YIJOM-4736; No of Pages 8

Int. J. Oral Maxillofac. Surg. 2021; xxx: xxx–xxx

https://doi.org/10.1016/j.ijom.2021.06.008, available online at https://www.sciencedirect.com

Systematic Review
Dental Implants

Dental implant procedures D. Burtscher1, D. Dalla Torre2

1
University Clinic of Prosthodontics,
Medical University Innsbruck, Innsbruck,
Austria; 2Private Practice, Vipiteno, Italy

in immunosuppressed
organ transplant patients:
a systematic review
D. Burtscher, D. Dalla Torre: Dental implant procedures in immunosuppressed
organ transplant patients: a systematic review. Int. J. Oral Maxillofac. Surg. 2019;
xxx: xxx–xxx. ã 2021 The Authors. Published by Elsevier Inc. on behalf of
International Association of Oral and Maxillofacial Surgeons. This is an open access
article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Abstract. During the last decades, the number of immunosuppressed organ transplant
patients has increased consistently. Nevertheless, immunosuppression has been
discussed as a contraindication for dental implant procedures for many years.
Hence, the purpose of this systematic review was to assess the survival rate and
outcomes of dental implants after solid organ transplantation. An electronic and
manual literature search was conducted up to March 2021. Publications describing
dental implants placed in patients after organ transplantation were included without
any limitations regarding study design or date of publication. Ten articles met the
inclusion criteria, leading to a sample of 93 patients with 249 implants. Implant
survival rates were 100% over a mean follow-up of 60 months. In every case,
implant surgery was performed under antibiotic coverage. No major medication-
related complications were reported. Despite the limited amount of evidence in the
literature, implant procedures seem to be a safe treatment option in
immunosuppressed organ transplant patients. The observance of appropriate
Key words: organ transplantation; review; im-
treatment protocols including a strict maintenance programme seems to be crucial munosuppression; dental implant; immunosup-
for the long-term success of such treatments. However, stringent data regarding pressive agents.
various influencing factors such as the prevalence of peri-implantitis are still
missing. Accepted for publication 30 June 2021

Dental implants were introduced more
than 40 years ago as a treatment option
to replace missing teeth, and the develop-
ment of implant procedures is still ongo-
ing. Meanwhile, implantology has become
a routine treatment performed not only
by specialists, but also by general
practitioners. The long-term success of
dental implants has been confirmed in
various studies and reviews, with encour-
aging high survival rates of more than
90% after 10 years1,2. With the progress
made over recent decades, implant proce-
dures have also become feasible in the
compromised clinical situation with a lack
of surrounding bone, through the applica-
tion of bone regeneration procedures or
the use of implants with a reduced diame-
ter or length. Moreover, due to the contin-
uous developments in implant techniques
and materials, implant therapy has also

0901-5027/000001+08 ã 2021 The Authors. Published by Elsevier Inc. on behalf of International Association of Oral and Maxillofacial Surgeons. This is an
open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
YIJOM-4736; No of Pages 8
2 Burtscher and Dalla Torre
been applied in patients with reduced
health conditions such as diabetes and
autoimmune disorders.
A fundamental prerequisite for success-
ful implant treatment is appropriate pa-
tient selection with regard to the patient’s
general health status and the influence of
pre-existing general diseases3, as well as
ensuring complication-free wound healing
and integration. Various immunological
disorders, pharmacological therapies with
specific drugs (e.g., bisphosphonates), and
the side effects of oncological treatment
(e.g., chemotherapy, radiotherapy) have
been associated with increased implant
complications and implant loss4–7.
Implant failure in the early stages occurs
mainly due to missing or insufficient
osseointegration, while peri-implantitis is
the main reason for long-term implant loss.
The immune system plays a crucial role in
every healing process, as well as in targeting
infections, e.g., in the case of mucositis/
peri-implantitis, by an adequate immune
response8,9. The complex mechanisms of
osseointegration that are required for suc-
cessful implant treatment may be partially
compared to the characteristics of bone
fracture healing, which depends directly
on an adequate immune response10. Immu-
nosuppression may influence both early and
late complications by either leading to early
infection and impaired osseointegration or
by promoting peri-implantitis due to a re-
duced immune response. For these reasons,
the viability of dental implant procedures in
immunosuppressed organ transplant
patients has been controversial and con-
tinues to be questioned. Additionally, be-
sides implant-related complications, health
risks for immunosuppressed patients due to
implant procedures have to be taken into
account.
Regarding the effect of immunosup-
pression on the osseointegration of dental
implants, a few animal studies conducted
in recent years investigated the influence
of cyclosporine A on the bone healing
around dental implants and demonstrated
a negative effect of the immunosuppres-
sive medication11–15. Immunosuppressed
rabbits showed significantly worse out-
comes in terms of bone to implant contact,
bone density around implants, and remov-
al torque compared to untreated rabbits.
Ideally, most organ transplant patients
should undergo a thorough dental exami-
nation prior to transplantation in order to
eliminate possible dental sources of infec-
tion (e.g., apical periodontitis, active peri-
odontitis). Consequently, many of these
patients experience extractions of one or
more teeth preoperatively, putting them in
need of dental rehabilitation afterwards.
Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
The aim of this review was to analyse
the currently available data regarding the
use of dental implants in immunosup-
pressed solid organ transplant patients,
in order to investigate the long-term sur-
vival, success, and safety of dental implant
procedures in this special patient group.
Materials and methods
Protocol and registration
The systematic research was performed
according to the Preferred Reporting Items
for Systematic Reviews and Meta-Analy-
ses (PRISMA) guidelines16 and was reg-
istered in the PROSPERO database
(CRD42020169485).
Literature search strategy
A systematic search of the literature was
conducted in the MEDLINE (PubMed),
Embase, and Cochrane Central Register of
Controlled Trials electronic databases
covering articles published until March
1, 2021. Specific search sequences were
defined to monitor the different databases.
For the MEDLINE (PubMed) database,
information was retrieved using the search
phrase ((Organ transplant) OR (organ
transplantation) OR (liver transplant)
OR (kidney transplant) OR (immunosup-
pression)) AND ((dental implantation,
endosseous) OR (dental implant) OR
(dental prosthesis, implant supported)
OR (Overdentures) OR (Removable den-
tal prosthesis) OR (fixed dental prosthesis)
OR (dental implantation*) OR (dental im-
plant) OR (implant supported fixed dental
prosthesis) OR (implant supported over-
denture) OR (Removable dental prosthe-
sis*) OR (Overdenture) OR (Implant
supported Overdenture) OR (Implant
assisted Overdenture)). For the other
two databases, comparable terms were
used but modified to meet specific criteria
of the search engine of the respective
database. Additionally, a manual search
was performed covering the reference lists
of the selected articles, the grey literature,
and several journals, including Interna-
tional Journal of Implant Dentistry, Inter-
national Journal of Oral Implantology,
Clinical Implant Dentistry and Related
Research, Clinical Oral Implants Re-
search, Journal of Oral Implantology,
Journal of Periodontology, Journal of
Clinical Periodontology, International
Journal of Oral and Maxillofacial
Implants. All steps were documented in
a protocol prior to execution (not pub-
lished).
Eligibility criteria
Articles meeting the following PICO cri-
teria were included in the review: popula-
tion (P): immunosuppressed organ
transplant patients; intervention (I): dental
implant insertion after organ transplanta-
tion; comparison (C): non-immunosup-
pressed patients (control group, if
available); outcome (O): implant survival
rate, with a follow-up of at least 6 months
in function, and implant-associated com-
plications.
All types of human studies (clinical
trials, case–control studies, cross-section-
al studies, cohort studies, case series, and
case reports) published in peer-reviewed
scientific journals were included. In vitro
studies and animal studies were excluded
from the review.
The study selection and data extraction
were performed by two independent
reviewers. The titles and abstracts were
checked with regard to the predefined
eligibility criteria. Abstracts with unclear
content were included in the full-text as-
sessment to avoid the exclusion of poten-
tially relevant articles. Ambiguities were
discussed among the two reviewers to
reach a consensus on inclusion or exclu-
sion.
Quality assessment – risk of bias
Quality assessment tools for case series
and case–control studies from the National
Heart, Blood, and Lung Institute (NHLBI,
Bethesda, MD, USA) were used to rate the
selected articles. The quality assessment
of case reports was performed according
to the Joanna Briggs Institute (Adelaide,
Australia). In the case of any doubt, the
authors were contacted for clarification or
to provide missing information. Three
groups were defined to classify the select-
ed articles: low risk of bias if all quality
criteria were judged as present, moderate
risk of bias if one or more key domains
were unclear, and high risk of bias if one
or more key domains were absent.
Data extraction and analysis
Information on the following data items
was extracted from each included study
(with the indicated values in brackets if
applicable): author, year of publication,
study type, number of patients included
in the study, type of solid organ transplant
(liver, kidney, heart), patient age (medi-
an), absolute number of inserted implants,
absolute number of failed implants, early
implant losses (prior to prosthetic load-
ing), late implant losses (after prosthetic
YIJOM-4736; No of Pages 8
Fig. 1. PRISMA flow diagram illustrating the literature search and selection process.
loading), time of implantation after organ
transplantation, minimum follow-up peri-
od, survival rate of implants, implant suc-
cess according to Albrektsson et al.17 or
Buser et al.18, type of prosthesis, types of
immunosuppressive drugs, prescribed an-
tibiotic drugs, additional clinical informa-
tion. The listed measurements and
characteristics available at the subject lev-
el were analysed using standard descrip-
tive measures.
Results
Study selection
Figure 1 depicts the flowchart of the
applied search strategy. A total of 1188
records were found through database
searching. Three additional records were
retrieved from reference lists of previous
reviews and full-text articles. After the
removal of duplicates, 931 originally
identified studies remained, of which
903 were excluded based on title and
abstract. No unpublished or ongoing stud-
ies were identified. From the 28 articles
selected for full-text review, seven were
excluded because they described animal
studies11–15,19,20, five articles represented
reviews21–25, one article did not deal with
Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
Dental implants in transplant patients
solid organ transplantation but with he-
matopoietic stem cell transplantation26,
four articles did not have a follow-up
of 6 months for the implants placed or
did not include sufficient data27–30, and
one article described implant placement
before solid organ transplantation31. In
total, 10 studies were included in the
review32–41.
Study characteristics
The included publications were divided
into two groups: case–control studies
(n = 4)35,39–41 and case series/case reports
(n = 6)32–34,36–38. The quality of three of
the case–control studies was assessed as
good39–41; the quality of the remaining
case–control study was judged to be mod-
erate, due to missing information regard-
ing medication and a short follow-up
period (24 months)35. All of the case–
control studies were classified as level
of evidence III according to the Agency
for Healthcare Research and Quality
(AHRQ) scale of research levels. Regard-
ing the case series/case reports, risk of bias
was defined as low for four publica-
tions33,34,37,38, while two reports were
judged to have a moderate risk of bias
due to a short follow-up (18–24
3
months)32,36. All case reports were classi-
fied as ‘low level of evidence’, level of
evidence V according to the AHRQ scale
of research levels.
Details of the population and patient
outcomes
Details of the included studies, including
the main characteristics of the study pop-
ulation, are reported in Table 1. The stud-
ies included a total of 93 patients with a
mean age of 54.8 years (range 39–
61 years) and 249 inserted dental implants.
Thirty-six (38.7%) patients were female
and 57 (61.3%) were male. Regarding the
transplanted organ, 41 (44.1%) patients
had undergone a kidney transplantation,
37 (39.8%) a liver transplantation, four
(4.3%) a combined kidney and pancreas
transplantation, and 11 (11.8%) a heart
transplantation. In all cases, implant sur-
gery was performed under oral antibiotic
coverage for at least 5 days. Regarding
medical immunosuppression, a single im-
munosuppressive therapy was described in
33 (35.5%) cases, whereas 60 (64.5%)
patients received a double-immunosup-
pressive regimen. The medications includ-
ed tacrolimus, mycophenolate mofetil
(MMF), cyclosporine A, sirolimus, and
azathioprine. Additionally, the intake of
steroids associated with the immunosup-
pressive regimen was reported in 71
(76.3%) cases. Regarding prosthodontic
aspects of the implant-related rehabilita-
tion, 242 (97.2%) out of the 249 implants
supported a fixed dental prosthesis (single
crown or bridge), whereas seven (2.8%)
implants were used for implant-supported
overdentures.
The included publications described an
implant survival rate of 100% with a mean
follow-up of 60 months (range 17–120
months). None of the studies described
early implant loss. Six study groups
assessed marginal bone loss (MBL) in
their implant evaluation33,35,37,39–41. Of
these, four study groups with a total of
109 implants gave detailed information on
MBL over time, ranging from 0.18 mm to
1.3 mm (mean 0.72 mm) after 17–60
months (mean 26 months) of follow-
up33,35,37,40. The remaining two studies
including 127 implants subdivided the
patients into three different groups accord-
ing to their MBL (MBL < 2.4 mm, MBL
2.4–3.7 mm, MBL > 3.7 mm) after a
mean follow-up of 8 years and 7 years,
respectively, and compared them to a
healthy control group39,41. One hundred
and three implants showed a
MBL < 2.4 mm, 20 implants presented a
MBL of 2.4–3.7 mm, and the remaining
 4

YIJOM-4736; No of Pages 8
Table 1. Characteristics of the included studies. (Case–control studies are highlighted in grey.).
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a

Implants, n

Burtscher and Dalla Torre

First author Patients Age (years) Placement time after Follow-up Survival Type of
Year Study type LOE Transplanted organ (F/M) (median) Placed Failed transplant (months) (months) rate prosthesis
Heckmann34 Case report V Liver 1 61 2 0 12 120 100% Overdenture
2004 (Low) 1F/0M
Gu33 Case series V Liver 13 58 45 0 42 36 100% FDP
2011 (Low) 3F/10M
Gu37 Case report V Liver 1 45 11 0 12 60 100% FDP
2011 (Low) 0F/1M
Montebugnoli35 Case–control III Liver (n = 2) 13 54 29 0 >24 17 100% FDP (n = 24)
2015 (Moderate) Heart (n = 11) 2F/11M Overdenture
(n = 5)
Dalla Torre32 Case report V Liver 1 60 6 0 28 18 100% FDP
2016 (Low) 0F/1M
Cengiz38 Case report V Kidney 1 54 2 0 120 120 100% FDP
2018 (Low) 1F/0M
Paredes39 Case–control III Liver 16 61 48 0 >18 96 100% FDP
2018 (Moderate) 4F/12M
Radzewski40 Case–control III Kidney (n = 15) 21 39 24 0 60 24 100% FDP
2019 (Moderate) Kidney + pancreas 10 F/11M
(n = 4)
Liver (n = 2)
Hernandez41 Case–control III Kidney 25 61 79 0 88 84 100% FDP
2019 (Moderate) 15 F/10M
Wychowanski36 Case report V Liver 1 55 3 0 24 24 100% FDP
2020 (Low) 0F/1M
First author
Year Immunosuppressive Steroids Antibiotics Clinical measurements in transplant patients
Heckmann34 CycA Prednisone (5 mg/day) Ceftriaxone (14 days) PD 3 mm after 10 years
2004
Gu33 Tacrolimus + MMF (n = 6) None Amoxicillin–clavulanic acid (5 7 implants >5 mm PD
2011 Tacrolimus (n = 5) days) or moxifloxacin (6 days) Mean MBL 1.3  1.27 mm
CycA + MMF (n = 2) 2 implants >4 mm MBL
Gu37 Tacrolimus None Moxifloxacin (6 days) MBL 0.62  0.22 mm
2011 PD <5 mm
Montebugnoli35 CycA (n = 11) Prednisone (n = 6; 5–12.5 mg/day) Amoxicillin–clavulanic acid (6 MBL 0.18  0.10 mm
2015 Tacrolimus (n = 2) No steroids (n = 7) days) PD change after loading 0.06 mm
Dalla Torre32 Tacrolimus + MMF Prednisone (7.5 mg/day) Amoxicillin–clavulanic acid (5 –
2016 days)
Cengiz38 CycA Prednisone (N/A) Clindamycin (5 days) PD 3 mm
2018
Paredes39 CycA + azathioprine (n = 2) Prednisone (N/A) Amoxicillin (8 days) 5% MBL > 3.7 mm in 5% of all implants
2018 CycA + MMF (n = 5) Mucositis in 78.6% of all implants
Tacrolimus + MMF (n = 8) Peri-implantitis in 7.1% of all implants
CycA (n = 1) Mean PD 2.95 mm
Radzewski40 Tacrolimus, CycA, sirolimus or MMF Prednisone or methylprednisolone Doxycycline (5 days) or MBL 0.325 mm
2019 Double immunosuppressive therapy (N/A) clindamycin (5 days)
(n = 12)
YIJOM-4736; No of Pages 8
Dental implants in transplant patients
Clinical measurements in transplant patients
BOP, bleeding on probing; CycA, cyclosporine A; F, female; FDP, fixed dental prosthesis; LOE, level of evidence; M, male; MBL, marginal bone loss; MMF, mycophenolate mofetil; N/A, not
four implants were affected by a
MBL > 3.7 mm. No significant difference
MBL > 3.7 mm in 2.5% of all implants
Peri-implantitis in 12% of all implants
could be found between transplant patients
and the healthy control population.
Mucositis in 72% of all implants
BOP in 71% of all implants Two case–control studies investigated
the prevalence of mucositis/peri-implanti-
tis in transplant patients 8 years and 7
years, respectively, after implantation
and compared the results with those of a
healthy control group39,41. Despite a high
prevalence of mucositis of 78.6% and 72%
and a peri-implantitis-prevalence of 7.1%
and 12%, respectively, in transplant
patients, values were similar in the control
–
groups. Thus, no statistically significant
correlation between mucositis/peri-
implantitis and organ transplantation
spiramycin–metronidazole (8 days)
was detected by the authors.
Amoxicillin–clavulanic acid (7
All publications excluded patients with
the need for any type of bone regeneration,
except one case report32, where an extend-
Amoxicillin (8 days) or
Antibiotics
ed ridge augmentation procedure was per-
formed prior to implant placement. The
mean interval between organ transplanta-
tion and the insertion of dental implants
was 40 months, with a minimum of 12
months, as stated in two reports34,37.
days)
Discussion
Ideally, before organ transplantation the
recipient should undergo a meticulous
dental examination in order to determine
possible dental sources of infection that
may flare up during immunosuppressive
Steroids
therapy and consequently compromise the
Prednisone (N/A)
patient’s health42. For this reason the indi-
cations for tooth extractions are numerous.
As a consequence, the need for dental
rehabilitation after the stabilization of crit-
None
ical oral health conditions is an important
issue in such patients. With the growing
number of solid organ transplant recipi-
ents, this has led to an increased demand
for dental implant procedures in this par-
ticular patient group.
At the moment, the level of evidence
Immunosuppressive
regarding these therapy options in immu-
Tacrolimus + MMF (n = 15)
nosuppressed organ transplant patients is
low. On the one hand, the impossibility of
CycA + MMF (n = 8)
Tacrolimus + MMF
randomized clinical trials due to ethical
Tacrolimus (n = 1)
reasons has to be considered. On the other
CycA (n = 1)
hand, because of its potential toxicity
regarding bone metabolism and the risk
available; PD, probing depth.
of infective complications, medical immu-
nosuppression in organ transplantation re-
cipients has previously been defined as an
Table 1 (Continued )
absolute or relative contraindication for
oral implantology5,22,43–46. This may ex-
Wychowanski36
plain the small number of publications.
Hernandez41
First author
Moreover, a few animal studies con-
ducted in recent years investigated the
2019
2020
influence of cyclosporine A on bone heal-
Year
ing around dental implants and detected a
Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
5
negative effect of the immunosuppressive
medication11–15. Immunosuppressed rab-
bits showed statistically significant worse
outcomes in terms of bone to implant
contact, bone density around implants,
and removal torque compared to untreated
rabbits.
In contrast, the implant survival rate found
in this systematic review was 100% during a
follow-up period of up to 120 months. No
early implant losses prior to prosthetic loading
or major complications concerning the heal-
ing period after implantation were described.
According to these data, dental implant pro-
cedures appear to be a safe treatment in the
short- and middle-term. The reported results
in terms of implant success are also compara-
ble to those of long-term studies on the out-
comes of dental implants in the general
healthy population, without any difference
in implant survival rates1,47–49.
None of the reviewed studies consid-
ered the evaluation of implant success
according to the criteria of Albrektsson
et al.17 or Buser et al.18. However, data on
MBL over time seem to be similar to those
for the healthy population, as demonstrat-
ed especially in two case–control stud-
ies39,41. Moreover, neither of these
studies revealed significantly higher
mucositis/peri-implantitis rates in organ
transplant patients when compared to
the healthy control group subjects. With
the limited data available, implant success
rates do not appear to be influenced sig-
nificantly by organ transplantation.
The time between organ transplantation
and the insertion of implants and, conse-
quently, the duration of immunosuppres-
sive therapy, do not seem to play a major
role in the treatment outcome. The exam-
ined publications described a time elapsed
of between 1 and 10 years without any
influence on implant survival. However,
all authors agreed that proper function of
the transplanted organ and an unimpaired
general health condition of the patient are
crucial for a successful treatment. There-
fore, it may be summarized that the deter-
mination of the ideal time point for
implant procedures should be driven by
a thorough evaluation of the patient’s
condition and should not be dictated by
a shorter or longer duration of the immu-
nosuppressive therapy.
Regarding the immunosuppressive ther-
apy, no differences between the various
medications in terms of implant survival
could be found. In particular for cyclo-
sporine A, negative effects of the immu-
nosuppression as described in the animal
studies mentioned above was not noted
in the reviewed publications. However,
Radzewski et al. detected a statistically
YIJOM-4736; No of Pages 8
6 Burtscher and Dalla Torre
significant higher MBL in patients treated
with two combined immunosuppressive
medications (e.g., tacrolimus + mycophe-
nolate mofetil) when compared to patients
treated with a single medication regi-
men40. Nevertheless, this difference did
not show any clinical impact on implant
stability or survival. Similarly, no evi-
dence of clinical differences in patients
with single- or double-immunosuppres-
sive therapy could be revealed in all other
publications. Therefore, it could be con-
cluded that the type of immunosuppres-
sive regimen does not influence clinical
parameters such as implant stability or
survival.
Despite the absence of a negative im-
pact on implant survival in humans, gin-
gival hyperplasia as a possible side effect
of immunosuppressant use, especially cy-
closporine A and older substances, is well
known50. Cengiz et al. described this com-
plication during the follow-up of their
reported case38. Prior to implant place-
ment such possible side effects have to
be taken into account, leading to a strict
maintenance protocol with special regard
to gingival health.
A second pharmacological issue con-
cerns the influence of steroids given in
addition to the immunosuppressive regi-
men. Additional intake of prednisone or
methylprednisolone was described in
76.3% of the cases. The effect of glucocor-
ticosteroids on bone tissue is well known
and reported51–54. Glucocorticoids have
deleterious effects on bone remodelling
and turnover, as they promote osteoblast
apoptosis and favour the differentiation of
bone marrow cells into adipocytes55. Addi-
tionally, steroids may have a negative im-
pact on soft tissue healing, increasing the
risk of infective complications56,57. How-
ever, none of the included studies, neither
the case–control studies nor the simple case
reports, described any major complication
that could be attributed to the use of steroids.
Similarly to the type of immunosuppres-
sion, steroid therapy seems not to have a
statistically significant negative impact on
implant survival.
In terms of the prevention of infection,
all studies applied oral antibiotic prophy-
laxis; however different medications were
used (mostly amoxicillin + clavulanic ac-
id, with clindamycin or moxifloxacin in
the case of allergies) with different dura-
tions (from 5 to 14 days). None of the
included publications detected major post-
operative infective complications, inde-
pendent of the antibiotic protocol applied.
The lack of knowledge regarding implant
procedures after organ transplantation has
also caused ambiguity in the recommended
Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
antibiotic protocol. Given the fact that vari-
ous authors advise the use of pre- and
postoperative antibiotics in medically com-
promised patients58,59 and also that immu-
nosuppressed patients have to be
considered as a high-risk group for postop-
erative infections, antibiotics should be
considered a standard measure in immuno-
suppressed organ transplant patients. More-
over, Ziebolz et al. found that most of the
transplantation centres questioned in their
study recommended systemic antibiotic
treatment after any oral surgery proce-
dure60. Regarding the duration of the anti-
biotic treatment, there was no clinical
difference in patient outcomes between a
standard antibiotic regimen of 5–6 days
(depending on the type of antibiotic) and
a prolonged intake of up to 14 days.
As is well known, antibiotics may have
a negative impact especially on the gut
microbiota, with negative effects on lipid
and glucose metabolism61. Additionally,
gastrointestinal disorders accompanied by
diarrhoea may affect the pharmacokinetics
of and exposure to the immunosuppressive
therapy, with resulting difficulties in the
maintenance of a constant serum level. On
the other hand, a physiological metabo-
lism may be of critical importance espe-
cially in organ transplant patients.
Summarizing these indications with the
findings in the reviewed publications, anti-
biotics seem to play a crucial role in implant
procedures in organ transplant patients;
however an unnecessarily prolonged anti-
biotic intake should be avoided. A standard
protocol of 5–6 days depending on the
antibiotic medication (first choice amoxi-
cillin + clavulanic acid; second choice clin-
damycin or moxifloxacin), starting 12–
24 hours prior to implant placement, seems
to fulfil these criteria and should be consid-
ered as standard prophylaxis in immuno-
suppressed organ transplant patients.
In all of the reviewed publications,
patients with completely healed sockets
underwent implant procedures. Except for
one case report32, all authors described
treatments without bony alveolar defects
and, therefore, without the need for guided
bone regeneration (GBR). A conservative
surgical approach with late implant place-
ment according to Gallucci et al.62 was
applied in every study, which may reduce
the risk of postoperative infections and the
need for additional bone grafting. Despite
the success of extended bone regeneration
in one case, GBR is not recommended
routinely in immunosuppressed patients.
Similarly, all authors applied a conven-
tional loading protocol with insertion of
the prosthesis after 3 months or later in
most cases. Due to the negative effect on
bone healing of immunosuppressants as
demonstrated in animal studies11–15, organ
transplant patients may benefit from a
prolonged dental implant healing period
in order to guarantee a sufficient osseoin-
tegration. Summarizing the available data
regarding implant placement and loading,
a type 4C protocol according to Gallucci
et al.62, meaning implant placement in
completely healed sites followed by con-
ventional loading of the implants at 2
months after implant placement, may be
defined as the treatment plan of choice in
this special patient group.
This review has some limitations. First,
the number of reported immunosup-
pressed organ transplant patients who
have undergone dental implant treatment
is still very small. Moreover, out of the 10
included articles, only four represented
case–control studies. Due to the small
number of such studies, it was decided
to include case reports in this review as
well. Therefore, publication bias may have
had a negative impact on the review,
leading to an only moderate level of evi-
dence of this review overall. Prospective
case–control studies with larger popula-
tions and follow-up periods of at least 5
years would be desirable, in order to in-
vestigate the features and complications of
implantology in immunosuppressed organ
transplant patients in more detail.
There is still uncertainty regarding the
influence of the type of prosthetic recon-
struction on implant survival in this spe-
cial patient group. The majority of the
inserted implants were installed to retain
fixed partial dentures (single crowns or
bridges), whereas only seven implants
supported a removable prosthesis. There-
fore, at the moment, indications regarding
the usefulness of implantology in immu-
nosuppressed organ transplant patients are
restricted to fixed implant prostheses. Fur-
ther studies investigating the success of
removable implant prostheses would be
desirable, as such an approach could sim-
plify dental rehabilitation with less inva-
sive and expensive procedures, especially
in edentulous patients.
In conclusion, despite the limited data
available, dental implant procedures in
immunosuppressed organ transplant
patients seem to be an important treatment
option in order to stabilize the patient’s
nutritional condition and consequently
improve their quality of life. Of course,
close cooperation between the dental team
and the transplant team has to be achieved in
order to guarantee safety in all steps. Finally
and maybe even more important compared
to healthy subjects, periodic follow-up and
maintenance has to be considered crucial
YIJOM-4736; No of Pages 8
after implant rehabilitation in this special
high-risk population group.
Funding
None.
Competing interests
None.
Ethical approval
Not required.
Patient consent
Not applicable.
References
1. Pjetursson BE, Thoma D, Jung R, Zwahlen
M, Zembic A. A systematic review of the
survival and complication rates of implant-
supported fixed dental prostheses (FDPs)
after a mean observation period of at least
5 years. Clin Oral Implants Res 2012;23
(Suppl 6):22–38. http://dx.doi.org/10.1111/
j.1600-0501.2012.02546.x.
2. Moraschini V, Poubel LA, Ferreira VF, Bar-
boza Edos S. Evaluation of survival and
success rates of dental implants reported in
longitudinal studies with a follow-up period
of at least 10 years: a systematic review. Int J
Oral Maxillofac Surg 2015;44:377–88.
http://dx.doi.org/10.1016/j.
ijom.2014.10.023.
3. Vissink A, Spijkervet F, Raghoebar GM. The
medically compromised patient: are dental
implants a feasible option? Oral Dis
2018;24:253–60. http://dx.doi.org/10.1111/
odi.12762.
4. Chrcanovic BR, Albrektsson T, Wennerberg
A. Dental implants in irradiated versus non-
irradiated patients: a meta-analysis. Head
Neck 2016;38:448–81. http://dx.doi.org/
10.1002/hed.23875.
5. Gomez-de Diego R, Mang-de la Rosa Mdel
R, Romero-Perez MJ, Cutando-Soriano A,
Lopez-Valverde-Centeno A. Indications and
contraindications of dental implants in med-
ically compromised patients: update. Med
Oral Patol Oral Cir Bucal 2014;19:e483–
9. http://dx.doi.org/10.4317/medoral.19565.
6. Kotsakis GA, Ioannou AL, Hinrichs JE,
Romanos GE. A systematic review of obser-
vational studies evaluating implant place-
ment in the maxillary jaws of medically
compromised patients. Clin Implant Dent
Relat Res 2015;17:598–609. http://dx.doi.
org/10.1111/cid.12240.
7. Manor Y, Simon R, Haim D, Garfunkel A,
Moses O. Dental implants in medically com-
plex patients—a retrospective study. Clin
Oral Investig 2017;21:701–8. http://dx.doi.
org/10.1007/s00784-016-1937-6.
Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
Dental implants in transplant patients
8. Kawai T, Akira S. Innate immune recognition
of viral infection. Nat Immunol 2006;7:131–7.
http://dx.doi.org/10.1038/ni1303.
9. Midwood KS, Williams LV, Schwarzbauer
JE. Tissue repair and the dynamics of the
extracellular matrix. Int J Biochem Cell Biol
2004;36:1031–7. http://dx.doi.org/10.1016/
j.biocel.2003.12.003.
10. Colnot C, Romero DM, Huang S, Rahman J,
Currey JA, Nanci A, Brunski JB, Helms JA.
Molecular analysis of healing at a bone–
implant interface. J Dent Res
2007;86:862–7. http://dx.doi.org/10.1177/
154405910708600911.
11. Sakakura CE, Marcantonio Jr E, Wenzel A,
Scaf G. Influence of cyclosporin A on quality
of bone around integrated dental implants: a
radiographic study in rabbits. Clin Oral
Implants Res 2007;18:34–9. http://dx.doi.
org/10.1111/j.1600-0501.2006.01253.x.
12. Duarte PM, Nogueira Filho GR, Sallum EA,
de Toledo S, Sallum EA, Nociti Junior FH.
The effect of an immunosuppressive therapy
and its withdrawal on bone healing around
titanium implants. A histometric study in
rabbits. J Periodontol 2001;72:1391–7.
http://dx.doi.org/10.1902/
jop.2001.72.10.1391.
13. Sakakura CE, Lopes BMV, Margonar R,
Queiroz TP, Nociti FH, Marcantonio E. Cy-
closporine-a and bone density around titani-
um implants: a histometric study in rabbits. J
Osseointegr 2011;3:25–9.
14. de Molon RS, Sakakura CE, Faeda RS,
Sartori R, Palhares D, Margonar R, Marcan-
tonio Jr E. Effect of the long-term adminis-
tration of cyclosporine A on bone healing
around osseointegrated titanium implants: a
histomorphometric study in the rabbit tibia.
Microsc Res Tech 2017;80:1000–8. http://
dx.doi.org/10.1002/jemt.22894.
15. El Hadary AA, Yassin HH, Mekhemer ST,
Holmes JC, Grootveld M. Evaluation of the
effect of ozonated plant oils on the quality of
osseointegration of dental implants under the
influence of cyclosporin A: an in vivo study.
J Oral Implantol 2011;37:247–57. http://dx.
doi.org/10.1563/AAID-JOI-D-09-00098.
16. Page MJ, McKenzie JE, Bossuyt PM, Bou-
tron I, Hoffmann TC, Mulrow CD, Shamseer
L, Tetzlaff JM, Akl EA, Brennan SE, Chou
R, Glanville J, Grimshaw JM, Hrobjartsson
A, Lalu MM, Li T, Loder EW, Mayo-Wilson
E, McDonald S, McGuinness LA, Stewart
LA, Thomas J, Tricco AC, Welch VA, Whit-
ing P, Moher D. The PRISMA 2020 state-
ment: an updated guideline for reporting
systematic reviews. BMJ 2021;372:n71.
http://dx.doi.org/10.1136/bmj.n71.
17. Albrektsson T, Zarb G, Worthington P, Eriks-
son AR. The long-term efficacy of currently
used dental implants: a review and proposed
criteria of success. Int J Oral Maxillofac
Implants 1986;1:11–25.
18. Buser D, Weber HP, Lang NP. Tissue inte-
gration of non-submerged implants. 1-year
results of a prospective study with 100 ITI
7
hollow-cylinder and hollow-screw implants.
Clin Oral Implants Res 1990;1:33–40. http://
dx.doi.org/10.1034/j.1600-
0501.1990.010105.x.
19. Duarte PM, Nogueira Filho GR, Sallum EA,
Sallum EA, Nociti Junior FH. Short-term
immunosuppressive therapy does not affect
the density of the pre-existing bone around
titanium implants placed in rabbits. Pesqui
Odontol Bras 2003;17:362–6.
20. Sakakura CE, Margonar R, Sartori R, Morais
JA, Marcantonio Jr E. The influence of cy-
closporin A on mechanical retention of den-
tal implants previously integrated to the
bone: a study in rabbits. J Periodontol
2006;77:2059–62. http://dx.doi.org/
10.1902/jop.2006.050290.
21. Bornstein MM, Cionca N, Mombelli A. Sys-
temic conditions and treatments as risks for
implant therapy. Int J Oral Maxillofac
Implants 2009;24(Suppl):12–27.
22. Hwang D, Wang HL. Medical contraindica-
tions to implant therapy: part I: absolute
contraindications. Implant Dent
2006;15:353–60. http://dx.doi.org/10.1097/
01.id.0000247855.75691.03.
23. Radzewski R, Osmola K. The use of dental
implants in organ transplant patients under-
going immunosuppressive therapy: an over-
view of publications. Implant Dent
2016;25:541–6. http://dx.doi.org/10.1097/
ID.0000000000000417.
24. Donos N, Calciolari E. Dental implants in
patients affected by systemic diseases. Br
Dent J 2014;217:425–30. http://dx.doi.org/
10.1038/sj.bdj.2014.911.
25. Duttenhoefer F, Fuessinger MA, Beckmann
Y, Schmelzeisen R, Groetz KA, Boeker M.
Dental implants in immunocompromised
patients: a systematic review and meta-anal-
ysis. Int J Implant Dent 2019;5:43. http://dx.
doi.org/10.1186/s40729-019-0191-5.
26. Etebarian A, Mirshamsi H, Sadeghi Hs,
Hemmati F. Oral rehabilitation in a patient
with sclerotic-phenotype chronic graft
versus host disease: a case report. Quintes-
sence Int 2019;50:208–13. http://dx.doi.org/
10.3290/j.qi.a41973.
27. Lee K, Dam C, Huh J, Park KM, Kim SY,
Park W. Distribution of medical status and
medications in elderly patients treated with
dental implant surgery covered by national
healthcare insurance in Korea. J Dent Anesth
Pain Med 2017;17:113–9. http://dx.doi.org/
10.17245/jdapm.2017.17.2.113.
28. Montebugnoli L, Venturi M, Cervellati F.
Bone response to submerged implants in
organ transplant patients: a prospective con-
trolled study. Int J Oral Maxillofac Implants
2012;27:1494–500.
29. Norrman A, Nylund K, Ruokonen H, Mauno
J, Mesimaki K, Haapaniemi A, Lassus P,
Helenius-Hietala J. Oral findings and treat-
ment of patients with face transplants in
Helsinki. Oral Surg Oral Med Oral Pathol
Oral Radiol 2021;4547. http://dx.doi.org/
10.1016/j.oooo.2021.01.006.
YIJOM-4736; No of Pages 8
8 Burtscher and Dalla Torre
30. Parihar AS, Madhuri S, Devanna R, Sharma
G, Singh R, Shetty K. Assessment of failure
rate of dental implants in medically compro-
mised patients. J Family Med Prim Care
2020;9:883–5. http://dx.doi.org/10.4103/
jfmpc.jfmpc_989_19.
31. Nakagawa A, Shitara N, Ayukawa Y,
Koyano K, Nishimura K. Implant treatment
followed by living donor lung transplant: a
follow-up case report. J Prosthodont Res
2014;58:127–31. http://dx.doi.org/10.1016/
j.jpor.2013.11.001.
32. Dalla Torre D, Burtscher D. Ridge augmen-
tation in an organ transplant patient. Int J
Oral Maxillofac Surg 2016;45:658–61.
http://dx.doi.org/10.1016/j.
ijom.2015.11.002.
33. Gu L, Yu YC. Clinical outcome of dental
implants placed in liver transplant recipients
after 3 years: a case series. Transplant Proc
2011;43:2678–82. http://dx.doi.org/
10.1016/j.transproceed.2011.06.037.
34. Heckmann SM, Heckmann JG, Linke JJ,
Hohenberger W, Mombelli A. Implant ther-
apy following liver transplantation: clinical
and microbiological results after 10 years. J
Periodontol 2004;75:909–13. http://dx.doi.
org/10.1902/jop.2004.75.6.909.
35. Montebugnoli L, Venturi M, Cervellati F,
Servidio D, Vocale C, Pagan F, Landini
MP, Magnani G, Sambri V. Peri-implant
response and microflora in organ transplant
patients 1 year after prosthetic loading: a
prospective controlled study. Clin Implant
Dent Relat Res 2015;17:972–82. http://dx.
doi.org/10.1111/cid.12207.
36. Wychowanski P, Szubinska-Lelonkiewicz D,
Osiak M, Nowak M, Kosieradzki M, Fiedor
P. New approach to treatment of high-risk
allograft recipients under chronic immuno-
suppression with tooth loss. Evaluation of
safety and longevity of dental implants: a
case report. Transplant Proc 2020;52:2558–
62. http://dx.doi.org/10.1016/j.transpro-
ceed.2020.02.103.
37. Gu L, Wang Q, Yu YC. Eleven dental implants
placed in a liver transplantation patient: a case
report and 5-year clinical evaluation. Chin
Med J (Engl) 2011;124:472–5.
38. Cengiz Mi, Cengiz S, Atalay N, Arik N. Out-
come of implants in kidney transplant patient
undergoing immunosuppressive therapy: case
report. J Int Dental Sci 2018;4:47–51. http://dx.
doi.org/10.21306/jids.2018.1.43.
39. Paredes V, Lopez-Pintor RM, Torres J, de
Vicente JC, Sanz M, Hernandez G. Implant
treatment in pharmacologically immunosup-
pressed liver transplant patients: a prospec-
tive-controlled study. Clin Oral Implants Res
2018;29:28–35. http://dx.doi.org/10.1111/
clr.13035.
40. Radzewski R, Osmola K. Osseointegration
of dental implants in organ transplant
patients undergoing chronic immunosup-
pressive therapy. Implant Dent
2019;28:447–54. http://dx.doi.org/10.1097/
ID.0000000000000916.
Please cite this article in press as: Burtscher D, Dalla D. Dental implant procedures in immunosuppressed organ transplant patients: a
systematic review, Int J Oral Maxillofac Surg (2021), https://doi.org/10.1016/j.ijom.2021.06.008
41. Hernandez G, Paredes V, Lopez-Pintor RM,
de Andres A, de Vicente JC, Sanz M. Implant
treatment in immunosuppressed renal trans-
plant patients: a prospective case-controlled
study. Clin Oral Implants Res 2019;30:524–
30. http://dx.doi.org/10.1111/clr.13437.
42. Kwak EJ, Kim DJ, Choi Y, Joo DJ, Park W.
Importance of oral health and dental treat-
ment in organ transplant recipients. Int Dent
J 2020;70:477–81. http://dx.doi.org/
10.1111/idj.12585.
43. Diz P, Scully C, Sanz M. Dental implants in
the medically compromised patient. J Dent
2013;41:195–206. http://dx.doi.org/
10.1016/j.jdent.2012.12.008.
44. Sugerman Pb, Barber MT. Patient selection
for endosseous dental implants: oral and
systemic considerations. Int J Oral Maxillo-
fac Implants 2002;17:191–201.
45. Alsaadi G, Quirynen M, Komarek A, van
Steenberghe D. Impact of local and systemic
factors on the incidence of late oral implant
loss. Clin Oral Implants Res 2008;19:670–6.
http://dx.doi.org/10.1111/j.1600-
0501.2008.01534.x.
46. Oczakir C, Balmer S, Mericske-Stern R.
Implant-prosthodontic treatment for special
care patients: a case series study. Int J
Prosthodont 2005;18:383–9.
47. Jemt T, Johansson J. Implant treatment in the
edentulous maxillae: a 15-year follow-up
study on 76 consecutive patients provided
with fixed prostheses. Clin Implant Dent
Relat Res 2006;8:61–9. http://dx.doi.org/
10.1111/j.1708-8208.2006.00003.x.
48. Astrand P, Ahlqvist J, Gunne J, Nilson H.
Implant treatment of patients with edentu-
lous jaws: a 20-year follow-up. Clin Implant
Dent Relat Res 2008;10:207–17. http://dx.
doi.org/10.1111/j.1708-8208.2007.00081.x.
49. Pikner SS, Grondahl K, Jemt T, Friberg B.
Marginal bone loss at implants: a retrospec-
tive, long-term follow-up of turned Brane-
mark System implants. Clin Implant Dent
Relat Res 2009;11:11–23. http://dx.doi.org/
10.1111/j.1708-8208.2008.00092.x.
50. Hallmon WW, Rossmann JA. The role of
drugs in the pathogenesis of gingival over-
growth. A collective review of current con-
cepts. Periodontol 2000 1999;21:176–96.
http://dx.doi.org/10.1111/j.1600-0757.1999.
tb00175.x.
51. Kulak CA, Borba VZ, Kulak Jr J, Custodio
MR. Osteoporosis after transplantation. Curr
Osteoporos Rep 2012;10:48–55. http://dx.
doi.org/10.1007/s11914-011-0083-y.
52. Stein E, Ebeling P, Shane E. Post-transplan-
tation osteoporosis. Endocrinol Metab Clin
North Am 2007;36:937–63. http://dx.doi.
org/10.1016/j.ecl.2007.07.008. viii.
53. van Staa TP. The pathogenesis, epidemiolo-
gy and management of glucocorticoid-in-
duced osteoporosis. Calcif Tissue Int
2006;79:129–37. http://dx.doi.org/10.1007/
s00223-006-0019-1.
54. Petsinis V, Kamperos G, Alexandridi F,
Alexandridis K. The impact of glucocorti-
costeroids administered for systemic dis-
eases on the osseointegration and survival
of dental implants placed without bone graft-
ing—a retrospective study in 31 patients. J
Craniomaxillofac Surg 2017;45:1197–200.
http://dx.doi.org/10.1016/j.
jcms.2017.05.023.
55. Fu JH, Bashutski JD, Al-Hezaimi K, Wang
HL. Statins, glucocorticoids, and nonsteroi-
dal anti-inflammatory drugs: their influence
on implant healing. Implant Dent
2012;21:362–7. http://dx.doi.org/10.1097/
ID.0b013e3182611ff6.
56. Guggenheimer J, Eghtesad B, Stock DJ.
Dental management of the (solid) organ
transplant patient. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2003;95:383–9.
http://dx.doi.org/10.1067/moe.2003.150.
57. Lopez-Pintor RM, Hernandez G, de Arriba
L, de Andres A. Comparison of oral lesion
prevalence in renal transplant patients under
immunosuppressive therapy and healthy
controls. Oral Dis 2010;16:89–95. http://
dx.doi.org/10.1111/j.1601-
0825.2009.01609.x.
58. Surapaneni H, Yalamanchili PS, Basha MH,
Potluri S, Elisetti N, Kiran Kumar MV.
Antibiotics in dental implants: a review of
literature. J Pharm Bioallied Sci 2016;8:
S28–31. http://dx.doi.org/10.4103/0975-
7406.191961.
59. Morris HF, Ochi S, Winkler S. Implant sur-
vival in patients with type 2 diabetes: place-
ment to 36 months. Ann Periodontol
2000;5:157–65. http://dx.doi.org/10.1902/
annals.2000.5.1.157.
60. Ziebolz D, Hrasky V, Goralczyk A, Hor-
necker E, Obed A, Mausberg RF. Dental
care and oral health in solid organ transplant
recipients: a single center cross-sectional
study and survey of German transplant cen-
ters. Transpl Int 2011;24:1179–88. http://
dx.doi.org/10.1111/j.1432-
2277.2011.01325.x.
61. van Olden C, Groen AK, Nieuwdorp M. Role
of intestinal microbiome in lipid and glucose
metabolism in diabetes mellitus. Clin Ther
2015;37:1172–7. http://dx.doi.org/10.1016/
j.clinthera.2015.03.008.
62. Gallucci GO, Hamilton A, Zhou W, Buser D,
Chen S. Implant placement and loading pro-
tocols in partially edentulous patients: a
systematic review. Clin Oral Implants Res
2018;29(Suppl 16):106–34. http://dx.doi.
org/10.1111/clr.13276.
Address:
Doris Burtscher
University Clinic of Prosthodontics
Medical University Innsbruck
Anichstrasse 35
6020 Innsbruck
Austria
Tel: +43 (0)512 504 27141. Fax: +43 (0)512
504 27157
E-mail: doris.burtscher@i-med.ac.at