Almpani K, Papageorgiou SN, Papadopoulos MA. Autotransplantation of teeth in humans - A systematic...

REVIEW

Autotransplantation of teeth in humans: a systematicreview and meta-analysis

Konstantinia Almpani1 & Spyridon N. Papageorgiou2,3,4& Moschos A. Papadopoulos1

Received: 1 July 2014 /Accepted: 5 April 2015# Springer-Verlag Berlin Heidelberg 2015

AbstractObjectives The aim of this investigation was to assess thecurrently available evidence concerning the complicationsa n d r i s k f a c t o r s i n f l u e n c i n g t h e o u t c ome o fautotransplantation of teeth in humans.Materials and methods Electronic searches were conducted toidentify randomized controlled and prospective clinical trials.Risk of bias within studies was assessed with the Downs andBlack tool. Random-effects meta-analyses were conducted topool the adverse event rates and relative risks with their 95 %confidence intervals. Risk of bias across studies was assessedwith the GRADE framework followed by sensitivity analyses.Results Thirty-eight studies were included in the analysis.Reported complications included the need for extraction, fail-ure, hypermobility, pulp necrosis, pulp obliteration, and rootresorption. Pooled complication event rates varied consider-ably, with small studies (<100 teeth) reporting greater compli-cation rates. The analysis of risk factors was associated withboth the primary outcome (extraction need) and secondaryoutcomes (failure, hypermobility, pulp necrosis, pulp obliter-ation, root resorption). The stage of root development seemsto influence both the future survival, as well as the success ofthe transplanted teeth. Teeth with open apex were less likely tobe extracted in comparison to teeth with closed apex (3

studies; 413 teeth; relative risk 0.3; 95 % confidence interval0.2–0.6).Conclusions Due to the small number of the contributingstudies, their methodological limitations, and the heteroge-neous results reported, no firm conclusions can be drawn.Clinical relevance Root development of the donor teeth hasbeen established as one themost important factor related to thesuccess of tooth autotransplantation.

Keywords Autotransplantation . Teeth . Transplantation .

Root development . Pulp necrosis . Pulp obliteration . Rootresorption

Introduction

Rationale

Autotransplantation is the transplantation of embedded inbone or erupted teeth in the same individual, from one siteto another, into extraction sites or surgically prepared sockets[1]. Autotransplantation of teeth has evolved into a viabletreatment option for replacing missing teeth, as successfullytransplanted teeth can function like totally normal teeth [2].

Indications for tooth autotransplantation include impactedor ectopic teeth, premature and/or traumatic tooth loss, loss ofteeth because of tumors or on iatrogenic grounds, congenitallymissing teeth in one arch in combination with arch lengthdiscrepancy or clinical signs of tooth crowding on the oppos-ing arch, replacement of teeth with bad prognosis, and/or de-velopmental dental anomalies [3–25]. Autotransplantation en-sures that alveolar bone volume is maintained, due to physio-logical stimulation of the periodontal ligament [26].Moreover, successful tooth transplantation offers improvedesthetics, arch form, dentofacial development, mastication,

* Moschos A. [email protected]

1 Aristotle University of Thessaloniki, Thessaloniki, Greece2 Department of Orthodontics, School of Dentistry,

University of Bonn, Bonn, Germany3 Department of Oral Technology, School of Dentistry,

University of Bonn, Bonn, Germany4 Clinical Research Unit 208, University of Bonn, Bonn, Germany

Clin Oral InvestDOI 10.1007/s00784-015-1473-9

and speech and arch integrity [27]. Autotransplanted teeth,unlike prosthetic restorations, provide proprioception duringfunction and have very good prognosis in growing patients[15, 26–29]. Nevertheless, clinical studies in adult patientshave also presented very satisfactory results [30–34].Finally, the total treatment cost is normally lower than othertreatment plans including dental implants, prosthetic restora-tion, and/or orthodontic space closure [29, 32], although thepatient in some cases might be burdened with extra costs forthe rehabilitation of the donor site.

The prognosis of autotransplanted teeth is influenced bypreoperative and peroperative conditions, which are recog-nized as prognostic factors [2]. The patient’s age [15, 21, 28,35], gender [36], the developmental stage [9, 12, 15, 21, 23,28, 37–45], and the root anatomy [4, 15, 21, 23, 37] of thedonor tooth, the existence of adequate alveolar bone supportin all dimensions at the recipient site [3, 4, 6, 11, 17, 25, 39,46–48], the use of an atraumatic surgical technique and ofproper preservation conditions for the donor tooth [4, 8, 15,17, 20, 21, 25, 29, 33, 35, 46, 49], the degree of adaptation ofthe donor tooth to the recipient socket [8, 26, 50], the durationand the method of stabilization of the teeth immediately aftertransplantation [3, 23, 24, 33, 40, 51–53], and their postoper-ative care [24, 25] have all been characterized by differentauthors as prognostic factors. In addition, the experience ofthe surgeon [54], the good health and oral hygiene of thecandidate patient, the absence of acute infection and chronicinflammation at the recipient site [17], the existence or not ofocclusal contacts during the healing period [2, 9, 11, 15, 16,25, 26, 29–32, 34, 39, 45, 54–60], and the timing and qualityof endodontic treatment of the autotransplanted teeth [4, 8, 10,16, 52, 53] have also been reported to influence the prognosisof autotransplantation of teeth in the same way.

Endodon t i c t r e a tmen t i n s t u d i e s o f d e n t a lautotransplantation is performed, either by protocol in all thedonor teeth, mainly in cases of teeth with complete root for-mation [2, 15, 25, 30, 32–34, 37, 53, 56, 59, 61, 62] or only incases where relevant clinical symptoms and/or radiographicdata indicate it, in order to avoid further complications [9, 15,26, 29, 58, 63].

The most frequently reported complications inautotransplantation of teeth include inflammatory and replace-ment root resorption or ankylosis [12, 13, 15, 22, 31, 37, 53,63], pulp necrosis [13, 15, 62], lack of or compromised peri-odontal healing [15, 46, 62], and reduction of final root length[9, 12, 19, 23, 40, 42, 51, 64–66].

Objectives

The objective of this study was to review existing evidencefrom prospective clinical studies and examine in an evidence-based manner the risk factors influencing the outcome andadverse effects of tooth autotransplantation in humans.

Materials and methods

Protocol and eligibility criteria

The protocol for this systematic review was made a prioriaccording to the Cochrane Handbook [67] and was approvedfrom all authors. This review is reported according to the PRISMA Statement [68] and its extension for abstracts [69].Specific inclusion/exclusion criteria were set (AppendixTable 6) to include randomized controlled trials (RCTs), pro-spective controlled trials (pCCTs), and prospective cohortstudies (pCTs).

Information sources and search

Electronic searches were conducted up to November 2012without any restrictions concerning publication year, publica-tion language, or publication status (i.e., published, unpub-lished, ongoing, etc.). The reference lists and citation lists ofarticles included in this systematic review were also scannedto identify additional studies.

Study selection, data collection process, and data items

The first author (KA) screened the titles and abstracts of iden-tified reports. When the decision was not straightforward, theother two authors were consulted until mutual agreement wasreached. If eligibility could not be decided by title or abstract,the full text of the article was retrieved. Study selection wasperformed unmasked, since scientific evidence does notstrongly recommend masked assessment [68].

Data collection was conducted by two authors indepen-dently (KA, SNP) using predefined data extraction forms in-cluding information on study design, participant characteris-tics, intervention, comparisons, and outcomes. Correspondingauthors of some of the included studies were contacted toobtain missing studies, clarifications on the published report,or additional data, where needed. Any differences were re-solved after consultation with the third author (MAP) until amutual agreement was reached.

The primary outcome of this systematic review was thesurvival failure of autotransplanted teeth, defined as the needto extract the tooth, due to untreatable clinical complications.This was the most objective and clinically relevant adverseeffect. The effect of failure of autotransplanted teeth, due toa number of different complications, as defined by the authorsof the included studies, despite their presence in the oral cav-ity, was a general secondary outcome that was also examined.Specific secondary outcomes were also reported includingankylosis, hypermobility, pulp necrosis, pulp obliteration,and inflammatory root resorption of the autotransplanted teeth[9, 13, 15, 16, 25, 31, 34, 35, 39, 40, 46, 54, 56, 59, 63, 70].

Clin Oral Invest

A number of patient, tooth, or operational factors wereincluded to assess their influence on the outcome ofautotransplantation: (a) patient age at the time of transplanta-tion (younger or older than 20 years of age, which is theaverage age of growth completion), (b) patient gender (maleor female), (c) donor teeth’s root development stage (eitheropen/closed apex or specifically according the classificationof Moorrees et al. [71], (d) donor teeth’s origin (maxilla ormandible), (e) recipient site (same tooth site as the site oforigin—i.e., premolar to premolar site), (f) donor tooth type(canines, first premolar, second premolar or molar), (g) surgi-cal technique (use of osseous graft or no graft), (h) fixationsplint type (suture splint or rigid splint), and (i) application oforthodontic forces on the transplanted tooth.

The influence of the age of the patients and the develop-mental stage of the roots of donor teeth, despite their obviousrelativity, are examined as separate factors. The reason is thatthere are also differences in tissue healing between growingpatients and adults, due to the existence of a denser vascular-ization of oral tissues and of an anatomically thicker perioste-um in children. The patient’s gender was also examined as afactor since relevant data was available, although it is notgenerally considered to be among the most important prog-nostic factors in autotransplantation of teeth.

Risk of bias in individual studies

The risk of bias of non-randomized studies (pCCTs and pCTs)was assessed with the Downs and Black scale [72]. Thecriteria were grouped in five main domains: reporting, exter-nal validity, internal validity—bias, internal validity—con-founding, and power. All items were given one point whenthe respective criterion was fulfilled, except for the Bpower^domain, where up to five points could be given, summing upto a maximum of 30 points per article. Serious methodologicallimitations were judged to exist when a non-randomized studycollected less than 17 points on the checklist.

The risk of bias of RCTs was planned to be assessed withthe Cochrane risk of bias tool.

Summary measures and synthesis of results

Data were summarized and considered suitable for pooling, ifsimilar interventions were used and similar outcomes werereported. A random-effects model as proposed byDerSimonian and Laird [73] was used, since the observedeffect was expected to differ across studies due to sampleand implementation differences [74]. Average event ratesacross studies were calculated with the corresponding 95 %confidence intervals (95 % CIs) for each adverse effect. Riskratios (RRs) with 95 % CIs were calculated to assess the in-fluence of each factor on the outcome of autotransplantation.

The number needed to treat (NNT) to prevent a transplant’sfailure was calculated for statistically significant RRs.

Between-studies heterogeneity was assessed by visual in-spection of the forest plots, while the size and impact of het-erogeneity were statistically measured with the tau2 and I2,respectively. Judgments of considerable heterogeneity weremade with I2 values greater than 75 % and taking into accountthe magnitude/direction of effects and the strength of evidencefor heterogeneity [75]. Subgroup analyses were planned to beperformed with a mixed-effects model, should data from fiveor more studies be eligible for inclusion in the analysis. Inmeta-analyses of three or more studies, 95 % prediction inter-vals (PIs) [75, 76] were calculated to predict treatment effectsin a future study (here reported only for significant meta-anal-yses—the remainder being available on request).

All analyses were conducted in Stata version 12 (StataCorpLP, College Station, TX) using the macros Bmetan,^ Brfdist,^Bheterogi,^ and Bmetabias^ (Appendix Table 7). The level ofsignificance was set at a two-sided P<0.05, except for the testof heterogeneity where it was set at P<0.10 [77].

Risk of bias across studies and additional analyses

Small study effects and publication bias were planned to beassessed with conventional methods, should 10 ormore studiesbe included in a meta-analysis [77] (a) by drawing and visualinspection of a Bcontour-enhanced funnel plot^ [78] and (b) byperforming the test proposed by Egger et al. [79]. If seriousindications of publication bias were found, assessment with theBtrim and fill^ procedure [80] was also planned. Sensitivityanalyses were planned according (a) to study design (random-ized vs. non-randomized studies), (b) study sample size (largevs. small studies), (c) improvement of the GRADE assessmentfor each outcome, and (d) length of follow-up.

Results

Study selection

The tables including detailed information regarding the selec-tion criteria and the electronic databases that were used can befound in the Appendix Table 8. The study selection procedure,the number of excluded studies, and the corresponding rea-sons for exclusion are provided in Fig. 1. A total of 38 pCTswere included in the qualitative and quantitative synthesis ofnegative outcomes related to autotransplantation. However,four published papers from Andreasen et al. [13, 46, 55, 64]reported on the same cohort of autotransplanted teeth and aregrouped together. Likewise, two papers from Nethander [70,81] were also synthesized into one dataset, as they examinedthe same cohort. Thus, in total, 34 datasets of the 38 includedstudies were assessed in the analysis.

Clin Oral Invest

Study characteristics and risk of bias within studies

The characteristics of the included studies regarding thepatient/tooth cohorts and the autotransplantation proto-cols used are given in Tables 1 and 2, respectively. Thesample size of the included studies ranged from 18 to368 patients, with a mean sample of 77 patients. Themajority of studies assessed autotransplantation in adultpatients, with a mean age of over 20 years, while thetypes of teeth most commonly transplanted were molarsand canines. Most of the studies reported the use of astandardized surgical protocol.

Reported complications of autotransplantation includedloss and/or failure of the transplanted teeth were inflammatoryand replacement root resorption, pulp necrosis, reduced/arrested root development, and periodontal problems(Table 3). However, not all studies examined the same factorsin the same way.

The assessment of study limitations in included non-randomized studies (risk of bias) is reported in AppendixTable 9. The studies scored an overall score between 4 and23 out of a maximum score of 31. Twenty-six studies scoredless than 17 points and were judged to have serious method-ological limitations.

A. Primary outcome (extraction need)

Synthesis of results and risk of bias across studies (GRADEassessment)

The meta-analyses of event rates for the primary outcome(extraction need) and the secondary outcomes from the 38included are presented in Fig. 2 and Table 4. The pooled needfor extraction in the included studies was found to be 7.8 %(95 % CI: 4.7–10.9 %). Caution is warranted, however, as thereported event rates were extremely inhomogeneous, and thiscould influence the effect’s precision.

The influence of the various patient, tooth, or operativecharacteristics on the extraction need of the transplants is seenin Fig. 3 and in Table 5, according to the GRADE approach[84]. The only factors that were found to be significantly as-sociated with the outcome of autotransplantation were thestage of root development at the time of transplantation andthe type of splint used. Transplants with open apex were lesslikely to be lost compared with transplants with closed apex(RR: 0.3; 95 % CI: 0.2–0.6). The calculated number needed totreat is 6, which means that for every six transplants with openapex, we would prevent one transplant in need of extractionpost-treatment compared to transplants with closed apex.

Records screened on basis of title and abstract, after duplicates removed (n=6373)

Full-text studies assessed for eligibility (n=79)

Studies detected after hand-searching of reference lists of

eligible articles(n=10)

Excluded studies (n=51)

Retrospective studies (n=31)

Uncontrolled case series (n=12)

Not relevant to the study (n=3)

Involving traumatic tissues (n=2)

Case reports (n=2)

In vitro studies (n=1)

Studies included in the qualitative and quantitative synthesis (n=38 studies; 34 datasets)

Records excluded on basis of title, abstract and non-existing abstract

(n=6294)

Records identified through database searching(n = 8815)

Number of duplicates removed (n = 2442)

Final number of full text studies assessed for eligibility (n=89)

Fig. 1 Flowchart of the selectionof the retrieved articles based onthe PRISMA guidelines

Clin Oral Invest

Tab

le1

Characteristicsof

the38

prospectivestudiesincluded

inthequalitativ

esynthesis

Study

Studydesign

Studysample-pts(M

/F)-teeth

Meanagein

years(range)

Group

ofteethused

Rootd

evelopmenta

Donor

site(s)/

recipientsite(s)

Two-stage

Tx

Meanfollo

w-upin

months(range)

Ahlberg

etal.[63]

pCT

29(21/12)pts-33

teeth

27.5(16.0–54.0)

C6

Max→

max

No

6.0

Akiyamaetal.[30]

pCT

23(13/12)pts-25

teeth

29.6(20.0–54.0)

M3

6Max/m

nd→

max/m

ndNo

(0.5–1.5)

Akkocaogluand

Kasaboglu

[31]

pCT

78pts-96

teeth

18.0–24.0

C/M

35–6

NR

No

1.0

Alto

nenetal.[35]

pCT

22pts-28

teeth

25.2(14.0–47.0)

C4–6

Max→

max

No

1.5(0.5–3.08)

Andreasen

etal.[13,

46,55,64]

pCCT

289(160/210)pts-370teeth

9.0–31.0

P1–6

NR→

max/m

ndNo

(1.0–13.0)

Arikanetal.[32]

pCT

30pts(9/21)-32teeth

34.3(25.0–55.0)

C6

Max→

max

No

5.9(2.0–8.0)

Azazetal.[56]

pCT

31pts(10/21)-37

teeth

13.0–36.0

C6

Max→

max

No

(2.0–7.0)

Bauss

etal.[16]

pCT

72pts(21/51)-76

teeth

17.9(16.3–20.3)

M3

3–4

Max→

max/m

ndMnd

→mnd

No

3.4(1.0–6.0)

Bauss

etal.[39]

pCCT

79pts(26/53)-85

teeth

17.7(16.1–20.3)

M3

3–4

NR

No

3.4(1.0–6.3)

Bauss

etal.[65]

pCCT

72pts(20/52)-75

teeth

17.4(16.1–19.3)

M3

3–4

Max→

max/m

ndMnd

→mnd

No

4.0(1.2–7.1)

Bauss

etal.[82]

pCCT

88pts(27/61)-91

teeth

17.3(16.1–19.3)

M3

3–4

Max→

max/m

ndMnd

→mnd

No

4.0(1.2–7.1)

Bauss

etal.[40]

pCCT

63pts(18/45)-65

teeth

17.8(16.3–20.1)

M3

3–4

Max→

max/m

ndMnd

→mnd

No

3.9(1.5–6.6)

Bauss

etal.[41]

pCCT

88pts(32/56)-90

teeth

17.6(15.8–20.1)

M3

3–4

Max→

max/m

ndMnd

→mnd

No

4.0(1.7–7.9)

Bauss

etal.[66]

pCCT

62pts(21/41)-64

teeth

17.6(15.8–20.3)

M3

3–4

Max→

max/m

ndMnd

→mnd

No

4.2(1.0–7.9)

Bauss

andKiliaridis[57]

pCT

136pts(42/94)-139teeth

17.6(16.1–20.3)

M3

3–4

Max→

max/m

ndMnd

→mnd

No

4.4(1.8–8.3)

Eliasson

etal.[33]

pCT

34pts(14/20)-36

teeth

27.5(19.0–47.0)

C/P/M

4–6

NR

No

4.6(1.0–10.1)

Kahnberg[25]

pCT

44pts(30/15)-51

teeth

10.0–70.0

I/C/P/M

2/M3

27%

at1–4;

73%

at5–6

NR

No

(0.5–10.0)

Kristerson[9]

pCT

87pts(41/46)-100teeth

10.0–58.0

P1–6

Max/m

nd→

NR

No

6.3(3.0–18.0)

Kristersonetal.[14]

pCT

18pts(7/11)-18teeth

39.8(24.0–58.0)

M3

6Max/m

nd→

NR

No

(1.5–6.0)

Lagerström

and

Kristerson[51]

pCCT

29pts(14/15)-59

teeth

12.7(10.0–16.0)

P1–6

NR→

max/m

ndNo

NR

LundbergandIsaksson

[15]

pCT

278pts(118/160)-278teeth

NR

C/P/M

73%

at1–4;

27%

at5–7

NR

No

NR

Marques-Ferreiraetal.[26]

pCT

26pts(14/12)-28

teeth

22.3(11.0–43.0)

Max

C/P/M

3;Mnd

M1/M3

54%

at1–4;

46%

at5–7

NR

Some

4.0(2.0–5.6)

Mejàreetal.[62]

pCT

50pts-50

teeth

36.7(21.0–66.0)

M3

NR

Max→

max/m

ndNo

4.0

Myrlund

etal.[45]

pCT

NR-153

teeth

NR

I/P/M

NR

NR

NR

4.0

Nethander

etal.[83]

pCT

53pts-57

teeth

30.7(13.0–65.0)

I/C/P/M

34–6

NR

Yes

NR–5.0

Nethander

[70]

and

Nethander

[81]

pCCT

71pts(29/42)-75

teeth

32.2(13.0–65.0)

I/C/P/M

6NR

Yes

(0.1–5.0)

Clin Oral Invest

Transplants with wire-composite splint were more likelybe extracted compared with transplants with suturesplint (RR: 3.7; 95 % CI: 1.1–12.6). The calculatednumber needed to treat is 7, which means that for everyseven transplants with suture splint, we would preventone transplant in need of extraction post-treatment com-pared to transplants with wire-composite splint. Thequality of clinical evidence was in all occasions judgedas low, which means that any estimate of effect is veryuncertain [84]. The main problems identified were theserious methodological limitations of included studies,heterogeneity between reported results, and imprecisionof the calculated effects due to limited number ofstudies.

B. Secondary outcomes

Synthesis of results for the secondary outcomes

The meta-analyses of pooled event rates for transplants’ fail-ure, ankylosis, hypermobility, pulp necrosis, pulp obliteration,and root resorption can be seen in Table 4. Again, caution iswarranted, as the reported event rates were extremely inhomo-geneous, and this could influence the effect’s precision.

The influence of various patient, tooth, or operatingcharacteristics on the secondary outcomes can be seenin Appendix Tables 10, 11, 12, 13, and 14. Taking intoconsideration however the limited number of contribut-ing studies and the multiple testing conducted, theseshould be seen as an exploratory overview of existingevidence. The only factor that seemed to consistentlyinfluence the prognosis of autotransplantation was thestage of root development. Ankylosis, pulp necrosis,a n d r oo t r e s o r p t i o n we r e l e s s l i k e l y t o b eseen/diagnosed in teeth with open apex at the time oftransplantation.

Additional analyses

Subgroup analyses were planned for the meta-analyses ofcomparisons with the RRs but not performed due to the scar-city of available data.

The existence and impact of Bsmall study effects^ andreporting biases (including publication bias) could be formallyassessed only for the pooling of adverse event rates, whichincluded more than 10 studies. Egger’s linear regression test[78] was significant in all instances and indicated that smallerstudies tended to overestimate the event rates (AppendixTable 15).

Sensitivity analyses for the direct comparisons with RRscould not be conducted, due to the limited number of studies.Sensitivity analyses for the pooled event rates were conductedby including only studies with at least 100 transplanted teethT

able1

(contin

ued)

Study

Studydesign

Studysample-pts(M

/F)-teeth

Meanagein

years(range)

Group

ofteethused

Rootd

evelopmenta

Donor

site(s)/

recipientsite(s)

Two-stage

Tx

Meanfollo

w-upin

months(range)

Ploderetal.[58]

pCT

23pts(8/15)-23teeth

21.9(15.0–33.0)

P/M3

52%

at1–4;

48%

at5–7

Max→

max/m

ndMnd

→mnd

No

1.0

Pogreletal.[11]

pCT

368pts(223/193)-416teeth

14.0–38.0

C/P/M

NR

Max/m

nd→

max/m

ndNo

(2.0–N

R)

Reich

[29]

pCT

32pts(14/18)-44

teeth

19.0(11.0–25.0)

M84

%at1–4;

16%

at5–7

NR

No

3.0

Sagneetal.[59]

pCT

26pts-31

teeth

15.0–52.0

Max

CNR

NR

No

2.7(0.5–8.7)

Sobhietal.[54]

pCT

50pts-50

teeth

25.0–40.0

M3

6NR

No

NR

Sugaietal.[2]

pCT

109pts(41/68)-117teeth

39.0(11.0–75.0)

I/P/M

4–6

NR

No

3.4(1.0–5.9)

Thomsson

etal.[34]

pCT

24pts(9/15)-26teeth

25.0(13.0–59.0)

C/P/M

36(exceptfor

8teeth)

NR

Yes

(1.0–N

R)

Yan

etal.[60]

pCT

34pts(6/28)-35teeth

24.0(16.0–39.0)

M3

5,6

Mnd

→mnd

No

5.2(1.0–11.0)

Ffemale,M

male,Man

mandible,Max

maxilla,NRnotreported,pC

CTprospectivecontrolledclinicaltrial,pC

Tprospectiveclinicaltrial,ptspatients,Txtreatm

ent

aThe

numbers1–6correlateto

theclassificatio

nsuggestedby

Moorreess

etal.[27]regardingthestages

ofroot

developm

ent

Clin Oral Invest

Tab

le2

Characteristicsof

the38

prospectivestudiesincluded

inthemeta-analysis

oftherisk

factors

Study

Surgicalprotocola

Splin

tingmethod(durationin

weeks)

Endodontic

treatm

entb

yprotocol

Orthodontically

treated

Ahlberg

etal.[63]

–Su

ture

splin

torbanded

topre-existin

gFA

(5.0

wks)

No—

in70

%No

Akiyamaetal.[30]

Splittin

gosteotom

yifno

pre-existin

gsocket

Prophylacticoralantib

ioticsfor5–10

days

(Cefuroxim

eAxetil

750mg/day)

Suture

splin

t(1.0wk)

and

Adhesiveresinsplin

t/bridgeandcircum

ferential

wiringor

wiresplin

t(4.3wks)

Infraocclusion

Yes—pulpectomy2.0–3.0wks

post-op/root

canalfilling4.0–6.0wks

post-op

No

AkkocaogluandKasaboglu

[31]

Oralantibiotics,anti-inflam

matorydrugs,and

chlorhexidinemouth

rinse

Noocclusalcontact

No—

in47

%of

Csand24

%of

M3s

No

Alto

nenetal.[35]

Atraumaticextractio

nSo

cketpreparation

Suture

splin

t(1.0wk)

Bandedto

partialFAor

acrylic

resinsplin

tor

Schuchardt’sarch

bar(6.0

wks)

No—

in32

%No

Andreasen

etal.[13,46,55,64]

Standardized

Suture

splin

t3–0

silk

(1.0

wk)

Rigid

splin

twith

FAYes—in

fully

developedteeth4wks

post-op

Yes—in

46%

Arikanetal.[32]

Rem

oval-to-transplantationtim

e≤1

5min

Interproximalenam

elreductionof

donorand

adjacent

torecipientareateeth,ifdonor

toothtoowide

Suture

splin

t[4–0silk]

Wire-compositesplin

t(4.0wks)

Yes—pulpectomyandCa(OH) 2placem

ent

4.0wks

post-op/root

canalfilling

1ypost-op

No

Azazetal.[56]

Rem

oval-to-transplantationtim

e≤2

5min

Surgicalor

orthodontic

wiresplin

t(10.0

wks)

Yes—with

zinc

oxide-eugenolp

asteand

gutta-perchapoints/apicoectomyin

case

ofpositio

ning

problems

No

Bauss

etal.[16]

Standardized

technique(A

ndreasen

xxx)


ioticsstartin

g1hpre-op

(amoxicillin

3×750mg)

andchlorhexidine

0.2%

mouth

rinsefor7days

Initialstability:suturesplin

t[2–0silk](1.0

wk)

Noinitialstability:w

ire(2.0

mm×0.5mm

stainlesssteel)-com

positesplin

t(4.0wks)

No—

in1%

No

Bauss

etal.[39]

Standardized

technique(A

ndreasen

xxx)

Splittin

gosteotom

yor

bone

autograftin

alveolar

atrophy

Ininfraocclusion


ioticsstartin

g1hpre-op

(amoxicillin

3×750mg)

andchlorhexidine

0.2%

mouth

rinsefor7days

Suture

splin

t2–0

(1.0

wk)

Ininadequatestability:w

ire(2

mm×0.5mm)-

compositesplin

t(4.0wks)

NR

No

Bauss

etal.[65]

Standardized

technique


ioticsstartin

g1h

pre-op

(amoxicillin

3×750mg)

and

chlorhexidine0.2%

mouth

rinsefor7days

Suture

splin

t(1.0wk)

Infraocclusion

1.0–3.0mm

NR

Yes

Bauss

etal.[66]

Standardized

technique(A

ndreasen

[16,39–41])


ioticsstartin

g1hpre-op

(amoxicillin

3×750mg)

andchlorhexidine

0.2%

mouth

rinsefor7days

Suture

splin

t(1.0wk)

Infraocclusion

1.0–6.5mm

No—

in12

%Yes—allw

ere

moved,31%

werederotated,

and23

%wereextruded

Bauss

etal.[40]

Standardized

technique

Antibiotic

coverage

for7days

Initialstability:suturesplin

t[2–0silk](1.0

wk)

NR

No

Clin Oral Invest

Tab

le2

(contin

ued)

Study

Surgicalprotocola

Splin


weeks)

Endodontic

treatm

entb

yprotocol

Orthodontically

treated

Noinitialstability:w

ire(2.0

mm×0.5mm

stainlesssteel)-com

positesplin

t(4.0wks)

Infraocclusion

Bauss

etal.[41]

Standardized

technique

Verticalalveolar

atrophy:

bone

autografts

Horizontalalveolaratrophy:

splittin

gosteotom

yProphylacticoralantib

ioticsstartin

g1hpre-op

(amoxicillin

3×750mg)

andchlorhexidine

0.2%

mouth

rinsefor7days

Suture

splin

t(1.0wk)

Infraocclusion

NR

No

Bauss

etal.[66]


iotics(amoxicillin

3×750mg)

and

chlorhexidine0.2%

mouth

rinsetwice

daily

for7days

Suture

splin

t(1.0wk)

Infraocclusion

NR

No

Bauss

andKiliaridis[57]

Standardized

technique

Antibiotic

coverage

for7days

Suture

splin

t(1.0wk)

Infraocclusion

1.0–6.5mm

No

Yes—in

66%

Eliasson

etal.[33]

–Acrylicsplin

tin70

%(3.8

wks)

Wire-compositesplin

torsurgicalcementin

30%

(3.8

wks)

Yes—pulpectomypre-op

orwith

in12.0

wks

post-op/root

canalfilling5.0–42.0

wks

post-op

No

Kahnberg[25]

–Su

ture

splin

tand

Acrylicstring-brackets-splin

tinmostcases

orAcrylicsplin

tin16

%(3.0–5.0

wks)

Infraocclusion

only

forpartially

developedteeth

Yes—in

fully

developedteeth:

pulpectomy

3.0–4.0wks

post-opandCa(OH) 2

placem

ent/rootcanalfilling

3.0–4.0monthslater

No

Kristerson[9]

–Teethunderthemucousmem

brane:suture

splin

t(1.0wk)

Teethin

infraocclusion:stainless

steelw

ire

occlusalof

thetooth

Teethin

occlusion:

FAs(1.0-m

orethan

6.0wks)

No—

in27

%No

Kristersonetal.[14]

Oralantibiotic

(penicillin

V2×

1g)

for8days

andchlorhexidine0.2%

mouth

rinsetwice

daily

for7days

Softarch

barwith

FAsand/or

composite

(2.0–3.0)

Yes—pulpectomywith

in2.0–3.0wks

post-op/root

canalfillingafter

6.0months

No

Lagerström

andKristerson[51]

–Su

ture

splin

tNo

Yes—in

50%

LundbergandIsaksson

[15]

Standardized

technique

Suture

splin

t(1.5wk)

Teethwith

closed

apices:FAs(1.0–3.0

wks)

Infraocclusion

fornotfully

developedteeth

Yes—in

fully

developedteeth:

pulpectomy

with

in3.0wks

post-opandCa(OH) 2

placem

ent/rootcanalfilling

3.0–12.0

monthslater

No


Extra-alveolartim

e<15

min

Acrylictoothreplicas

used

forsocketpreparation

10days

pre-op

Suture

splin

t[3–0silk](1.5

wk)

Infraocclusion

No—

in39

%No

Mejàreetal.[62]

Silver

toothreplicas

used


Incontactw

ithadjacent

teeth;

nocontact

with

theopposing

teeth

Oralantibiotic

(penicillin

V2g1hpre-op

and3×

1gfor10

days

post-op)

Interdentalsutures

inmostcases

(1.5

wk)

Com

positeresinsplin

tin20

%(1.5

wk)

Yes—pulpectomypost-opandCa(OH) 2

placem

entw

ithin

4.0wks

post-op/root

canalfillingwith

in3.0monthspost-op

No

Clin Oral Invest

Tab

le2

(contin

ued)

Study

Surgicalprotocola

Splin


weeks)

Endodontic

treatm

entb

yprotocol

Orthodontically

treated

Analgesicscontaining

paracetamol

andcodeine

ornon-steroidanti-inflam

matorydrugs

prescribed

Myrlund

etal.[45]

Standardized

technique(SlagsvoltandBjercke,

1967

xxx)

NR

NR

No

Nethander

etal.[83]

Socketprepared

2.0wks

pre-op

Com

positeresinsplin

t(2.0wks)

Yes—4wks

post-op

No

Nethander

[70]

andNethander

[81]

Socketprepared

2.0wks

pre-op

Com

positeresinsplin

t(2.0wks)

Yes—4wks

post-op

No

Ploderetal.[58]

Ininfraocclusion

Nofixatio

nin

26%

Suture

splin

t[3–0]

in65

%(2.0

wks)

Acrylicsplin

tin9%

(3.0

wks)

No

No

Pogreletal.[11]

Extensive

drillingor

labialosteoplasticflap

Postoperativeantib

ioticsfor3days

Plastic

vacuform

splin

tcoveringtransplant

and1–2

adjacent

teethin

mostcases

(3.0

wks)

Castsilv

ersplin

ts(4.0

wks)

No

No

Reich

[29]

Inter-radicularbone

removalandbone

removal

beyond

theapex

Alltransplantsplaced

infour-w

alledsockets

Ininfraocclusion

1.0–2.0mm

Oralantibiotics(penicillin

V2gor

clindamycin

600mg)

prophylacticandfor5days

Instructions

forliq

uid,then

pureed,and

then

softdietfor4wks

Suture

splin

tsilk

3–0(2.0

wks)

NR

No

Sagneetal.[59]

Oralantibiotics(penicillin

V2×

2g)

post-op

for10

days

FAswith

0.016×0.016″

wire(6.0–8.0

wks)

Yes—pulpectomy6.0–8.0wks

post-op/root

canalfilling1.0ylater

Yes

Sobhietal.[54]

Inslight

infraocclusion

Instructions

forsoftdiet

Pre-op

andpost-opantib

ioticsprescribed

Suture

splin

t,fine

wireor

arch

bar

(2.0–3.0

wks)

Yes—operatively

No

Sugaietal.[2]

Standardized

technique(A

ndreasen

[16,39–41])

Suture

splin

t4–0

silk

(1.0

wk)

orWire-compositesplin

t(3.0wks)

Yes—pulpectomy3.0wks

post-op/root

canalfillinglater

No

Thomsson

etal.[34]

Teethcultivatedfor3.0–17.0

wks

inEagle’s

medium

pre-op

Acrylictooth-replicaused


Wire-compositesplin

t(6.4wks)

Yes—in

fully

developedteethandin

three

teethwith

incompleteroot

form

ation

No

Yan

etal.[60]

Standardized

technique

(modifiedTsukiboshi’smethod)

Oralantibiotics

Instructions

forsoftdietfor1wk

Wirefixatio

n,wheninitialstability

not

achieved

(1.0

wk)

Yes—in

fully

developedteeth

4.0wks

post-op

No

FAfixedappliances,w

kweek

aCom

mon

descriptionof

thesurgicalprotocol

formosto

fstudies:atraum

aticextractio

n/storagein

originalpositio

nor

insalin

euntil

transplantation/socketenlargem

ento

rcreatio

n

Clin Oral Invest

Tab

le3

Characteristicsof

theincluded

studiesregardingprim

aryandsecondaryoutcom

es

Study

Survivalrate%

(n)

Success

rate%

(n)

Ankylosis%

(n)

Arrestedroot

developm

ent

%(n)

Hypermobility

%(n)

Periodontalp

roblem

s%

(n)

Pulpnecrosis%

(n)

Pulpobliteration

(partialand/or

total)%

(n)

Rootresorption

(internaland/or

inflam

matory)

%(n)

Ahlberg

etal.[63]

88%

(29/33)

NR

100%

(33/33)

NR

NR

12%

(4/33)

57.6

%(19/33)

NR

75%

(25/33)

Akiyamaetal.[30]

100%

(25/25)

100%

(25/25)

NR

NR

NR

0%

(0/25)

Byprotocol

NR

0%

(0/25)

AkkocaogluandKasaboglu

[31]

85%

(83/96)

85%

(82/96)

NR

NR

NR

NR

49%

(47/96)

NR

8%

(8/96)

Altonenetal.[35]

86%

(24/28)

NR

18%

(5/28)

NR

36%

(10/28)

Attachmentloss:37

%(10/28)

Pocket>3mm:2

5%

(7/28)

89%

(25/28)

14%

(4/28)

50%

(14/28)

Andreasen

etal.[55]

NR

NR

NR

NR

NR

NR

NR

NR

NR

Andreasen

etal.[13]

99%

(367/370)

NR

NR

NR

NR

NR

16%

(58/370)

82%

(304/370)

NR

Andreasen

etal.[46]

NR

NR

6%

(21/370)

NR

NR

Attachmentloss:1%

(3/370)

NR

NR

10%

(35/370)

Andreasen

etal.[64]

NR

NR

NR

Total:14

%(23/164)

Partial:65

%(107/164)

NR

NR

NR

NR

NR

Arikanetal.[32]

94%

(30/32)

NR

NR

NR

NR

NR

Byprotocol

NR

6%

(2/32)

Azazetal.[56]

62%

(23/37)

89%

(33/37)

32%

(12/37)

NR

NR

NR

Byprotocol

NR

24%

(9/37)

Bauss

etal.[16]

100%

(76/76)

84%

(64/76)

5%

(4/76)

22%

(17/76)

4%

(3/76)

3%

(2/76)

9%

(7/76)

91%

(69/76)

NR

Bauss

etal.[39]

100%

(85/85)

86%

(73/85)

5%

(4/85)

19%

(16/85)

6%

(5/85)

6%

(5/85)

NR

87%

(74/85)

8%

(7/85)

Bauss

etal.[65]

100%

(75/75)

NR

NR

17%

(13/75)

NR

NR

NR

NR

NR

Bauss

etal.[82]

100%

(91/91)

85%

(77/91)

3%

(3/91)

NR

3%

(3/91)

15%

(14/91)

12%

(11/91)

88%

(80/91)

12%

(11/91)

Bauss

etal.[40]

100%

(65/65)

100%

(65/65)

NR

NR

3%

(2/65)

NR

NR

NR

NR

Bauss

etal.[41]

100%

(90/90)

NR

NR

11%

(10/90)

NR

5%

(5/107)

8%

(9/107)

NR

NR

Bauss

etal.[66]

100%

(64/64)

NR

NR

11%

(7/64)

NR

NR

NR

NR

NR

Bauss

andKiliaridis[57]

100%

(139/139)

NR

NR

NR

NR

NR

NR

NR

NR

Eliasson

etal.[33]

89%

(32/36)

67%

(24/36)

6%

(2/36)

NR

NR

6%

(2/36)

Byprotocol

NR

22%

(8/36)

Kahnberg[25]

98%

(50/51)

NR

8%

(4/51)

NR

12%

(6/51)

Reduced

bone

anchorage12

%(6/51)

Byprotocol

atfully

developedroots

NR

12%

(6/51)

Kristerson[9]

93%

(93/100)

77%

(77/100)

12%

(12/100)

NR

NR

8%

(8/100)

26%

(26/100)

73%

(73/100)

7%

(7/100)

Kristersonetal.[14]

89%

(16/18)

83%

(15/18)

6%

(1/18)

NR

NR

Pocket≥5

mm

(7/18)

50%

(9/18)

NR

6%

(1/18)

Lagerström

andKristerson[51]

100%

(59/59)

100%

(59/59)

0%

(0/59)

NR

NR

NR

NR

NR

0%

(0/59)

LundbergandIsaksson

[15]

99%

(275/278)

62%

(254/278)

5%

(14/278)

57%

(159/278)

NR

Increasedpockets:5%

(15/278)

3%

(8/278)

NR

1%

(4/278)


93%

(26/28)

NR

NR

NR

NR

NR

39%

(11/28)

NR

NR

Mejàreetal.[62]

86%

(43/50)

NR

NR

NR

NR

4%

(2/50)

Byprotocol

NR

10%

(5/50)

Myrlund

etal.[45]

99%

(150/153)

91%

(138/153)

NR

27%

(41/153)

NR

NR

NR

NR

NR

Nethander

etal.[83]

90%

(51/57)

72%

(41/57)

NR

NR

NR

NR

NR

NR

21%

(12/57)

Nethander[70]

89%

(67/75)

NR

NR

NR

5%

(4/75)

Attachmentloss:50

%(36/75)

Bleedingon

probing:

40%

(30/75)

NR

NR

NR

Nethander[81]

89%

(67/75)

NR

5%

(4/75)

NR

5%

(4/75)

Attachmentloss:50

%(36/75)

NR

NR

5%

(4/75)

Ploderetal.[58]

100%

(18/18)

NR

0%

(0/18)

NR

NR

0%

(0/18)

50%

(9/18)

NR

6%

(1/18)

Pogreletal.[11]

83%

(346/416)

72%

(302/416)

NR

NR

NR

NR

4%

(16/416)

NR

14%

(58/416)

Clin Oral Invest

(Appendix Table 16) or by including only studies with a meanfollow-up of at least 6 months (Appendix Table 17). In mostoccasions, sensitivity analyses differed considerably from theoriginal analyses, and thus, caution is warranted by the inter-pretation of the pooled rate of each adverse effect.

The data from the rest of the analyses that were carried outin the context of the existing meta-analysis and were proved tobe of lower statistical and/or clinical importance is also includ-ed in the Appendix.

Discussion

Summary of evidence

Existing evidence about autotransplanted teeth in humans andfactors associated with their failure has been proved to belimited. According to the results of this analysis, the stage ofroot development seems to significantly influence the successof autotransplantation, which confirms the results of previousstudies [9, 21, 33, 35, 40, 41, 64, 85], but no other significanteffects could be identified.

Moreover, although a total of 38 studies were included inthe qualitative synthesis, most of them were pCTs withoutcontrolled conditions, while no RCT was possible to be in-cluded. It must also be noted that the follow-up period in theincluded studies differed considerably, with 5 out of the 38studies following all or a number of autotransplanted teeth forless than 1 year [25, 30, 34, 35, 70, 81]. The latter discrepancymight have had a profound effect on the reported outcomes.Ankylosis, for example, can occur up to 2 years postopera-tively [11]. In this direction, it would help if official guidelinesexisted about the minimum observation period forautotransplanted teeth.

In this systematic review, various outcomes were consid-ered, but the main focus was on the primary outcome of sur-vival failure of the transplanted tooth (i.e., the need for extrac-tion). The remaining assessments of secondary outcomes canbe viewed only as exploratory analyses, especially after takinginto consideration the existing dangers of spurious significantfindings due to multiple testing and the limited number ofstudies contributing to them.

Survival of the autotransplanted teeth was significantly as-sociated with the developmental stage of their roots at the timeof transplantation. Teeth with open apex were in considerablylower risk of failure compared to teeth with closed apex at thetime of transplantation. Although the three studies that con-tributed to this comparison presented evidence of low quality,according to the GRADE approach, the magnitude of the ef-fect was considerable (RR=0.3). The NNT indicated that forevery six transplanted teeth with open apex, one additionaltooth would survive, which would have failed, if the teethwere transplanted after the apex was closed. This is inT

able3

(contin

ued)

Study

Survivalrate%

(n)

Success

rate%

(n)

Ankylosis%

(n)

Arrestedroot

developm

ent

%(n)

Hypermobility

%(n)

Periodontalp

roblem

s%

(n)

Pulpnecrosis%

(n)

Pulpobliteration

(partialand/or

total)%

(n)

Rootresorption

(internaland/or

inflam

matory)

%(n)

Reich

[29]

96%

(42/44)

96%

(42/44)

0%

(0/44)

NR

NR

NR

0%

(0/44)

NR

0%

(0/44)

Sagneetal.[59]

100%

(31/31)

NR

NR

NR

NR

0%

(0/31)

Byprotocol

NR

3%

(1/31)

Sobhietal.[54]

NR

88%

(35/50)

NR

94%

(47/50)

12%

(6/50)

Deeppockets:8%

(4/50)

Gingivitis:1

2%

(6/50)

Percussion

sensitivity:

8%

(4/50)

Poor

attachment:4%

(2/50)

Fistulae:2%

(1/50)

NR

6%

(3/50)

Sugaietal.[2]

84%

(98/117)

88%

(103/117)

4%

(5/117)a

NR

NR

4%

(5/117)a

NR

NR

NR

Thomsson

etal.[34]

69%

(18/26)

NR

19%

(5/26)

NR

69%

(18/26)

31%

(8/26)

81%

(21/26)

NR

NR

Yan

etal.[60]

94%

(33/35)

NR

0%

(0/35)

100%

(16/16)

NR

NR

Closedapex

teeth:

byprotocol

Openapex

teeth:

13%

(2/16)

NR

6%

(2/35)

NRnotreported

aAnkylosiswith

periodontalinflammationobserved

forfive

transplanted

teeth

Clin Oral Invest

accordance with older reports of lower success rates forautotransplantation of teeth with complete root formation[21, 56, 63, 86, 87].

A considerable difference between teeth with open orclosed apex was found regarding the risk of failure due to pulppathology. Teeth with fully developed roots are usually end-odontically treated prior to transplantation [13, 21, 30, 32, 33,53, 69], because revascularization and pulpal healing are lesslikely to occur, due to their dependence on the diameter of the

root foramen and the length of the root [26, 88]. In this way,inflammatory procedures that could endanger their prognosisare usually prevented [4, 62, 70]. In contrast, teeth with de-veloping roots and open apices are usually endodonticallytreated only when symptoms of periapical inflammation aredetected, as the prognosis for pulpal healing is generally better[26, 46, 89], risking probably in some cases, the occurrence ofmore serious complications, in case of delayed or wrongdiagnosis.

(-3.90, 19.49)with estimated predictive interval

Overall (I2=88%; tau2=26.744)

Myrlund 2004

Nethander 1998

Kristerson 1991

Reich 2008

Yan 2010

Eliasson 1988

Pogrel 1987

Kahnberg 1987

Kristerson 1985

Sugai 2010

Nethander 1988

Mejare 2004

Study

Ahlberg 1983

Lundberg 1996

Andreasen 1990

1

8

1

2

2

4

70

1

7

19

6

7

Events

4

11

3

74

75

18

44

35

36

416

51

100

117

25

49

Sample

33

278

370

7.80 (4.65, 10.94)

1.35 (-1.28, 3.98)

10.67 (3.68, 17.65)

5.56 (-5.03, 16.14)

4.55 (-1.61, 10.70)

5.71 (-1.98, 13.40)

11.11 (0.85, 21.38)

16.83 (13.23, 20.42)

1.96 (-1.84, 5.77)

7.00 (2.00, 12.00)

16.24 (9.56, 22.92)

24.00 (7.26, 40.74)

14.29 (4.49, 24.08)

12.12 (0.99, 23.26)

3.96 (1.67, 6.25)

0.81 (-0.10, 1.72)

100.00

9.01

6.52

4.60

7.03

6.10

4.75

8.54

8.43

7.73

6.70

2.58

4.97

Weight

4.36

9.15

9.54

Rate% (95% CI)

% Event Rate

0% 10% 25% 40%

Fig. 2 Forest plot with the meta-analysis of the pooled rate of the primary outcome (extraction need of the transplanted tooth) sorted from top to bottomwith increasing standard error

Table 4 The pooled estimates of primary and secondary negative outcomes (adverse event rates) from the 38 studies included in the analysis

Adverse event Studies % Event ratea (95 % CI) 95 % PIa I2 (95 % CI)a

Primary

Extraction need 15 7.8 (4.7, 10.9) 0.0, 10.9 88 % (83, 91 %)

Secondary

Failure 17 14.6 (10.1, 19.1) 0.0, 32.8 86 % (78, 90 %)

Ankylosis 11 6.2 (4.5, 7.8) 3.0, 9.3 18 % (0, 60 %)

Hypermobility 8 8.0 (4.1, 11.9) 0.0, 19.9 70 % (20, 84 %)

Pulp necrosis 10 34.3 (21.1, 47.4) 0.0, 83.9 98 % (97, 98 %)

Pulp obliteration 5 53.4 (28.3, 78.5) 0.0, 100.0 98 % (97, 98 %)

Root resorption 19 10.4 (7.0, 13.7) 0.0, 24.0 88 % (83, 91 %)

CI confidence interval, PI prediction intervala Negative values and values over 100 omitted

Clin Oral Invest

The effect of splint type on the transplants’ prognosiscould not be adequately assessed since only one studywas possible to be included in the analysis. The magni-tude of the observed effect was great (RR=3.7), and itreached statistical significance (P=0.036), with a suturesplint appearing to be more favorable compared to awire-composite splint. This is in accordance with theresearchers who believe that appropriate functionalmovement of the transplanted teeth during the fixationperiod is crucial for a successful periodontal healing[15, 64]. It must, however, be pointed out that Bausset al. [16] used a rigid 2.0 mm×0.5 mm wire-composite

splint. In more recent studies, flexible or semi-rigidsplints, such as the titanium trauma splint and othertypes of wire-composite splints, are considered as moreappropriate. Therefore, the use of more flexible types ofsplints, which enable some degree of functional move-ment in cases of autotransplanted teeth, could possiblyhave a significant effect on the present results [90–92].

Finally, gender-related risk factors have not been identified,since no statistically significant relationships resulted from theanalysis of the available data. This is something alreadyknown from previous studies, which was also confirmed inthe present review.

NOTE: Weights are from random-effects analysis

Inestimable predictive distribution with <3 studies



with estimated predictive interval





.

Donor site (Ref: maxilla; Exp: mandible)

Pogrel 1987Eliasson 1988Subtotal (I2 = 65%, P = 0.947)

Patient age (Ref: ≥20 years; Exp: <20 years)

Pogrel 1987Altonen 1978Subtotal (I2 = 0%, P = 0.676)

Patient gender (Ref: female; Exp: male)

Pogrel 1987Akkocaoglou 2005Subtotal (I2 = 0%, P = 0.685)

Recipient site (Ref: other than donor; Exp: same as donor)

Lundberg 1996Subtotal (I2 =NA, P = 0.533)

Root development stage (Ref: closed apex; Exp: open apex)

Lundberg 1996Yan 2010Kristerson 1985Subtotal (I2 = 0%, P < 0.001)

Splinting (Ref: suture splint; Exp: wire-composite splint)

Bauss 2002Subtotal (I2 =NA, P = 0.036)

Surgical technique (Ref: no bone graft; Exp: bone graft)

Bauss 2004aSubtotal (I2 =NA, P = 0.269)

Transplanted tooth (Ref: molar; Exp: canine)

Akkocaoglou 2005Lundberg 1996Pogrel 1987Subtotal (I2 = 43%, P = 0.482)

Study

233

480

614

15

1203

9

3

5160

Events

12416

1797

22342

171

2041682

34

19

4710162

Sample

751

674

549

7

1224

3

2

81638

Events

22520

23721

19354

105

741918

42

33

49177187

Sample

. ( - , - )

. ( - , - )

. ( - , - )

. (., .)

. (0.00, 20.17)

. (., .)

. (., .)

. (0.00, 1644.46)

0.56 (0.37, 0.84)3.75 (0.43, 32.70)1.06 (0.18, 6.23)

0.95 (0.69, 1.30)0.31 (0.02, 5.06)0.94 (0.68, 1.28)

0.57 (0.19, 1.73)

1.32 (0.55, 3.12)1.32 (0.55, 3.12)

0.36 (0.17, 0.77)0.24 (0.01, 4.57)0.16 (0.04, 0.67)0.30 (0.16, 0.57)

3.71 (1.09, 12.63)

2.61 (0.48, 14.23)2.61 (0.48, 14.23)

1.11 (0.16, 7.52)1.82 (1.29, 2.58)

RR (95% CI)

0.98 (0.72, 1.33)

0.94 (0.70, 1.27)

3.71 (1.09, 12.63)

0.65 (0.23, 1.85)

1.29 (0.63, 2.62)

66.1633.84100.00

98.751.25100.00

92.667.34

100.00100.00

4.7921.26100.00

100.00100.00

100.00100.00

28.0011.4960.51100.00

100.00

73.95

Weight

0.01

More events in Ref More events in Exp

1 82.6

Experimental Reference

Fig. 3 Forest plot with the meta-analysis of factors influencing the primary outcome: extraction need of the transplanted tooth. CI confidence interval,Exp experimental group, Ref reference group, RR relative risk

Clin Oral Invest

Tab

le5

GRADEsummaryof

findings

tableformeta-analyses

onprim

aryoutcom

e(extractionneed)

Factor

(follow-up)

Illustrativ

ecomparativ

erisks(95%

CI)

Relativeeffect(95%

CI)

No.of

teeth(studies)

Qualityof

evidence

(GRADE)

Com

ments

Assum

edrisk

Corresponding

risk

≥20years

<20

years

⊕○○

○Patient

age

237per1000

237per1000

(166

to308)

RR0.9(0.7to

1.3)

444(2

studies)[11,35]

lowa

P=0.676;

I2=0%

Fem

ale

Male

⊕○○

○Patient

gender

223per1000

223per1000

(156

to290)

RR0.9(0.7to

1.3)

512(2

studies)[11,31]

lowa

P=0.685;

I2=0%

Maxilla

Mandible

⊕○○

○Donor

site

192per1000

192per1000

(38to

845)

RR1.1(0.2to

6.2)

385(2

studies)[11,33]

lowa,b,c

P=0.947;

I2=65

%

Other

than

donor

Sameas

donor

⊕○○

○Recipient

site

67per1000

87per1000

(33to

207)

RR1.3(0.6to

3.1)

276(1

study)

[15]

lowa,c

P=0.533;

I2=NA

Canine

Molar

⊕○○

○Transplantedtooth

163per1000

228per1000

(147

to359)

RR1.3(0.6to

2.6)

632(3

studies)[11,15,31]

lowa

P=0.482;

I2=43

%(0

to76

%)

Closedapex

Openapex

⊕○○

○Rootd

evelopmentstage

245per1000

74per1000

(49to

147)

RR0.3(0.2to

0.6)

413(3

studies)[9,15,60]

lowa

NNT=6;

P≤0

.001;I

2=0%

(0to

73%);95

%PI=0.0to

20.2)

Nobone

graft

Bonegraft

⊕○○

○Su

rgicaltechnique

152per1000

365per1000

(61to

2006)

RR2.6(0.5to

14.2)

52(1

study)

[13,46,55,64]

lowc,d

P=0.269;

I2=NA

Suturesplin

tWire-compositesplin

t⊕○○

○Sp

lintin

g71

per1000

221per1000

(64to

771)

RR3.7(1.1to

12.6)

76(1

study)

[16]

lowa,d

NNT=7;

P=0.036;

I2=NA

Patients:patientswith

missing

teeth,im

pacted

caninesor

anyindicatio

nfortoothtransplantation

Settings:university

clinics(China,D

enmark,Finland,Germany,Sweden,T

urkey,USA

)

Interventio

n:autotransplantationof

teeth

Com

parison:

variouspatient,tooth

oroperatingcharacteristics

Outcome:failu

reof

thetransplanted

toothdefinedas

theneed

forextractio

naDow

ngradedby

1:seriousmethodologicallim

itatio

nin

included

studies(<17

pointsin

themodifiedDow

nsandBlack

scale)

bDow

ngradedby

1:moderateheterogeneity

andconfidence

regardingclinicaldecision

couldbe

affected

byheterogeneity

cDow

ngradedby

1:im

precisionof

estim

ated

effect,asboth

significanth

arm

andsignificantb

enefitisincluded

inthe95

%CI

dDid

notu

pgrade

by1:

largeeffectmagnitude

found,buto

ther

reasonsfordowngrading

present(seriousmethodologicallim

itatio

nsor

imprecision)

CIconfidence

interval,N

Anotapplicable,N

NTnumberneeded

totreat,PIpredictio

ninterval,R

Rrelativ

erisk

Clin Oral Invest

On the other hand, it is impossible to perform an analysisbased on the available data regarding the use of single- andmulti-rooted donor teeth. The main reason is that there was aconsiderable number of studies included in their sample teethof both categories, without any differentiation in the results [2,11, 15, 25, 26, 33, 34, 45, 58, 70, 81, 83]. In addition, whenpremolars or third molars are used as donor teeth, the numberof roots, unless specifically reported, remains unknown [9, 13,16, 29–31, 39, 40, 46, 51, 53–55, 57, 60, 62, 64].

Similarly, because of the absence of adequate and/or uni-form data regarding the rest of the commonly discussed prog-nostic factors, like the experience of the surgeon, the use of anatraumatic surgical technique, the extra-alveolar preservationtime duration and conditions for the donor teeth, the timingand quality of the endodontic treatment, in cases where itapplies, the occlusal status of the autotransplanted teeth post-autotransplantation, and their overall postoperative care, nofurther analyses could be performed.

Recently, a relevant systematic review was published re-garding autotransplantation of teeth with complete root forma-tion in humans [93]. Although the authors concluded that theadministration of systemic antibiotics, the splinting methodused, and the timing of endodontic treatment influenced thesuccess of autotransplanted teeth, no comparison can be madewith the present review, as (i) only studies aboutautotransplanted teeth with complete root formation were in-cluded, (ii) the analyses of the systematic review were of in-direct nature (comparing event rates among studies and notevents within studies as in our review), and (iii) all reportedincidence rate ratios were statistically non-significant (95 %CIs included the value 1).

Strengths and limitations

Despite the extensive literature search, the number of studieswith controlled methodology that investigated the influence ofvarious factors on the prognosis of autotransplanted teeth waslimited. Despite the fact that a number of prospective cohortstudies were found, only a few controlled studies were possi-ble to be included in this review and the corresponding meta-analysis, while most of the included studies presented seriousmethodological limitations.

In addition, the randomization of treatment in patients withmissing teeth is not considered as appropriate for ethical rea-sons. This is apparently the mean reason why randomizedcontrolled trials have not been performed in this case andare, therefore, absent from the present review.

Furthermore, the quantitative synthesis provided evidenceof low quality, due to existing imprecision and heterogeneity.Various factors like differing lengths of the follow-up periods,the inexistence of an official surgical protocol and of specificcriteria determining the success of dental autotransplantation

might have been also contributed to the existence ofheterogeneity.

Conclusions

A number of complications have been found to be as-sociated with tooth autotransplantation in humans.However, existing evidence is scarce and derives mainlyfrom uncontrolled studies. The results of this meta-analysis should be interpreted with some caution, dueto the number and quality of the included studies.Reporting of most adverse effects is inconsistent amongstudies, and there is a tendency in small studies (lesst h a n 100 au t o t r a n s p l a n t e d t e e t h ) f o r e f f e c toverestimation.

With regard to the adverse outcomes of autotransplantedteeth, it can be concluded that

& The need to extract an autotransplanted tooth seems to beon average smaller than 10 %, although existing evidenceprecludes accurate estimation.

& Root development stage seems to be a significant factor inthe prognosis of the autotransplanted teeth, with openapex teeth having the risk of extraction need decreasedby 70 % (RR=0.3, 95 % CI=0.2–0.6) compared to closedapex teeth.

& Root development stage also seems to influence negativeoutcomes like ankylosis, pulp necrosis, and root resorp-tion of the autotransplanted teeth.

Solid evidence provided by prospectively planned,non-randomized, controlled trials and blinded studies thatassess specific factors regarding the patients, the teethused, the surgical and/or the post-surgical techniques,and th e i r i n f l u ence on th e p rognos i s o f t h eautotransplanted teeth is required in future studies. Inaddition, proper sample size calculation conducted apriori is important to provide adequate power to thestudy, while split-mouth designs, for some factors wherethey are applicable, might increase efficiency and de-crease patient variability. Furthermore, since root devel-opment of the donor teeth has been established as onethe most important factors related to the success of toothautotransplantation, it would be wiser to perform separatestudies and analyses for or between mature and immatureteeth in the future. Finally, standardization of the opera-tive protocols would certainly aid in assessing existingevidence in this field.

Conflict of interest The authors declare that they have no conflict ofinterest.

Clin Oral Invest

Appendix

Table 7 Commands used in the program Stata for the statistical analysis (database available upon request)

Analysis Stata codea

Meta-analysis of pooled event rates (Table 4, Appendix Tables 16 and 17, Fig. 2) metan p se, random rfdist

Meta-analysis of direct comparisons with relative risk (Table 5, Appendix Tables 10, 11, 12, 13, and 14, Fig. 3) metan exn exnon ctn ctnon,rr randomi rfdist

Calculation of I2 and its 95 % confidence intervals heterogi [Q] [df], nc

Assessment of reporting bias (Appendix Table 15) metabias p se, egger

a Bold lettering indicates the variables of each analysis: p proportion, se standard error of the proportion, exn events in the experimental group, exnon non-events in the experimental group, ctn events in the control group, ctnon non-events in the control group,Q amount of heterogeneity found, df degrees offreedom

Table 6 Eligibility criteria used in this meta-analysis

Criteria category Inclusion criteria Exclusion criteria

Outcome Studies investigating the success/survival rateof autologous transplantation of teeth in humans,including information about the developmental stageof the teeth used and/or the age of the participants,as well as the surgical protocol that was followed.

Investigations not relevant to the subject of this studyXeno-, etero-, allo-, and homo- or iso-transplantation studies

Study design Randomized controlled clinical trialsProspective clinical trials

Narrative reviewsSystematic reviewsMeta-analysesRetrospective clinical trialsCross-sectional surveysCase series without a controlCase reportsCase-control observational studiesUnsupported opinion of expertEditor’s choicesReplies to the author/editorBooks’ abstractsConferences’ abstractsOngoing studiesAnimal studiesIn vitro studiesIn silico studiesStudies on molecular biology, histology, or geneticsStudies with missing English abstract or/and havingno abstract at all

Studies without follow-up of the patients

Participants’ characteristics Studies included should involve onlyhuman subjects of any ageand of both sexes

Clinical trials with inadequate sample size groups,i.e., studies of less than ten participants

Studies not reporting the size of the examined sample/groupStudies with inadequate information about thetransplantation protocol

Studies including teeth and/or periodontal tissues involved intraumatic incidents

Investigations in patients with syndromes or genetic disordersStudies providing no information regarding thedevelopmental stage of the transplanted teeth

Outcomes’ characteristics Studies providing information regardingthe success/survival rate of autologoustransplantation of teeth in theshort- or/and long-term

Studies providing no information regarding thesuccess/survival rate of autologous tooth transplantationneither in the short nor in the long-term

Clin Oral Invest

Tab

le8

The

electronicdatabasessearched,the

search

strategy

used,and

thecorrespondingresults

(asof

Novem

ber20,2012)

Electronicdatabase

Search

strategy

Ext

endof

search

Hits

MEDLIN

ESearched

viaPu

bMed

www.ncbi.nlm

.nih.

gov/sites/entrez/

(autotransplantatio

n*OR(autologousANDtransplantation))A

ND(teethORtoothORdent*ORincisor*

ORcanine*OR

cuspid*ORbicuspid*ORprem

olar*ORmolar*ORwisdomtoothORwisdomteeth)

ANDBhum

ans^[M

eSHTerm

s]Lim

itedto

humans

Inallfields

1463

ElsevierBookSeriesandHealth

Sciences

SearchedviaHEALlin

khttp://www.

sciencedirect.com

/

(autotransplantatio



ORcanine*OR


olar*ORmolar*ORwisdom

toothORwisdom

teeth)

Inallfields

2192

WileyOnlineLibrary

Searchedviahttp://onlin

elibrary.wiley.com/

(autotransplantatio

n*OR(autologous)AND(transplantatio

n))inarticletitlesAND(teethORtoothORdent*ORincisor*

ORcanine*ORcuspid*ORbicuspid*ORmolar*ORwisdom

toothORwisdom

teeth)

Inallfields

466

Scopus

Searchedviawww.scopus.com

(autotransplantatio



ORcanine*OR



toothORwisdom

teeth))AND(LIM

IT-TO(LANGU

AGE,BEnglish^)

Lim

itedto

English

Inallfields

1444

GoogleScholar

Beta

Searchedviawww.scholar.google.com

(autotransplantatio

n)AND(teeth

ORtoothORdentalORincisorORcanine

ORcuspid

ORbicuspid

ORmolar

OR

wisdom

ORtoothORwisdom

ORteeth)

Intitle

101

(autologousORtransplantation)

AND(teethORtoothORdentalORincisorO

Rcanine

ORcuspidORbicuspidORmolar

ORwisdom

ORtoothORwisdom

ORteeth

574

LILACSdatabase

Searchedviahttp://bases.bvs.br

autotransplantationANDtooth

autotransplantationANDdental

autologous

ANDtransplantationANDtooth

autologous

ANDtransplantationANDdental

Inallfields

141

Biblio

grafiaBrasileirade

Odontologia

Searchedviahttp://bases.bireme.br/

(autotransplantatio



ORcanine*OR



ANDBhum

ans^[M

eSHTerm

s]Lim

itto

English

Inallfields

252

Oviddatabase

SearchedviaHeal-lin

kon

http://ovidsp.ovid.

com/autologin.htm

l

(autotransplantatio



ORcanine*OR



toothORwisdom

teeth)

Lim

itto

English

Inallfields

863

LippincottW

illiams&

Wilk

ins(LWW)

Searchedviahttp://journals.lw

w.com

(autotransplantatio



ORcanine*OR



toothORwisdom

teeth

Inallfields

83

BioMed

Central

Searchedviahttp://www.biomedcentral.com

/search

(autotransplantatio



ORcanine*OR



toothORwisdom

teeth)

Inallfields

258

ProQ

uest

Searchedviahttp://search.proquest.com

/(autotransplantatio



ORcanine*OR



ANDBhum

ans^[M

eSHTerm

s]Lim

itedto

humans

Inallfields

913

Cohrane

Library

Searchedviahttp://onlin

elibrary.wiley.com/

cochranelib

rary/

autotransplantationORautologous

transplantationANDteethORtoothORdentalORincisorORcanine

ORcuspidOR

bicuspid

ORmolar

ORwisdom

toothORwisdom

teeth

Intitle,abstract,

keyw

ords

47

African

JournalsOnline

Searchedviahttp://www.ajol.info

autotransplantationORautologous

transplantationANDteethORtoothORdentalORincisorORcanine

ORcuspidOR

bicuspid

ORmolar

ORwisdom

toothORwisdom

teeth

Inallfields

17

Total

8815

Clin Oral Invest

http://www.sciencedirect.com/

http://www.sciencedirect.com/

http://onlinelibrary.wiley.com/

http://www.scopus.com/

http://www.scholar.google.com/

http://bases.bvs.br/

http://bases.bireme.br/

http://ovidsp.ovid.com/autologin.html

http://ovidsp.ovid.com/autologin.html

http://journals.lww.com/

http://www.biomedcentral.com/search

http://www.biomedcentral.com/search

http://search.proquest.com/

http://onlinelibrary.wiley.com/cochranelibrary/

http://onlinelibrary.wiley.com/cochranelibrary/

http://www.ajol.info/

Tab

le9

Riskof

bias

analysisof

theincluded

studiesaccordingto

theDow

nsandBlack

(1998)

Study

Reportin

gExternalv

alidity

Internalvalid

ity-bias

Internalvalid

ity-confounding

Power

Sum

Judgment

12

34

56

78

910

1112

1314

1516

1718

1920

2122

2324

2526

27Ahlberg

etal.[63]

11

00

01

01

00

11

10

00

01

01

11

00

00

011

Seriouslim

itatio

nsAkiyamaetal.[30]

01

10

00

00

00

00

00

00

00

00

11

00

00

04

Seriouslim

itatio

nsAkkocaogluandKasaboglu

[31]

10

10

11

00

00

00

10

00

00

01

10

00

00

18

Seriouslim

itatio

nsAltonenetal.[35]

11

11

11

01

10

11

10

00

00

01

11

00

01

015

Seriouslim

itatio

nsAndreasen

etal.[13,46,55,64]

11

10

01

10

11

11

10

00

11

11

11

00

11

523

Noseriouslim

itations

Arikanetal.[32]

11

11

11

11

00

10

10

00

01

11

01

00

10

015

Seriouslim

itatio

nsAzazetal.[56]

11

10

11

01

10

11

10

00

10

11

11

00

00

015

Seriouslim

itatio

nsBauss

etal.[16]

11

10

11

01

01

00

10

00

11

11

11

00

10

116

Seriouslim

itatio

nsBauss

etal.[41]

11

10

11

01

01

00

10

00

11

11

11

00

10

116

Seriouslim

itatio

nsBauss

etal.[65]

11

10

11

11

01

00

10

00

11

11

11

10

10

118

Noseriouslim

itations

Bauss

etal.[82]

11

10

11

11

01

00

10

00

11

11

11

10

10

118

Noseriouslim

itations

Bauss

etal.[40]

11

10

11

11

11

00

00

00

01

11

00

00

00

012

Seriouslim

itatio

nsBauss

etal.[41]

11

10

11

01

01

11

10

10

11

11

11

00

10

119

Noseriouslim

itations

Bauss

etal.[66]

11

10

11

11

01

00

10

00

11

11

11

10

10

118

Noseriouslim

itations

Bauss

andKiliaridis[59]

11

10

11

11

11

11

10

00

01

11

11

10

11

222

Noseriouslim

itations

Eliasson

etal.[33]

11

10

01

01

00

00

10

00

10

11

11

00

00

011

Seriouslim

itatio

nsKahnberg[25]

01

10

11

01

00

11

10

00

10

11

11

00

00

114

Seriouslim

itatio

nsKristerson[9]

11

10

01

01

00

11

10

00

01

11

11

00

00

215

Seriouslim

itatio

nsKristersonetal.[14]

11

10

01

00

00

00

10

00

10

11

11

00

00

010

Seriouslim

itatio

nsLagerström

andKristerson[51]

11

10

01

00

01

00

10

00

01

01

00

00

00

19

Seriouslim

itatio

nsLundbergandIsaksson

[15]

11

10

01

00

00

11

10

00

01

11

11

00

01

013

Seriouslim

itatio

nsMarques-Ferreiraetal.[26]

11

10

01

00

00

00

10

00

01

11

11

00

01

011

Seriouslim

itatio

nsMejareetal.[62]

10

00

11

11

11

11

10

00

11

11

11

00

01

118

Noseriouslim

itations

Myrlund

etal.[45]

11

00

11

11

00

00

00

00

01

01

00

00

00

311

Seriouslim

itatio

nsNethanderetal.[83]

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Clin Oral Invest

Table 10 Meta-analysis of factors associated with the secondary outcome: ankylosis of autotransplanted teeth

Factor Reference Comparison Studies RR (95 % CI) 95 % PI P value I2 (95 % CI)

Age ≥20 years <20 years 1 0.6 (0.1, 2.9) NA 0.497 NA

Gender Female Male 1 0.2 (0.0, 2.7) NA 0.204 NA

Root development Closed apex Open apex 2 0.2 (0.1, 0.3) NA <0.001 0 % (NA)

Donor site Maxilla Mandible 1 0.4 (0.0, 6.4) NA 0.531 NA

Recipient site Other than donor Same with donor 1 4.4 (0.3, 70.7) NA 0.296 NA

Canines vs. molars Canines Molars 1 4.7 (0.3, 72.5) NA 0.266 NA

Splint Suture Rigid 1 11.6 (0.6, 198.5) NA 0.103 NA

Orthodontic Tx No Yes 1 1.7 (0.2, 18.2) NA 0.655 NA

CI confidence interval, NA non-applicable, PI prediction interval, RR relative risk, Tx treatment

Table 11 Meta-analysis of factors associated with the secondary outcome: hypermobility of autotransplanted teeth


Splint Suture Rigid 2 0.5 (0.1, 3.1) NA 0.450 0 % (NA)

CI confidence interval, NA non-applicable, PI prediction interval, RR relative risk

Table 12 Meta-analysis of factors associated with the secondary outcome: pulp necrosis of autotransplanted teeth


Age ≥20 years <20 years 1 0.2 (0.0, 2.2) NA 0.165 NA

Gender Female Male 2 1.5 (1.0, 2.1) NA 0.037 0 % (NA)

Root development Closed apex Open apex 4 0.1 (0.1, 0.2) 0.0, 0.7 <0.001 0 40 % (0, 68 %)

Donor site Maxilla Mandible 2 1.2 (0.7, 1.9) NA 0.580 0 % (NA)

Recipient site Other than donor Same with donor 1 0.4 (0.3, 0.7) NA 0.001 NA

Canines vs. molars Canines Molars 1 1.9 (1.1, 3.4) NA 0.028 NA

First vs. second premolars Second premolars First premolars 1 2.6 (1.5, 4.4) NA <0.001 NA

Splint Suture Rigid 2 2.6 (0.8, 8.0) NA 0.102 36 % (NA)


CI confidence interval, NA non-applicable, PI prediction interval, RR relative risk, Tx treatment

Table 13 Meta-analysis of factors associated with the secondary outcome: pulp obliteration of autotransplanted teeth


Surgical technique No bone graft Bone graft use 1 0.9 0.7, 1.1) NA 0.175 NA




Clin Oral Invest

Table 14 Meta-analysis of factors associated with the secondary outcome: root resorption of autotransplanted teeth


Age ≥20 years <20 years 2 0.7 (0.4, 1.3) NA 0.239 0 % (NA)

Gender Female Male 2 1.2 (0.2, 5.7) NA 0.860 42 % (NA)

Root development Closed apex Open apex 3 0.2 (0.1, 0.3) 0.0, 11.20 <0.001 17 % (0, 78 %)

Donor site Maxilla Mandible 2 0.9 (0.3, 2.9) NA 0.914 4 29 % (NA)

Recipient site Other than donor Same with donor 2 0.9 (0.5, 1.8) NA 0.760 0 % (NA)

Canines vs. molars canines molars 1 0.4 (0.0, 5.0) NA 0.467 NA

First vs. second premolars Second premolars First premolars 2 2.0 (1.1, 3.7) NA 0.024 0 % (NA)

Surgical technique No bone graft Bone graft use 2 1.0 (0.5, 2.4) NA 0.925 0 % (NA)


Orthodontic treatment No Yes 2 2.4 (0.3, 17.2) NA 0.384 74 % (NA)


Table 15 Assessment of reporting biases in the meta-analyses of adverse events’ rates

Adverse event Studies Funnel plot asymmetry Egger’s intercept (95 % CI) P value

Extraction need 15 Yes 2.8 (1.1, 4.5) 0.003

Failure 17 Yes 2.1 (−0.8, 5.1) 0.146

Ankylosis 11 Yes 1.3 (−0.1, 2.6) 0.057

Hypermobility 8 Yes NA –

Pulp necrosis 10 Yes 8.0 (4.0, 12.0) 0.002

Pulp obliteration 5 Yes NA –

Root resorption 19 Yes 3.5 (2.0, 4.9) <0.001

CI confidence interval

Table 16 Sensitivity analyses of the pooled event rates according to study sample size using a cutoff of 100 transplanted teeth pro included study

Small and large studies Large studies

Adverse event Studies % Event ratea (95 % CI) 95 % PIa I2 (95 % CI)a Studies % Event ratea (95 % CI) 95 % PIa I2 (95 % CI)a

Primary

Extraction need 15 7.8 (4.7, 10.9) 0.0, 10.9 88 % (83, 91 %) 5 8.6 (2.6, 14.6) 0.0, 31.5 96 % (93, 97 %)

Secondary

Failure 17 14.6 (10.1, 19.1) 0.0, 32.8 86 % (78, 90 %) 3 16.0 (3.7, 28.3) 0.0, 100.0 96 % (NA)

Ankylosis 11 6.2 (4.5, 7.8) 3.0, 9.3 18 % (0, 60 %) 3 7.0 (4.4, 9.5) 0.0, 31.5 41 % (NA)

Hypermobility 8 8.0 (4.1, 11.9) 0.0, 19.9 70 % (20, 84 %) – – – –

Pulp necrosis 10 34.3 (21.1, 47.4) 0.0, 83.9 98 % (97, 98 %) 3 13.9 (1.1, 26.8) 0.0, 100.0 97 % (NA)

Pulp obliteration 5 53.4 (28.3, 78.5) 0.0, 100.0 98 % (97, 98 %) 1 43.0 (33.3, 52.7) – –

Root resorption 19 10.4 (7.0, 13.7) 0.0, 24.0 88 % (83, 91 %) 4 3.9 (1.4, 6.4) 0.0, 14.2 71 % (0, 88 %)


Clin Oral Invest

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Table 17 Sensitivity analyses for the pooled estimates of primary and secondary negative outcomes (adverse event rates) by including studies with amean follow-up of at least 6 months

Primary analysis Sensitivity analyses

Adverse event Studies % Event ratea (95 % CI) 95 % PIa I2 (95 % CI)a Studies % Event ratea (95 % CI) 95 % PIa I2 (95 % CI)a

Primary

Extraction need 15 7.8 (4.7, 10.9) 0.0, 10.9 88 % (83, 91 %) 3 5.1 (0.0, 11.2) 0.0, 75.6 79 % (0, 91 %)

Secondary

Failure 17 14.6 (10.1, 19.1) 0.0, 32.8 86 % (78, 90 %) – – – –

Ankylosis 11 6.2 (4.5, 7.8) 3.0, 9.3 18 % (0, 60 %) 2 8.1 (2.1, 14.2) – 70 %

Hypermobility 8 8.0 (4.1, 11.9) 0.0, 19.9 70 % (20, 84 %) – – – –

Pulp necrosis 10 34.3 (21.1, 47.4) 0.0, 83.9 98 % (97, 98 %) 2 40.9 (10.0, 71.8) – 91 %

Pulp obliteration 5 53.4 (28.3, 78.5) 0.0, 100.0 98 % (97, 98 %) 1 43.0 (33.3, 52.7) – –

Root resorption 19 10.4 (7.0, 13.7) 0.0, 24.0 88 % (8, 91 %) 3 11.1 (2.5, 19.8) 0.0, 100.0 86 % (34, 94 %)


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Almpani K, Papageorgiou SN, Papadopoulos MA. Autotransplantation of teeth in humans - A systematic...

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