dental implants in irradiated versus nonirradiated ... · dental implants in irradiated versus...
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CLINICAL REVIEW David W. Eisele, MD, Section Editor
Dental implants in irradiated versus nonirradiated patients: A meta-analysis
Bruno Ramos Chrcanovic, DDS, MSc,1* Tomas Albrektsson, MD, PhD,1,2 Ann Wennerberg, DDS, PhD1
1Department of Prosthodontics, Faculty of Odontology, Malm€o University, Malm€o, Sweden, 2Department of Biomaterials, G€oteborg University, G€oteborg, Sweden.
Accepted 17 September 2014
Published online 16 June 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23875
ABSTRACT: The purpose of the present meta-analysis was to test thenull hypothesis of no difference in dental implant failure rates, postopera-tive infection, and marginal bone loss for patients being rehabilitated bydental implants and being previously irradiated in the head and neckregion versus nonirradiated patients against the alternative hypothesis of adifference. The study suggests that irradiation negatively affects the sur-vival of implants, as well as the difference in implant location (maxilla vsmandible), but there is no statistically significant difference in survivalwhen implants are inserted before or after 12 months after radiotherapy.
The study failed to support the effectiveness of hyperbaric oxygen therapyin irradiated patients. It was observed that there was a tendency of lowersurvival rates of implants inserted in the patients submitted to higher irra-diation doses. The results should be interpreted with caution because ofthe presence of uncontrolled confounding factors in the included studies.VC 2015 Wiley Periodicals, Inc. Head Neck 38: 448–481, 2016
KEY WORDS: dental implants, radiotherapy, infection, marginal boneloss, meta-analysis
INTRODUCTIONIn an attempt to decrease implant failure rates, moreattention is being placed on understanding the etiologicand risk factors that lead to the failure of dentalimplants.1 The question of whether or not patients irradi-ated in the head and neck region are more at risk of los-ing dental implants has been receiving increasingattention in the last years, as implants have been increas-ingly used in patients with oral cancer.
Radiotherapy is largely used for the treatment of headand neck cancer, as primary therapy, adjuvant to surgery,as well as in conjunction with concurrent chemotherapy, oras palliative treatment for late stage and untreatable headand neck malignancies. Although the radiotherapy canincrease cure rates, the irradiated patient is susceptible tosecondary effects and a series of potential orofacial compli-cations. Radiotherapy may result in progressive fibrosis ofblood vessels and soft tissues, in xerostomia, in osteoradio-necrosis, and in reduction of bone-healing capacity, amongothers.2–4 Because of the cumulative effects of radiation onbone vascularity, the regenerative capacity of these tissuesis limited, and this may have a deleterious impact on subse-quent implant osseointegration.5
The ability to anticipate outcomes is an essential partof risk management in an implant practice. Recognizing
conditions that place the patient at a higher risk of failurewill allow the surgeon to make informed decisions andrefine the treatment plan to optimize the outcomes.1 Theuse of implant therapy in special populations requiresconsideration of potential benefits to be gained from thetherapy. To better appreciate this potential, we conducteda systematic review and meta-analysis to compare the sur-vival rate of dental implants, postoperative infection, andmarginal bone loss of dental implants inserted in irradi-ated and nonirradiated patients.
MATERIALS AND METHODSThis study followed the Preferred Reporting Items for
Systematic reviews and Meta-Analyses (PRISMA) state-ment guidelines.6 A review protocol does not exist.
Objective
The purpose of the present review was to test the nullhypothesis of no difference in the implant failure rates,postoperative infection, and marginal bone loss forpatients being rehabilitated by dental implants and beingirradiated or previously irradiated in the head and neckregion versus nonirradiated patients against the alternativehypothesis of a difference.
Search strategies
An electronic search without time or language restric-tions was undertaken in April 2014 in the following data-bases: PubMed, Web of Science, and the Cochrane OralHealth Group Trials Register. The following terms wereused in the search strategy on PubMed: ((dental implant[Text word]) AND irradiated [Text word]); (dental implant[Text word]) AND radiotherapy [Text word]); (dental
*Corresponding author: Bruno R. Chrcanovic, Department of Prosthodontics,Faculty of Odontology, Malm€o University, Carl Gustafs v€ag 34, SE-205 06,Malm€o, Sweden. E-mail: [email protected];[email protected]
Contract grant sponsor: CNPq, Conselho Nacional de DesenvolvimentoCient�ıfico e Tecnol�ogico – Brazil.
448 HEAD & NECK—DOI 10.1002/HED MARCH 2016
implant [Text word]) AND radiation [Text word]); (dentalimplant [Text word]) AND radiation therapy [Text word])).
The following terms were used in the search strategyon Web of Science, in all databases: ((dental implant[Topic]) AND irradiated [Topic]); (dental implant[Topic]) AND radiotherapy [Topic]); (dental implant[Topic]) AND radiation [Topic]); (dental implant [Topic])AND radiation therapy [Topic])).
The following terms were used in the search strategy onthe Cochrane Oral Health Group Trials Register: ((dentalimplant OR dental implant failure OR dental implant sur-vival OR dental implant success AND (irradiated OR radio-therapy OR radiation OR radiation therapy)).
A manual search of dental implants-related journals,including British Journal of Oral and Maxillofacial Sur-gery, Clinical Implant Dentistry and Related Research,Clinical Oral Implants Research, European Journal ofOral Implantology, Head & Neck, Implant Dentistry,International Journal of Oral and Maxillofacial Implants,International Journal of Oral and Maxillofacial Surgery,International Journal of Periodontics and RestorativeDentistry, International Journal of Prosthodontics, Jour-nal of Clinical Periodontology, Journal of DentalResearch, Journal of Oral Implantology, Journal of OralRehabilitation, Journal of Craniofacial Surgery, Journalof Cranio-Maxillofacial Surgery, Journal of Maxillofacialand Oral Surgery, Journal of Oral and Maxillofacial Sur-gery, Journal of Oral Rehabilitation, Journal of Perio-dontology, Oral Oncology, and Oral Surgery OralMedicine Oral Pathology Oral Radiology and Endodon-tology, was also performed.
The reference list of the identified studies and the rele-vant reviews on the subject were also scanned for possi-ble additional studies. Moreover, online databasesproviding information about clinical trials in progresswere checked (clinicaltrials.gov; www.centerwatch.com/clinicaltrials; www.clinicalconnection.com).
Inclusion and exclusion criteria
Eligibility criteria included clinical human studies,either randomized or not, comparing implant failure, post-operative infection, and/or marginal bone loss in patientsirradiated for head and neck cancers versus nonirradiatedpatients. For this review, implant failure represents thecomplete loss of the implant. Implants that were placedand could not be used because of positional problems (theso-called “sleepers”) were here not considered as failures.Exclusion criteria were case reports, technical reports,animal studies, in vitro studies, and review articles.
Study selection
The titles and abstracts of all reports identified through theelectronic searches were read independently by the 3 authors.For studies appearing to meet the inclusion criteria, or forwhich there were insufficient data in the title and abstract tomake a clear decision, the full report was obtained. Disagree-ments were resolved by discussion among the authors.
Quality assessment
The quality assessment was performed by using the rec-ommended approach for assessing risk of bias in studies
included in Cochrane reviews.7 The classification of therisk of bias potential for each study was based on the 4following criteria: sequence generation (random selectionin the population), allocation concealment (steps must betaken to secure strict implementation of the schedule ofrandom assignments by preventing foreknowledge of theforthcoming allocations), incomplete outcome data (clearexplanation of withdrawals and exclusions), and blinding(measures to blind study participants and personnel fromknowledge of which intervention a participant received).The incomplete outcome data will also be consideredaddressed when there are no withdrawals and/or exclu-sions. A study that included all the criteria mentionedabove was classified as having a low risk of bias, a studythat did not include one of these criteria was classified ashaving a moderate risk of bias. When 2 or more criteriawere missing, the study was considered to have a highrisk of bias.
Data extraction and meta-analysis
From the studies included in the final analysis, the fol-lowing data were extracted (when available): year of pub-lication, study design, unicenter or multicenter study,number of patients, patients’ age, follow-up, days of anti-biotic prophylaxis, mouth rinse, implant healing period,failed and placed implants, postoperative infection, mar-ginal bone loss, implant surface modification, radiother-apy, timespan between irradiation and implant surgery,hyperbaric oxygen therapy (HBO), type of prostheticrehabilitation, jaws receiving implants (maxilla and/ormandible), grafting procedures, observed occurrences ofdeath during the follow-up period, presence of smokersand/or alcohol drinkers among the patients, and adjunc-tive chemotherapy. Contact with authors for possiblemissing data was performed.
Implant failure and postoperative infection were thedichotomous outcome measures evaluated. Weightedmean differences were used to construct forest plots ofmarginal bone loss, a continuous outcome. The statisticalunit for “implant failure” and “marginal bone loss” wasthe implant, and for “postoperative infection” was thepatient. Whenever outcomes of interest were not clearlystated, the data were not used for analysis. The I2 statisticwas used to express the percentage of the total variationacross studies because of heterogeneity, with 25% corre-sponding to low heterogeneity, 50% to moderate, and75% to high. The inverse variance method was used forrandom-effects or fixed-effects model. Where statisticallysignificant (p < .10) heterogeneity was detected, arandom-effects model was used to assess the significanceof treatment effects. Where no statistically significant het-erogeneity was found, analysis was performed using afixed-effects model.8 The estimates of relative effect fordichotomous outcomes were expressed in risk ratio (RR)and in mean difference in millimeters for continuous out-comes, both with a 95% confidence interval (CI). Only ifthere were studies with similar comparisons reporting thesame outcome measures was meta-analysis to beattempted. In the case where no events (or all events)were observed in both groups, the study provided noinformation about relative probability of the event andwas automatically omitted from the meta-analysis. In this
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 449
(these) case(s), the term “not estimable” is shown underthe column of RR of the forest plot table. The softwareused here automatically checks for problematic zerocounts, and adds a fixed value of 0.5 to all cells of studyresults tables where the problems occur.
A funnel plot (plot of effect size vs SE) will be drawn.Asymmetry of the funnel plot may indicate publicationbias and other biases related to sample size, although theasymmetry may also represent a true relationship betweentrial size and effect size.
The data were analyzed using the statistical software ReviewManager (version 5.2.11, The Nordic Cochrane Centre, TheCochrane Collaboration, Copenhagen, Denmark, 2014).
RESULTS
Literature search
The study selection process is summarized in Figure 1.The search strategy resulted in 1683 articles. Four combi-nations of terms were used for PubMed and Web of Sci-ence, which resulted in a number of 686 duplicates. The3 reviewers independently screened the abstracts for thosearticles related to the focus question. The initial screeningof titles and abstracts resulted in 78 full-text articles; 919were excluded for not being related to the topic. The full-text reports of the remaining 78 articles led to the exclu-sion of 24 because they did not meet the inclusion criteria
(9 did not state the number of implants per group, 6 eval-uated implants only in irradiated mandibles, 3 evaluatedimplants for craniofacial prostheses, 2 were earlierfollow-ups of the same study, 2 were the same study pub-lished in another journal, 1 did not insert implants in irra-diated bone, and 1 article was not evaluating implantfailures). Additional hand-searching of the reference listsof selected studies did not yield additional articles. Thus,a total of 54 publications were included in the review.
Description of the studies
Detailed data of the 54 included studies are listed inTables 1 and 2. Ten controlled clinical trials9–18 and 44retrospective studies5,19–61 were included in the meta-analysis. When the e-mail of one or more authors of thearticles was found, questions were sent to request infor-mation about missing data. Authors of 3 studies59–61
replied with the requested information.Seventeen studies5,10,11,16,19,21,25,26,30,32,33,39,42,53,58,60,61 had
a maximum follow-up from 5 to 9 years, whereas 18studies13,23,24,27,36–38,41,43–46,50,51,54–56,59 had a maximumfollow-up of at least 10 years. From the studies with availabledata of patients’ range age, 10 studies12,25,36,38,44–46,50,53,59
included non-adult patients. Eight studies5,19,21,23,29,43,52,57 didnot inform of the patients’ age. Only 6 studies22,24,28,47,48,59
provided information about postoperative infection, with 35
FIGURE 1. Study screening process.
CHRCANOVIC ET AL.
450 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE1.
Detaileddataoftheincluded
studies–part1
Authors
Published
Studydesign
No.ofpatients
(no.perg
roup)
Patients’age
range,y(%)
Follow-up
visits(ra
nge)
Days
ofantibiotics/
mouthrin
seNo
.offailed/
placed
implants
Implantfailure
rate(%)
pvalue
Postoperative
infection
pvalue
Albrektsson
etal19
1988
RA(multicenter)
1641
(NM)
NM3–8y
NM3/49
(G1)
6.12
(G1)
NMNM
NM270/7996
(G2)
3.38
(G2)
3/16
(GRM
x)18.75(GRM
x)0/33
(GRM
d)0(GRM
d)218/3089
(Gn-RM
x)7.06
(Gn-RM
x)52/4907(Gn-RM
d)1.06
(Gn-RM
d)
Sclaroffetal20
1994
RA(unicenter)
22(15,G1
;7,
G2)
23–79(58.7)
3y2mo
NM0/80
(G1)
0(G1)
NMNM
NM2/34
(G2)
5.9(G2)
Franz� en
etal21
1995
RA(unicenter)
5(3,G<50
Gy;
2,G�50
Gy)
NM3–6y
10/NM
0/13
(G<50
Gy)
0(G<50
Gy)
NMNM
NM1/7(G�50
Gy)
14.29(G�50
Gy)
Aldegheri
etal22
1996
RA(unicenter)
7(1,G
Mx;6,
GMd)
44–66(55)
Mean2.7y(1–4)
NM0/6(GRM
x)0(GRM
x)NM
0(GRM
x)NM
0/13
(GRM
d)0(GRM
d)1(GRM
d)
Eckertetal23
1996
RA(unicenter)
20(6,G
Mx;18,
GMd)*
NM12
yNM
8/22
(GRM
x)36.36(GRM
x)NM
NMNM
1/89
(GRM
d)1.12
(GRM
d)
Weischer
etal9
1996
CCT(unicenter)
27(13,G1
;14,
G2)
44–70(56,G1
)26
mo
10/NM
4/57
(G1)
7.02
(G1)
NMNM
NM42–70(57,G2
)3/48
(G2)
6.25
(G2)
Alietal24
1997
RA(unicenter)
10(3,G
Mx;7,
GMd)
39–82(62.6)
Mean33
mo
(11–64)
5/NM
6/10
(GRM
x)60
(GRM
x)NM
0(GRM
x)NM
0/32
(GRM
d)0(GRM
d)1(GRM
d)
Chan
etal25
1997
RA(unicenter)
17(5,G
1;12,
G2)
11–78(55)
Mean32
mo
(6–84)
NM4/23
(G1)
17.39(G1)
NMNM
NM0/46
(G2)
0(G2)
Esserand
Wagner26
1997
RA(unicenter)
78(64,G1
;14,
G2;6,G
Mx;72,
GMd)
37–79(55-58,
G1)
5y
NM39/249
(65,G1
)†15.66(G1)
NMNM
NM
48–58(54,G2
)7/71
(5,G
2)†
9.86
(G2)
6/28
(13,GR
Mx)
†21.43(GRM
x)40/292
(57,GM
d)†
13.70(GMd)
33/221
(GRM
d)14.93(GRM
d)7/71
(Gn-RM
d)9.86
(Gn-RM
d)
Jisander
etal10
1997
CCT(unicenter)
17(NM)
47–78(67)
Mean21
mo
(1–62)
10/NM
3/38
(GRM
x)7.89
(GRM
x)NM
NMNM
2/65
(GRM
d)3.08
(GRM
d)
Kelleretal27
1997
RA(unicenter)
19(8,G
RBG;
11,
GRNB
)24–84(60)
10y
NM1/26
(GRB
G)3.85
(GRB
G)NM
NMNM
0/72
(GRN
B)0(GRN
B)
Markeretal28
1997
RA(unicenter)
12(6,G
1;6,G2
)42–81(71)
Mean14
mo
(7–47)
7/14
0/19
(G1)
0(G1)
NM0(G1)
NM0/19
(G2)
0(G2)
0(G2)
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 451
TABLE1.
Cont
inue
d
Authors
Published
Studydesign
No.ofpatients
(no.perg
roup)
Patients’age
range,y(%)
Follow-up
visits(ra
nge)
Days
ofantibiotics/
mouthrin
seNo
.offailed/
placed
implants
Implantfailure
rate(%)
pvalue
Postoperative
infection
pvalue
McGhee
etal29
1997
RA(unicenter)
6(5,G
1;1,G2
)NM
3y
NM2/21
(G1)
9.52
(G1)
NMNM
NM0/5(G2)
0(G2)
0/9(GRB
G)0(GRB
G)2/12
(GRN
B)16.67(GRN
B)0/5(Gn-RG
B)0(Gn-RG
B)
Niimietal30
1997
RA(multicenter)
24(9,G
Mx;16,
GMd;7,GH
BO;
18,G
n-HB
O)
NM(64.8)
2–73
mo
NM9/39
(GRM
x)23.08(GRM
x)NM
NMNM
3/71
(GRM
d)4.23
(GRM
d)4/31
(GHB
O)12.90(GHB
O)8/79
(Gn-HB
O)10.13(Gn-HB
O)7/67
(G�45
Gy)
10.45(G�45
Gy)
5/51
(G>45
Gy)
9.80
(G>45
Gy)
Roum
anas
etal31
1997
RA(unicenter)
20(11,G1
;9,
G2)
25–78
1–49
mo
NM0/45
(G1)
0(G1)
NMNM
NM1/35
(G2)
2.9(G2)
0/39
(GRB
G)0(GRB
G)1/32
(Gn-RB
G)3.1(Gn-RB
G)0/5(GRN
B)0(GRN
B)0/4(Gn-RN
B)0(Gn-RN
B)
Andersson
etal32
1998
RA(unicenter)
15(*)
62–74(68)
5y
10/NM
0/12
(GRM
x)0(GRM
x)NM
NMNM
2/78
(GRM
d)2.56
(GRM
d)
Brogniez
etal33
1998
RA(NM)
19(NM)
37–74(53)
Mean38
mo
(6–68)
NM0/3(2,G
RMx)
†0(GRM
x)NM
NMNM
2/50
(13,GR
Md)
†4(GRM
d)
Iharaetal34
1998
RA(multicenter)
18(10,G1
;8,
G2;4,G
HBO;
6,Gn-HBO
)
22–82(64.2)
Mean27.6mo
NM6/39
(G1)
15.38(G1)
>.05
(GHB
O)NM
NM9/35
(G2)
25.71(G2)
3/19
(GHB
O)15.79(GHB
O)3/20
(Gn-HB
O)15
(Gn-HB
O)
Esseretal35
1999
RA(unicenter)
62(34,G1
;28,
G2)
40–76(54.7,G1
)Mean58.2mo
NM9/148(G1)
6.08
(G1)
>.05
NMNM
44–77(55.3,G2
)3/128(G2)
2.34
(G2)
Fosteretal36
1999
RA(unicenter)
22(3,G
1;19,
G2)
12–82(49)
11y
NM0/15
(GRG
B)0(GRG
B)NM
NMNM
7/89
(Gn-RG
B)7.87
(Gn-RG
B)
Granstr€ om
etal37
1999
RA(unicenter)
78(52,G1
;26,
G2;20,GH
BO;
32,G
n-HB
O)‡
23–94(64.9)
0.1–15.1y
NM87/246
(G1)
35.37(G1)
NMNM
NM12/89(G2)
13.48(G2)
8/99
(GHB
O)‡
8.08
(GHB
O)79/147
(Gn-HB
O)53.74(Gn-HB
O)
Kelleretal38
1999
RA(unicenter)
54(2,G
1;52,
G2)
15–73(48)
12y
NM0/11
(G1)
0(G1)
NMNM
NM33/237
(G2)
13.92(G2)
CHRCANOVIC ET AL.
452 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE1.
Cont
inue
d
Authors
Published
Studydesign
No.ofpatients
(no.perg
roup)
Patients’age
range,y(%)
Follow-up
visits(ra
nge)
Days
ofantibiotics/
mouthrin
seNo
.offailed/
placed
implants
Implantfailure
rate(%)
pvalue
Postoperative
infection
pvalue
Mericske–Stern
etal11
1999
CCT(unicenter)
17(11,G1
;6,
G2)
38–81(58)
Mean37
mo
(12–84)
NM8/33
(G1)
24.24(G1)
NMNM
NM0/20
(G2)
0(G2)
0/12
(GMx)
0(GMx)
8/41
(GMd)
19.51(GMd)
Weischerand
Mohr39
1999
RA(unicenter)
40(18,G1
;22,
G2)
43–75(55)
Mean37
mo
(6–117)
NM10/83(G1)
12.05(G1)
>.05
NMNM
5/92
(G2)
5.43
(G2)
Werkm
eister
etal40
1999
RA(unicenter)
29(12,G1
;17,
G2)
35–79(55)
3y
NM8/30
(G1)
26.67(G1)
<.05
(G1–G2
)NM
NM19/79(G2)
24.05(G2)
14/45(Gn-RB
G)31.11(Gn-
RBG)
8/30
(GRN
B)26.67(GRN
B)5/34
(Gn-RN
B)14.71(Gn-
RNB)
5/16
(G>54
Gy)
31.25(G>54
Gy)
3/14
(G<54
Gy)
21.43(G<54
Gy)
Gotoetal41
2002
RA(unicenter)
36(23,GR
BG;
13,G
RNB)
20–83(52.9)
Mean1881
d(72–3901)
NM11/92(G1)
11.96(G1)
NMNM
NM4/88
(G2)
4.55
(G2)
11/52(GMx)
21.15(GMx)
4/128(GMd)
3.13
(GMd)
4/68
(GRB
G)5.88
(GRB
G)11/112
(GRN
B)9.82
(GRN
B)
vanSteen-
berghe
etal12
2002
CCT(unicenter)
234(NM)
15–80(50)
3y
NM2/33
(G1)
6.06
(G1)
<.01
NMNM
25/1230(G2)
2.03
(G2)
Vischetal13
2002
CCT(unicenter)
130(30,
Gy<50
Gy;100,
G�50
Gy)
34–87(62)
Upto14
y(every12
mo)
“Prescribed”
33/108
(GRM
x)28.70(GRM
x).001
(GMx-GM
d)NM
NM
31/338
(GRM
d)9.76
(GRM
d).05(G
50Gy)
19/207
(G<50
Gy)9.18
(G<50
Gy)
>.05
(G12)
45/239
(G�50
Gy)18.83(G�50
Gy)
29/175
(G<12)
16.57(G<12)
35/271
(G�12)
12.92(G�12)
Caoand
Weischer42
2003
RA(unicenter)
27(12,G1
;15,
G2)
45–79(NM)
5y
NM18/53(G1)
33.96(G1)
<.01
NMNM
11/78(G2)
14.10(G2)
Granstr€ om43
2003
RA(unicenter)
45(30,GH
BO;
15,G
n-HB
O;25,
GRMx;20,
GRMd)
NMMean9.8y
(2.2–22)
NM5/133(GHB
O)3.8(GHB
O)NM
NMNM
17/73(Gn-HB
O)23.3(Gn-HB
O)14/109
(GRM
x)12.8(GRM
x)8/97
(GRM
d)8.2(GRM
d)0/40
(GRB
G)0(GRB
G)2/14
(GRN
B)14.3(GRN
B)
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 453
TABLE1.
Cont
inue
d
Authors
Published
Studydesign
No.ofpatients
(no.perg
roup)
Patients’age
range,y(%)
Follow-up
visits(ra
nge)
Days
ofantibiotics/
mouthrin
seNo
.offailed/
placed
implants
Implantfailure
rate(%)
pvalue
Postoperative
infection
pvalue
Granstr€ om44
2005
RA(unicenter)
207(107,G
1;100,G2
)12–90(59.1,G1
)Mean6.3y
(0.5–23)
NM147/631(G1)
23.30(G1)
NMNM
NM15–88(58,G2
)76/614
(G2)
12.38(G2)
29/340
(GHB
O)8.53
(GHB
O)117/291(Gn-HB
O)40.21(Gn-HB
O)
Shaw
etal45
2005
RA(unicenter)
77(34,G1
;43,
G2;33,GB
G;63,
GNB;16,G
HBO;
18,G
n-HB
O;24,
GRMd;29,G
n-RM
d)§
15–80(58)
Mean3.5y
(0.3–14)
NM31/172
(G1)
18.02(G1)
.34(GRM
D-Gn-RMd)
NMNM
25/192
(G2)
13.02(G2)
32/123
(GBG
)26.02(GBG
)24/241
(GNB
)9.96
(GNB
)15/77(GHB
O)14.29(GHB
O)17/95(Gn-HB
O)17.89(Gn-HB
O)1/89
(GRM
d)1.12
(GRM
d)15/110
(Gn-RM
d)13.64(Gn-RM
d)11/44(G<50
Gy)
25(G<50
Gy)
12/78(G
550
Gy)
15.38(G
550
Gy)
8/33
(G>50
Gy)
24.24(G>50
Gy)
8/42
(GMx)
19.05(GMx)
16/199
(GMd)
8.04
(GMd)
Teoh
etal46
2005
RA(unicenter)
24(7,G
1;17,
G2;3,G
HBO;
4,Gn-HBO
)
6.7–80.5(42)
Mean51.7mo
(1.3–138)
NM5/30
(G1)
16.67(G1)
.02
(G1–G2
)NM
NM
1/72
(G2)
1.39
(G2)
.005
(HBO
)5/15
(GHB
O)33.33(GHB
O)0/15
(Gn-HB
O)0(Gn-HB
O)
Bodard
etal47
2006
RA(unicenter)
33(NM)
42–80(60.3)
Mean31.9mo
10/NM
0/6(GRM
x)0(GRM
x)NM
0(GRM
x)NM
0/62
(GRM
d)0(GRM
d)0(GRM
d)
Landes
and
Kov� acs
482006
RA(unicenter)
30(19,G1
;11,
G2)
47–83(63)
Mean36
mo
(24–46)
6/6(3%
hydro-
genperoxide)
1/72
(G1)
1.39
(G1)
NM1(G1)
NM0/42
(G2)
0(G2)
1(G2)
Schepers
etal49
2006
RA(unicenter)
48(21,G1
;27,
G2)
NM(65,men;
68,w
omen)
Mean29.6mo
afterlastradia-
tionsession
NM2/61
(G1)
3.28
(G1)
NMNM
NM0/78
(G2)
0(G2)
Yeritetal50
2006
RA(NM)
71(NM)
16–84(57.8)
Mean5.42
y(0.3–13.6)
NM29/154
(G1)
18.83(G1)
<.05
(G1–G2
)NM
NM
15/162
(G2)
9.26
(G2)
.42
(G<12–
G>12)
13/78(Gn-RB
G)16.67(Gn-
RBG)
29/154
(GRN
B)18.83(GRN
B)2/84
(Gn-RN
B)2.38
(Gn-RN
B)29/143
(G<12)
20.28(G<12)
15/173
(G>12)
8.67
(G>12)
CHRCANOVIC ET AL.
454 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE1.
Cont
inue
d
Authors
Published
Studydesign
No.ofpatients
(no.perg
roup)
Patients’age
range,y(%)
Follow-up
visits(ra
nge)
Days
ofantibiotics/
mouthrin
seNo
.offailed/
placed
implants
Implantfailure
rate(%)
pvalue
Postoperative
infection
pvalue
Nelson
etal51
2007
RA(unicenter)
93(29,G1
;64,
G2)
26–89(59)
Mean10.1y
(5–161
mo)
4/NM
7/124(G1)
5.65
(G1)
.08
NMNM
4/311(G2)
1.29
(G2)
Schoen
etal14
2007
CCT(unicenter)
26(13,GH
BO;
13,G
n-HB
O)47–77(60.1)
1yafterplace-
mentofthe
prostheses
14/NM
8/54
(GHB
O)14.81(GHB
O)NM
NMNM
3/49
(Gn-HB
O)6.12
(Gn-HB
O)
Alsaadietal52
2008
RA(unicenter)
412(2,G
1;410,
G2)
NMUp
to2yafter
abutment
connection
NM3/15
(G1)
20(G1)
.003
NMNM
98/1499(G2)
6.54
(G2)
Schoen
etal15
2008
CCT(unicenter)35
(50k)(19,G
1;16,G
2)41–81(61.5)
1yafterplace-
mentofthe
prostheses
NM2/76
(G1)
2.63
(G1)
NMNM
NM2/64
(G2)
3.13
(G2)
Cuesta–G
iletal53
2009
RA(unicenter)
111(79,G1
;32,
G2)
13–79(52)
6mo–9y
NM75/395
(G1)
18.99(G1)
NMNM
NM6/311(G2)
1.93
(G2)
(GBG
-GNB
)
Kleinetal54
2009
RA(unicenter)
43(27,G1
;16,
G2;13,
G<50
Gy;14,
G�50
Gy)
NM(58.4)
12y
NM13/116
(G1)
11.21(G1)
NMNM
NM12/74(G2)
16.22(G2)
4/55
(G<50
Gy)
7.27
(G<50
Gy)
9/61
(G�50
Gy)
14.75(G�50
Gy)
Korfage
etal16
2010
CCT(unicenter)
50(31,G1
,19,
G2)
41–81(61.5)
6wk,1and5y
NM13/123
(G1)
10.57(G1)
<.05
NMNM
1/72
(G2)
1.39
(G2)
Salinas
etal5
2010
RA(unicenter)
44(26,G1
;18,
G2)
NMMean41
mo
(4–108)
NM23/90(G1)
25.56(G1)
.57
(G1–G2
)NM
NM
8/116(G2)
6.90
(G2)
.27
(GBG
-GN
B)14/51(GRB
G)27.45(GBG
)9/39
(GRN
B)23.08(GNB
)6/63
(Gn-RB
G)9.52
(Gn-RB
G)2/53
(Gn-RN
B)3.77
(Gn-RN
B)
Barrow
man
etal55
2011
RA(unicenter)
31(NM)
20–76(50.7)
15y
NM5/48
(G1)
10.42(G1)
NMNM
NM0/67
(G2)
0(G2)
0/35
(GMx)
0(GMx)
5/80
(GMd)
6.25
(GMd)
0/9(Gn-RN
B-Mx)
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 455
TABLE1.
Cont
inue
d
Authors
Published
Studydesign
No.ofpatients
(no.perg
roup)
Patients’age
range,y(%)
Follow-up
visits(ra
nge)
Days
ofantibiotics/
mouthrin
seNo
.offailed/
placed
implants
Implantfailure
rate(%)
pvalue
Postoperative
infection
pvalue
Buddula
etal56
2011
RA(unicenter)
48(NM)
NM(60.2)
12y
NM20/62(GRM
x)32.36(GRM
x)NM
NMNM
13/209
(GRM
d)6.22
(GRM
d)8/59
(GRB
G)13.56(GRB
G)25/212
(GRN
B)11.79(GRN
B)
Heberer
etal17
2011
CCT(unicenter)
20(NM)
NM(61.1)
Mean14.4mo
(12–26)
4/NM
0/55
(GRM
x)0(GRM
x)NM
NMNM
2/42
(GRM
d)¶
4.76
(GRM
d)
Sammartino
etal18
2011
(CCT)
(multicenter)
69(9,G
Mx;60,
GMd;49,
G<50
Gy;20,
G�50
Gy)
28–63(55.8)
Atleast3
yNM
18/42(GRM
x)42.86(GRM
x)<.05
(GMx-GM
d)NM
NM
2/130(GRM
d)1.54
(GRM
d)<.05(G
50Gy)
7/111(G<50
Gy)
6.31
(G<50
Gy)
13/61(G�50
Gy)
21.31(G�50
Gy)
12/127
(G<12)
9.45
(G<12)
8/61
(G�12)
13.11(G�12)
Fenlon
etal57
2012
RA(multicenter)
41(12,G1
;29,
G2)
NM3y
NM15/35(G1)
42.86(G1)
NMNM
NM3/110(G2)
2.73
(G2)
Linsen
etal59
2012
RA(unicenter)
66(NM)
6–82
(55.7)
Mean48
mo
(12–140)
NM8/127(G1)
6.30
(G1)
NM18
(G1)
NM6/135(G2)
4.44
(G2)
13(G2)
1/49
(GMx)
2.04
(GMx)
13/213
(GMd)
6.10
(GMd)
1/17
(GRM
x)**
5.88
(GRM
x)7/110(GRM
d)**
6.36
(GRM
d)0/32
(Gn-RM
x)**
0(Gn-RM
x)6/103(Gn-RM
d)**
5.83
(Gn-RM
d)8/79
(GBG
)10.13(GBG
)6/183(GNB
)3.28
(GNB
)
Manchade
laPlataetal60
2012
RA(unicenter)
50(30,G1
;20,
G2)
40-74(55.5,G1
)Mean45
mo
(range6-96)
NM22/225
(G1)
9.78
(G1)
.063
(G1–G2
)NM
NM18-80(56.2,G2
)6/130(G2)**
4.62
(G2)
7/94
(GRM
x)**
7.45
(GRM
x)15/131
(GRM
d)**
11.45(GRM
d)
Katsoulis
etal61
2013
RA(unicenter)
28(46†
†)(20,
G1;26,G2
)NM
(57.7)
2–5y
NM14/62(G1)
22.58(G1)
NMNM
NM4/42
(G2)
9.52
(G2)
4/24
(GMx)**
16.67(GMx)
10/80(GMd)**
12.5(GMd)
6/20
(GRB
G)30
(GRB
G)8/42
(GRN
B)19.05(GRN
B)2/26
(Gn-RB
G)7.69
(Gn-RB
G)2/16
(Gn-RN
B)12.5(Gn-RN
B)
CHRCANOVIC ET AL.
456 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE1.
Cont
inue
d
Authors
Published
Studydesign
No.ofpatients
(no.perg
roup)
Patients’age
range,y(%)
Follow-up
visits(ra
nge)
Days
ofantibiotics/
mouthrin
seNo
.offailed/
placed
implants
Implantfailure
rate(%)
pvalue
Postoperative
infection
pvalue
Jacobsen
etal58
2014
RA(unicenter)
23(19,G1
;4,
G2)
20–69(52.4)
Mean67
mo
5/NM
14/47(G1)
29.79(G1)
NMNM
NM13/93(G2)
13.98(G2)
8/13
(GRB
G)61.54(GRB
G)6/34
(GRN
B)17.65(GRN
B)12/86(Gn-RB
G)13.95(Gn-
RBG)
1/7(Gn-RN
B)14.29(Gn-RN
B)
Abbreviations:R
A,retrospectiveanalysis;N
M,n
otmentioned;
G1,g
roup
irradiatedpatients;G2
,group
nonirradiatedpatients;GR
Mx,groupofimplantsinsertedintheirradiatedmaxilla;GR
Md,groupofimplantsinsertedintheirradiatedmandible;Gn-RMx,groupof
implantsinsertedinthenonirradiatedmaxilla;Gn-RMd,groupofimplantsinsertedinthenonirradiatedmandible;CC
T,controlledclinicaltrial;G
RBG,
implantsinsertedintheirradiatedjawsreconstructed
with
bone
graft;GR
NB,implantsinsertedintheirradiatednative
bone;G
n-RN
B,implantsinsertedinthenonirradiatednativebone;G
Mx,xxx;GM
d,xxx;GH
BO,group
patientstreated
with
hyperbaricoxygen
therapy;Gn-HBO
,group
patientsnottreated
with
hyperbaricoxygen
therapy;Gn-RBG
,implantsinsertedinthenonirradiated
jawsreconstructed
with
bone
graft;GB
G,xxx;GN
B,xxx;HB
O,hyperbaricoxygen
therapy;Gn-RNB
,xxx.
G<12,G�12,implantsinserted<12
moand�12
moafterthe
endofradiotherapy,respectively;G<50
Gy,G
550
Gy,G�50
Gy,implantsinsitesthatreceived<50
Gray,5
50Gray,and�50
Gray,respectively.
*Som
epatientsreceived
implantsinthemaxillaandinthemandible.
†Implantslostduetodeathofthepatient.
‡Therewas
anadditional10irradiatedpatientswho
hadlostmostoftheirimplantsreceived
newones
afterH
BOtreatment.Thesepatientsarenotbeing
considered
here.
§Somepatientsreceived
implantsingraftedbone
andinthenativebone.
kTherewere50
patientsinthestudy,butonlythe35
patientswith
functioning
implant-supportedprostheses
wereconsidered
here.
¶On
epatienthadarecurrence
oftumorresulting
inasecond
surgicalinterventionduringwhich
5mandibularimplantswereremoved
duetoblockresection.Theseimplantswereexcluded
fromthestudy.
**Unpublishedinform
ationwas
obtained
bypersonalcommunicationwith
oneoftheauthors.
††Thestudyincluded
46patients,butonly28
received
implants.
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 457
TABLE2.
Detaileddataoftheincluded
studies–part2
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Albrektsson
etal19
1988
NMNM
Turned
(Brånemark,
Nobelpharm
a,G€ oteborg,
Sweden)
NMNM
NM/maxillaandmandible
–
Sclaroffetal20
1994
7mo
NMTurned
(Brånemark,
Nobelpharm
a,G€ oteborg,
Sweden;n
536),acid-
etched
(Osseotite(3i/
ImplantInnovations,
Palm
BeachGardens,
FL;n
578)
Generally
30treatmentsof
200rads
pertreatment,
radiotherapy.Implants
wereplaced
from4–
6wkbeforeradiotherapy
(exceptin2patients).
NPFixed,overdenture/
mandible
4patientsdied
duringthe
follow-up,graft(iliac
crest,
fibulaflap)
Franz� enetal21
1995
31= 2-6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
25–64Gy.Implantswere
placed
2yafter
radiotherapy.
NPFixed/mandible
2sm
okers,2diabetics,
adjunctivechem
otherapy
in1patient,graftNM
Aldegheri
etal22
1996
4–10
mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
50–70Gy.Implantswere
placed
from5–96
mo
afterradiotherapy(mean
44).
NPOverdenture/maxillaand
mandible
Adjunctivechem
otherapy
in3
patients,graft(iliac
crest)
Eckertetal23
1996
NMNM
NM2005–6480cGy.
NPFixed,overdenture,
obturator/m
axillaand
mandible
GraftN
M
Weischeretal9
1996
6mo(G1)
NMTurned
(Brånemark,Nobel
BiocareAB,G
€ oteborg,
Sweden;n
535),TPS
(IMZ,Friadent,
Mannheim,G
ermany;
n5
32),sandblasted
andacid-etched(Frialit-2
system
,FriatecAG
,Mannheim,G
ermany;
n5
38)
Dose
ranged
between36
and75
Gy(average
42.5),fractions
of5
dosesof2Gy/wkor4
dosesof2.5Gy/wk.
Implantswereplaced
from13–72moafter
radiotherapy.
NPFixed,overdenture/
mandible
Adjunctivechem
otherapy
in7
patientsofG1
,bonegrafts
in15
patients(7inG1
,8in
G2)
3–6mo(G2)
Alietal24
1997
6–12
mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
2500–5750cGy
NPFixed,overdenture/maxilla
andmandible
GraftN
M
Chan
etal25
1997
4–6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden),TPS(IM
Z,FriatecAG
,Mannheim,
Germ
any)
60Gy
NPFixed,overdenture/maxilla
andmandible
1patientdied
duringthe
follow-up,graftN
M
CHRCANOVIC ET AL.
458 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Esserand
Wagner26
1997
Usually
6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden;n
5178),TPS
(IMZ,InterporeInt.,
Irvine,CA
;n5
71)
Totaldoseof36
Gyin
conventional
fractionation,anditwas
restrictedtopatients
who
hadatumorsize
of>3cm
ormanifested
cervicalmetastases.
Intervalbetweentheend
ofradiotherapy
and
implantplacementw
asatleast9
mo.
NPFixed,overdenture/maxilla
andmandible
17patientsdied
duringthe
follow-up,grafts(1
bicorticaliliaccrest,3
spongiosachips)
Jisanderetal10
1997
Mean6mo
(range3–11)
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden;n
598),
titanium-blasted
(Astra,
Astra
Tech
AB,M
€ olndal,
Sweden;n
55)
>50
Gy(8
patients),<
50Gy
(9patients),implantswere
placed
intheirradiated
jawsaftera
periodof
18–228
mo(mean
88mo).
7patients
Fixed(n
522)/m
axillaand
mandible
Fixedprostheses,6
patients
died
duringthefollow-up,
graftsNM
Kelleretal27
1997
3–7mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
Mean5600
cGy(range,
2755–7000).Implants
insertedinamedian
periodof72
mo(range,
16–168)after
irradiation.
NPFixed,overdenture/
mandible
2patientsdied
duringthe
follow-up(10implants),
graft(iliac
crest,fibula,
scapula)
Markeretal28
1997
NMNM
TPS(Bonefit,ITI,
Waldenburg,
Switzerland)
40–50Gy,5
fractions
of2Gy
perw
k.Implants
wereplaced
inthe
irradiatedjawsaftera
periodof8–32
mo
(mean,23).
NMOverdenture/maxillaand
mandible
4patientsdied
duringthe
follow-up,graft(iliac
crest,
rib)
McGheeetal29
1997
4–8mo
NMHA
-coated(Steri-Oss
DentalImplants,Los
Angeles,CA
)
>50
Gydelivered
overa
6–8wkperiod.Implants
placed
3–22
moafter
theinitialresection/
reconstruction.
NPOverdenture/mandible
University,graft(fibula)
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 459
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Niimietal30
1997
4–“�
13”mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
Theintervalbetween
implantsurgeryand
radiotherapy
ranged
from1–240mo.
7patients(20“dives”
beforeand10
“dives”
afterimplantplacement,
with
2.4absolute
atmosphericpressure
for9
0min)
Fixed(64implants–2
lost),overdentures
(46
implants–10
lost)/m
ax-
illaandmandible
University,nobone
grafts
Roum
anas
etal31
1997
6mo
NMTurned
(Brånemark,
Nobelpharm
a,G€ oteborg,
Sweden)
9patientsreceived
pre-
implantradiotherapy
and2patientspost-
implantradiotherapy.
NMFixed,overdenture/
mandible
2patientsdied
duringthe
follow-up(4implants),graft
(fibula)
Andersson
etal32
1998
6mo(maxilla)
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
44Gy
(n53),50Gy
(n5
7),60Gy
(n51),
68Gy
(n5
4).Implant
placem
entm
ean
22.1mo(range,8–
65mo)after
radiotherapy.
NPFixed/maxillaandmandibleUniversity,adjunctive
chem
otherapy
in1patient,
3patientsdied
duringthe
follow-up(15implants),
graftN
M
3–6mo
(mandible)
Brogniez
etal33
1998
5–8mo
NMHA
-coated(NM;n
542)
Averagedose
57Gy
(range,40–74).The
minimum
waitingperiod
betweencompletionof
irradiationandthe
placem
entofimplants
was
5mo(range,5–
192,mean,17).
NPFixed,overdenture/maxilla
andmandible
6patientsdied
duringthe
follow-up(15implants),
someimplantsplaced
inbone
grafts,buttheexact
numbernotinform
ed
“uncoated”
(NM;
n5
11)
Iharaetal34
1998
Mean9.1mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
Mean62.3Gy
(radiotherapy
before
implantplacement;
meanperiodbefore
implantplacement:
77.3mo),m
ean79.8Gy
(radiotherapy
both
beforeandafterimplant
placem
ent;meanperiod
betweenradiotherapy
andplacem
entw
as6.5mobeforeand
13moafterplacement),
60.8Gy
(radiotherapy
afterimplantplacement;
radiotherapy
1moafter).
4patients
Overdenture/maxilla
Chem
otherapy
in7patientsof
G1and1patientofG2
CHRCANOVIC ET AL.
460 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Esseretal35
1999
5mo(range,
4–8)
NMTurned
(Brånemark,Nobel
Biocare,G€ oteborg,
Sweden)
60Gy.M
eaninterval
betweenimplantsurgery
andradiotherapy:
23.1mo(range,10–
101).
NPFixed,overdenture/
mandible
38sm
okers(20,G1
:18,G2
),17
patients(13G1
,4G2
)died
duringthefollow-up
(56implantsG1
,19
implantsG2
)
Fosteretal36
1999
NMNM
NMNM
NMNM
/mandible
University,allpatients
receivinggrafts(iliaccrest,
fibula)
Granstr€ om
etal37
1999
NMNM
Turned
(Brånemark,Nobel
Biocare,G€ oteborg,
Sweden)
Mean57.7Gy
(range,25–
145)
20tim
esbeforesurgery
and10
times
postoperatively.Pure
oxygen
delivered
at250
kPa,for9
0min
NM/maxillaandmandible
University,14patientsdied
duringthefollow-up,only
implantsexposedand
loaded
andinnativebone
Kelleretal38
1999
4–6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
55–61Gy
NPFixed,overdenture/maxillaGraft(iliac
crest-
allpatients)
Mericske-Stern
etal11
1999
3–16
mo
NMTPS(ITI,Waldenburg,
Switzerland)
50–74Gy.7
implants
placed
after
radiotherapy,17before
radiotherapy,9
implants
placed
after
osteoradionecrosis.
2patients
Fixed,overdenture/maxilla
andmandible
University,11sm
okers,8
drinking
alcohol,graft(9
patients–fibula,scapula,
iliac
crest),5patientsdied
duringthefollow-up
Weischerand
Mohr39
1999
Mean5.5mo
(range,3–10,
G1)
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden;n
553),
sandblastedandacid-
etched
(Frialit-2
system
,FriatecAG
,Mannheim,
Germ
any;
n5
80;
Ankylos,Dentsply-Fria-
dent,M
annheim,
Germ
any;
n5
6),TPS
(IMZcylinder,Friatec,
Mannheim,G
ermany;
n5
36)
36–72Gy.M
eaninterval
fromtheendof
irradiationtoimplant
placem
ent:48
mo
(range,13–189).
NPFixed,overdenture/maxilla
andmandible
University,graft(iliaccrest)
Mean
3.2mo
(range,3–6,
G2)
Werkm
eister
etal40
1999
NMNM
NMMean54
Gy(range,42–
64).Implantsplaced
atleast24moafter
irradiation.
NPNM
/mandible
University,graft(iliaccrest)
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 461
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Gotoetal41
2002
NMNM
NMNM
NMNM
/maxillaandmandible
University,graft(21patients-
19inmandible,2in
maxilla)
vanSteen-
berghe
etal12
2002
6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
NMNP
NM/maxillaandmandible
University,adjunctive
chem
otherapy
was
perform
edinsome
patients,butthe
exact
numberw
asnotinformed,
graftN
M
Vischetal13
2002
Atleast6
mo
NMHA
-coated(Dyna,Dyna
DentalEngineeringBV,
Bergen
opZoom
,Netherlands;
n5
390;
Screw-Vent,Zimmer
Dental,C
arlsbad,CA
;n
556)
2–6MV,externalbeam
s,daily
fractions:2
Gray,5
fractions/wk.The
intervalbetweenimplant
surgeryand
radiotherapy
ranged
from6moto22
y.
NPNM
/maxillaandmandible
University,implantsinserted
withoutperiodontal
infection,2-stageprotocol,
50patients(38%
)died
duringthefollow-up.Thirty-
fiveimplants(8%)w
ere
insertedintojawstreated
with
bone
resections
(partialm
axillectomyand
partialorsegm
ental
mandibulectom
y).The
survivaloftheseimplants
was
significantly(p
5.04)
worse
comparedwith
that
ofimplantsinjawswithout
thesesurgicaltreatments
(61%
and83%,
respectively).
Caoand
Weischer42
2003
5–8mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden),sandblasted
andacid-etched(Frialit-
2system
,FriatecAG
,Mannheim,G
ermany)
From
36–76Gy
(Co/MeV
photons,4–5fractions
of2–2.5Gy
perw
eek).
Implants6moafter
radiotherapy.
NPOverdentures
(n5
21),
fixed
fulldentures
(n5
3),implant-sup-
portedfixed
bridge
(n5
1)/maxilla
Adjunctivechem
otherapy
in4
patients,sinusfloor
elevationwith
aniliac
bone
graftin4patients,7
implantinthezygomatic
region
Granstr€ om43
2003
NMNM
NM48–120
GyPerform
edin30
patients
NM/maxillaandmandible
Graft
CHRCANOVIC ET AL.
462 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Granstr€ om44
2005
NMNM
Turned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
21–120
Gy.528
implants
installedinan
irradiation
field,58implants
exposedtoradiotherapy
afterinstallation,and14
implantsinstalledinan
irradiationfieldand
wereadditionally
exposedtoradiotherapy
afterinstallation.
Perform
ed(protocolnot
inform
ed)
Fixed,overdenture/maxilla
andmandible
University,42patientsdied
duringthefollow-up(36G1
,6G2
),55
smokersinG1
,adjunctivechem
otherapy
in29
patients(177
implants),
nografts,implantsinthe
craniomaxillofacialarea
Shaw
etal45
2005
3–6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)?(Im
tec,Imtec
Corporation,Ardm
ore,
OK),(Brånemark
1Imtec;
n5
35),
sandblastedandacid-
etched
(Frialit-2
system
,FriatecAG
,Mannheim,
Germ
any;
n5
196),TPS
(IMZ,InterporeInt.,
Irvine,CA
;n5
155)
40–66Gy.Implant
placem
entscheduled
approximately1yafter
surgeryor1yafter
completionof
postoperative
radiotherapy.
24patients,20
dives(2.4
atmfor9
0min)before
insertion
and10
dives
afterinsertion
Fixed,overdenture/maxilla
andmandible
University,grafts
(iliaccrest,
fibula,radius),1patient
died
duringthefollow-up
Teoh
etal46
2005
Atleast6
mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden),acid-etched
(Osseotite3i/Im
plant
Innovations,PalmBeach
Gardens,FL)
60–79Gy,given
overa6–
8wkperiod,6patients
received
radiotherapy
beforeimplant
placem
entand
1patient
hadradiotherapy
after
dentalimplantswere
placed.
3patients,20
sessions
at2.4atmbeforeimplant
placem
entand
another
10sessions
afterward
Fixed,overdenture/
mandible
Hospital,graft(fibulafree-
flap),submergedimplants,
2patientsdied
duringthe
follow-up,adjunctive
chem
otherapy
in6patients
Bodard
etal47
2006
7mo
NMSandblasted(Ciny,Serf
Dedienne
sant
� e,Lyon,
France;n
562),turned
(BrånemarkMKIII,Nobel
BiocareAB
,G€ oteborg,
Sweden;n
54),
sandblastedandacid-
etched
(Ankylos,
Dentsply-Friadent,
Mannheim,G
ermany;
n5
2)
Averagedose
ofradiotherapy
was
60.5Gy
(range,40–
100).The
delaybetween
radiotherapy
and
implantationwas
54mo
(range,4–120).
NPFixed,overdenture/maxilla
andmandible
Adjunctivechem
otherapy
in7
patients,graftN
M
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 463
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Landes
and
Kov� acs
482006
Average25
d1y,1
60.8
(G1)
Sandblastedandacid-
etched
(SLA,
Straum
ann,Walderburg,
Switzerland;n
599),
TPS(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden;n
515)
57Gy,atsingledosesof
1.9Gy.The
average
timeperiod(range)
betweentumortherapy
andimplantplacement
was
16.5(3–55)mo,21
(4–55)mobetween
irradiationandimplant
insertion
and8(3–20)
mobetweenoperation
andimplantinsertionin
nonirradiatedpatients.
NMOverdenture(telescoped)/
mandible(interforaminal
only)
University,adjunctive
chem
otherapy
in13
patientsofG1
,90%
ofthe
patientsedentulous,non-
subm
ergedimplants,3
died
nottum
or-related,2
diabetics,no
bone
grafts
0.4
60.5
(G2)
2y, 1.4
60.9
(G1)
0.4
60.5
(G2)
Schepers
etal49
2006
Mean9mo
(G1)
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
60–68Gy
asaboostdose
ontheprimarytumor
site(within6wkof
ablationofthetumor)
and10–68Gy
onthe
symphysealarea,
implantswereplaced
duringtumorresection.
NPNM
/mandibular
(interforaminal)
University,nobone
grafts,7
patientsdied
duringthe
follow-up(22implants),34
implantswerenotusedfor
retentionofadental
prosthesis(15G1
,19G2
)
Mean
4.7mo(G2)
Yeritetal50
2006
Atleast6
mo
NMTPS(IM
Z,Friadent,
Mannheim,G
ermany;
n5
282),sandblasted
andacid-etched(Frialit-
2,Friadent,M
annheim,
Germ
any;
n5
26),
sandblastedandacid-
etched
(Xive,Friadent,
Mannheim,G
ermany;
n5
8).
Daily
fractions
of2Gy
givenon
25d(totaldose
of50
Gy).About4–8
wk
afterirradiation27show
[zaq
no="AQ2
"]?>
respective
surgeryofthecancer
was
perform
edtogether
primaryreconstruction
ofthemouthflooror
mandibulard
efectw
ithamicrovascularflap.
Implantinsertionwas
applied1.41
y(mean)
afterthe
reconstructive
surgery.
NPOverdenture/mandible
Chem
otherapy
perform
edin
allpatients,38
patients
died
duringthefollow-up
CHRCANOVIC ET AL.
464 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Nelson
etal51
2007
3mo
(mandible)
NMSandblastedandacid-
etched
(CAM
LOGRO
OT-
LINE
,CAM
LOG
Biotechnologies,Basel,
Switzerland;n
5156),
acid-etched(Steri-Oss,
NobelBiocareAB
,Goteborg,Sweden;
n5
127),turned
(BrånemarkMKII,Nobel
BiocareAB
;n5
113),
TPS(ITI,Straum
annAG
,Basel,Sw
itzerland;
n5
39)
Upto72
Gy,delivered
infractions
of2Gy
given
daily
for5
deach
wk.
NMFixed,overdenture/maxilla
andmandible
University,6
patientsdied
duringthefollow-up(28
implants),graft(iliac
crest,
fibula),adjunctive
chem
otherapy
was
perform
edinsome
patients,butthe
exact
numberw
asnotinformed
6mo
(maxilla)
Schoen
etal14
2007
6mo
0.6
60.6
(GHB
O)Turned
(Brånemark,Nobel
Biocare,G€ oteborg,
Sweden)
Mean61
Gy(range,46–
116)
100%
oxygen
at2.5
atmospheres
for8
0min
(4periods
of20
min),20
sessions
beforeand10
afterimplantsurgery.
Overdenture/mandible
(interforaminal)
University,8
patientsdied
duringthefollow-up,no
grafts
0.7
60.7
(Gn-HB
O)
Alsaadietal52
2008
NMNM
Turned
(Brånemark,Nobel
Biocare,G€ oteborg,
Sweden;n
51316),
oxidized
(MkIII,TiUnite,
NobelBiocare,G
€ oteborg,
Sweden;n
5198)
NMNM
61sm
okers(223
implants),
graftN
M
Schoen
etal15
2008
9mo(G1)
0.6
60.4(G1;
n5
76)
Turned
(Brånemark,Nobel
Biocare,G€ oteborg,
Sweden)
60–64Gy.R
adiotherapy
starting6wkafter
implants(insertedatthe
endoftheablative
tumorsurgery).
NPOverdenture/mandible
(interforaminal)
University,com
pletely
edentulous
patients,12
patientsdied
duringthe
follow-up
3mo(G2)
0.3
60.4
(G2;
n5
64)
Cuesta–G
iletal53
2009
8mo(G1)
NMHA
-coated(NM)
50–60Gy.Implantsplaced
beforeirradiation(45
patients)andplaced
ata
minimum
of12
moafter
theconclusion
ofradiotherapy
(34
patients).
NPFixed,overdenture/maxilla
andmandible
University,graft(iliaccrest,
fibula,radial,scapular)
6mo(G2)
Kleinetal54
2009
Mean6mo
NMNM
Patientsreceived
radiation
dosesuntil70
Gy.
NPNM
/mandible
University,graft(iliaccrest)
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 465
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Korfage
etal16
2010
9mo(G1)
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
Dose>40
Gy,starting
within6wkafter
surgery.
NPOverdenture/mandible
University,com
pletely
edentulous
patients,grafts
NM,implantsinstalled
duringablativetumor
surgery,2-stageprotocol,
12and26
patientsdead
after1
and5y,
respectively.
3mo(G2)
Salinas
etal5
2010
Atleast6
mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
>6000
cGytothe
mandibleafterthe
fibula
flapbutbeforeimplant
placem
ent.Four
patients
received
theradiation
treatmentsafterimplant
placem
ent,and
thereforeadjunctiveHB
Owas
notusedinthese
patients.
20dives(100%
oxygen,
2.4atmospheres
absolutepressure,
90min)beforeand10
divesafterthe
placem
entofdental
implants
Fixed/mandible
University,graft(fibulaflaps),
adjunctivechem
otherapy
in11
patients,23
smokers,
19patientswith
alcohol
abuse
Barrow
man
etal55
2011
NMNM
Turned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden)
NM12
patients.20
treatments
beforeplacem
entof
dentalimplantsand10
treatmentssubsequently
at2–2.5ATAfor6
0min
Fixed,overdenture/maxilla
andmandible
Hospital,graft(iliac
crest,
fibula),submerged
implants,5
patientsdied
duringthefollow-up
Buddulaetal56
2011
NMNM
NMMean60.7Gy
(range,
50.2–67.5).The
mean
timeintervalbetween
radiationandfirst
implantplacementw
as3.4y.
57patients(14GB
G,43
GNB)
NM/maxillaandmandible
Privateclinic,graft(iliaccrest,
scapula,femur)
Hebereretal17
2011
Mean10.2wk
(maxilla)and
6.9wk
(mandible)
Provided
infor-
mationcon-
cerningSLA
vsmodSLA
inthemax-
illaand
mandible
Sandblastedandacid-
etched
(SLA,
Straum
ann,Walderburg,
Switzerland)
Radiotherapy
upto72
Gy,
delivered
infractions
of2Gy
givendaily
for5
deach
wkover6wk.
Implantplacementw
asperform
edaftera
minimum
of6moafter
theradiationtherapy.
NPFixed,overdenture/maxilla
andmandible
University,chemotherapy
perform
edinallpatients,no
smokers
CHRCANOVIC ET AL.
466 HEAD & NECK—DOI 10.1002/HED MARCH 2016
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Sammartino
etal18
2011
6mo
(mandible)
NMMostfrequently
used:
“standardsolid-screw
implantw
ithmicrostructured
surface”
Dose
classifiedas<50
Gyand>50
Gy.The
mean
timebetweenthelast
irradiationandimplant
placem
entw
as9.4mo.
NPFixed,overdenture/maxilla
andmandible
University,nobone
grafts,no
smokers,no
diabetics
8mo
(maxilla)
Fenlon
etal57
2012
6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden),titanium-
blasted(Astra,Astra
Tech
AB,M
€ olndal,
Sweden),porous-
beaded
(Endopore,
Sybron,O
range,CA
)
66Gy
NPFixed/maxillaandmandiblePublichospitals,145
implants
placed
in47
vascularized
grafts,56implantsplaced
inresidualbone
Linsen
etal59
2012
3–8mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden;n
5258),
titaniumoxideionized
(Straum
ann,Freiburg,
Germ
any;
n5
4)
Postoperativeradiation
therapywas
delivered
beforeimplant
placem
entto34
patientsindaily
fractions
of2Gy.The
targetvolumewas
treated
toatotaldoseof
36Gy
in26
patientsand
atotaldoseof60
Gyin
8patients.Thetim
eintervalbetweenradical
oralcancersurgery,
radiationtherapyand
implantplacement,
respectively,ranged
from6–126mo.
NPFixed,overdenture/maxilla
andmandible
University,submerged
implants,4
patientsdied
duringthefollow-up(16
implants),adjunctive
chem
otherapy
in59
implants,graft(79
implants)
Manchade
laPlataetal60
2012
3–6mo
NMReabsorbableBlastM
edia
(MGOsseous-Mozograu,
Valladolid,Spain)
50–70Gy.The
mean
periodfromtheendof
radiotherapy
toimplant
placem
entw
as33.4
618.1mo(range,
12–96).
In4patientswho
developed
osteoradionecrosis
Fixed,overdenture/maxilla
andmandible
University,6
patientswere
smokersanddrinkers,
adjunctivechem
otherapy
in4patients(39implants),
graft(iliac
crest,calvaria,
40implants)
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 467
TABLE2.
Cont
inue
d
Authors
Published
Healingperiod/
loading
Mean
6SD
ofmarginalbone
loss,m
mImplantsurface
modification(brand)
Radiotherapy
Hyperbaric
oxygen
therapy
Type
ofprosthetic
rehabilitation/jaws
receivingimplants
Studyenvironm
ent,
chem
otherapy,cases
ofdeath,
bone
graft,
smokers,alcohol
abuse,observations
Katsoulis
etal61
2013
NMNM
NM56–81Gy
NMFixed,overdenture/maxilla
andmandible
University,25patientswere
smokersand/ordrinkers,
adjunctivechem
otherapy
in13
patients(allinG1
),13
patientsdied
duringthe
follow-up
Jacobsen
etal58
2014
6mo
NMTurned
(Brånemark,Nobel
BiocareAB
,G€ oteborg,
Sweden),oxidized
(TiUnite,N
obelBiocare
AB,G
€ oteborg,Sw
eden),
sandblasted,acid-
etched,and
chem
ically
treated
(Neoss,N
eoss,
Cologne,Germ
any)
63Gy
(range,50–73).O
naverage,thedental
implantswereinserted
17mo(range,4–48
mo)
afterreconstruction,but
beforetheirradiation
NPFixed/mandible
University,5
patientsdied
duringthefollow-up(13
implants),78%
smokers,
52%
drankalcohol
regularly,graft(fibulaflap)
Abbreviations:N
M,notmentioned;NP
,notperform
ed;cGY,xxx;G
1,groupirradiatedpatients;G2
,group
nonirradiatedpatients;HA
,XXX;TPS,titanium
plasma-sprayed;GH
BO,group
patientstreated
with
hyperbaricoxygen
therapy;Gn-HBO
,group
patientsnottreated
with
hyperbaricoxygen
therapy;HB
O,hyperbaricoxygen
therapy;GB
G,XXX;GN
B,XXX;SLA,XXX;modSLA,xxx.
CHRCANOVIC ET AL.
468 HEAD & NECK—DOI 10.1002/HED MARCH 2016
occurrences in a total of 158 patients receiving 543 implants.Three22,24,47 of the 6 studies compared postoperative infectionbetween implants inserted in irradiated maxillae and irradiatedmandibles, and the other 3 studies28,48,59 between implantsinserted in irradiated and nonirradiated patients. Only 4 stud-ies14,15,17,48 provided information about marginal bone loss.Thirteen studies19,23,28,36,37,40,41,43,44,52,55,56,61 did not informof the healing period of the implants before loading.
Twenty-seven studies10,11,13–16,20,25–28,31–33,35,37,44–46,48–51,55,58,59,61
informed of the death occurrences among the patients during thefollow-up. Eighteen studies5,9,12,17,21,22,32,34,42,44,46–48,50,51,59–61 hadpatients who were also submitted to adjunctive chemo-therapy. In 2 studies,17,50 all patients were submitted tochemotherapy. Part of the patients in 9 stud-ies5,11,21,35,44,52,58,60,61 were smokers, and 2 studiesexcluded smokers.17,18 It was informed in 5 stud-ies5,11,58,60,61 that some of the patients were frequent con-sumers of alcoholic beverages.
Patients were submitted to bone grafting procedures in29 studies.5,9,11,20,22,26–29,31,33,36,38–43,45,50,51,53,55–61 Fourstudies18,37,48,49 evaluated implants in native bone only.Eighteen studies5,9,14–16,20,21,29,31,35,36,38,40,48–50,54,58 eval-uated implants inserted in the mandible only, of which 4studies14,15,48,49 assessed the implants in the inter-foraminal region only, and 3 studies34,38,42 only in themaxilla. HBO was performed in patients of14 studies.5,10,11,14,30,34,37,43–46,55,56,60
The most commonly used implants used was the turnedBranemark (Nobel Biocare AB, G€oteborg, Sweden), in 35 stud-ies,5,9,10,12,14–16,19–22,24–27,30–32,34,35,37–39,42,44–47,49,51,52,55,57–59 butnot exclusively in 12 studies.9,10,20,25,26,39,42,45–47,51,52 Eight stud-ies23,36,40,41,43,54,56,61 did not inform of what kind of implantswas used. Sixteen studies5,12,13,16,18,34,35,39,40,42,45,46,50–52,60
informed whether there was a statistically significant differenceor not between the implant failure rates between the procedures,whereas 1 study28 showed no implant failures. Thirteen stud-ies9,10,13,14,17,21,24,28,32,47,48,51,58 provided information about theuse of prophylactic antibiotics, and only 3 studies13,28,48 aboutmouth rinse by the patients.
The comparisons concerning the outcome “implantfailure” are summarized in Table 3.
Quality assessment
Each trial was assessed for risk of bias, and the scoresare summarized in Table 4. All studies were judged to beat high risk of bias.
Meta-analysis
A summary of the meta-analyses comparisons concern-ing implant failures is presented in Table 3. The forestplots are presented in Figures 2–11.
Six studies22,24,28,47,48,59 provided information aboutpostoperative infection. A fixed-effects model was used,because of lack of statistically significant heterogeneityeither when comparing implants inserted in irradiatedversus in nonirradiated patients (p 5 .52; I2 5 0%;Figure 12) or when comparing implants inserted in irra-diated maxilla versus in irradiated mandible (p 5 .86;I2 5 0%; Figure 13). The results showed that therewas no statistically significant difference in the 2 com-parisons (RR 5 1.40; 95% CI 5 0.73–2.68; p 5 .31
and RR 5 0.81; 95% CI 5 0.09–7.27; p 5 .85,respectively).
Only 2 studies15,48 provided information about the mar-ginal bone loss with SD, necessary for the calculation ofcomparisons in continuous outcomes, comparing implantsinserted in irradiated versus in nonirradiated patients.There was statistically significant difference (mean differ-ence 5 0.62; 95% CI 5 0.21–1.03; p 5 .003; heterogene-ity: I2 5 92%; p < .00001, random-effects model; Figure14) between the groups concerning the marginal boneloss, favoring nonirradiated patients. One study14 pro-vided information comparing marginal bone loss inimplants inserted in irradiated patients being submittedversus not submitted to HBO. A meta-analysis for thiscomparison was not performed.
Publication bias
The funnel plot did not show asymmetry when thestudies reporting the outcome “implant failure” in thecomparison between irradiated and nonirradiated patientswas analyzed, indicating possible absence of publicationbias (see Figure 15).
DISCUSSIONOne relevant question in the present study is whether
the lack of a difference between irradiated and nonirradi-ated patients in some studies concerning implant failurerates is a real finding or is due to the lack of statisticalpower, given the small number of patients and/orimplants per group. However, a statistically and clinicallysignificant difference favoring the nonirradiated patientswas found after the meta-analyses, stressing the impor-tance of meta-analyses to increase sample size of individ-ual trials to reach more precise estimates of the effects ofinterventions. The significantly higher failure rates in irra-diated compared to nonirradiated patients might be causedby the long-term effects of reduced vascularization com-promising the implantation site.50 In general, radiationtherapy has 2 antagonistic effects with regard to recoveryof irradiated tissue: a short-term positive cellular effectresulting in the improvement of reduced bone-healingcapacity,62 and a long-term negative effect resulting inpermanent damage of osteoprogenitor cells63 and a grad-ual, progressive endarteritis obliterans, with thrombosis ofsmall blood vessels, fibrosis of the periosteum andmucosa, and damage to osteocytes, osteoblasts, and fibro-blasts.64 Moreover, irradiation of tissues that contain inte-grated implants increases the risk of soft tissuedehiscences around the implants, and osteoradionecrosismay lead to loss of the implants.65 This failure differenceafter radiation therapy was observed in several studiesincluded here, although the radiation dosage and observa-tion period varied in the majority of these cases.
Another aspect to consider is the use of HBO. There isno strict consensus about the use of adjunctive HBO ther-apy, but many studies stressed the advantages of HBOtreatment for wound healing in the irradiated soft andhard tissue.50 As a result, some authors use HBO as anadditive therapy when implant therapy in irradiated boneis planned. It is stated in the literature that HBO resultsin an increased oxygen tension in the irradiated ischemic
DENTAL IMPLANTS AND IRRADIATION
HEAD & NECK—DOI 10.1002/HED MARCH 2016 469
TABLE3.
Summaryofthecomparisonsconcerning
implantfailures
No.ofimplantsfailed/placed
(%)
Risk
ratio
(95%
CI)
pvalue
Heterogeneity
No.ofstudies
Forestplot–figurenumber
Irradiated
Nonirradiated
2.18
(1.71–2.79)
<.00001
I25
52%,p
5.0002,
random
-effectsmodel
37,5,9,11,12,15,16,19,20,25,26,28,29,31,34,35,37–42,44–46,48–55,57–61
2640/3914
(16.35)
684/14514(4.71)
Irradiated
1HB
OIrradiatedwithoutH
BO0.61
(0.27–1.39)
.24
I25
86%,p<.00001,
random
-effectsmodel
814,30,34,37,43–46
377/768
(10.02)
244/769(31.73)
Irradiatedmaxilla
Irradiatedmandible
3.16
(1.76–5.68)
.0001
I25
70%,p<.0001,
random
-effectsmodel
1710,13,17–19,22–24,26,30,32,33,43,47,56,59,60
4128/667(19.19)
121/1771
(6.83)
Irradiatedmaxilla
Nonirradiatedmaxilla
2.85
(1.07–7.57)
.04
I25
0%,p
5.67,
fixed-effectsmodel
219,59
54/33
(12.12)
218/3121
(6.98)
Irradiatedmandible
Nonirradiatedmandible
0.80
(0.27–2.34)
.68
I25
58%,p
5.07,
random
-effectsmodel
419,26,45,59
641/453
(9.05)
80/5191(1.54)
Irradiatedgrafted
Irradiatednativebone
1.35
(0.93–1.94)
.44
I25
48%,p
5.06,
random
-effectsmodel
95,27,29,31,41,43,56,58,61
741/325
(12.61)
63/542
(11.62)
Irradiatedgrafted
Nonirradiatedgrafted
3.31
(2.02–5.41)
<.00001
I25
27%,p
5.24,
fixed-effectsmodel
65,29,31,36,58,61
828/147
(19.05)
28/301
(9.30)
Irradiatednativebone
Nonirradiatednativebone
2.74
(1.49–5.04)
.001
I25
24%,p
5.26,
fixed-effectsmodel
65,31,40,50,58,61
960/304
(19.74)
12/198
(6.06)
Higherirradiationdose
Lowerirradiationdose
1.64
(0.98–2.75)
.06
I25
47%,p
5.08,
random
-effectsmodel
713,18,21,30,40,45,54
1098/542
(18.08)
51/515
(9.90)
<12
mo
>12
mo
1.37
(0.76–2.45)
.29
I25
64%,p
5.06,
random
-effectsmodel
313,18,50
1170/445
(15.73)
58/505
(11.49)
Abbreviations:95%
CI,95%
confidenceinterval;<
12mo,>12
mo,implantsinserted<12
moand>12
moafterthe
endofradiotherapy,respectively.
CHRCANOVIC ET AL.
470 HEAD & NECK—DOI 10.1002/HED MARCH 2016
bone and provokes capillary neoangiogenesis63 and boneformation.66 The exact correlation between HBO doseand duration of antifibrotic response is not yet settled. Ithas been convincingly demonstrated that such treatmentdramatically decreases the risk of trauma-induced osteora-dionecrosis by promoting vascular proliferation, collagen
synthesis, bone remodeling activities, and healing of bonewounds in irradiated tissues.67 Moreover, HBO therapyincreases the amount of force necessary to unscrew inte-grated titanium implants in irradiated bone,68 which sug-gests that promoted integration has occurred. Larsenet al66 showed a difference of 13.9% in mean percent of
TABLE 4. Results of quality assessment
Authors PublishedSequence generation
(randomized?)Allocation
concealmentIncomplete outcomedata addressed Blinding
Estimated potentialrisk of bias
Albrektsson et al19 1988 No Inadequate Yes No HighSclaroff et al20 1994 No Inadequate No No HighFranz�en et al21 1995 No Inadequate No No HighAldegheri et al22 1996 No Inadequate No No HighEckert et al23 1996 No Inadequate No No HighWeischer et al9 1996 No Inadequate No No HighAli et al24 1997 No Inadequate No No HighChan et al25 1997 No Inadequate Yes No HighEsser and Wagner26 1997 No Inadequate Yes No HighJisander et al10 1997 No Inadequate Yes No HighKeller et al27 1997 No Inadequate Yes No HighMarker et al28 1997 No Inadequate Yes No HighMcGhee et al29 1997 No Inadequate No No HighNiimi et al30 1997 No Inadequate No No HighRoumanas et al31 1997 No Inadequate Yes No HighAndersson et al32 1998 No Inadequate Yes No HighBrogniez et al33 1998 No Inadequate Yes No HighIhara et al34 1998 No Inadequate No No HighEsser et al35 1999 No Inadequate Yes No HighFoster et al36 1999 No Inadequate No No HighGranstr€om et al37 1999 No Inadequate Yes No HighKeller et al38 1999 No Inadequate No No HighMericske-Stern et al11 1999 No Inadequate Yes No HighWeischer and Mohr39 1999 No Inadequate No No HighWerkmeister et al40 1999 No Inadequate No No HighGoto et al41 2002 No Inadequate No No Highvan Steenberghe et al12 2002 No Inadequate No No HighVisch et al13 2002 No Inadequate Yes No HighCao and Weischer42 2003 No Inadequate Yes No HighGranstr€om43 2003 No Inadequate No No HighGranstr€om44 2005 No Inadequate Yes No HighShaw et al45 2005 No Inadequate Yes No HighTeoh et al46 2005 No Inadequate Yes No HighBodard et al47 2006 No Inadequate No No HighLandes and Kov�acs48 2006 No Inadequate No No HighSchepers et al49 2006 No Inadequate Yes No HighYerit et al50 2006 No Inadequate No No HighNelson et al51 2007 No Inadequate Yes No HighSchoen et al14 2007 No Inadequate Yes No HighAlsaadi et al52 2008 No Inadequate No No HighSchoen et al15 2008 No Inadequate Yes No HighCuesta–Gil et al53 2009 No Inadequate No No HighKlein et al54 2009 No Inadequate Yes No HighKorfage et al16 2010 No Inadequate Yes No HighSalinas et al5 2010 No Inadequate No No HighBarrowman et al55 2011 No Inadequate Yes No HighBuddula et al56 2011 No Inadequate No No HighHeberer et al17 2011 No Inadequate No No HighSammartino et al18 2011 No Inadequate Yes No HighFenlon et al57 2012 No Inadequate No No HighLinsen et al59 2012 No Inadequate Yes No HighMancha de la Plata et al60 2012 No Inadequate Yes No HighKatsoulis et al61 2013 No Inadequate Yes No HighJacobsen et al58 2014 No Inadequate Yes No High
DENTAL IMPLANTS AND IRRADIATION
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integration after 4 months in irradiated versus nonirradi-ated animals. This difference dropped to 6.38% when ani-mals received HBO before and after implantation. Thedifference was shown to be significant, although withoutestablishing whether this reduction is of significance inrelation to implant support. As long as the direct bone-implant interface is sufficiently large to support the supra-structure, it can be argued that additional support to theimplant surface is unnecessary, particularly in light ofpatient inconvenience and the cost of HBO treatment.32
Moreover, results from animal experiments may onlypartly be extrapolated to clinically relevant conditions forendosseous implants in irradiated bone. Apart from con-siderable methodological limitations in the simulation ofthe therapeutic reality and temporal restrictions, eventsduring the follow-up (induction of neoplasms, loss ofimplants, osteoradionecrosis, etc), differences related tocell cycles, structural peculiarities of the bone matrix, theperiosteal situation, and the enzyme system of the specieshave to be taken into account.69 It is no less impor-tant to mention that several studies included
here9,10,14,15,17,19,21,23,26–28,30–33,35,47–49,51,59,60 demon-strated a high survival rate for the implants placed in irra-diated jaws without the use of adjunctive HBO therapy. Itmight have been expected that there was a significantlyhigher failure for patients submitted to HBO, becausemost of the patients selected for HBO could have been ata higher risk for osteoradionecrosis because of a higherirradiation dose, and consequently at a higher risk ofimplant loss. For example, the difference in implant sur-vival between the HBO and non-HBO treated patientsobserved in the study of Schoen et al14 was remarkable,but was mainly caused by 1 HBO-treated patient whodeveloped osteoradionecrosis and subsequently lost all 4implants. However, the present meta-analysis found nostatistically significant difference when comparingimplant failures in irradiated patients receiving or notHBO, which is most likely the result of the small samplesize in many studies and selection bias. There are still norandomized, controlled, double-blind studies conducted toprove that HBO really has a significant osseointegrationstimulating effect in irradiated patients. However, there
FIGURE 2. Forest plot for the event “implant failure” in the comparison between irradiated versus nonirradiated patients. [Color figure can beviewed in the online issue, which is available at wileyonlinelibrary.com.]
CHRCANOVIC ET AL.
472 HEAD & NECK—DOI 10.1002/HED MARCH 2016
are certain technical difficulties related to designing sucha study, such as blinding a chamber treatment and thedesign of the placebo treatment.37
The timespan between the irradiation and the implantsurgery may influence the survival of the dental implants,but recommendations for an optimal time interval areinconsistent. Dental implants can be inserted during theablative surgery or after completed radiotherapy. Whenthe implants are inserted during the ablative surgical ses-sion, a large part of the integration will occur in theperiod between surgery and radiotherapy (ie, within 4–6weeks).70 However, a clear majority of studies herereviewed report on implants installed after radiotherapy.The advantage of placement after radiotherapy is that theanatomic situation, residual function, and prognosis canbe taken into account in the decision of whether to useimplants. Moreover, tumor recurrence has been reported
to occur most often between 8 and 12 months after sur-gery, according to 1 study,71 or within 2 years accordingto another one,21 thus, oral rehabilitation may be delayeduntil this period of highest risk has passed. The disadvant-age is that patients are often psychologically and physi-cally weakened by the therapy, resulting in postponementor even cancellation of prosthetic rehabilitation.72 More-over, after radiotherapy, the vascularization and regenera-tive ability of the irradiated tissues can be decreased,which may lessen the prospect of successful osseointegra-tion of the dental implants.11 The subject is controversial.King et al73 indicated that blood vessels that weredestroyed radiologically show partial recovery after 3 to 6months. W€achter and Stoll74 conducted histomorphomet-ric studies, the results of which state that implantationcan be performed, at the earliest, 12 to 18 months afterthe conclusion of irradiation. Jacobsson62 reported an
FIGURE 3. Forest plot for the event “implant failure” in the comparison between irradiated patients receiving versus not receiving hyperbaricoxygen (HBO). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 4. Forest plot for the event “implant failure” in the comparison between irradiated maxilla versus irradiated mandible. [Color figure can beviewed in the online issue, which is available at wileyonlinelibrary.com.]
DENTAL IMPLANTS AND IRRADIATION
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improvement in the bone healing capacity by a factor ofalmost 2.5 during a 12-month period after irradiation.According to the author, functional self-regeneration ofthe damaged tissue would provide sufficient implant heal-ing and osseointegration capacities of the bone 1 yearafter radiation therapy. On the other side, Marx and John-son63 stated that after 6 months, fibrosis is expected tostart in the irradiated tissues as a result of reduced cellreproducibility and progressive ischemia. This processwill increase with time, especially when curative doses ofradiotherapy have been given. The present meta-analysisfound no statistically significant difference when failureof implants was compared for the implants installedbefore and after a period of 12 months from the radio-therapy, and this is most likely the fact that only 3 stud-ies13,18,50 performed this comparison. Two other studiesdid not report a defined time point to make the compari-son, but did not find any influence of time of implanta-tion on the implant failure rates.10,48
Concerning the radiation dose, the implants insertedinto locations irradiated with �50 Gray (Gy) in 4 stud-ies13,18,21,54 had a lower survival rate than implants inlocations that are irradiated with <50 Gy. The same hap-pened in another study,40 but comparing different dosethresholds (>54 vs <54 Gy). Generally, high radiationdoses >50 Gy have been reported to result in chroniccomplications like radioxerostomia and impaired woundhealing.75 Also, irradiation doses above 65 Gy may sig-nificantly increase the risk of development of osteoradio-necrosis,76 which may also be a reason for implantfailures. Moreover, it was shown that there is a distinctdose-dependent relationship between the duration andextent of irradiation and the resulting reduced osteogene-
sis.77 Bone healing was delayed at lower doses of radia-tion with the formation of more impaired fibrous tissueand nonlamellar bone, and bone healing was severely dis-turbed at radiation doses used to treat head and neck can-cer.78 However, the present meta-analysis was not able tofind a significantly higher risk of losing an implant inpatients receiving higher doses of radiotherapy. Onceagain, this result may have been influenced by the limitednumber of studies performing this comparison. The com-parable survival rates of both groups in the study of Niimiet al30 and even a higher survival rate of implants insertedinto locations of higher doses in the study of Shaw et al45
might be caused by the effects of reduced vascularizationthat compromises both irradiated and nonirradiatedlocations.63
Another circumstance that may increase implant failureis the anatomy of the implantation site. Oral anatomymay change after ablative surgery and eventually afterreconstruction by grafts and flaps, and the resultingdefects and bulky areas or the presence of insufficientsoft tissues for coverage may compromise prosthetic reha-bilitation.41,79 One could speculate that the bony sectionof the graft may have been nonvital from the time ofplacement or that placement of implants in the graftedblock of bone may have compromised the vitality of theblock.57 Some studies on this topic address the increasedimplant loss in augmented bone to the reduced primarystability of dental implants because of impaired mechani-cal bone quality as well as to increased bone resorptionkinetics.80–82 The lower survival of implants in thegrafted bone may be the result of differences in bonequality, bone volume, and revascularization comparedwith the original residual bone. There is also a difference
FIGURE 5. Forest plot for the event “implant failure” in the comparison between irradiated versus nonirradiated maxilla. [Color figure can beviewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 6. Forest plot for the event “implant failure” in the comparison between irradiated versus nonirradiated mandible. [Color figure can beviewed in the online issue, which is available at wileyonlinelibrary.com.]
CHRCANOVIC ET AL.
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when it comes to the graft type. Vascularized bone flapsmaintain their viability even after prolonged periods ofischemia provided that the medullary nutrient blood sup-ply is later restored.83 This is unlike nonvascularizedbone grafts, where implant placement must await alengthy delay to allow for “creeping substitution”84 tooccur. Even with all these disadvantages, the presentstudy found no statistically significant difference concern-ing failures of dental implants when inserted in irradiatedgrafted bone or in irradiated native bone. This could berelated to the assumption that the clinical courses ofimplants may not be affected by the presence of graftedbone once the graft has succeeded,41 even if this is diffi-cult to ascertain, as not every study included in the pres-ent review provided detailed information about graftingprocedures. On the other side, when the failure rates werecompared in irradiated versus nonirradiated patients, therewas a statistically significant difference for implantsinserted in grafted bone and in native bone. Once again,when the term “irradiation” is inserted into the equation,there are significant differences.
Concerning the different jaws, it was observed in 1study13 that the most dominant variable influencingimplant survival in irradiated bone is the implant’s loca-
tion in the maxilla or mandible. The side effects ofradiotherapy seem to be more serious in the mandiblethan in the maxilla because of the inferior blood supplyof the former bone.10 However, according to the resultsof the present meta-analysis, it seems that implant fail-ure in the maxilla follows a similar course in irradiatedand nonirradiated patients. The results comparingimplant failures in irradiated and nonirradiated max-illa19,59 and in irradiated and nonirradiated mandi-ble19,26,45,59 must be interpreted with caution because ofthe limited number of studies reporting this information(2 and 4, respectively). It is also important to considerwhether all implants had been inserted in the field ofirradiation, even though this information was rarely pro-vided by the included studies. In the case of the mandi-ble, for example, the external beam radiation therapy fororal malignancies does not always include the wholemandible and, hence, implants inserted anterior to themental foramina might be inserted in a field of lowerradiation dose. This will naturally affect the outcome forthe implants.37
When it comes to postoperative infection, soft tissuemay be affected by irradiation, and the causes might bethe postoperative and postirradiation xerostomia, different
FIGURE 7. Forest plot for the event “implant failure” in the comparison between irradiated grafted bone versus irradiated native bone. [Color figurecan be viewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 8. Forest plot for the event “implant failure” in the comparison between irradiated versus nonirradiated grafted bone. [Color figure can beviewed in the online issue, which is available at wileyonlinelibrary.com.]
DENTAL IMPLANTS AND IRRADIATION
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saliva quantity and quality, and altered microflora as wellas the presence of scar tissues after reconstruction and theloss of attached and keratinized gingiva adjacent to theimplants.48,50 It may be suggested that stable soft tissueconditions are crucial for the possibility to perform oralhygiene and can influence the clinical performance of theimplants in irradiated patients.17 This could influence theincidence of peri-implantitis and consequently the mar-ginal bone loss. The present meta-analysis showed thatthere was a statistically significant difference between the
irradiated versus nonirradiated patients concerning themarginal bone loss, favoring nonirradiated patients. How-ever, this result must be interpreted with caution becauseof the limited number of studies that evaluated the condi-tion. The same can be said about the meta-analysis resultsfor the outcome postoperative infection.
The studies included here have a considerable numberof confounding factors, and most of the studies, if not all,did not inform how many implants were inserted and sur-vived/lost in several different conditions.
FIGURE 9. Forest plot for the event “implant failure” in the comparison between irradiated versus nonirradiated native bone. [Color figure can beviewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 10. Forest plot for the event “implant failure” in the comparison between higher versus lower irradiation dose. [Color figure can be viewedin the online issue, which is available at wileyonlinelibrary.com.]
CHRCANOVIC ET AL.
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First, bone resections may result in unfavorable pros-thetic circumstances by producing bulky and soft areas.In these situations, (removable) prosthetic appliances areoften complicated and may cause overloading of theimplants.79 This negative influence may be responsiblefor lower survival rate of implants inserted into jawstreated with bone resections, compared with that ofimplants inserted into jaws that did not undergo bonesurgery.13
Second, the percentage of patients who had receivedpostoperative radiotherapy may have decreased over timeamong the survivors, as it was observed in many studies,which could have contributed to the relatively low failurerate of implants in irradiated bone. Those patientsselected to be submitted to radiotherapy may be thepatients with cancers of the worst prognosis.
Third, in the analysis of implant survival, it is impor-tant to ascertain whether the implants that were placedand considered osseointegrated were, in fact, used for thefinal implant-supported prosthesis.85 A longer follow-upperiod can lead to an increase in the failure rate, espe-cially if it extended beyond functional loading, may leadto an increase in the failure rate, because other prostheticfactors can influence implant failure from that pointonward. This might have led to an underestimation ofactual failures in some studies. However, it is hard todefine what would be considered a short follow-up periodto evaluate implant failures when comparing thesetechniques.
Fourth, most patients with oral cancer have a history ofpoor oral hygiene, smoking, and drinking.29 The local
environment is less favorable to dental implants than inhealthy subjects. Saliva quantity and quality as well asoral microflora change considerably after salivary glandresection. Landes and Kov�acs48 observed that plaque andperi-implant bleeding index remained typically high com-pared with noncancer patients. Oral hygiene and compli-ance were limited, although patients received individualoral hygiene instructions. On the other hand, a rapid pla-que accumulation and bleeding tendency was concomitantwith postoperative and postirradiation xerostomia, alteredmicroflora, saliva quantity and quality, smoking, anddrinking. Irradiation leaves a less viable bone that isprone to infection; furthermore, oral xerostomia postradio-therapy complicates the situation.40
Fifth, as oral cancer represents around 3% of the totalcancer incidence,86 most of the studies were not able tocreate a homogenous collective for more factors, such asoral squamous cell carcinoma, edentulousness, or severelyreduced tooth number. By breaking down the study byeach variable, the authors of the studies may have hadserious doubts regarding the clinical value in a study thatis not totally homogenous in tumor staging, precise doseof irradiation, etc. It can be said that in order to have suf-ficient group sizes and a clinically relevant conclusion,groups in the studies were therefore not supposedly bro-ken down further. Homogenous or matched collectiveshave a somewhat higher significance but they tend to beinhibited by small case numbers.48
Sixth, it is known that the surface properties of dentalimplants, such as topography and chemistry, are relevantfor the osseointegration process influencing ionic
FIGURE 11. Forest plot for the event “implant failure” in the comparison between insertion of implants within 12 months after radiotherapy versusafter 12 months after radiotherapy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 12. Forest plot for the event “postoperative infection” in the comparison between irradiated versus nonirradiated patients. [Color figurecan be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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interaction, protein adsorption, and cellular activity at thesurface.87 The studies included here made use of implantswith different brands and surface treatments. Titaniumwith different surface modifications shows a wide rangeof chemical, physical properties, and surface topographiesor morphologies, depending on how they are preparedand handled,88–90 and it is not clear whether, in general,one surface modification is better than another.87
Seventh, there was a great variation of the implanthealing time before the prosthetic loading. In irradiatedtissue, the local healing ability is impaired30,40 and thevulnerable time period after insertion becomes jeopar-dized with early loading. Possible overloading of theimplants, induced by altered oral anatomy after ablativesurgery or reconstruction by grafts and flaps may alsoincrease implant failure in patients with malignant cancercompared with healthy patients.78 The optimal head andneck oncology treatment-related healing time of implantsbefore loading is still in need of further research andprobably can be shortened significantly.15
Eighth, patients in some studies were subjected toadjunctive chemotherapy. The effect of chemotherapy onthe osseointegration and survival of endosteal implants isnot well established, even though it was shown that therisk of irradiation-induced bone damage is increased bychemotherapy.91 It is suggestive by animal model studiesthat chemotherapeutic agents have an adverse effect onnormal physiological bone turnover, especially osteoblas-tic activity, and would also be expected to alter fracture-healing and bone-allograft incorporation by these samemechanisms.92,93 However, chemotherapy did not have adetrimental effect on the survival and success of dentalimplants in some studies,17,46,94 even though implantinsertion in these studies was performed after at least 6
months after chemotherapy. Thus, it is unknown whetherthe time point of chemotherapy might be decisive.
Ninth, it is important that the patients are followed uplong enough before reporting implant success in irradiatedbone.37 However, because the life-span prognosis formost patients with oral malignant tumors is rather poorand the 5-year survival rate is reached by only approxi-mately 50% of the patients, it is difficult to collect long-term data on implants placed in these patients.11 More-over, 1 study61 showed that the early dropout after thefinal prosthetic treatment was high and that some patientswere hindered to attend the regular recall sessionsbecause of serious health conditions, which makes it evenmore difficult to collect substantial data in the long term.It is also important to stress that the patients with betteroral and general health conditions are usually the oneswho are more willing to pay a recall visit.
Tenth, reports of implants in tumor patients included alltypes of restorations. Data on the rehabilitation of a well-defined patient collective are rare. This does not allowidentifying common characteristic traits and comparingvarious types of prostheses with regard to function andaesthetics.61
Thus, the results of the present study have to be inter-preted with caution because of its limitations. First of all,all confounding factors may have affected the long-termoutcomes and not just the fact that implants were placedin patients who were submitted to radiation therapy ornot, and the impact of these variables on the implant sur-vival rate, postoperative infection, and marginal bone lossis difficult to estimate if these factors are not identifiedseparately between the 2 different procedures in order toperform a meta-regression analysis. The lack of control ofthe confounding factors limited the potential to draw
FIGURE 13. Forest plot for the event “postoperative infection” in the comparison between irradiated maxilla versus irradiated mandible. [Color fig-ure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 14. Forest plot for the event “marginal bone loss” in the comparison between irradiated versus non-irradiated patients. [Color figure canbe viewed in the online issue, which is available at wileyonlinelibrary.com.]
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robust conclusions. Second, most of the included studieshad a retrospective design, and the nature of a retrospec-tive study inherently results in flaws. These problemswere manifested by the gaps in information and incom-plete records. Furthermore, all data rely on the accuracyof the original examination and documentation. Itemsmay have been excluded in the initial examination or notrecorded in the medical chart.95–97 Third, much of theresearch in the field is limited by small cohort size andshort follow-up periods.
The failure of dental implants in irradiated patients istherefore subjected to many considerations and predict-ability is dependent upon issues like the use of HBO andchemotherapy, the timing of the implant placement inrelation to radiation therapy, the radiation dosage, theinsertion of implants in native of grafted bone, selectionof anatomic site, the patients’ oral hygiene conditions andhabits (smoking, drinking), the implant surface treatment,the prosthetic loading conditions, the type of prostheticrestoration, the period of follow-up, and risk ofosteoradionecrosis.
CONCLUSIONThe results of the present review should be interpreted
with caution because of the presence of uncontrolled con-founding factors in the included studies, none of themrandomized. Within the limitations of the existing investi-gations, the present study suggests that irradiation nega-tively affects the survival rates of dental implants, as wellas the difference in the implant location (ie, maxilla ormandible). The study has failed to support the effective-ness of HBO therapy in irradiated patients requiring den-tal implants. It also suggests that there is no statisticallysignificant difference in survival when implants areinserted before or after 12 months after the radiotherapy.It was observed that there was a tendency to a lower sur-vival rate of implants inserted in the patients submitted tohigher irradiation doses.
AcknowledgmentsThe authors thank Dr. Christian Walter, Dr. V�eroniqueBrogniez, and Dr. Jean-Louis Blanc for having sent us
their articles, and Dr. Sabine Linsen, Dr. Regina Mer-icske–Stern, and Dr. Mar�ıa Mancha de la Plata, who pro-vided us with some missing information about theirstudies.
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