Dental implants in the medically compromised patient

Review
Dental implants in the medically compromised patient
Pedro Diz a,
*, Crispian Scully b
, Mariano Sanz c
a
Grupo de Investigacioń en Odontologıá Me´dico-Quiru´ rgica (OMEQUI), School of Medicine and Dentistry, University of Santiago de
Compostela, Spain
b
University College London, UK
c
Grupo de Investigacioń en Etiologıá y Terapeútica Periodontal (ETEP), School of Dentistry, Complutense University of Madrid, Spain
1. Introduction
In medically healthy patients, the success rates of some dental
implant (DI) systems have reported to be between 90 and 95%
at 10 years.1
DI may fail, however, due to a lack of
osseointegration during early healing, or when in function
due to breakage, or infection of the peri-implant tissues
leading to loss of implant support. Early complications after
implant installation, can include pain, infection or occasion-
ally neuropathy.1
Severe early complications such as hae-
morrhage (e.g. in the floor of the mouth) or descending
necrotizing mediastinitis are rare.2–6
The longer term outcome of implant therapy can be
affected by local or systemic diseases or other compromising
factors, in fact, it has been suggested that some local and
systemic factors could represent contraindications to DI
treatment.7–10
2. Dental implants in medically compromised
patients
The impact of health risks on the outcome of implant therapy
is unclear, since there are few if any randomized controlled
trials (RCTs) evaluating health status as a risk indicator. In
j o u r n a l o f d e n t i s t r y 4 1 ( 2 0 1 3 ) 1 9 5 – 2 0 6
a r t i c l e i n f o
Article history:
Received 14 December 2011
Received in revised form
3 December 2012
Accepted 27 December 2012
Keywords:
Dental implants
Osseointegration
Systemic diseases
Contraindication
a b s t r a c t
Objective: It has been suggested that some local and systemic factors could be contra-
indications to dental implant treatment. The objective of this paper was to evaluate whether
success and survival rates of dental implants are reduced in the medically compromised
patient.
Data/sources: An extensive literature search was conducted using PubMed/Medline, Scopus,
Scirus and Cochrane databases up to November 8, 2012.
Conclusions: There are very few absolute medical contraindications to dental implant
treatment, although a number of conditions may increase the risk of treatment
failure or complications. The degree of systemic disease-control may be far more
important that the nature of the disorder itself, and individualized medical control
should be established prior to implant therapy, since in many of these patients
the quality of life and functional benefits from dental implants may outweigh any
risks.
# 2013 Elsevier Ltd. All rights reserved.
* Corresponding author at: Stomatology Department, School of Medicine and Dentistry, Santiago de Compostela University, c/Entrerrıós
sn, 15782 Santiago de Compostela, La Corun˜ a, Spain. Tel.: +34 881812344.
E-mail address: pedro.diz@usc.es (P. Diz).
Available online at www.sciencedirect.com
journal homepage: www.intl.elsevierhealth.com/journals/jden
0300-5712/$ – see front matter # 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jdent.2012.12.008

principle, only patients with an ASA (American Society of
Anaesthesiologists) grade I or II should qualify for an elective
surgical procedure, such as DI placement and the patient’s
surgical risks should be weighed against the potential benefits
offered by the DI.11
Even though there are statements in the implant literature
such as: ‘‘certain conditions such as uncontrolled diabetes, bleeding
disorders, a weakened immune system, or cognitive problems that
interfere with postoperative care increase the risk of implant failure’’
(http://www.dentalphobia.com/lsd-procedures_im-
plants.htm) these are un-substantiated by scientific evidence.
Other authors have recommended as relative contra-
indications for DI, certain patient groups or conditions7
:
Children adolescents
Epileptic patients
Severe bleeding tendency
Endocarditis risk
Osteoradionecrosis risk
Myocardial infarction risk
Other reported relative contraindications include: adoles-
cence, ageing, osteoporosis, smoking, diabetes, positive
interleukin-1 genotype, human immunodeficiency virus posi-
tivity, cardiovascular disease, hypothyroidism and Crohn
disease.8,9
Suggested absolute contraindications include: recent myo-
cardial infarction and cerebrovascular accident, transplant or
valvular prosthesis surgery, profound immunosuppression,
severe bleeding issues, active treatment of malignancy, drug
abuse, psychiatric illness, as well as intravenous bispho-
sphonate use10
but there is, however, little or no evidence to
support most of these contentions.
It is, therefore, the aim of this review to evaluate the
scientific evidence through PubMed/Medline, Scopus, Scirus
and Cochrane databases searches up to November 8, 2012,
using as keywords: implants, contraindications, and the
following disease categories, which had been highlighted as
possible contraindications in more than one publication12,13
:
Alcoholism
Bleeding disorders
Bone disease
Cancer patients
Cardiac disease
Corticosteroids
Diabetes
Hyposalivation
Immunocompromised patients
Mucosal disease
Neuro-psychiatric disorders
Titanium allergy
This evidence has been drawn from a wide range of
sources, ranging from case reports to controlled cohort
investigations, including both human and animal studies.
Implant outcome assessment has varied from histological and
radiographic outcomes, to objective and subjective determi-
nations of implant and treatment failure. The aim of this study
was to evaluate the level of evidence of the available literature
on contraindications to DI therapy in medically compromised
patients. Contraindications are mainly based on both the risk
of medical complications related to implant surgery (e.g.
haemorrhage risk in patients with bleeding disorders) and the
rate of DI success in medically compromised patients (e.g. in
patients with head and neck cancer receiving radiotherapy).
This review, hence, summarizes this evidence applying
recognized evidence-based criteria.14
3. Alcoholism
We could not identify any reliable evidence indicating that
alcoholism might be a contraindication to DI. Negative effects
of alcohol intake on bone density and osseointegration in
animal models, however, have been demonstrated.15,16
In
humans, there is evidence of increased peri-implant marginal
bone loss and DI failures in patients with high levels of alcohol
consumption.17,18
In general terms, however, it is worth
considering before implants are placed that alcoholism:
is often associated with tobacco smoking,
may via liver disease, cause bleeding problems,
may cause osteoporosis,
may impair the immune response,
may impair nutrition, especially folate and B vitamins.
In summary, although there is no evidence that alcoholism
is a contraindication to implants, these patients may be at
increased risk of complications (Table 1).
4. Bleeding disorders
Even though haemorrhage can be a relatively common
complication in DI placement,19
there is no reliable evidence
to suggest that bleeding disorders are a contraindication to the
placement of implants: even haemophiliacs have successfully
been treated with DI.20
Nevertheless, any oral surgical
procedure may lead to haemorrhage and blood loss and, if
this bleeding reaches the fascial spaces of the neck, it can
hazard the airway. In fact, upper airway obstruction second-
ary to severe bleeding in the floor of the mouth is a rare but
potentially life-threatening complication of DI placement.4
Usually arterial impingement is produced when perforating
the lingual cortical plate affecting the lingual arteries or the
inferior alveolar canal, affecting the inferior alveolar vessels.6
DI placed in the first mandibular premolar position are the
higher risk for this bleeding complication.21
In patients with bleeding disorders, haemorrhage associated
with implant surgeries is more common and can be pro-
longed,22
particularly with warfarin or acenocoumarol. In these
patients, the current recommendation is to undertake the
implant surgical procedure without modifying the anticoagula-
tion, provided the INR is less than 3 or 3.5.22
In this context,
implantsurgerycouldberegardedintermsofsurgicaltraumato
the extraction of three teeth. There is evidence that antic-
oagulated patients (INR 2–4) without discontinuing the antico-
agulant medication do not have a significantly higher risk of
post-operative bleeding and, topical haemostatic agents are

Table 1 – Dental implants (DI) in medically compromised patients.
Condition Evidence condition
is an absolute/relative
contraindication to DI
DI success rate
compared to healthy
population (level
of evidencea
)
Other considerations Management
modifications that
may be indicated
Alcoholism – Similar (5) Tobacco use These patients may
be at increased risk
of complications
Bleeding
Osteoporosis
Impaired immunity
Malnutrition
Behavioural problems
Bleeding disorder Medical advice should be
taken first in congenital
bleeding disorders
Similar (3) in oral
anticoagulants and
antiplatelet treatment
Possibility of blood
borne infections
These patients may
be at increased risk
of complications
Bone disease
Rheumatoid arthritis – Similar (4) Peri-implantitis
and marginal bone
resorption increase
with concomitant
connective tissue
diseases
–
Osteoporosis – Similar (2a) – Sinus lifts may be
contraindicated
Osteoporosis and
oral bisphosphonates
– Similar (1b) –
Cancer and intravenous
bisphosphonatesb
Contraindicated (5) Reduced (4) – –
Head neck cancer
patients
– Reduced (1b) (following
radiotherapy)
Cancer prognosis Surgery best carried
out 21 days before
radiotherapy
Similar (3b) (following
chemotherapy)
Hyperbaric oxygen
should be given if
50 Gy used
(controversial)
Defer DI for 9 months
Consider antimicrobial
cover
No immediate loading
Cardiac disease Medical advice should be
taken first
Similar (5) May be anticoagulated Avoid general
anaesthesia
Poor risk for general
anaesthesia
Consider endocarditis
prophylaxis
Corticosteroid therapy – Similar (5) May be impaired
immunity
Corticosteroid cover
Antibiotic prophylaxis
Diabetes mellitus – Slightly reduced in
bad metabolic control
patients (2a)
Microvascular disease HbA1c level for patient
selection
Similar in good metabolic
control patients (2b)
Osteoporosis Avoid hypoglycaemia
Impaired immunity Use chlorhexidine
Hyposalivation – Similar (4) – –
Immunocompromised
patients
Medical advice should be
taken first
Similar in organ
transplantation
patients (4)
May be blood borne
infections
Use chlorhexidine
Similar in HIV
infected
patients (3a)
Mucosal disease – Similar (4) – –
Neuropsychiatric
disorders
Medical advice should
be taken first
Similar (4) Behavioural Consider general
anaesthesia
j o u r n a l o f d e n t i s t r y 4 1 ( 2 0 1 3 ) 1 9 5 – 2 0 6 197

effective in preventing post-operative bleeding.23
Oral antico-
agulant discontinuation is thus not recommended for dentoal-
veolar surgery, such as implant placement, provided that this
does not involve autogenous bone grafts, extensive flaps or
osteotomy preparations extending outside the bony envelope.
In a recently published case series involving 50 consecutive
patients receiving oral anticoagulant therapy (warfarin) with-
out interruption or modifications to their therapy, it was shown
that a standard protocol of local haemostasis in dental implant
surgery is able to prevent bleeding complications in patients on
oral anticoagulants, allowing these surgical procedures to be
performed on an outpatient basis.24
The bleeding risk is also low in patients treated with
heparin.25
In patients on single or dual antiplatelet therapy,
the frequency of oral bleeding complications after invasive
dental procedures is low to negligible and, therefore, the risks
of altering or discontinuing use of the antiplatelet medications
– increased risk of thromboembolism – far outweigh the low
risk of haemorrhage.26
In summary, there is no evidence that any bleeding
disorders are an absolute contraindication to DI surgery,
although these patients may be at risk of prolonged haemor-
rhage and blood loss, and medical advice should be taken first
especially in congenital bleeding disorders (Table 1).
5. Bone diseases
There are few reported cases in the literature of DI placement
and subsequent rehabilitation of patients with these bone
diseases such as osteogenesis imperfecta,27–32
polyarthritis,33
or ankylosing spondylitis,34
and to our knowledge no relevant
case series have been published up to date. On the contrary, at
least two retrospective series on dental implants outcomes
involving 34 and 22 females suffering from autoimmune
rheumatoid arthritis with or without concomitant connective
tissue diseases have been published, the authors concluding
that a high implant and prosthodontic success rate can be
anticipated in rheumatoid arthritis patients, but peri-implant
marginal bone resorption and bleeding are more pronounced
in those with concomitant connective tissue diseases.35,36
In summary, a number of bone disorders may potentially
influence the outcome of DI, but few studies have evaluated
scientifically this risk (i.e. DI in patients with rheumatoid
arthritis),35
being most of the published investigations related
to the relationship between bone density and implant success.
Osteoporosis is the most studied bone-related disease. It is
a common condition characterized by generalized reduction
in bone mass with no other bone abnormality. When
evaluating whether DI in osteoporotic patients have a
different long-term outcome, even though failure rates have
been reportedly higher in animal models37
and patients,38,39
a
systematic review revealed no association between systemic
bone mineral density (BMD) status, mandibular BMD status,
bone quality, and implant loss, concluding that the use of DI in
osteoporosis patients is not contraindicated.40
In a cross-
sectional study no relation was found between osteoporosis
and peri-implantitis41
and even patients with severe osteopo-
rosis have been successfully rehabilitated with DI-supported
prostheses.42,33
There are, however, some case–control stud-
ies reporting a weak association between osteoporosis and the
risk of implant failure43
and some authors have alluded to a
correlation between BMD of the mandible with BMD measure-
ments at other skeletal sites.44
It is, therefore, recommended
to thoroughly evaluate the jawbone quality prior implant
placement, rather than undertaking systemic BMD and
osteoporotic status assays.43,45
Dentists should perform an
accurate analysis of bone quality by means of tomography and
modify treatment planning if indicated (e.g. using larger
implant diameter and with surface treatment).46
A further potential complication in osteoporotic patients
is the possible effect on bone turnover at the DI interface
of systemic anti-resorptive medication. This risk in
patients using bisphosphonates (BPs) is well recognized,47
in terms of bisphosphonate-related osteonecrosis of the jaws
(BRONJ).48–50
The largest series of patients developing BRONJ
following DI published to date involved 27 patients on BPs, 11
orally and 16 intravenously. BRONJ developed after mean
periods of 68 months, 16 months, and 50 months in patients
on alendronate, zoledronic acid, and pamidronate, respec-
tively. There was a mean duration of 16 months from
implants placement until the appearance of BRONJ.51
Recently, in a series of BRONJ following DI involving 14
patients on BPs, 5 orally and 9 intravenously, it has been
suggested that posteriorly placed implants seem to be of
higher risk of BRONJ development.52
Table 1 (Continued )
Condition Evidence condition
is an absolute/relative
contraindication to DI
DI success rate
compared to healthy
population (level
of evidencea
)
Other considerations Management
modifications that
may be indicated
Titanium allergy – Reduced (4) Allergic symptoms
after implant
placement or
unexplained implant
failures
Use alternative
materials
In patients allergic to
other metals long-term
clinical and radiographic
follow-up is recommended
Adapted from Scully et al.12
a
OCEBM Levels of Evidence Working Group.14
b
To reduce skeletal-related morbidity.

BRONJ is a real issue for patients treated with intravenous
BPs but the occurrence of BRONJ in patients receiving oral BPs
medication is minimal. The use of oral BPs at the time of
implant placement and during healing do not seems to affect
early implant success.53
In a retrospective survey of 115
patients on oral BPs receiving DI (72 returned to the clinic for
evaluation), oral bisphosphonate therapy did not appear to
significantly affect implant success and no cases of BRONJ
were registered54
and similarly, in a large survey performed in
South Australia the estimated prevalence of BRONJ in patients
under oral BPs was less than 1%.55
In 2007, the American Association of Oral and Maxillofa-
cial Surgeons56
produced guidelines for patients treated
with oral BPs, based on the clinical situation of the patient
and the length of treatment with the drug, indicating that
greater caution prior and subsequent to surgery should be
taken during 3 years after discontinuing BP treatment. A
systematic review analysing one prospective and three
retrospective series (217 patients) showed that the place-
ment of a DI in patients with chronic intake of oral-BPs did
not lead to BRONJ and did not influence short-term (1–4
years) implant survival rates. This study concluded that DI
might be considered a safe procedure in patients taking oral
BPs for 5 years.57
Similarly, in another review that included
12 studies (7 case reports and 5 retrospective studies), the
authors concluded that dental implants can osseointegrate
and remain functionally stable in patients treated with
bisphosphonates.58
In summary, there is a consensus on contraindicating
implants in cancer patients treated with intravenous BPs.57
In
patients with osteoporosis treated with BPs, they should be
informed of the risk of possible implant loss59
the risk of
suffering bony necrosis and a poor outcome from sinus lifts,60
and adequate informed consent prior to dental implant
surgery should be obtained (Table 1).
6. Head and neck cancer patients
Surgical resection of head and neck cancer can be severely
mutilating. DI in oral cancer patients are successfully used for
dental rehabilitation after bony reconstruction of the jaws,
and for retention of a prosthetic device (e.g.: palatal
obturator), used as the primary means of maxillary recon-
struction.61,62
Combinations of microvascular surgical tech-
niques and the use of DI can considerably improve the
rehabilitation of people with severe head and neck defects,
but there may be an increased risk of implant failure in
irradiated free flap bone.63
It has been suggested that some
patients may benefit from having the placement of DI during
ablative tumour surgery.64,65
Radiotherapy can significantly affect DI outcomes13
mainly
during the healing period66
. Radiotherapy may induce endar-
teritis obliterans, and hence can predispose to osteoradione-
crosis of the jaw. Twelve studies involving 643 DI placed in
adult patients who have received radiotherapy, reported lower
success rates, ranging from 40 to 100%.67
There are, however,
several clinical studies demonstrating that DI can osseointe-
grate and remain functionally stable in patients who had
received radiotherapy.68
In a series of 275 DI placed in 63
patients with oropharyngeal squamous cell carcinoma, no
increase in osteoradionecrosis was reported.69
It has been
suggested that DI may represent an acceptable option for oral
rehabilitation in patients who had suffered previous osteor-
adionecrosis (5 year survival rate of 48.3%).70
Even successful
DI placed during early childhood in patients treated with full
dose radiation for malignant midface tumours has been
reported.71
Other authors have reported successful DI but
occurrence of late complications, such as bone loss and
mucosal recession, possible due to altered saliva flow and
increased bacterial colonization.72
Several case–control studies have shown evidence of
improved outcomes in patients with history of radiotherapy
and DI with the addition of hyperbaric oxygen therapy (HBO)
mainly through reduction in the occurrence of osteoradione-
crosis and failing implants.73
However, a systematic review
found only one RCT comparing HBO with no HBO for DI
treatment in irradiated patients and was unable to find any
strong evidence to either support or refute the use of HBO
therapy for improving implant outcome.74
To increase implant success in irradiated head neck
cancer patients, the following precautions should be consid-
ered73
Implant surgery is best carried out 21 days before
radiotherapy
Total radiation dose should be 66 Gy if the risks of ORN are
to be minimized or 50 Gy to reduce osseointegration
failure: avoiding implant site/portals
Hyperbaric oxygen should be given if 50 Gy radiation is
used
No implant surgery should be carried out during radiother-
apy
No implant surgery should be carried out during mucositis
Defer implant placement for 9 months after radiotherapy
Use implant-supported prostheses without any mucosal
contact Avoid immediate loading
Ensure strict asepsis
Consider antimicrobial prophylaxis.
In a study of 30 postsurgical oral cancer patients receiving
106 dental mandibular implants and adjuvant chemotherapy
with either cisplatin or carboplatin plus 5-FU, there was no
significant difference in implant survival at 10 years follow-up
when compared with matched controls. None of the patients
had been treated with radiotherapy (Table 1).75
To the best of
our knowledge, two case series have been published reporting
that cancer chemotherapy appears not to significantly impair
the success of DI.75,76
7. Cardiovascular disease
It has been suggested that some cardiovascular events such as
recent myocardial infarction, stroke, and cardiovascular
surgery, might represent an absolute contraindication to
implant therapy.10
In a retrospective analysis of 246 consecu-
tively treated DI patients, including cardiovascular disease
patients, patients with a history of other systemic disease, and
healthy controls, there were no significant differences in

implant failure rates between the groups.77
Moreover, in
several retrospective DI cohort studies where data regarding
local and systemic risk factors for implant failure had been
recorded, hypertension and coronary artery disease were not
associated with a significant increase in either early or late
implant failures.13,39,78
In a recent case–control study, it has been suggested that
intravenous sedation using midazolam and propofol during DI
surgery prevented excessive increases in blood pressure, and
stabilized haemodynamics,79
which could be useful in
patients with cardiovascular disease. However intravenous
midazolam does not prevent the myocardial arrhythmias that
may arise during DI placement.80
We could find no evidence that cardiac disorders are a
contraindication to DI but it is important to consider other
issues such as the occurrence of bleeding, or cardiac ischaemic
during DI insertion in these patients, and therefore, medical
advice should be procured before DI surgery (Table 1).22
8. Corticosteroid therapy
Corticosteroid adverse effects include reduced bone density,
increased epithelial fragility and immunosuppression.22
In
consequence, the use of systemic glucocorticoids might
compromise DI osseointegration and peri-implant healing.81
In animal models, osseointegration of implants in rabbits
under experimental osteoporosis-like bone induced by gluco-
corticoids appeared to be compromised, which could affect
biomechanical stability of implants.82
However, in most of
these studies implants were placed in extraoral bones (i.e.
femur or tibia), and it has been suggested that steroid
administration could have less effect on the osseointegration
of titanium implants in the mandible than in the skeletal
bone.83
To the best of our knowledge no relevant series have
been published to demonstrate if DI failure rate and/or
perioperative morbidity may increase in patients under
systemic corticosteroids.
There is no evidence that corticosteroid therapy is a
contraindication to DI, but it is important to consider that
systemic corticosteroids can cause suppression of the
hypothalamo–pituitary–adrenal axis and therefore, stan-
dard recommendations for any oral surgery in patients on
steroid therapy should be implemented.22
The Medicines
Control Agency still advise in patients who have finished a
course of systemic corticosteroids of less than 3 weeks
duration and might be under stresses such as trauma,
surgery or infection and who are at risk of adrenal
insufficiency, to receive systemic corticosteroid cover
during these periods (http://www.mca.gov.uk/ourwork/
monitorsafequalmed/currentproblems/volume24-
may.htm). In patients on less than 10 mg prednisolone daily
(as recommended by Nicholson et al),84
no significant events
have been reported after oral surgery without steroid
cover.85
In summary, although there is no evidence that cortico-
steroid therapy is a contraindication to DI, medical advice
should be procured in these patients prior to DI and medico-
legal and other considerations suggest that steroid cover
should be provided (Table 1).
9. Diabetes mellitus
Most caseseries, cohort studies, andsystematicreviews support
that DI in diabetics with good metabolic control have similar
success rates when compared to matched healthy controls,86–89
maintenance programme receiving conventional or advanced
implant surgery (sinus floor elevation, immediate loading, and
guided bone regeneration).90
However, impaired implant inte-
gration has been reported in relation to hyperglycaemic
conditions in diabetic patients91
and in animal models.37,92
In
a systematic literature search including 18 studies published up
to 2009, the authors concluded that poorly controlled diabetes
negatively affects implant osseointegration.93
This fact is
consistent with the known effects of hyperglycaemic states
on impaired immunity, microvascular complications and/or
osteoporosis.Paradoxically,inarecentcriticalreviewithasbeen
suggested that clinical evidence is lacking for the association of
glycaemic control with implant failure, because the identifica-
tion and reporting of glycaemic control was insufficient or
lacking in most of the published studies.94
In summary, there is no evidence that diabetes is a
contraindication to DI therapy, but as HbA1C (glycosylated
haemoglobin) may represent an independent factor correlated
with postoperative complications90
and due to the known
effects of hyperglycaemic states on healing, medical advice
and strict glycaemic control before and after DI therapy are
recommended (Table 1).22,87,95,96
Antimicrobial cover using
penicillin, amoxicillin, clindamycin or metronidazole should
be provided during the implant surgery.97
These patients
should also quit smoking, optimize oral hygiene measures and
use antiseptic mouthrinses to prevent the occurrence of
periodontal and peri-implant infections.88,93,95
As implant
surgery is never a matter of urgency, it has been suggested that
patients should be conjointly selected and prepared by both
dental practitioner and diabetes clinician.95
10. Hyposalivation
Theoretically DI may help prosthesis retention in patients
with dry mouth (hyposalivation). Although cases with
hyposalivation have been successfully managed with DI98,99
and even 7 out of 8 patients with Sjo¨gren syndrome improved
their oral comfort levels with implant-retained prostheses,100
there are no systematic studies evaluating the outcomes of DI
therapy in these patients (Table 1).
A retrospective study on patients suffering from rheu-
matic disorders such as rheumatoid arthritis and other
connective tissue diseases and compromised salivary flow
showed high implant survival rates (cumulative 3-year
implant success rate of 96.1%). Patients with rheumatoid
arthritis demonstrated acceptable marginal bone resorption
and good soft tissue conditions, while other connective
tissue diseases patients showed increased bone resorption
and peri-implant soft tissue alterations in scleroderma
patients and patients suffering from Sjo¨ gren syndrome.36
The severity of the salivary flow alteration, together with the
patient’s medical condition should be evaluated before
recommending DI placement.98

Anecdotally, a case report has been published on an
innovative saliva electrostimulation device fixed on a DI,
placed in the lower third molar area.101
11. Immunocompromised patients
It would be reasonable to assume that DI might be contra-
indicated in immunocompromised patients. In fact, in animal
models it has been shown that ciclosporin impairs peri-
implant bone healing and implant osseointegration.102
How-
ever, many patients receiving organ transplantation (mainly
liver and kidney) with long-term ciclosporin therapy, have had
successful DI therapy.103–106
Similarly, no significant problems after dento-alveolar
surgery have been reported in HIV-positive patients.107,108
In
a series of 20 HIV-positive subjects with mean CD4 count of
467 cells/mm3
(range: 132–948), two dental implants were
placed in the anterior mandible to support an overdenture,
and the short-term (6 months) success rate was 100%.109
In a
recently published case–control series of HIV-positive patients
receiving different regimens of highly active anti-retroviral
therapy, after assessing peri-implant health at 6 and 12
months, the authors concluded that DI may represent a
reasonable treatment option in HIV-positive patients, regard-
less of CD4 cell count, viral load levels and type of antiretrovi-
ral therapy.110
It seems that DI are well tolerated and have
predictable short-term outcomes for HIV-infected individuals,
but published evidence is scarce and the predictability of the
long-term success remains unknown. It would seem prudent
to carry out DI when CD4 rates are high and the patient is on
antiretroviral therapy.
Crohn’s disease has also been suggested as a relative
contraindication for DI.8
Crohn’s disease is associated with
nutritional and immune defects, and hence, it may impair DI
success.39
However, in a retrospective study 11 of 12 DI placed
in Crohn’s disease patients integrated successfully.13
Severe periodontitis is frequent in patients with congenital
neutrophil deficiencies and therefore, high occurrence of peri-
implant infection should be expected when implants are
placed in these patients. There are, however, some case
reports of successful implant placement in patients with
Papillon-Lefevre syndrome111
and von Gierke syndrome.112
In summary, there is no evidence that immunoincompe-
tence is a contraindication to DI therapy, but medical advice
should be procured before considering DI therapy and strict
anti-infective measures should be enforced when treating
these patients (Table 1).22
12. Mucosal disease
There are numerous case reports and case series documenting
the success of DI in patients with a range of mucosal
conditions113
including ectodermal dysplasia,114–117
epider-
molysis bullosa118–120
and in lichen planus (Table 1).121
DI is often the treatment of choice in patients with
ectodermal dysplasia with severe oligodontia or hypodontia.
The largest published series report outcomes in 51 and 33
patients, with 264 and 186 implants respectively.118,122
Presence of a limited amount of bone was a common finding,
particularly in the upper arch, and often requires extensive
bone regenerative procedures. Some case-series have shown
that results of DI and bone grafts in adult patients affected by
ectodermal dysplasia were similar to those achieved in
unaffected patients.123
Most series demonstrate an excellent implant success rate
in adults with ectodermal dysplasia,113
although results
reported in children and adolescents mainly when implants
were placed in the maxilla or the symphyseal region of the
anterior mandible have been less encouraging.124,125
The most
appropriate age for dental implant treatment in growing
children remains controversial.117,126
A recent review, included 7 studies describing 17 patients
with epidermolysis bullosa receiving 102 implants and being
followed for 12 to 108 months: the implant success rate was
close to 100%.127
In a small case series DI showing dehiscence
or fenestration were placed simultaneously with particulated
bone grafts to cover exposed threads, all implants surviving
after a minimum follow-up of 12 months.128
The main
reported complication during the implant surgical procedure
was the formation of bleeding blisters by minimal trauma.
During the follow-up period many patients also developed
ulcers in the areas of prosthesis contact, but these complica-
tions did not affect the successful implant outcome. A fixed
full-arch short-expand prostheses supported by four DI has
been successfully used in patients with recessive dystrophic
epidermolysis bullosa, minimizing oral mucosa surface
contact and improving the patients’ quality of life. 129
It has been suggested that dental implants are not ideal for
patients with oral lichen planus because of the limited
capacity of the involved epithelium to adhere to the titanium
surface.7
Despite the generalized use of DI, very few case
reports have been documented, all of them with successful
outcome.121,130
Recently, two case–control studies including
14 and 18 oral lichen planus patients have been published,
with no implant failure recorded during the follow-up period
(12–53 months).131,132
Peri-implant mucositis and peri-implan-
titis seem to be slightly more frequent in patients with oral
lichen planus than in controls, and desquamative gingivitis
was associated with a higher rate of peri-implant mucositis.132
Implant placement does not influence the disease manifesta-
tions.131
As malignant transformation has been observed in
few cases of oral lichen planus, careful long-term monitoring
of both lesions and dental implants is recommended.113
13. Neuro-psychiatric disorders
The literature with respect to DI placement in patients with
neuro-psychiatric disorders is sparse and contradictory. Some
case reports and case series have shown DI treatment to be
successful in some patients with various degrees of both
intellectual and physical disability, including cases of cerebral
palsy, Down syndrome, psychiatric disorders, dementia,
bulimia, Parkinson disease and severe epilepsy.133–141
Howev-
er, poor oral hygiene, oral parafunctions such as bruxism,
harmful habits such as repeated introduction of the fingers
into the mouth and behavioural problems are not uncommon
in patients with neuro-psychiatric diseases, and DI in such

patients may lead to complications. Therefore, the success of
oral rehabilitation depends fundamentally on appropriate
patient selection141
and adequate medical advice should be
seeked prior to implant therapy (Table 1).139
14. Titanium allergy
Degradation products of metallic biomaterials may result in
metal hypersensitivity reactions.142
Recently, it has been
suggested that titanium, formerly considered an inert
material, can induce toxicity or allergic type I or IV reactions
in susceptible patients and could play a critical role in
implant failure.143,144
In a systematic review including 7
studies it has been shown that titanium allergy develops
among patients at every age, the most common clinical
manifestations being dermal inflammatory conditions and
gingival hyperplasia.145
The prevalence of titanium allergy
remains unknown but it has been estimated to be 0.6%
among DI patients.146
A significantly higher risk of positive
allergic reactions was found in patients showing allergic
symptoms after implant placement or unexplained implant
failures.146
The risk of an allergy to titanium is increased in patients
who are allergic to other metals. In these patients, an
evaluation of allergy is recommended, in order to exclude
any problem with titanium medical devices,143
and long-term
clinical and radiographic follow-up has been recom-
mended.144
Even in confirmed titanium-allergic patients it
may be possible by using alternative materials (e.g. zirconium
oxide dental implants) to achieve DI rehabilitation.147
15. Conclusions
In conclusion there are very few absolute contraindications to
DI treatment, although a number of conditions may increase
the risk of treatment failure or complications. However, due to
the scarcity of prospective studies the impact of health risks
on implant outcome remains unclear and well-designed
observational studies are needed.
The degree of disease-control may be far more important
that the nature of the systemic disorder itself, and individu-
alized medical control should be procured prior to implant
therapy, since in many of these patients the quality of life and
functional benefits of dental implants may outweigh any
risks.
As in any clinical decision in dentistry, the range of
treatment options and their relative advantages and dis-
advantages should be carefully assessed in relation to the
patient’s needs and wishes. In patients with systemic
conditions, it is important to weigh carefully the cost-benefit
analysis with the patient’s quality of life and life expectancy
and it is very important to undertake the implant surgical
procedures with strict asepsis, minimal trauma, and avoiding
stress and undue haemorrhage. Equally it is very important in
these patients to ensure proper maintenance therapy with
optimal standards of oral hygiene, without smoking and with
avoidance of any other risk factors that may affect the
outcome of dental implants.
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