implant (left) and the site with a
(test) implant without primary stability (right).

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Lioubavina-Hack et al . Primary implant stability and osseointegration

Results
One animal assigned to the group with a
1-month healing period developed an abscess in the operated area 2 weeks postsurgically. This animal was excluded from
evaluation.

New bone formation at stable implants

100

% of implant hight

The histometric assessments were performed in an Olympus microscope (Olympus Denmark AS, Ballerup, Denmark)
with a vertical grid with a minimal scale
of 0.2 mm. The mean
SD values of each
parameter were calculated for each implant, and then, for each healing period.
Because of the small number of animals
assigned to each group, a statistical analysis
was not performed.

90

MOB

80

OB

70

PIB

60
50
40
30
20
10
0
1

3
6
Months of healing

Fig. 2. Diagram showing the height of peri-implant bone (PIB), the height of bone in contact (OB), and the
amount of mineralized bone in contact (MOB) with the primary stable implant after 1, 3, 6 and 9 months, and
expressed in percentage of the total implant length.

Primary stable implants (controls)

The results of the histometric analysis

showed that the IH available for osseointegration was similar for all control implants,
with a mean of 3.2
0.1 mm.
One-month specimens

One of the 1-month capsules was displaced

and contained mainly connective- and
muscle tissue and limited amounts of
newly formed bone. This specimen was
excluded from further evaluation. Thus,
only two specimens were available for
histometric analysis in the 1-month observation group. The mean height of PIB was
44.3
8.3% (range 38.450.2%) of the IH
(Fig. 2). On average, 38
8.5% (range 32
44%) of the implant surface was in direct
contact with the newly mineralized bone
and the bone marrow (OB), while 28.1

2.3% (range 14.441.7%) was in direct
contact with the mineralized bone (MOB).
The new bone had the appearance of a
woven bone with irregular trabeculae and
large marrow spaces (Fig. 3). Bone trabeculae with osteoid seams were present around
blood vessels. The area adjacent to the
capsule sealing appeared empty. The upper
parts of the implant surface and the surface
of the newly formed bone were lined by
highly vascularized, loose connective tissue in continuation with the bone marrow.
Three-month specimens

The height of PIB was 74.6
10.6%

(range 6182.1%). The mean extent of osseointegration (OB) was 52.9
26.4% (range

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Clin. Oral Impl. Res. 17, 2006 / 244250

Fig. 3. Microphotograph of a 1-month primary stable implant. Peri-implant newly formed bone (NB) in
contact with the implant surface (OB). The new bone contains marrow spaces (MS) with fat cells. Loose
connective tissue (CT) on top of the new bone. Direct bone-to-implant contact also seen inside the hollow
cylinder (arrows). r, mandibular ramus. Toluidine blue, original magnification  6.5.

22.467.6%), and on average, 28.9

10.9% (16.435.7%) of the implant surface
was in direct contact with mineralized
bone (MOB) (Fig. 2). Most of the capsules
presented substantial amounts of newly
formed bone covered by a periosteum-like
connective tissue (Fig. 4). The lower portions of the newly formed bone had the
appearance of lamellar bone, while the top
layer was woven bone. Osteoid seams and
resorption lacunae were often observed on
trabeculae adjacent to the bone marrow,
which contained fat cells. Osseointegration
was also observed inside the hollow cylinders of all implants.

Six-month specimens

The height of PIB was 88.2
2.3% (range

85.791.1%). The mean extent of osseointegration (OB) was 64.6
18.1% (range
45.987%), and the length of mineralized
bone in contact (MOB) averaged 52.6

17.6% (range 30.370%) of the implant
length (Fig. 2). All capsules contained a
considerable amount of new trabecular
bone (Fig. 5). The portions of the newly
formed bone facing the capsule surface
were less organized and contained larger
marrow spaces than the portions near the
implants. The bone near the implants had
thicker and more mineralized packets of

Lioubavina-Hack et al . Primary implant stability and osseointegration

Fig. 5. Microphotograph of a 6-month primary stable implant. New bone (NB) almost filling the capsule (C) and
in direct contact with the implant surface (arrows). The marrow spaces (MS) adjacent to the implant are smaller
than those in the periphery of the capsule. r, mandibular ramus. Toluidine blue, original magnification  12.5.

Fig. 4. Microphotograph of a 3-month primary stable

implant. Peri-implant newly formed bone (NB) in
contact with the implant surface (OB). Marrow
spaces (MS) with fat cells. Loose conective tissue
(CT) on top of the new bone. r, ramus of the mandible. Toluidine blue, original magnification  6.5.

lamellar bone, and the marrow spaces containing fat cells were smaller than formed
adjacent to the capsule. In some parts, the
trabeculae were lined by an osteoid seam,
while resorption lacunae were seen in other
parts. A thin layer of loose connective
tissue was interposed between the capsule
sealing and the new bone.

Nine-month specimens

One implant was obviously displaced and

had totally lost contact with the mandibular ramus. This implant was excluded from
the analysis. Thus, three primary stable
implants were available for histometric
analysis. The mean height of PIB was
94.1
5.7% (range 88.6100%), the
mean extent of osseointegration (OB) was
81.3
23.2% (range 54.696.1%), and
the mean length of mineralized bone in
contact with the implant (MOB) was
69.6
28.5% (range 36.887.1%) of the
implant length (Fig. 2). The new lamellar
bone adjacent to the implant was predominantly in contact with its surface. A thin
layer of connective tissue was interposed
between the sealing of the capsule and the
newly formed bone (Fig. 6). The osteoid
seams and the resorption lacunae on the

Fig. 6. Microphotograph of a 9-month primary stable implant. Capsule completely filled with new bone. Implant
almost entirely osseointegrated (arrows). r, mandibular ramus. Toluidine blue, original magnification  8.

bone trabeculae were less predominant

than at 6 months.
Non-stable implants (test)

Histological analysis did not reveal any

osseointegration at any observation time
of the 11 implants without primary stability. Therefore, these specimens were subjected only to a descriptive histological
analysis.
The amount of newly formed PIB in the
capsules with the instable implants increased gradually from one to 9 months.
The total height of the new bone was
similar to that observed in the contralateral
capsules containing stable implants at the
corresponding observation times. However, despite the presence of newly formed
bone near the implant surface, a layer of
connective tissue was always interposed

between the implant and the new bone

(Fig. 7). The new bone formed inside the
capsule contained thin mineralized lamellae and large marrow spaces. A larger
amount of connective tissue was found in
all specimens with unstable implants than
in sites with stable implants. The histologic appearance of this soft tissue varied
between the specimens. In some of them,
the connective tissue resembled nonmineralized bone or bone marrow and
was interposed between the new bone and
the implant surface. In other specimens,
the connective tissue had a more dense and
fibrous appearance (Fig. 8). In four specimens, such dense connective tissue had
apparently penetrated the capsule through
a gap that had developed between the
capsule sealing and the implant surface.
Surfaces of irregular shape characteristic

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Lioubavina-Hack et al . Primary implant stability and osseointegration

Fig. 7. Microphotograph of a 6-month specimen of a

primary instable implant. Although a substantial
amount of newly formed bone (NB) is seen adjacent
to the implant (I), osseointegration has not occurred.
A layer of loose and fibrous connective tissue (CT,
arrows) is interposed between the new bone and the
implant surface. r, mandibular ramus; C, capsule.
Toluidine blue, original magnification  12.5.

of resorption were frequently observed in

the layer of new bone facing this fibrous
tissue.

Discussion
In the present study, titanium implants
were placed in a secluded space created
for the formation of new bone, either in
contact with the bone surface of the mandibular ramus or not. While the former
were stable after installation (controls),
the latter could easily be moved (test),
even by applying small forces. It is likely
that muscle forces applied on the small
portion of the unstable implants sticking
out of the top of the capsule have consistently caused movement of the implants
during the healing periods.
All primary stable implants presented
increasing percentages of direct bone-toimplant contact during the experimental
period, reaching about 80% of the entire
implant length after 9 months. Primary
unstable implants, on the other hand,
failed to present osseointegration at any
observation time, despite the formation of
considerable amounts of new PIB inside the

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Clin. Oral Impl. Res. 17, 2006 / 244250

Fig. 8. Microphotograph of a 9-month primary instable implant (I). New bone with large marrow spaces
(MS) with fat cells occupying most of the capsule area. No osseointegration has occurred. A dense connective tissue (CT) is interposed between the new bone and the implant surface. It appears that
some connective tissue has invaded the capsule through the hole in the top. Toluidine blue, original
magnification  6.5.

capsules. This finding indicates that primary implant stability is a prerequisite for
obtaining osseointegration of titanium oral
implants. This histologic finding confirms
previous clinical observations (Jovanovic
et al. 1992; Lehmann et al. 1992; Lang et
al. 1994a; Hurzeler et al. 1995; Glauser et
al. 2001; Hammerle & Lang 2001).
The model used in the present study
allowed histological evaluation of osseointegration of the stable implants in newly
augmented bone. Like in the present study,
it was previously established that newly
formed bone proliferating from the calvaria
of rabbits may grow into direct contact
with a titanium implant, provided primary
stability was achieved (Schmid et al. 1991).
Furthermore, the fact found in the present
study that newly formed bone generated
beyond the skeletal envelope by the use of
the GTR principle may lead to osseointegration is supported by various experimental and clinical studies (Gotfredsen et al.
1991; Jovanovic et al. 1992; Kostopoulos &
Karring 1994). In addition, osseointegration of titanium implants has also been
demonstrated following GTR treatment of
large PIB defects (Dahlin et al. 1989; Buser
et al. 1991; Becker et al. 1994; Scipioni
et al. 1997).
In the present study, a gradual increase
from 28.1% to 69.6% in mineralized boneto-implant contact was observed from 1 to
9 months around the primary stable
implants. This increase occurred concomi-

tant with the maturation of the newly

formed bone that initially had the characteristics of woven bone, but later, presented
thickening of the trabeculae and a reduction in the number and size of marrow
spaces. Such a maturation process was
also described in a dog study in which the
bone was augmented around implants
(Becker et al. 1994; Cochran et al. 1998).
In the present study, the new bone adjacent to the implants was always more
mineralized and contained smaller marrow
spaces than that located in the periphery of
the capsule or the new bone formed around
the unstable implants. This observation
indicated that the establishment of a direct
bone-to-implant contact (osseointegration)
may have a favorable effect on the structure
of PIB.
In the specimens with primary unstable
implants that most likely were subjected to
movements during healing, a layer of connective tissue was always interposed between the implant and the newly formed
bone at all observation times. This finding
corroborates the results of a study on premature loading of implants with machined
surface where encapsulation with fibrous
tissue was consistently seen (Brunski
1988). This finding may be explained by
the observation of Yen & Rodan (1984) that
micro-motion of implants resulted in a
biologic response in the bone tissue surrounding the implants that is characterized
by fibroplasia.

Lioubavina-Hack et al . Primary implant stability and osseointegration

The finding that overloading of oral implants may result in complete loss of osseointegration and replacement of bony by
fibrous tissue has been documented previously (Sanz et al. 1991; Quirynen et al.
1992; Sagara et al. 1993; Becker et al. 1994;
Isidor 1996, 1997). In the present study,
osseointegration was prevented by not providing primary implant stability. It may be
assumed that immediate or early loading of
implants, especially in situations with very
loose trabecular bone, may also result in
primary unstability of the implants, thus
jeopardizing the establishment of a direct
bone-to-implant contact similar to the situation created by the present capsule
model. For instance, it has been reported
in a clinical study (Glauser et al. 2001) that
only 66% of implants placed in poorly
mineralized trabecular bone in the posterior maxilla were successfully integrated
after 1 year following immediate loading
in comparison with 91% successful implants placed in mineralized bone. Furthermore, in the same study, implants inserted
into patients with parafunctional habits
(bruxers) were lost more frequently than
those placed in patients with no parafunction (41% vs. 12%). This, again, confirmed that occlusal overloads during

healing should be considered as a hazard

for osseointegration.
In the present study, four out of 11
primary unstable implants had developed
a gap between the capsule sealing and the
implant during healing. It appeared that
this may have allowed connective tissue
from the surroundings to penetrate into the
capsule. The newly formed bone encounter
such penetrating connective tissue had an
irregular appearance, indicating resorption.
Thus, improper adaptation of barrier membranes around implants subjected to GTR
treatment also appears to jeopardize bone
regeneration and the establishment of osseointegration by the fact that undesirable
cells are allowed to migrate into the
wound area.
In conclusion, the results of the present
study indicate that primary implant stability is a prerequisite for successful osseointegration. Moreover, primary unstability of
implants will result in fibrous encapsulation of the implants.

Acknowledgement: This study was

supported by a grant from the ITI
Foundation for the Study of Oral
Implantology (ITI Center, Basel,
Switzerland).

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