Is Marginal Bone Loss around Oral Implants

the Result of a Provoked Foreign Body Reaction?

Tomas Albrektsson, MD, PhD, RCPSG;*,† Christer Dahlin, DDS, PhD;*,‡ Torsten Jemt, DDS, PhD;§,||
Lars Sennerby, DDS, PhD;¶ Alberto Turri, DDS, PhD cand;*,|| Ann Wennerberg, DDS, PhD†

ABSTRACT
Background: When a foreign body is placed in bone or soft tissue, an inflammatory reaction inevitably develops. Hence,
osseointegration is but a foreign body response to the implant, which according to classic pathology is a chronic inflam-
matory response and characterized by bone embedding/separation of the implant from the body.
Purpose: The aim of this paper is to suggest an alternative way of looking at the reason for marginal bone loss as a
complication to treatment rather than a disease process.
Materials and Methods: The present paper is authored as a narrative review contribution.
Results: The implant-enveloping bone has sparse blood circulation and is lacking proper innervation in clear contrast to
natural teeth that are anchored in bone by a periodontal ligament rich in blood vessels and nerves. Fortunately, a balanced,
steady state situation of the inevitable foreign body response will be established for the great majority of implants, seen as
maintained osseointegration with no or only very little marginal bone loss. Marginal bone resorption around the implant
is the result of different tissue reactions coupled to the foreign body response and is not primarily related to biofilm-
mediated infectious processes as in the pathogenesis of periodontitis around teeth. This means that initial marginal bone
resorption around implants represents a reaction to treatment and is not at all a disease process. There is clear evidence that
the initial foreign body response to the implant can be sustained and aggravated by various factors related to implant
hardware, patient characteristics, surgical and/or prosthodontic mishaps, which may lead to significant marginal bone loss
and possibly to implant failure. Admittedly, once severe marginal bone loss has developed, a secondary biofilm-mediated
infection may follow as a complication to the already established bone loss.
Conclusions: The present authors regard researchers seeing marginal bone loss as a periodontitis-like disease to be on the
wrong track; the onset of marginal bone loss around oral implants depends in reality on a dis-balanced foreign body
response.
KEY WORDS: bone loss, dental implants, foreign body reaction, osseointegration, peri-implantitis

INTRODUCTION
*Department of Biomaterials, Göteborg University, Göteborg,
Osseointegration was discovered when working with
Sweden; †Department of Prosthodontics, Malmö University, Malmö,
Sweden; ‡Department of Oral& Maxillofacial Surgery, NU Hospital implants in research animals1 at the very same labo-
Group, Trollhättan, Sweden; §Department of Prosthetic Dentistry/ ratory of the Göteborg University where the senior
Dental Material Science, University of Göteborg, Göteborg, Sweden;
|| authors behind this publication were once trained. The
The Brånemark Clinic, Public Dental Health Service, Göteborg,
Sweden; ¶Department of Oral and Maxillofacial Surgery, Göteborg discovery was made around 1962, and it has meant an
University, Göteborg, Sweden enormous advancement for clinical treatment of oral
Reprint requests: Professor Tomas Albrektsson, Department of implants. The advent of osseointegration represented
Biomaterials, Sahlgrenska Academy, PO Box 412, Göteborg SE 405 30, a true clinical breakthrough; for the first time ever, reli-
Sweden; e-mail: [email protected]
able long-term clinical results of oral implants were
© 2013 Wiley Periodicals, Inc. reported.1–3 As a reflection of the substantial contribu-
DOI 10.1111/cid.12142 tion to clinical development we have seen with oral

1
2 Clinical Implant Dentistry and Related Research, Volume *, Number *, 2013

Figure 1 Events occurring when an oral implant is placed in the jaw bone. A foreign body reaction is inevitable; good clinical results
follow the establishment of a foreign body equilibrium. However, the equilibrium may be disturbed by unsuitable implants, improper
clinical handling, various adverse patient factors, remnants of cement or new loading situations which, acting together, may result in
marginal bone loss around the implant. A reestablishment of the foreign body equilibrium is possible, but if this does not occur,
implants will lose gradually more bone and may eventually fail.

implants, thousands and thousands again of patients maintain the foreign body equilibrium represented by
have benefitted from osseointegration. Although no reli- osseointegration.
able documentation exists, it has been estimated that When an oral implant is to be placed in bone
approximately 12 million osseointegrated oral implants (Figure 1), the sequence starts by preparing the defect.
are placed annually in a global perspective. In the light Surgical preparation results in breakage of blood vessels,
of this tremendous clinical success, the dissection destruction of bone tissue with a necrotic border zone
of osseointegration under a critical histopathological inevitably developing,4 and an acute inflammatory
analysis is indeed a delicate task. response following. The latter is an important step in the
Our aim is (1) to describe histopathological and healing cascade leading to the preferred bony anchorage
clinical events when an implant is placed in the man- of the implant. Thereafter, two possible events follow the
dible or maxilla of patients, (2) to discuss different sug- placement of the implant: Either a foreign body
gested mechanisms behind marginal bone loss around response develops, characterized by a chronic inflamma-
oral implants, (3) to perform a resumé of previous tory response with the implant shielded off from the rest
research efforts on implants and foreign body responses of the organism by an enveloping bone tissue layer that
to them, (4) to critically analyze whether threats to gradually condenses,5 or, for reasons not fully known,
osseointegration such as the initiation of marginal bone the foreign body response results in the implant being
loss is a mirror image of what happens to teeth, and embedded (encapsulated) in soft tissues, thereby repre-
(5) to summarize how we, from a clinical aspect, best senting a primary clinical failure. The latter problem is
 Osseointegration as a Foreign Body Reaction 3

A B C

Figure 2 The foreign body response around any oral implant may be noticeable in radiograms of successful implants. In A, the
implant is seen immediately after placement. In B, we see the same implant at 2 years after placement with a clear condensation
around it. C depicts the same implant at 8 years with a condensed bone layer found in many foreign body situations.

rare with modern implants placed by trained clinicians example, if nearby teeth have failed. This late dis-balance
but was a more common problem in the infancy of may lead to marginal bone loss and micromovements as
osseointegration.1 The following events may likewise well as an increasing inflammatory response in the same
follow two possible routes: the foreign body equilibrium manner as seen with the early dis-balance. However, a
with a mild chronic inflammation (that we call osseoin- dis-balance, whether early or late, need not result in
tegration) or a resulting early dis-balance where bone clinical failure; for example, in the case of removed
resorption dominates over bone formation and where cement particles in soft tissues another foreign body
the inevitable chronic inflammatory state is activated. In equilibrium may result, if with some bone resorption
contrast, the foreign body equilibrium is characterized around the implant. Infection is a late response to
by a steady state situation in the bone and only a mild already dis-balanced implants. It cannot at all be com-
chronic inflammation. By time, the bone encapsulated pared to the infection seen around teeth that we term
implant will be covered by an increasingly thicker bone periodontitis. The question in the implant case is
layer, especially observed at the crestal part of the whether infection really has any true implications for the
implant6 (Figure 2) Similar encapsulation of foreign fate of the implant. In contrast, in the good clinical case,
bodies may be observed in primitive animals such as the osseointegration remains undisturbed, that is, a contin-
pearl oyster or fruit fly.7 There is evidence from the ued balance in form of foreign body equilibrium, which
literature that the unwanted dis-balance is triggered by has been documented over 20 years or more in oral
using nonoptimal implant designs, traumatic clinical implantology.10
handling, and by placing implants in anatomically
and/or medically compromised sites of patients,8 with Alternative Mechanisms behind
other words it represents a clinical complication not a Marginal Bone Resorption
disease process. Furthermore, systemic, general health The authors of the present paper see marginal bone loss
aspects have been associated with this unfavorable around oral implants as a consequence of an aggravated
response in the peri-implant bone.9 In the case of a foreign body response inevitable when placing foreign
continued foreign body response equilibrium, all is fine materials in bone. It is, in fact, impossible to understand
from a clinical standpoint, whereas the dis-balance situ- original reasons for marginal bone loss without realizing
ation results in marginal bone loss with time, possibly the histopathological background: the role of the type
leading to micromovements of the implant.8 Lamenta- of foreign body reaction that we term osseointegration.
bly, there are cases where a late dis-balance occurs, for Foreign body reactions are commonly described to a
example, genetic disposition, because of developing sys- number of different types of implants placed in the body
temic disease of the patient to remnants of cement par- but have, for one reason or the other, been so far more or
ticles in the soft tissues or to a new loading situation, for less ignored in the dental implant literature with the
4 Clinical Implant Dentistry and Related Research, Volume *, Number *, 2013

exception of some pioneering papers by the late German summarize. The first investigators incriminating foreign
pathologist Karl Donath.5,11 body reactions as important cofactors in the response
Marginal bone loss around oral implants has to a bacterial expositions were Elek and Conen.22 These
been reported in most clinical follow-up studies. In the authors infected sutures (foreign bodies) with cocci
majority of cases, marginal bone loss is a process most bacteria in human volunteers and reported a dramatic
pronounced during the first year after placement, prob- reduction of the minimum inoculum required to
ably as an adaptive response to healing and loading that produce pus compared to the situation where the
will not threaten implant anchorage and is not neces- stitches were immediately removed from the tissues.
sarily of predictive values for later changes of the bone They reported “orange size” infectious tumors and high
level.12 However, in other cases, more rapid bone loss fever reactions in patients with the sutures but also an
may develop that represents a hazard for long-term understandable difficulty to recruit new volunteering
survival of the implant. For many clinicians, bone patients to further test foreign body reactions. Their
resorption is seen as more or less synonymous to a work inspired animal studies reporting minor or no
biofilm-mediated infectious disease peri-implantitis.13 problems when mice were injected subcutaneously with
We believe this is misconceived – there is, in fact, no staphylococci in contrast to a demonstrated bacterial
proper evidence that progressing bone resorption gen- multiplication at the suture sites.23,24
erally is initiated by any form of an infectious disease With respect to foreign body reactions to implants,
25
process. This was also the notion when peri-implantitis Bos analyzed failed hip joints finding evidence of such
(originally coined by Levignac14 and Mombelli et al.15) reactions, and Thiele and colleagues26 described foreign
became an accepted term at the first European Work- body reaction to resorbable polylactide screws used for
shop on Periodontology in 1993.16 The term peri- fixation purposes. In oral implantology, the potential
implantitis was then agreed upon as a general name for problem of foreign body reactions has been largely
destructive peri-implant inflammatory processes. In line overlooked. Anderson and Rodriguez27 have summa-
with this, we see late significant bone loss as an unfavor- rized foreign body reactions to biomaterials in a recent
able change of the clinical balance between the foreign overview. The immune complement is dependent on
body response and external impact/or internal host a protein reaction that is the first part of the immune
response factors.17 Having said this, if a purulent infec- system that recognizes foreign bodies entering the
tion is present, microorganisms may be involved but not body.28 The injury inevitable when drilling in bone
necessarily the cause for marginal bone resorption, as elicits an inflammatory cell infiltration that further
also pointed out by Mombelli and Décaillet.18 We are not results in monocyte adhesion and macrophage differen-
alone in this critical attitude toward peri-implantitis as a tiation followed by macrophage fusion into foreign
primarily infectious disease. Koka and Zarb19 suggested body giant cell formation.27 Foreign body giant cells are
that when implants lose their marginal bone support, routinely seen at oral implant interfaces11 (Figure 3).
the term osseoseparation should be used to separate Complement activation is likely to amplify the inflam-
marginal bone loss from any particular disease process. matory reaction. Adherent macrophages and foreign
We concur with these authors about the lack of evi- body giant cells are known to lead to degradation of
dence behind any development of a disease as the start- biomaterials with subsequent implant failure. Adherent
ing point of marginal bone loss, as do Becker20 and macrophages on biomaterials may become activated
Chvartszaid and Koka21 who neither see any convinc- in an attempt to phagocytose the implant, so-called
ing evidence pointing to specific bacteria starting the frustrated phagocytosis. It is possible that the clinical
process of marginal bone resorption. events may be influenced by materials’ surface proper-
ties such as chemistry and topography;27 furthermore,
On Foreign Body Responses to Implants nanotopography has been found to attenuate immune
Pioneering research efforts on possible side effects of the complement activation.28
foreign body response have involved deliberate injec- In oral implantology, it seems essential to identify
tions of bacteria in sites with or without the presence of host-related as well as external risk factors for the later
a foreign body. The research may be far away from the development of marginal bone loss that may jeopardize
world of oral implants but is nevertheless important to future ossseointegration of the implant. Certainly, once
 Osseointegration as a Foreign Body Reaction 5

dysfunction due to hereditary problems or smoking,

and clinical shortcomings in form of poor surgery and
poor prosthodontics or occlusal overload.3,8,31–34 Typical
to problems related to these factors is that the summed
effect of them is more negative than would be assumed
if one analyzed each one of them separately – a sum-
mation effect.35–38 These problems can be exemplified
by experience from a recently used oral implant system
where clinical recommendations in form of grinding
down the implant in situ and then loading it directly
were not in accordance with above-suggested biological
recommendations.39

What Is an Appropriate Term for Foreign Body

Figure 3 Foreign body giant cells are routinely found in the Reactions Leading to Marginal Bone Loss?
interface of oral implants.
“A day of reckoning for so called ‘peri-implantitis’ is
well overdue, and it is time to expunge the term from
peri-implantitis with or without infection has been routine use.”40 We concur with these authors if peri-
manifested, research must be directed how to, if pos- implantitis is regarded synonymous to a disease process.
sible, treat the condition. However, this is not a simple However, one characteristic of the foreign body reac-
endeavor, and the treatment of choice may be critically tion is that it results in a chronic inflammation. With
discussed.29,30 long-term successful implants, this chronic inflamma-
When an oral implant is placed, chemistry, physi- tion would be of a very minor magnitude and hardly
cal state, and electrochemical potential of the material noticeable in the clinic. However, when marginal
determine the severity of the chronic inflammatory bone resorption has developed around an implant, the
response.11 Even a relatively stable material such as inflammation may be more noticeable and may eventu-
commercially pure titanium elicits a foreign body ally be further compromised by plaque accumulation
response in the tissues, exemplified by what we call and infection. A Google search on the suffix “-itis”
osseointegration. It is true that osseointegration has informs that the ending is used “in pathological terms
been a positive contribution because so stabilized that denote inflammation.” Because an inflammatory
implants may remain in the body over long periods of response is characteristic of any oral implant as part
time and, for example, serve as anchorage elements for a of a foreign body response that is further activated
dental prosthesis, which in no way is in opposition to in case of tissue dis-balance, we believe that the term
that the basic body reaction is one of a foreign body peri-implantitis is quite appropriate, even if it is not a
type. The implanted object is in a delicate balance to primary disease at all. In fact, the tissue sequel is a com-
avoid rapid or late rejection; what will decide the plication because of a clinically unfavorable dis-balanced
outcome is dependent on the summed reactions to it.3,31 foreign body reaction that is the starting point of the
More than 30 years ago, it was found imperative to pathological process, nothing else.
more or less simultaneously control six different factors To further elaborate on the inflammatory aspect,
for proper osseointegration.3 These factors were (1) another dogma that needs to be addressed is the pres-
the biocompatibility, (2) the design and (3) the sur- ence of suppuration or pus adjacent to implants. This
face of the implant, (4) the status of the host bed, (5) has been taken as direct evidence of an ongoing infec-
the surgical and (6) the loading conditions. In fact, tious process adjacent to the respective implants, and
there is evidence8 that marginal bone resorption may subsequent active anti-infectious clinical measures have
follow disturbance of these factors including material been proposed. However, if you look more closely at the
shortcomings (“nonbiocompatible materials”), implant definition of suppuration from an immunologic stand-
design errors resulting in high levels of marginal bone point and as part of the complement activation, it is
resorption, too rough or too smooth surfaces, patient by definition of pus: “A fluid product of inflammation
6 Clinical Implant Dentistry and Related Research, Volume *, Number *, 2013

consisting of a liquid containing leucocytes and the the soft tissue margin. Bacterial leakage from the inter-
debris of dead cells and tissue elements liquefied by face between the implant body and the abutment has
the proteolytic and histolytic enzymes (leukoprotease) been another incriminated source for infectious devel-
that are elaborated by polymorphonuclear leucocytes.”41 opments (for review see Qian et al.8).
Hence, suppuration is part of an unspecific inflamma- The notion that biofilm-mediated infection is the
tory reaction toward foreign bodies where bacteria are cause for marginal bone loss at implants derives from
only one of several possible causes for the immunologic extrapolations of findings from experimental and clini-
complement activation. cal studies on implants and teeth. For instance, it has
been demonstrated that the presence of a biofilm on
Mixing of Two Conceptually Different Entities implant components at the soft tissue margin induces
– Tooth versus Foreign Body Response an inflammation and that this inflammation can be
Peri-implantitis as a disease entity builds on several pos- reduced by removing the biofilm.42 Histology from dog
tulates. One such postulate is that the implant and tooth studies has demonstrated a similar size and composition
are similar entities and hence, the pathogenesis of peri- of the inflammatory infiltrate as a response to a biofilm
implantitis is identical to that of periodontitis. Another formation at teeth and implants after 3 weeks.43
postulate claims a situation free from inflammation at Accordingly, the postulate of a similarity between
the implant in analogy with what can be expected at implants and teeth seems a far-fetched one from a bio-
natural teeth, a situation that can be questioned in the logical perspective (Figure 4.). The successful implant
light of the chronic foreign body inflammation that is has an interface of bone tissue, with only minor vas-
inevitable around oral implants. Furthermore, claims cularization and almost total lack of innervation in
are related to the origin of the involved microorganisms contrast to the tooth with an abundant vascularization
to be either an infection from the time of implant place- and innervation of the periodontal ligament. Donath5
ment or a biofilm-mediated infection originating from pointed out that the bone tissues around an implant

Figure 4 The tooth is anchored in a periodontal ligament characterized by rich innervation and blood perfusion. This is in sharp
contrast to the implant that is anchored in foreign body bone with very sparse innervation and blood flow.
 Osseointegration as a Foreign Body Reaction 7

are devoid of an independent blood circulation in con- into a healthy organism. This is also in line with
trast to the gingiva of the tooth with a subepithelial and Mombelli and Décaillet18 who concluded that microor-
dentogingival plexus. Possibly, blood vessels are formed ganisms may be present but not necessarily the cause of
at the outer border of the bone capsule by time. Further- peri-implantitis. Recent associations between systemic
more, the implant is stable (ankylotic), whereas the factors and bone loss open up for alternative factors that
tooth is mobile. The dentogingival complex with its may disrupt the favorable biological balance.9
specialized tissues is the result of evolution, whereas Another interesting observation follows inspection
the implant is constructed by outside technology. “Clini- of tissue breakdown because of the alleged disease
cally there is a difference in the tissue reaction to the peri-implantitis where commonly, but not always, even
pathogenic flora. The gingiva of a natural tooth shows craters seem to have formed in the bird’s eye view
all the signs of inflammation with a raised secular fluid (Figure 5). A pure disease would in all probability result
rate, while this is not the case in the mucosa around in a much more uneven anatomy of the defect. What
an implant . . . where the sulcular fluid rate is not we see instead is an even bone resorption present-
elevated.”5 ing defined distances between the bone rims and the
We concur with Chvartszaid and colleagues31 that implant margins, indicative of a combined problem that
similar tissue reactions to the greatly different interfacial may involve not only inflammation/infection but also a
situations around an implant and a tooth seem most foreign body response that acts in combination with
unlikely. Not very surprisingly, the anatomical image of these other mechanisms defining the final distance from
bone resorption due to periodontitis or peri-implantitis the implant that is affected by the bone resorption; that
differs from one another, in many situations with very is, what is resorbed may be predominantly, if not exclu-
wide bone craters being typical for the implant but sively, the foreign body bone, whereas resorption of the
not for the tooth. When long-term, follow-up implant properly vascularized host bone is potentially lacking.
systems have been analyzed with respect to subgingival The disease explanation is furthermore most
microbiota and compared to the outcome with the unlikely in view of numerous clinical situations docu-
natural dentition, it was concluded in one study that mented with subsequent marginal bone loss (for review
subgingival plaque samples from implants did not see Qian et al.8). It seems difficult, if not impossible, to
reach the concentration of pathogens, even after 12 years couple such clinically observed marginal bone loss to a
of function. Furthermore, bone levels were stable with disease. This is exemplified by the correlation between
minimal bone resorption, and the presence of perio- individual clinicians and higher failure rates as well as
pathogens did not necessarily result in bone loss.44 A
very interesting observation that strongly supports the
hypothesis that marginal bone loss around implants
could be linked more to a foreign body reaction and not
having an infectious origin was recently described by
Becker and colleagues45 who compared transcriptome
profiling using mRNA from patients suffering from
either peri-implantitis or periodontitis. A gene ontology
analysis revealed various pathways. In peri-implantitis
tissues, the regulation of transcripts related primarily to
innate immune responses and defense responses while
in periodontitis bacterial response systems prevailed.
“When peri-implant tissue destruction occurs, little
is known about the initiating process,” one academic
periodontist wrote recently.46 Koch’s postulate47,48 with
Figure 5 In many clinical cases of peri-implantitis with
the suggested revision by Fredericks and Relman49 has advanced bone resorption, we have observed that even bone
not been demonstrated applicable to oral implants; the craters may form if inspected in the bird’s eye view. It is
possible that the even borders appear when the anchoring
microorganism allegedly involved in peri-implantitis foreign body bone has been resorbed, whereas adjacent richly
has not been found causing disease when introduced vascularized bone is more resistant to resorption.
8 Clinical Implant Dentistry and Related Research, Volume *, Number *, 2013

higher levels of marginal bone resorption compared respectively 2.65% maxillary and 1.53% mandibular
to their peers, despite them using the same implant failures between 2003 to 2010. This considerable drop
system.32,33 A particular approach, to use ligatures in maxillary failure rates coincided with the transi-
to elicit bone resorption and infection,50 is another tion from “machined” to TiUnite surfaces. The list of
example of a foreign body response, or rather two compromising factors where improved early results
foreign body responses. Here, we have the initial foreign have been seen to modern, moderately rough surfaces
body response to the implant, then another foreign includes patient smoking, the use of short implants,
body in form of the ligature that is added to the previous irradiation, or bone grafting (for review see
implants, and it is not at all surprising that such a Qian et al.8).
combined provocation will result in adverse tissue reac- We realize that improved surgical skills may posi-
tions in the form of marginal bone loss. With time, the tively influence clinical results in comparisons between
inflammatory response worsens and a suprainfection previously and more recently published papers, even if
may occur in what may be described as secondary we regard the improved early success rates with max-
peri-implantitis.8 illary implants as described by Olsson and collegues52
to point to a clear positive contribution from the new
How to Best Maintain a Foreign surfaces; improvements were too rapid to be explained
Body Equilibrium in any other way. We further realize that many other
In fact, most clinical efforts have been directed to main- factors than those discussed in the present Review may
taining osseointegration; that is, succeeding with having influence implant survival/failure including over
an undisturbed, if with signs of mild chronical inflam- instrumentation and high occlusal loads to mention
mation, foreign body equilibrium. From a strict clinical but a few.
results point of view, we have gradually improved clini- However, to decide “the best” surface, we cannot
cal outcome of implants compared to the pioneering necessarily use figures on levels of marginal bone
days of osseointegration.1,51 This clinical improvement is contact to different surfaces because we do not know the
due to a combination of improved clinical handling and, ideal such percentage of bone to implant contact. A
possibly, to new improved implant types. Having said stronger initial bone response need not be coupled to
this, modern simplifications in the form of possibilities improved long-term clinical outcome, instead it may
for a direct loading of implants represent a simultane- indicate a stronger foreign body reaction compared with
ously increased clinical risk because the foreign body that found to other implants, and the only way to find
equilibrium may be disturbed during this early phase of out whether this reaction is positive or negative would
function. This risk may be substantial if patients with seem to be scrutiny of long-term clinical data.
poor bone beds are treated by poorly trained clinicians,
an example of combined effects that may disturb Concluding Remarks
osseointegration.8 The osseointegrated interface remains in a very delicate
From the perspective of increasing early implant balance where adverse individual tissue reactions
success rates, the response is simple: moderately rough may combine with the foreign body reaction to cause
surfaces outperform minimally rough ones (such as unwanted sequel in form of marginal bone loss or
turned [“machined”] Branemark implants) and rough implant failure. The locus resistentiae minoris created by
implants (such as old plasma sprayed ones). Jimbo and the foreign body reaction53–55 has resulted in a series of
Albrektsson51 compared five-year clinical outcomes for events potentially leading to implant failure.
machined and moderately rough implants with a signifi- This reasoning implies the necessity of clinical
cantly enhanced failure rate for maxillary implants of control of the implant situation. Learned and skillful
the former. Olsson and colleagues52 analyzed the early clinicians would simply have better a clinical outcome
failure rate of implants placed at the Branemark clinic than their counterparts because they will minimize
between 1986 and 2010. A total of 35.444 implants were setting off a cascade of triggering factors that may
inserted with a mean incidence of early first implant combine with the foreign body reactions to cause
failure between 1986 and 2002 being 8.95% in the implant problems. The fact that the clinical problem of
maxilla and 1.84% in the mandible compared with marginal bone resorption is related to by whom and how
 Osseointegration as a Foreign Body Reaction 9

the implant is placed makes attempted consensus state- 3. Albrektsson T, Brånemark PI, Hansson HA, Lindström J.
ments such as assuming the frequency of peri-implantitis Osseointegrated titanium implants requirements for ensur-
to be 20% of all treated patients meaningless.56 ing a long-lasting, direct bone anchorage in man. Acta
Orthop Scand 1981; 52:155–170.
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the basic mechanism behind marginal bone loss 5. Donath K. Pathogenesis of bony pocket formation around
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lesions. 6. Strid KG. Radiographic results. In: Brånemark PI, Zarb G,
ALbrektsson T, eds. Tissue integrated prostheses. Chicago,
(2) The initial reaction to an oral implant is of a
IL: Quintessence Co, 1985:187–198.
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an example. melanogaster. Annu Rev Immunol 2007; 25:697–743.
(3) The foreign body reaction inevitable when plac- 8. Qian J, Wennerberg A, Albrektsson T. Reasons for marginal
ing an oral implant may combine with various bone loss around oral implants. Clin Implant Dent Relat Res
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failure. means of osseointegrated implants: a 5-year follow up study
on one- or two- stage surgery, number of implants, implant
(4) The foreign body reaction presents with a locus
surfaces and age at surgery. Clin Implant Dent Relat Res
resistentiae minoris characterized by an increased
2013. Accepted for publication.
vulnerability for the osseointegrated implant. 10. Ekelund JA, Lindquist LW, Carlsson GE, Jemt T. Implant
(5) Secondarily, a worsened inflammatory response or treatment in the edentulous mandible: a prospective study
even infection may develop as a complication, on Brånemark system implants over more than 20 years. Int
further threatening the implant longevity. J Prosthodont 2003; 16:602–608.
(6) The use of controlled implants and skillful 11. Donath K, Laass M, Günzl HJ. The histopathology of differ-
clinicians result in very good, long-term results ent foreign body reactions in oral soft tissue and bone tissue.
Virchows Arch A Pathol Anat Histopathol 1991; 420:131–
of osseointegrated oral implants with a due, long-
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12. Pikner SS, Gröndahl K. Radiographic analyses of “advanced”
(7) Patient factors such a hereditary disease, con- marginal bone loss around Brånemark dental implants. Clin
sumption of certain drugs, or smoking habits may Implant Dent Relat Res 2011; 11:120–133.
represent a threat to increased marginal bone loss 13. Rosen P, Clem D, Cochran D, et al. Peri-implant mucositis
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ACKNOWLEDGMENTS 436–443.
14. Levignac J. L’ostéolyse périimplantaire. Périimplantose –
The authors are indebted to Professors Peter Thomsen Périimplantite. Rev Fr Odontostomatol 1965; 12:1251–
and Pentti Tengwall, Department of Biomaterials, 1260.
University of Göteborg for their advice and for giving 15. Mombelli A, Van Osten MAC, Shürach E, Lang NP. The
valuable comments to this paper prior to submission. microbiota associated with successful or failing osseointe-
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has supported this research project economically. 2:145–151.
16. Albrektsson T, Isidor F. Consensus report session. In: Lang
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