Review

Dental implants in the medically compromised patient

Pedro Diz a,*, Crispian Scully b, Mariano Sanz c

aGrupo de Investigacion en Odontologıa Medico-Quiru rgica (OMEQUI), School of Medicine and Dentistry, University of Santiago de

Compostela, SpainbUniversity College London, UKcGrupo de Investigacion en Etiologıa y Terapeutica Periodontal (ETEP), School of Dentistry, Complutense University of Madrid, Spain

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.

Available online at www.sciencedirect.com

journal homepage: www.intl.elsevierhealth.com/journals/jden

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

* Corresponding author at: Stomatology Department, School of Medicisn, 15782 Santiago de Compostela, La Coruna, Spain. Tel.: +34 881812

E-mail address: pedro.diz@usc.es (P. Diz).

0300-5712/$ – see front matter # 2013 Elsevier Ltd. All rights reservedhttp://dx.doi.org/10.1016/j.jdent.2012.12.008

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 compromisedpatients

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

ne and Dentistry, Santiago de Compostela University, c/Entrerrıos344.

.

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 6196

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.17,18In 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,

implant surgery could be regarded in terms of surgical trauma to

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 conditionis an absolute/relativecontraindication to DI

DI success ratecompared to healthy

population (levelof evidencea)

Other considerations Managementmodifications thatmay 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

Antibiotic prophylaxis

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)

Antibiotic prophylaxis

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

Table 1 (Continued )

Condition Evidence conditionis an absolute/relativecontraindication to DI

DI success ratecompared to healthy

population (levelof evidencea)

Other considerations Managementmodifications thatmay 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.

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 6198

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

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 6 199

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

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 6200

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 case series, cohort studies, and systematic reviews 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, in a recent critical review it has been

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 Sjogren 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 Sjogren syndrome.36

The severity of the salivary flow alteration, together with the

patient’s medical condition should be evaluated before

recommending DI placement.98

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 6 201

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

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 6202

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.

r e f e r e n c e s

1. Spiekermann H, Jansen VK, Richter EJ. A 10-year follow-upstudy of IMZ and TPS implants in the edentulous mandibleusing bar-retained overdentures. International Journal of Oraland Maxillofacial Implants 1995;10:231–43.

2. Li KK, Varvares MA, Meara JG. Descending necrotizingmediastinitis: a complication of dental implant surgery.Head and Neck 1996;18:192–6.

3. Mordenfeld A, Andersson L, Bergstrom B. Hemorrhage inthe floor of the mouth during implant placement in theedentulous mandible: a case report. International Journal ofOral and Maxillofacial Implants 1997;12:558–61.

4. Givol N, Chaushu G, Halamish-Shani T, Taicher S.Emergency tracheostomy following life-threateninghemorrhage in the floor of the mouth during immediateimplant placement in the mandibular canine region.Journal of Periodontology 2000;71:1893–5.

5. Isaacson TJ. Sublingual hematoma formation duringimmediate placement of mandibular endosseousimplants. Journal of the American Dental Association2004;135:168–72.

6. Kalpidis CD, Setayesh RM. Hemorrhaging associated withendosseous implant placement in the anterior mandible: areview of the literature. Journal of Periodontology 2004;75:631–45.

7. Sugerman PB, Barber MT. Patient selection for endosseousdental implants: oral and systemic considerations.International Journal of Oral and Maxillofacial Implants2002;17:191–201.

8. Balshi TJ, Wolfinger GJ. Management of the posteriormaxilla in the compromised patient: historical, current,and future perspectives. Periodontology 2000 2003;33:67–81.

9. Hwang D, Wang HL. Medical contraindications to implanttherapy. Part II. Relative contraindications. Implant Dentistry2007;16:13–23.

10. Hwang D, Wang HL. Medical contraindications to implanttherapy. Part I. Absolute contraindications. ImplantDentistry 2006;15:353–60.

11. Meijer GJ, Cune MS. Surgical dilemmas. Medicalrestrictions and risk factors. Nederlands Tijdschrift VoorTandheelkunde 2008;115:643–51.

12. Scully C, Hobkirk J, Dios PD. Dental endosseous implants inthe medically compromised patient. Journal of OralRehabilitation 2007;34:590–9.

13. Alsaadi G, Quirynen M, Komarek A, van Steenberghe D.Impact of local and systemic factors on the incidence oflate oral implant loss. Clinical Oral Implants Research 2008;19:670–6.

14. OCEBM Levels of Evidence Working Group. ‘‘The Oxford2009 Levels of Evidence’’. Oxford Centre for Evidence-BasedMedicine. http://www.cebm.net/index.aspx?o=1025[accessed November 2011].

15. Koo S, Konig Jr B, Mizusaki CI, Allegrini Jr S, Yoshimoto M,Carbonari MJ. Effects of alcohol consumption onosseointegration of titanium implants in rabbits. ImplantDentistry 2004;13:232–7.

16. Marchini L, de Deco CP, Marchini AP, Barbara MA,Vasconcellos LM, Rocha RF, et al. Negative effects of alcoholintake and estrogen deficiency combination onosseointegration in a rat model. Journal of Oral Implantology2011. April 19 [Epub ahead of print].

17. Galindo-Moreno P, Fauri M, Avila-Ortiz G, Fernandez-Barbero JE, Cabrera-Leon A, Sanchez-Fernandez E.Influence of alcohol and tobacco habits on peri-implantmarginal bone loss: a prospective study. Clinical OralImplants Research 2005;16:579–86.

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 6 203

18. Alissa R, Oliver R. Influence of prognostic risk indicators onosseointegrated dental implant failure: a matched case–control analysis. Journal of Oral Implantology 2011;38:51–61.

19. Goodacre CJ, Bernal G, Rungcharassaeng K, Kan JY. Clinicalcomplications with implants and implant prostheses.Journal of Prosthetic Dentistry 2003;90:121–32.

20. Gornitsky M, Hammouda W, Rosen H. Rehabilitation of ahemophiliac with implants: a medical perspective and casereport. Journal of Oral and Maxillofacial Surgery 2005;63:592–7.

21. Kalpidis CD, Konstantinidis AB. Critical hemorrhage in thefloor of the mouth during implant placement in the firstmandibular premolar position: a case report. ImplantDentistry 2005;14:117–24.

22. Scully C. Medical problems in dentistry. 6th ed. London:Elsevier; 2010.

23. Madrid C, Sanz M. What influence do anticoagulants haveon oral implant therapy? A systematic review. Clinical OralImplants Research 2009;20:96–106.

24. Bacci C, Berengo M, Favero L, Zanon E. Safety of dentalimplant surgery in patients undergoing anticoagulationtherapy: a prospective case–control study. Clinical OralImplants Research 2011;22:151–6.

25. Hong CH, Napenas JJ, Brennan MT, Furney SL, Lockhart PB.Frequency of bleeding following invasive dentalprocedures in patients on low-molecular-weight heparintherapy. Journal of Oral and Maxillofacial Surgery 2010;68:975–9.

26. Napenas JJ, Hong CH, Brennan MT, Furney SL, Fox PC,Lockhart PB. The frequency of bleeding complications afterinvasive dental treatment in patients receiving single anddual antiplatelet therapy. Journal of the American DentalAssociation 2009;140:690–5.

27. Zola MB. Staged sinus augmentation and implantplacement in a patient with osteogenesis imperfecta.Journal of Oral and Maxillofacial Surgery 2000;58:443–7.

28. Lee CY, Ertel SK. Bone graft augmentation and dentalimplant treatment in a patient with osteogenesisimperfecta: review of the literature with a case report.Implant Dentistry 2003;12:291–5.

29. Binger T, Rucker M, Spitzer WJ. Dentofacial rehabilitationby osteodistraction, augmentation and implantationdespite osteogenesis imperfecta. International Journal of Oraland Maxillofacial Surgery 2006;35:559–62.

30. Prabhu N, Duckmanton N, Stevenson AR, Cameron A. Theplacement of osseointegrated dental implants in a patientwith type IV B osteogenesis imperfecta: a 9-year follow-up.Oral Surgery Oral Medicine Oral Pathology Oral Radiology andEndodontics 2007;103:349–54.

31. Payne MA, Postlethwaite KR, Smith DG, Nohl FS. Implant-supported rehabilitation of an edentate patient withosteogenesis imperfecta: a case report. International Journalof Oral and Maxillofacial Implants 2008;23:947–52.

32. Wannfors K, Johansson C, Donath K. Augmentation of themandible via a ‘‘tent-pole’’ procedure and implanttreatment in a patient with type III osteogenesisimperfecta: clinical and histologic considerations.International Journal of Oral and Maxillofacial Implants2009;24:1144–8.

33. Eder A, Watzek G. Treatment of a patient with severeosteoporosis and chronic polyarthritis with fixed implant-supported prosthesis: a case report. International Journal ofOral and Maxillofacial Implants 1999;14:587–90.

34. Barker D, Nohl FS, Postlethwaite KR, Smith DG. Case reportof multiple implant failure in a patient with ankylosingspondylitis. European Journal of Prosthodontics and RestorativeDentistry 2008;16:20–3.

35. Krennmair G, Seemann R, Piehslinger E. Dental implants inpatients with rheumatoid arthritis: clinical outcome and

peri-implant findings. Journal of Clinical Periodontology2010;37:928–36.

36. Weinlander M, Krennmair G, Piehslinger E. Implantprosthodontic rehabilitation of patients with rheumaticdisorders: a case series report. International Journal ofProsthodontics 2010;23:22–8.

37. Glosel B, Kuchler U, Watzek G, Gruber R. Review of dentalimplant rat research models simulating osteoporosis ordiabetes. International Journal of Oral and MaxillofacialImplants 2010;25:516–24.

38. Blomqvist JE, Alberius P, Isaksson S, Linde A, Hansson BG.Factors in implant integration failure after bone grafting:an osteometric and endocrinologic matched analysis.International Journal of Oral and Maxillofacial Surgery1996;25:63–8.

39. Alsaadi G, Quirynen M, Komarek A, van Steenberghe D.Impact of local and systemic factors on the incidence oforal implant failures, up to abutment connection. Journal ofClinical Periodontology 2007;34:610–7.

40. Slagter KW, Raghoebar GM, Vissink A. Osteoporosis andedentulous jaws. International Journal of Prosthodontics2008;21:19–26.

41. Dvorak G, Arnhart C, Heuberer S, Huber CD, Watzek G,Gruber R. Peri-implantitis and late implant failures inpostmenopausal women: a cross-sectional study. Journal ofClinical Periodontology 2011;38:950–5.

42. Friberg B, Ekestubbe A, Mellstrom D, Sennerby L.Branemark implants and osteoporosis: a clinicalexploratory study. Clinical Implant Dentistry and RelatedResearch 2001;3:50–6.

43. Bornstein MM, Cionca N, Mombelli A. Systemic conditionsand treatments as risks for implant therapy. InternationalJournal of Oral and Maxillofacial Implants 2009;24:12–27.

44. Dao TT, Anderson JD, Zarb GA. Is osteoporosis a risk factorfor osseointegration of dental implants? InternationalJournal of Oral and Maxillofacial Implants 1993;8:137–44.

45. Holahan CM, Wiens JL, Weaver A, Assad D, Koka S.Relationship between systemic bone mineral density andlocal bone quality as effectors of dental implant survival.Clinical Implant Dentistry and Related Research 2011;13:29–33.

46. Gaetti-Jardim EC, Santiago-Junior JF, Goiato MC, Pellizer EP,Magro-Filho O, Jardim Junior EG. Dental implants inpatients with osteoporosis: a clinical reality? Journal ofCraniofacial Surgery 2011;22:1111–3.

47. Starck WJ, Epker BN. Failure of osseointegrated dentalimplants after diphosphonate therapy for osteoporosis: acase report. International Journal of Oral and MaxillofacialImplants 1995;10:74–8.

48. Ferlito S, Liardo C, Puzzo S. Bisphosphonates and dentalimplants: a case report and a brief review of literature.Minerva Stomatologica 2011;60:75–81.

49. Flichy-Fernandez AJ, Balaguer-Martınez J, Penarrocha-Diago M, Bagan JV. Bisphosphonates and dental implants:current problems. Medicina Oral Patologıa Oral y Cirugıa Bucal2009;14:E355–60.

50. Wang HL, Weber D, McCauley LK. Effect of long-term oralbisphosphonates on implant wound healing: literaturereview and a case report. Journal of Periodontology2007;78:584–94.

51. Lazarovici TS, Yahalom R, Taicher S, Schwartz-Arad D,Peleg O, Yarom N. Bisphosphonate-related osteonecrosis ofthe jaw associated with dental implants. Journal of Oral andMaxillofacial Surgery 2010;68:790–6.

52. Jacobsen C, Metzler P, Rossle M, Obwegeser J, Zemann W,Gratz KW. Osteopathology induced by bisphosphonatesand dental implants: clinical observations. Clinical OralInvestigations 2012. [Epub ahead of print].

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 6204

53. Memon S, Weltman RL, Katancik JA. Oral bisphosphonates:early endosseous dental implant success and crestal bonechanges. A retrospective study. International Journal of Oraland Maxillofacial Implants 2012;27:1216–22.

54. Grant BT, Amenedo C, Freeman K, Kraut RA. Outcomes ofplacing dental implants in patients taking oralbisphosphonates: a review of 115 cases. Journal of Oral andMaxillofacial Surgery 2008;66:223–30.

55. Goss A, Bartold M, Sambrook P, Hawker P. The nature andfrequency of bisphosphonate-associated osteonecrosis ofthe jaws in dental implant patients: a South Australiancase series. Journal of Oral and Maxillofacial Surgery 2010;68:337–43.

56. Advisory Task Force on Bisphosphonate-relatedOstenonecrosis of the Jaws. American Association of Oraland Maxillofacial Surgeons. American Association of Oraland Maxillofacial Surgeons position paper onbisphosphonate-related osteonecrosis of the jaws. Journalof Oral and Maxillofacial Surgery 2007;65:369–76.

57. Madrid C, Sanz M. What impact do systemicallyadministrated bisphosphonates have on oral implanttherapy? A systematic review. Clinical Oral Implants Research2009;20:87–95.

58. Javed F, Almas K. Osseointegration of dental implants inpatients undergoing bisphosphonate treatment: aliterature review. Journal of Periodontology 2010;81:479–84.

59. Otomo-Corgel J. Osteoporosis and osteopenia: implicationsfor periodontal and implant therapy. Periodontology 20002012;59:111–39.

60. Maurer P, Sandulescu T, Kriwalsky MS, Rashad A, HollsteinS, Stricker I, et al. Bisphosphonate-related osteonecrosis ofthe maxilla and sinusitis maxillaris. International Journal ofOral and Maxillofacial Surgery 2011;40:285–91.

61. Kim DD, Ghali GE. Dental implants in oral cancerreconstruction. Dental Clinics of North America 2011;55:871–82.

62. Nelson K, Heberer S, Glatzer C. Survival analysis andclinical evaluation of implant-retained prostheses in oralcancer resection patients over a mean follow-up period of10 years. Journal of Prosthetic Dentistry 2007;98:405–10.

63. Barrowman RA, Wilson PR, Wiesenfeld D. Oralrehabilitation with dental implants after cancer treatment.Australian Dental Journal 2011;56:160–5.

64. Jokstad A. Patients undergoing craniofacial tumourablation surgery may benefit from having the implantsplaced simultaneously instead of waiting. Evidence BasedDentistry 2010;11:52–3.

65. Korfage A, Schoen PJ, Raghoebar GM, Roodenburg JL,Vissink A, Reintsema H. Benefits of dental implantsinstalled during ablative tumour surgery in oral cancerpatients: a prospective 5-year clinical trial. Clinical ImplantDentistry and Related Research 2010;21:971–9.

66. Linsen SS, Martini M, Stark H. Long-term results ofendosteal implants following radical oral cancer surgerywith and without adjuvant radiation therapy. ClinicalImplant Dentistry and Related Research 2012;14:250–8.

67. Harrison JS, Stratemann S, Redding SW. Dental implantsfor patients who have had radiation treatment for headand neck cancer. Special Care in Dentistry 2003;23:223–9.

68. Javed F, Al-Hezaimi K, Al-Rasheed A, Almas K, RomanosGE. Implant survival rate after oral cancer therapy: areview. Oral Oncology 2010;46:854–9.

69. Wagner W, Esser E, Ostkamp K. Osseointegration of dentalimplants in patients with and without radiotherapy. ActaOncologica 1998;37:693–6.

70. Mancha de la Plata M, Gıas LN, Dıez PM, Munoz-Guerra M,Gonzalez-Garcıa R, Lee GY, et al. Osseointegrated implantrehabilitation of irradiated oral cancer patients. Journal ofOral and Maxillofacial Surgery 2012;70:1052–63.

71. Kahnberg KE. Functional rehabilitation using orthognathicsurgery, bone transplants and implants after irradiation ofmalignancy in early childhood. Swedish Dental Journal2002;26:99–106.

72. Landes CA, Kovacs AF. Comparison of early telescopeloading of non-submerged ITI implants in irradiated andnon-irradiated oral cancer patients. Clinical Oral ImplantsResearch 2006;17:367–74.

73. Granstrom G. Radiotherapy, osseointegration andhyperbaric oxygen therapy. Periodontology 2000 2003;33:145–62.

74. Coulthard P, Patel S, Grusovin GM, Worthington HV,Esposito M. Hyperbaric oxygen therapy for irradiatedpatients who require dental implants: a cochrane review ofrandomised clinical trials. European Journal of OralImplantology 2008;1:105–10.

75. Kovacs AF. Influence of chemotherapy on endostealimplant survival and success in oral cancer patients.International Journal of Oral and Maxillofacial Surgery2001;30:144–7.

76. Karr RA, Kramer DC, Toth BB. Dental implants andchemotherapy complications. Journal of Prosthetic Dentistry1992;67:683–7. [Review].

77. Khadivi V, Anderson J, Zarb GA. Cardiovascular diseaseand treatment outcomes with osseointegration surgery.Journal of Prosthetic Dentistry 1999;81:533–6.

78. Moy PK, Medina D, Shetty V, Aghaloo TL. Dental implantfailure rates and associated risk factors. International Journalof Oral and Maxillofacial Implants 2005;20:569–77.

79. Taguchi T, Fukuda K, Sekine H, Kakizawa T. Intravenoussedation and hemodynamic changes during dentalimplant surgery. International Journal of Oral and MaxillofacialImplants 2011;26:1303–8.

80. Romano MM, Soares MS, Pastore CA, Tornelli MJ, deOliveira Guare R, Adde CA. A study of effectiveness ofmidazolam sedation for prevention of myocardialarrhythmias in endosseous implant placement. Clinical OralImplants Research 2012;23:489–95.

81. Bencharit S, Reside GJ, Howard-Williams EL. Complexprosthodontic treatment with dental implants for apatient with polymyalgia rheumatica: a clinical report.International Journal of Oral and Maxillofacial Implants2010;25:1241–5.

82. Keller JC, Stewart M, Roehm M, Schneider GB.Osteoporosis-like bone conditions affect osseointegrationof implants. International Journal of Oral and MaxillofacialImplants 2004;19:687–94.

83. Fujimoto T, Niimi A, Sawai T, Ueda M. Effects of steroid-induced osteoporosis on osseointegration of titaniumimplants. International Journal of Oral and MaxillofacialImplants 1998;13:183–9.

84. Nicholson G, Burrin JM, Hall GM. Peri-operative steroidsupplementation. Anaesthesia 1998;53:1091–104.

85. Thomason JM, Girdler NM, Kendall-Taylor P, Wastell H,Weddel A, Seymour RA. An investigation into the need forsupplementary steroids in organ transplant patientsundergoing gingival surgery. A double-blind, split-mouth,cross-over study. Journal of Clinical Periodontology1999;26:577–82.

86. Dowell S, Oates TW, Robinson M. Implant success inpeople with type 2 diabetes mellitus with varying glycemiccontrol: a pilot study. Journal of the American DentalAssociation 2007;138:355–61.

87. Michaeli E, Weinberg I, Nahlieli O. Dental implants in thediabetic patient: systemic and rehabilitativeconsiderations. Quintessence International 2009;40:639–45.

88. Anner R, Grossmann Y, Anner Y, Levin L. Smoking,diabetes mellitus, periodontitis, and supportiveperiodontal treatment as factors associated with dental

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 6 205

implant survival: a long-term retrospective evaluation ofpatients followed for up to 10 years. Implant Dentistry2010;19:57–64.

89. Turkyilmaz I. One-year clinical outcome of dental implantsplaced in patients with type 2 diabetes mellitus: a caseseries. Implant Dentistry 2010;19:323–9.

90. Tawil G, Younan R, Azar P, Sleilati G. Conventional andadvanced implant treatment in the type II diabetic patient:surgical protocol and long-term clinical results.International Journal of Oral and Maxillofacial Implants2008;23:744–52.

91. Oates TW, Dowell S, Robinson M, McMahan CA. Glycemiccontrol and implant stabilization in type 2 diabetesmellitus. Journal of Dental Research 2009;88:367–71.

92. Wang F, Song YL, Li DH, Li CX, Wang Y, Zhang N, et al. Type2 diabetes mellitus impairs bone healing of dental implantsin GK rats. Diabetes Research and Clinical Practice 2010;88:7–9.

93. Javed F, Romanos GE. Impact of diabetes mellitus andglycemic control on the osseointegration of dentalimplants: a systematic literature review. Journal ofPeriodontology 2009;80:1719–30.

94. Oates TW, Huynh-Ba G, Vargas A, Alexander P, Feine J. Acritical review of diabetes, glycemic control, and dentalimplant therapy. Clinical Oral Implants Research 2011. [Epubahead of print].

95. Marchand F, Raskin A, Dionnes-Hornes A, Barry T, DuboisN, Valero R, et al. Dental implants and diabetes: conditionsfor success. Diabetes & Metabolism 2012;38:14–9.

96. Courtney Jr MW, Snider TN, Cottrell DA. Dental implantplacement in type II diabetics: a review of the literature.Journal of the Massachusetts Dental Society 2010;59:12–4.

97. Beikler T, Flemmig TF. Implants in the medicallycompromised patient. Critical Reviews in Oral Biology andMedicine 2003;14:305–16.

98. Payne AG, Lownie JF, Van Der Linden WJ. Implant-supported prostheses in patients with Sjogren’s syndrome:a clinical report on three patients. International Journal ofOral and Maxillofacial Implants 1997;12:679–85.

99. Binon PP. Thirteen-year follow-up of a mandibularimplant-supported fixed complete denture in a patientwith Sjogren’s syndrome: a clinical report. Journal ofProsthetic Dentistry 2005;94:409–13.

100. Isidor F, Brondum K, Hansen HJ, Jensen J, Sindet-PedersenS. Outcome of treatment with implant-retained dentalprosthesis in patients with Sjogren syndrome. InternationalJournal of Oral and Maxillofacial Implants 1999;14:736–43.

101. Ami S, Wolff A. Implant-supported electrostimulatingdevice to treat xerostomia: a preliminary study. ClinicalImplant Dentistry and Related Research 2010;12:62–71.

102. Sakakura CE, Marcantonio Jr E, Wenzel A, Scaf G. Influenceof cyclosporin A on quality of bone around integrateddental implants: a radiographic study in rabbits. ClinicalOral Implants Research 2007;18:34–9.

103. Heckmann SM, Heckmann JG, Linke JJ, Hohenberger W,Mombelli A. Implant therapy following livertransplantation: clinical and microbiological results after10 years. Journal of Periodontology 2004;75:909–13.

104. Gu L, Yu YC. Clinical outcome of dental implants placed inliver transplant recipients after 3 years: a case series.Transplant Proceedings 2011;43:2678–82.

105. Gu L, Wang Q, Yu YC. Eleven dental implants placed in aliver transplantation patient: a case report and 5-yearclinical evaluation. Chinese Medical Journal (English)2011;124:472–5.

106. Dijakiewicz M, Wojtowicz A, Dijakiewicz J, Szycik V,Rutkowski P, Rutkowski B. Is implanto-prosthodontictreatment available for haemodialysis patients? NephrologyDialysis Transplantation 2007;22:2722–4.

107. Porter SR, Scully C, Luker J. Complications of dental surgeryin persons with HIV disease. Oral Surgery Oral Medicine andOral Pathology 1993;75:165–7.

108. Scully C, Watt-Smith P, Dios P, Giangrande PLF.Complications in HIV-infected and non-HIV-infectedhemophiliacs and other patients after oral surgery.International Journal of Oral and Maxillofacial Surgery2002;31:634–40.

109. Stevenson GC, Riano PC, Moretti AJ, Nichols CM,Engelmeier RL, Flaitz CM. Short-term success ofosseointegrated dental implants in HIV-positiveindividuals: a prospective study. Journal of ContemporaryDental Practice 2007;8:1–10.

110. Oliveira MA, Gallottini M, Pallos D, Maluf PS, Jablonka F,Ortega JL. The success of endosseous implants in humanimmunodeficiency virus-positive patients receivingantiretroviral therapy: a pilot study. Journal of the AmericanDental Association 2011;142:1010–6.

111. Ahmadian L, Monzavi A, Arbabi R, Hashemi HM. Full-mouth rehabilitation of an edentulous patient withPapillon-Lefevre syndrome using dental implants: aclinical report. Journal of Prosthodontics 2011. October 4[Epub ahead of print].

112. Diz Dios P, Ocampo Hermida A, Fernandez Feijoo J.Quantitative and functional neutrophil deficiencies.Medicina Oral 2002;7:206–21.

113. Candel-Marti ME, Ata-Ali J, Penarrocha-Oltra D,Penarrocha-Diago M, Bagan JV. Dental implants in patientswith oral mucosal alterations: an update. Medicina OralPatologıa Oral y Cirugıa Bucal 2011;16:e787–93.

114. Rad AS, Siadat H, Monzavi A, Mangoli AA. Full mouthrehabilitation of a hypohidrotic ectodermal dysplasiapatient with dental implants: a clinical report. Journal ofProsthodontics 2007;16:209–13.

115. Kirmeier R, Gluhak C, Marada P, Wegscheider WA, Eskici A,Jakse N. Oral rehabilitation of adult twins with severe lackof bone due to hypohidrotic ectodermal dysplasia – a 12-month follow-up. Journal of Oral and Maxillofacial Surgery2009;67:189–94.

116. Kearns G, Sharma A, Perrott D, Schmidt B, Kaban L,Vargervik K. Placement of endosseous implants in childrenand adolescents with hereditary ectodermal dysplasia. OralSurgery Oral Medicine Oral Pathology Oral Radiology andEndodontics 1999;88:5–10.

117. Guckes AD, Scurria MS, King TS, McCarthy GR, Brahim JS.Prospective clinical trial of dental implants in persons withectodermal dysplasia. Journal of Prosthetic Dentistry2002;88:21–599.

118. Penarrocha M, Serrano C, Sanchis JM, Silvestre FJ, Bagan JV.Placement of endosseous implants in patients with oralepidermolysis bullosa. Oral Surgery Oral Medicine OralPathology Oral Radiology and Endodontics 2000;90:587–90.

119. Larrazabal-Moron C, Boronat-Lopez A, Penarrocha-DiagoM, Penarrocha-Diago M. Oral rehabilitation with bone graftand simultaneous dental implants in a patient withepidermolysis bullosa: a clinical case report. Journal of Oraland Maxillofacial Surgery 2009;67:1499–502.

120. Penarrocha M, Rambla J, Balaguer J, Serrano C, Silvestre J,Bagan JV. Complete fixed prostheses over implants inpatients with oral epidermolysis bullosa. Journal of Oral andMaxillofacial Surgery 2007;65:103–6.

121. Esposito SJ, Camisa C, Morgan M. Implant retainedoverdentures for two patients with severe lichen planus: aclinical report. Journal of Prosthetic Dentistry 2003;89:6–10.

122. Garagiola U, Maiorana C, Ghiglione V, Marzo G, Santoro F,Szabo G. Osseointegration and guided bone regeneration inectodermal dysplasia patients. Journal of Craniofacial Surgery2007;18:1296–304.

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 6206

123. Grecchi F, Zingari F, Bianco R, Zollino I, Casadio C, CarinciF. Implant rehabilitation in grafted and native bone inpatients affected by ectodermal dysplasia: evaluation of 78implants inserted in 8 patients. Implant Dentistry2010;19:400–8.

124. Sweeney IP, Ferguson JW, Heggie AA, Lucas JO. Treatmentoutcomes for adolescent ectodermal dysplasia patientstreated with dental implants. International Journal ofPaediatric Dentistry 2005;15:241–8.

125. Bergendal B, Ekman A, Nilsson P. Implant failure in youngchildren with ectodermal dysplasia: a retrospectiveevaluation of use and outcome of dental implanttreatment in children in Sweden. International Journal of Oraland Maxillofacial Implants 2008;23:520–4.

126. Percinoto C, Vieira AE, Barbieri CM, Melhado FL, MoreiraKS. Use of dental implants in children: a literature review.Quintessence International 2001;32:381–3.

127. Feijoo JF, Bugallo J, Limeres J, Penarrocha D, Penarrocha M,Diz P. Inherited epidermolysis bullosa: an update andsuggested dental care considerations. Journal of theAmerican Dental Association 2011;142:1017–25.

128. Penarrocha-Oltra D, Aloy-Prosper A, Ata-Ali J, Penarrocha-Diago M, Penarrocha-Diago M. Implants placedsimultaneously with particulated bone graft in patientsdiagnosed with recessive dystrophic epidermolysis bullosa.Journal of Oral and Maxillofacial Surgery 2012;70:e51–7.

129. Penarrocha-Oltra D, Penarrocha-Diago M, Balaguer-Martınez J, Ata-Ali J, Penarrocha-Diago M. Full-arch fixedprosthesis supported by four implants in patients withrecessive dystrophic epidermolysis bullosa. Oral SurgeryOral Medicine Oral Pathology Oral Radiology and Endodontics2011;112:e4–10.

130. Reichart PA. Oral lichen planus and dental implants.Report of 3 cases. International Journal of Oral andMaxillofacial Surgery 2006;35:237–40.

131. Czerninski R, Eliezer M, Wilensky A, Soskolne A. Orallichen planus and dental implants – a retrospective study.Clinical Implant Dentistry and Related Research 2011. [Epubahead of print].

132. Hernandez G, Lopez-Pintor RM, Arriba L, Torres J, deVicente JC. Implant treatment in patients with oral lichenplanus: a prospective-controlled study. Clinical OralImplants Research 2012;23:726–32.

133. Rogers JO. Implant-stabilized complete mandibulardenture for a patient with cerebral palsy. Dental Update1995;22:23–6.

134. Ambard A, Mueninghoff L. Rehabilitation of a bulimicpatient using endosteal implants. Journal of Prosthodontics2002;11:176–80.

135. Lopez-Jimenez J, Romero-Domınguez A, Gimenez-Prats MJ.Implants in handicapped patients. Medicina Oral2003;8:288–93.

136. Kubo K, Kimura K. Implant surgery for a patient withParkinson’s disease controlled by intravenous midazolam:a case report. International Journal of Oral and MaxillofacialImplants 2004;19:288–90.

137. Ekfeldt A. Early experience of implant-supportedprostheses in patients with neurologic disabilities.International Journal of Prosthodontics 2005;18:132–8.

138. Oczakir C, Balmer S, Mericske-Stern R. Implant-prosthodontictreatment for special care patients: a case series study.International Journal of Prosthodontics 2005;18:383–9.

139. Addy L, Korszun A, Jagger RG. Dental implant treatmentfor patients with psychiatric disorders. European Journalof Prosthodontics and Restorative Dentistry 2006;14:90–2.

140. Cune MS, Strooker H, Van der Reijden WA, de Putter C,Laine ML, Verhoeven JW. Dental implants in persons withsevere epilepsy and multiple disabilities: a long-termretrospective study. International Journal of Oral andMaxillofacial Implants 2009;24:534–40.

141. Feijoo JF, Limeres J, Diniz M, Del Llano A, Seoane J, Diz P.Osseointegrated dental implants in patients withintellectual disability: a pilot study. Disability andRehabilitation 2012;34:2025–30.

142. Basko-Plluska JL, Thyssen JP, Schalock PC. Cutaneous andsystemic hypersensitivity reactions to metallic implants.Dermatitis 2011;22:65–79.

143. Evrard L, Waroquier D, Parent D. Allergies to dental metals.Titanium: a new allergen. Revue Medicale de Bruxelles2010;31:44–9.

144. Siddiqi A, Payne AG, De Silva RK, Duncan WJ. Titaniumallergy: could it affect dental implant integration? ClinicalOral Implants Research 2011;22:673–80.

145. Javed F, Al-Hezaimi K, Almas K, Romanos GE. Is titaniumsensitivity associated with allergic reactions in patientswith dental implants? A systematic review. Clinical ImplantDentistry and Related Research 2011. [Epub ahead of print].

146. Sicilia A, Cuesta S, Coma G, Arregui I, Guisasola C, Ruiz E,et al. Titanium allergy in dental implant patients: a clinicalstudy on 1500 consecutive patients. Clinical Oral ImplantsResearch 2008;19:823–35.

147. Oliva X, Oliva J, Oliva JD. Full-mouth oral rehabilitation in atitanium allergy patient using zirconium oxide dentalimplants and zirconium oxide restorations. A case reportfrom an ongoing clinical study. European Journal of EstheticDentistry 2010;5:190–203.