Esposito 2013

Interventions for replacing missing teeth: different times for
loading dental implants (Review)
Esposito M, Grusovin MG, Maghaireh H, Worthington HV
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2013, Issue 3
http://www.thecochranelibrary.com
Interventions for replacing missing teeth: different times for loading dental implants (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . 24
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Analysis 1.1. Comparison 1 Immediate versus conventional loading, Outcome 1 Patients with prosthesis failures. . . 81
Analysis 1.2. Comparison 1 Immediate versus conventional loading, Outcome 2 Patients with implant failures. . . 82
Analysis 1.3. Comparison 1 Immediate versus conventional loading, Outcome 3 Marginal bone level changes. . . . 83
Analysis 2.1. Comparison 2 Early versus conventional loading, Outcome 1 Patients with prosthesis failures. . . . . 84
Analysis 2.2. Comparison 2 Early versus conventional loading, Outcome 2 Patients with implant failures. . . . . 84
Analysis 2.3. Comparison 2 Early versus conventional loading, Outcome 3 Marginal bone level changes. . . . . . 85
Analysis 3.1. Comparison 3 Immediate versus early loading, Outcome 1 Patients with prosthesis failures. . . . . 85
Analysis 3.2. Comparison 3 Immediate versus early loading, Outcome 2 Patients with implant failures. . . . . . 86
Analysis 3.3. Comparison 3 Immediate versus early loading, Outcome 3 Marginal bone level changes. . . . . . 87
Analysis 4.1. Comparison 4 Occlusal versus non-occlusal loading, Outcome 1 Patients with prosthesis failures. . . 87
Analysis 4.2. Comparison 4 Occlusal versus non-occlusal loading, Outcome 2 Patients with implant failures. . . . 88
Analysis 4.3. Comparison 4 Occlusal versus non-occlusal loading, Outcome 3 Marginal bone level changes. . . . 89
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 94
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Interventions for replacing missing teeth: different times for loading dental implants (Review) i
[Intervention Review]
Interventions for replacing missing teeth: different times for

loading dental implants
Marco Esposito1 , Maria Gabriella Grusovin2 , Hassan Maghaireh3 , Helen V Worthington1

1 Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Manchester, UK. 2 Private practice, Gorizia, Italy.
3
Department of Oral and Maxillofacial Surgery, School of Dentistry, The University of Manchester, Manchester, UK
Contact address: Marco Esposito, Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Coupland 3
Building, Oxford Road, Manchester, M13 9PL, UK. [email protected].
Editorial group: Cochrane Oral Health Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 3, 2013.
Review content assessed as up-to-date: 20 February 2013.
Citation: Esposito M, Grusovin MG, Maghaireh H, Worthington HV. Interventions for replacing missing teeth: differ-
ent times for loading dental implants. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD003878. DOI:
10.1002/14651858.CD003878.pub5.
ABSTRACT
Background
To minimise the risk of implant failures after their placement, dental implants are kept load-free for 3 to 8 months to establish
osseointegration (conventional loading). It would be beneficial if the healing period could be shortened without jeopardising implant
success. Nowadays implants are loaded early and even immediately and it would be useful to know whether there is a difference in
success rates between immediately and early loaded implants compared with conventionally loaded implants.
Objectives
To evaluate the effects of (1) immediate (within 1 week), early (between 1 week and 2 months), and conventional (after 2 months)
loading of osseointegrated implants; (2) immediate occlusal versus non-occlusal loading and early occlusal versus non-occlusal loading;
(3) direct loading versus progressive loading immediately, early and conventionally.
Search methods
The following electronic databases were searched: the Cochrane Oral Health Group’s Trials Register (to 8 June 2012), the Cochrane
Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2012, Issue 4), MEDLINE via OVID (1946 to 8 June 2012)
and EMBASE via OVID (1980 to 8 June 2012). Authors of identified trials were contacted to find unpublished randomised controlled
trials (RCTs). There were no restrictions regarding language or date of publication.
Selection criteria
All RCTs of root-form osseointegrated dental implants, having a follow-up of 4 months to 1 year, comparing the same implant type
immediately, early or conventionally loaded, occlusally or non-occlusally loaded, or progressively loaded or not. Outcome measures
were: prosthesis and implant failures and radiographic marginal bone level changes.
Data collection and analysis
Data were independently extracted, in duplicate, by at least two review authors. Trial authors were contacted for missing information.
Risk of bias was assessed for each trial by at least two review authors, and data were extracted independently, and in duplicate. Results
were combined using fixed-effect models with mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous
outcomes with 95% confidence intervals (CI). A summary of findings table of the main findings was constructed.
Interventions for replacing missing teeth: different times for loading dental implants (Review) 1
Main results
Forty-five RCTs were identified and, from these, 26 trials including a total of 1217 participants and 2120 implants were included.
Three trials were at low risk of bias, 12 were at high risk of bias and for the remaining 11 the risk of bias was unclear. In nine of
the included studies there were no prosthetic failures within the first year, with no implant failures in 7 studies and the mean rate of
implant failure in all 26 trials was a low 2.5%. From 15 RCTs comparing immediate with convential loading there was no evidence of
a difference in either prosthesis failure (RR 1.87; 95% CI 0.70 to 5.01; 8 trials) or implant failure (RR 1.65; 95% CI 0.68 to 3.98; 10
trials) in the first year, but there is some evidence of a small reduction in bone loss favouring immediate loading (MD -0.10 mm; 95%
CI -0.20 to -0.01; P = 0.03; 9 trials), with some heterogeneity (Tau² = 0.01; Chi² = 14.37, df = 8 (P = 0.07); I² = 44%). However,
this very small difference may not be clinically important. From three RCTs which compared early loading with conventional loading,
there is insufficient evidence to determine whether or not there is a clinically important difference in prosthesis failure, implant failure
or bone loss. Six RCTs compared immediate and early loading and found insufficient evidence to determine whether or not there is a
clinically important difference in prosthesis failure, implant failure or bone loss. From the two trials which compared occlusal loading
with non-occlusal loading there is insufficient evidence to determine whether there is a clinically important difference in the outcomes
of prosthesis failure, implant failure or bone loss. We did not identify any trials which evaluated progressive loading of implants.
Authors’ conclusions
Overall there was no convincing evidence of a clinically important difference in prosthesis failure, implant failure, or bone loss associated
with different loading times of implants. More well-designed RCTs are needed and should be reported according to the CONSORT
guidelines (www.consort-statement.org/).
PLAIN LANGUAGE SUMMARY

Interventions for replacing missing teeth: different times for loading dental implants
When people have dental implants in their jaws, they usually wait several months for the bone around the implants to heal before
artificial teeth are attached to the implant. During this period they use removable dentures. This review looked at the effects of attaching
artificial teeth either the same day that the implant was placed, or early (after only 6 weeks) compared to the usual delay of at least
3 months. Some studies also compared the artifical tooth being attached so that it did not touch the opposite tooth (non-occlusal
loading). The review found no evidence that attaching artificial teeth either immediately, after 6 weeks (early) or after at least 3 months
(conventional) led to any important differences in the failure of the implant or the artifical tooth, or to the amount of bone which
surrounded the implant (any bone loss would be an undesirable consequence). More research is needed in this area.
S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]
Conventional compared with immediate loading of dental implants
Patient or population: patients requiring dental implants

Settings: dental practice
Intervention: immediate loading
Comparison: conventional loading
Outcomes Illustrative comparative risks* (95% CI) Relative effect No of participants Quality of the evidence Comments
(95% CI) (studies) (GRADE)
Assumed risk Corresponding risk
Conventional Immediate
Prosthesis failure Low risk population RR 1.87 (0.70 to 5.01) 381 +++O2 As the incidence of fail-
at 1 year (8) moderate ure is so low future stud-
10 per 10001 19 per 1000 ies are unlikely to in-
(7 to 50) crease the precision sub-
stantially
High risk population
100 per 1000 187 per 1000
(70 to 501)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the
comparison group and the relative effect of the intervention (and its 95% CI).
1. the prosthetic failure rate in the conventional loading group is 1.2%

2. five studies high, two unclear and one at low risk of bias
CI = confidence interval
RR = risk ratio
GRADE Working Group grades of evidence:
High quality (++++): Further research is very unlikely to change our confidence in the estimate of effect.
Moderatn quality (+++O): Further research is likely to have an important impact on our confidence in the estimate of effect and may
change the estimate.
3
Low quality (++OO): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely
to change the estimate.
Very low quality (+OOO): We are very uncertain about the estimate.
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4
BACKGROUND
Why it is important to do this review
It would be useful to know whether there are differences in success
rates between immediately or early loaded implants compared with
Description of the condition conventionally loaded implants in different clinical indications
Missing teeth and supporting oral tissues have traditionally been such as in full and partial edentulism, in mandibles and maxillae,
replaced with dentures or bridges to restore the ability of patients and if there are some surface modifications of the implants able to
to eat and speak and improve appearance. However, in several promote faster bone healing. The role of the surface characteristics
instances, patients are not satisfied with the function of removable is considered in another Cochrane review (Esposito 2007).
dentures and it is not always possible to place a fixed bridge if the It is likely that the effect of loading at different times would be-
number of remaining abutment teeth is insufficient. come apparent during the first 4 months to 1 year of loading and
therefore it was decided to make all comparisons at 4 months to
1 year after loading, preferably at 1 year when possible.
A few systematic reviews (Ioannidou 2005; Del Fabbro 2006,
Description of the intervention Sennerby 2008) have been published after the previous versions of
Since the 1970s, osseointegrated dental implants have offered an the present review, however, they did not focus on the highest level
alternative (Brånemark 1977). They are surgically inserted into the of evidence (randomised controlled trials), therefore their results
jaw bones to support a dental prosthesis and are retained because have to be interpreted with great caution.
of the intimacy of bone growth onto their surface (osseointegra-
tion). Dental implants have undoubtedly been one of the most
significant scientific breakthroughs in dentistry over the past 30
years.
Primary implant stability and lack of micromovements are con- OBJECTIVES
sidered to be two of the main factors necessary for achieving pre-
dictable high success of osseointegrated oral implants (Albrektsson
1981). A successful osseointegrated oral implant is anchored di- 1. To determine the effects of osseointegrated dental implants
rectly to bone, however, in the presence of movement a soft tissue loaded immediately, early or conventionally on clinical
interface may encapsulate the implant causing its failure (Brunski outcomes: prosthesis failure, implant failure and bone level.
1979). To minimise the risk of soft tissue encapsulation, it has been
2. To determine the effects of osseointegrated dental implants
recommended to keep the implants load-free during the healing
loaded occlusally or non-occlusally immediately or early during
period: 3 to 4 months in mandibles (lower jaws) and 6 to 8 months
the osseointegration period, on clinical outcomes: prosthesis
in maxillae (upper jaws) (Brånemark 1977).
failure, implant failure and bone level.
3. To determine the effects of osseointegrated dental implants

directly or progressively loaded immediately, early and
How the intervention might work
conventionally on clinical outcomes: prosthesis failure, implant
In general, during the healing period removable prostheses are failure and bone level.
used, however, many patients find these temporary prostheses
rather uncomfortable and it would therefore be beneficial if the
healing period could be shortened without jeopardising implant
success. In 1990, the first longitudinal clinical trial was published METHODS
suggesting that implants could be loaded immediately or early in
the mandibles of selected patients (Schnitman 1990). Nowadays,
immediately and early loaded implants are commonly used, par-
ticularly in mandibles of good bone quality (Brånemark 1999). Criteria for considering studies for this review
Some authors also advocate that the use of some specific implant
surface preparation is able to reduce the healing time (Roccuzzo
2001). To decrease the risk of immediately loaded implants failing
Types of studies
early, various ’clinical tricks’ have been suggested such as under-
preparation of the implant site to achieve high primary stability Randomised controlled trials (RCTs) of parallel group design and
(Cannizzaro 2003); the use of a non-occluding temporary pros- of split-mouth design including root-form osseointegrated dental
thesis during the first 2 months of healing (Testori 2003); or the implants having a follow-up of 4 months to 1 year after loading
progressive loading of the prostheses (Appleton 2005). (whenever possible the 1-year data were used).
Types of participants and detailed in box 6.4.c of the Cochrane Handbook for Systematic
Patients who are having osseointegrated root-form dental im- Reviews of Interventions Version 5.1.0 (updated March 2011).
plants. We searched the following electronic databases.
• The Cochrane Oral Health Group’s Trials Register (to 8
June 2012) (see Appendix 2)
Types of interventions • The Cochrane Central Register of Controlled Trials
1. Trials comparing the same osseointegrated root-form dental (CENTRAL) (The Cochrane Library 2012, Issue 4) (see
implants loaded at different times. For the purpose of this review Appendix 3)
’immediate’ loading was defined as an implant put in function • MEDLINE via OVID (1946 to 8 June 2012) (see
within 1 week after its placement; ’early’ loading as those Appendix 1)
implants put in function between 1 week and 2 months; and • EMBASE via OVID (1980 to 8 June 2012) (see Appendix
’conventional’ (also termed ’delayed’) loading as those implants 4)
loaded after 2 months. In particular the following comparisons
The search of EMBASE was linked to the Cochrane Oral Health
were planned: (1) immediately versus conventionally loaded
Group filter for identifying RCTs (see Appendix 4). There were
implants; (2) early versus conventionally loaded implants; (3)
no restrictions on language or date of publication.
immediately versus early loaded implants. Both ’occlusally’ and
’non-occlusally’ immediately loaded implants were considered as
immediately loaded implants in this review. ’Non-occlusally Searching other resources
loaded’ implants are those implants provisionally rehabilitated
with restorations not in direct occlusion in static or dynamic
lateral movements with the antagonistic dentition. Unpublished studies
2. Trials comparing the same osseointegrated root-form dental
We wrote to all the authors of the identified RCTs to identify any
implants occlusally or non-occlusally loaded during the
unpublished studies and we checked the bibliographies of all iden-
osseointegration phase (immediately and early loading).
tified RCTs and relevant review articles. We used personal contacts
3. Trials comparing the same osseointegrated root-form dental
in an attempt to identify unpublished or ongoing RCTs. In the first
implants directly or progressively loaded, immediately, early or
version of this review we also wrote to more than 55 oral implant
conventionally. Progressive loading is defined as the load of the
manufacturers and we requested information on trials through
implants obtained by gradual height increase of the occlusal table
an internet discussion group ([email protected]),
in increments from a state of infraocclusion to full occlusion.
however, we discontinued this due to poor yield.
Types of outcome measures

Handsearching
• Prosthesis failure if secondary to implant failure.
Handsearching was done as part of the Cochrane Worldwide
• Implant failures (implant mobility and removal of stable
Handsearching Programme, see the Cochrane Masterlist of the
implants dictated by progressive marginal bone loss).
journals searched to date.
• Radiographic marginal bone level changes on intraoral
The following journals have been identified as being important to
radiographs taken with a parallel technique.
be handsearched for this review.
• British Journal of Oral and Maxillofacial Surgery
• Clinical Implant Dentistry and Related Research
Search methods for identification of studies • Clinical Oral Implants Research
• European Journal of Oral Implantology
• Implant Dentistry
Electronic searches • International Journal of Oral and Maxillofacial Implants
For the identification of studies included or considered for this • International Journal of Oral and Maxillofacial Surgery
review, we developed detailed search strategies for each database to • International Journal of Periodontics and Restorative Dentistry
be searched. These were based on the search strategy developed for • International Journal of Prosthodontics
MEDLINE (OVID) but revised appropriately for each database. • Journal of Clinical Periodontology
The MEDLINE search (Appendix 1) used a combination of con- • Journal of Dental Research
trolled vocabulary and free text terms and was linked with the • Journal of Oral Implantology
Cochrane Highly Sensitive Search Strategy (CHSSS) for identi- • Journal of Oral and Maxillofacial Surgery
fying randomised trials (RCTs) in MEDLINE: sensitivity max- • Journal of Periodontology
imising version (2008 revision), as referenced in Chapter 6.4.11.1 • Journal of Prosthetic Dentistry
Where these have not already been searched as part of the Cochrane For each trial the following data were recorded.
Worldwide Handsearching Programme, the journals were hand- • Year of publication, country of origin and source of study
searched by one review author up to the month in which the last funding.
electronic search was undertaken. • Details of the participants including demographic
characteristics and criteria for inclusion.
• Details of the type of intervention.
Data collection and analysis • Details of the outcomes reported, including method of
assessment, and time intervals.
Selection of studies
The titles and abstracts (when available) of all reports identified Assessment of risk of bias in included studies
through the electronic searches were scanned independently by The risk of bias assessment of the included trials was undertaken
two review authors. For studies appearing to meet the inclusion independently and in duplicate by two review authors as part of the
criteria, or for which there were insufficient data in the title and data extraction process. In the case that the paper to be assessed had
abstract to make a clear decision, the full report was obtained. The one or more review authors in the authors list, it was independently
full reports obtained from all the electronic and other methods evaluated only by those review authors not involved in the trial.
of searching were assessed independently by two review authors This was conducted using the recommended approach for assess-
to establish whether the studies did meet the inclusion criteria or ing risk of bias in studies included in Cochrane reviews (Higgins
not. Disagreements were resolved by discussion. Where resolution 2011). It is a two-part tool, addressing the six specific domains
was not possible, a third review author was consulted. All studies (namely sequence generation, allocation concealment, blinding,
meeting the inclusion criteria then underwent validity assessment incomplete outcome data, selective outcome reporting and ’other
and data extraction. Studies rejected at this or subsequent stages issues’). Each domain includes one specific entry in a ’Risk of bias’
were recorded in the ’Characteristics of excluded studies’ table, table. Within each entry, the first part of the tool involves describ-
and reasons for exclusion recorded. ing what was reported to have happened in the study. The second
part of the tool involves assigning a judgement relating to the risk
Data extraction and management of bias for that entry. This is achieved by answering prespecified
questions about the adequacy of the study in relation to the entry.
Data were extracted by two review authors independently and
in duplicate using specially designed data extraction forms. The
data extraction forms were piloted on several papers and modi-
Summarising risk of bias for a study
fied as required before use. Any disagreement was discussed and a
third review author consulted where necessary. All study authors After taking into account the additional information provided by
were contacted for clarification or missing information. Data were the authors of the trials, studies were grouped into the following
excluded until further clarification was available or if agreement categories. We assumed that the risk of bias was the same for all
could not be reached. outcomes and each study was assessed as follows.
Risk of bias Interpretation Within a study Across studies
Low risk of bias Plausible bias unlikely to seriously Low risk of bias for all key domains Most information is from studies at
alter the results low risk of bias
Unclear risk of bias Plausible bias that raises some Unclear risk of bias for one or more Most information is from studies at
doubt about the results key domains low or unclear risk of bias
High risk of bias Plausible bias that seriously weak- High risk of bias for one or more The proportion of information
ens confidence in the results key domains from studies at high risk of bias is
sufficient to affect the interpreta-
tion of results
Further quality assessment was carried out to assess sample size
calculations, definition of exclusion/inclusion criteria, and com- models were used when there were more than three studies in
parability of control and test groups at entry. The quality assess- a meta-analysis. Data from split-mouth studies were to be com-
ment criteria were pilot tested using several articles. bined with data from parallel group trials with the method out-
lined by Elbourne (Elbourne 2002), using the generic inverse vari-
ance method in RevMan. The techniques described by Follmann
were used to estimate the standard error (SE) of the difference
Measures of treatment effect for split-mouth studies, where the appropriate data were not pre-
For dichotomous outcomes, the estimates of effects of interven- sented and could not be obtained (Follmann 1992). Numbers
tions were expressed as risk ratios (RR) together with 95% confi- needed to treat (NNT) were to be calculated for participants af-
dence intervals (CI). For continuous outcomes, mean differences fected by implant failures. The Cochrane Handbook recommen-
(MD) and standard deviations (SD) were used to summarise the dations were followed for RCTs with parallel design with zero-cell
data for each group using mean differences and 95% CIs. counts (Higgins 2011). The fixed value of 0.5 was automatically
added to all cells with zero-cell counts and risk ratios calculated
with the RevMan software. If there were no events in both arms,
Unit of analysis issues no calculations were undertaken because in this situation the study
The statistical unit was the participant and not the prosthesis or does not provide any indication of the direction or magnitude of
implant, unless the clustering of the implants within the partici- the relative treatment effect.
pants had been taken into account in the analysis. One study presented the mean difference (SE) for the mesial and
distal radiographic scores separately (Lindeboom 2006). To calcu-
late the total score, the mean differences were averaged and a con-
Dealing with missing data
servative standard error was calculated assuming zero correlation.
All trial authors were contacted to retrieve missing data when nec- For rare events, odds ratios (OR) for split-mouth trials were calcu-
essary. Data were excluded until further clarification was available lated using the Becker-Balagtas methods outlined in Curtin 2002.
if agreement could not be reached. Methods in section 7.7.3 of As OR are similar to RR when the event rate is low we have simply
the Cochrane Handbook were used to estimate missing standard used this value in place of RR for these studies. When using the
deviations (Higgins 2011). generic inverse variance to combine studies of parallel design with
studies of split-mouth design, studies with both zero events could
not be imputed in the meta-analyses because RevMan 5 software
Assessment of heterogeneity
does not allow it.
The significance of any discrepancies in the estimates of the treat-
ment effects from the different trials was to be assessed by means
of Cochran’s test for heterogeneity, and heterogeneity would have Subgroup analysis and investigation of heterogeneity
been considered significant if P < 0.1. The I² statistic, which de-
scribes the percentage total variation across studies that is due to The following subgroup analyses were planned, however, there
heterogeneity rather than chance, was to be used to quantify het- were insufficient studies in the meta-analysis to undertake this.
erogeneity with I² over 50% being considered substantial hetero- 1. Whether implants were placed in mandibles or maxillae.
geneity. 2. Whether single or multiple splinted implants were used.
Assessment of reporting biases Sensitivity analysis

If there had been sufficient numbers of trials (more than 10) in any It was planned to undertake sensitivity analyses to examine the
meta-analysis, publication bias would have been assessed accord- effect of the study quality on the overall estimates of effect. In
ing to the recommendations on testing for funnel plot asymmetry addition, the effect of including unpublished literature on the
(Egger 1997), as described in the Cochrane Handbook (Higgins review’s findings was also to be examined. There were too few trials
2011). If asymmetry was identified we would have examined pos- in the meta-analyses to undertake these analyses to investigate to
sible causes. what extent the risk of bias might have influenced the results. This
will be done in future updates as soon as sufficient numbers of
trials having different risk of bias ratings are available.
Data synthesis
A meta-analysis was only done when there were studies of simi-
lar comparisons reporting the same outcome measures. Risk ra- Presentation of main results
tios were combined for dichotomous data, and mean differences Summary of findings tables were developed for the comparisons of
for continuous data, using fixed-effect models. Random-effects different loading times for the outcome ’prosthesis failure’, which
were considered the main results. The quality of the body of evi- 2008b; Cannizzaro 2008d; Crespi 2008; Donati 2008; Merli
dence was assessed with reference to the overall risk of bias of the 2008; Schincaglia 2008; Cannizzaro 2010; Meloni 2012), three
included studies, the directness of the evidence, the inconsistency in New Zealand (Payne 2002; Tawse-Smith 2002; Hall 2006),
of the results, the precision of the estimates, the risk of publication two in The Netherlands (Lindeboom 2006; den Hartog 2011),
bias, and the magnitude of the effect. The quality of the body two in Turkey (Turkyilmaz 2007; Güncü 2008), one in Swe-
of evidence for each of the main results was categorised as high, den (Fischer 2004), one in Belgium (De Rouck 2009), one in
moderate, low or very low. Switzerland (Enkling 2010), one in USA (Oh 2006), one in Egypt
(Assad 2007), and one was run in several countries (Zöllner 2008).
Twenty-three trials had a parallel group study design and three
a split-mouth study design (Cannizzaro 2008d; Güncü 2008;
RESULTS Meloni 2012). One trial of parallel group design had 10 partic-
ipants treated according to a split-mouth design (Donati 2008);
these 10 participants were excluded from the calculations in the
Description of studies
present review.
See: Characteristics of included studies; Characteristics of excluded Fifteen trials were conducted at university dental clinics (
studies. Chiapasco 2001; Payne 2002; Romeo 2002; Tawse-Smith 2002;
Hall 2006; Lindeboom 2006; Oh 2006; Assad 2007; Turkyilmaz
Characteristics of the trial settings and investigators 2007; Crespi 2008; Güncü 2008; Schincaglia 2008; De Rouck
2009; Enkling 2010; den Hartog 2011), eight in private practices
Of the 45 potentially eligible trials (Polson 2000; Chiapasco
(Cannizzaro 2003; Testori 2007; Cannizzaro 2008a; Cannizzaro
2001; Roccuzzo 2001; Payne 2002; Romeo 2002; Tawse-Smith
2008b; Cannizzaro 2008d; Donati 2008; Merli 2008; Cannizzaro
2002; Cannizzaro 2003; Testori 2003; Fischer 2004; Salvi
2010), one in a specialist public clinic (Fischer 2004), and two in
2004; Appleton 2005; Ottoni 2005; Hall 2006; Lindeboom
both university clinics and private practices (Zöllner 2008; Meloni
2006; Oh 2006; Romanos 2006; Turkyilmaz 2006; Assad 2007;
2012).
Göthberg 2007; Testori 2007; Turkyilmaz 2007; Cannizzaro
Sixteen trials received support from industry (Payne 2002; Tawse-
2008a; Cannizzaro 2008b; Cannizzaro 2008c; Cannizzaro 2008d;
Smith 2002; Fischer 2004; Hall 2006; Lindeboom 2006; Oh
Crespi 2008; Donati 2008; Güncü 2008; Merli 2008; Schincaglia
2006; Testori 2007; Turkyilmaz 2007; Cannizzaro 2008d; Donati
2008; Zöllner 2008; Degidi 2009; Degidi 2009; De Rouck 2009;
2008; Merli 2008; Zöllner 2008; Cannizzaro 2010; Enkling 2010;
Cannizzaro 2010; Enkling 2010; Shibly 2010; Van de Velde 2010;
den Hartog 2011; Meloni 2012). All studies included only adults.
den Hartog 2011; Jokstad 2011, Kim 2011; Mackie 2011; Tealdo
2011; Barewal 2012; Meloni 2012), 19 trials had to be excluded.
Eight trials were excluded because they were not randomised con- Characteristics of participants
trolled trials (RCTs) (Ottoni 2005; Romanos 2006; Turkyilmaz The mean age of the participants ranged from 35 to 63 with a
2006; Degidi 2009; Degidi 2010; Mackie 2011; Tealdo 2011; minimum age of 18 and a maximum age of 80, however, some trials
Barewal 2012), five trials because of various additional con- failed to report the mean age (five trials: Payne 2002; Tawse-Smith
founding factors (Roccuzzo 2001; Testori 2003; Göthberg 2007; 2002; Assad 2007; Enkling 2010; Meloni 2012), and some the age
Cannizzaro 2008c; Van de Velde 2010), three trials because they range (eight trials: Fischer 2004; Turkyilmaz 2007; Donati 2008;
tested comparisons outside the scope of the present review (Salvi Zöllner 2008; De Rouck 2009; Enkling 2010; den Hartog 2011;
2004; Jokstad 2011; Kim 2011), one trial was excluded due to in- Meloni 2012). The number of males and females was unclear in
sufficient data presented (Polson 2000), one trial because of con- four trials (Tawse-Smith 2002; Hall 2006; Enkling 2010; Meloni
flicting data presented (Shibly 2010), and one trial because data 2012). One trial only included male participants (Assad 2007).
were mixed by the parallel-group and split-mouth design and par- The remaining 21 trials included more women than men (or equal
ticipants with problems were removed from the analyses (Appleton numbers).
2005). The trials included between 10 and 266 participants, with a me-
Of the 26 included trials (Chiapasco 2001; Payne 2002; Romeo dian of 30. Eleven trials placed multiple implants in participants:
2002; Tawse-Smith 2002; Cannizzaro 2003; Fischer 2004; seven in the mandible (Chiapasco 2001; Payne 2002; Romeo
Hall 2006; Lindeboom 2006; Oh 2006; Assad 2007; Testori 2002; Tawse-Smith 2002; Assad 2007; Turkyilmaz 2007; Enkling
2007; Turkyilmaz 2007; Cannizzaro 2008a; Cannizzaro 2008b; 2010), two in the maxilla (Fischer 2004; Cannizzaro 2008b) and
Cannizzaro 2008d; Crespi 2008; Donati 2008; Güncü 2008; two in both jaws (Testori 2007; Merli 2008), all participants being
Merli 2008; Schincaglia 2008; Zöllner 2008; De Rouck 2009; edentulous in the specific jaw. Nine trials placed single implants
Cannizzaro 2010; Enkling 2010; den Hartog 2011; Meloni 2012), in each participant: seven in the maxilla (Hall 2006; Lindeboom
13 were conducted in Italy (Chiapasco 2001; Romeo 2002; 2006; Oh 2006; Crespi 2008; Donati 2008; De Rouck 2009; den
Cannizzaro 2003; Testori 2007; Cannizzaro 2008a; Cannizzaro Hartog 2011), one in the mandible (Schincaglia 2008), and one in
either jaw (Cannizzaro 2010). All these participants were partially • Missing two teeth and enough bone to allow placement of
edentulous. Two trials placed both single and multiple implants two 7 mm long implants and the bone thickness at implant sites
in participants in either jaw (Cannizzaro 2003; Zöllner 2008). had to be of at least 5.5 mm (Cannizzaro 2008d).
A further three split-mouth trials placed one implant from each • Missing one or more single teeth in the anterior (premolar
comparison group in each participant: two trials in the mandible to premolar) maxilla allowing the placement of at least 8 mm
(Güncü 2008; Meloni 2012), and one in either jaw (Cannizzaro long implants with a 3.4 mm diameter with no bone fenestration
2008d). (Lindeboom 2006).
• Missing one or more single teeth in the anterior (premolar
to premolar) jaws allowing the placement of at least 8 mm long
Inclusion and exclusion criteria implants with a 4 mm diameter with no bone fenestration
(Donati 2008).
The majority of trials, with seven exceptions (Testori 2007; • Missing a single tooth with residual bone height of at least
Cannizzaro 2008a; Cannizzaro 2008b; Cannizzaro 2008d; Donati 10 mm and width of at least 5 mm (Cannizzaro 2010).
2008; Schincaglia 2008; Cannizzaro 2010), used quite strict inclu- • Single fresh extraction sockets in the anterior maxilla (15 to
sion criteria and included mainly ideal participants. This choice is 25) in presence of four bone walls and at least 4 mm of bone
understandable since it is common sense to load implants imme- beyond the root apex (Crespi 2008).
diately or early only in selected cases, for instance when implants • Single fresh extraction sockets in the anterior maxilla (15 to
are placed with high insertion torques in good quality bone of 25) in presence of an intact buccal wall, at least 5 mm of bone
adequate volume in participants not having parafunctional habits. beyond the root apex and of both neighbouring teeth (De Rouck
2009).
• 13 to 15 mm of residual anterior mandibular bone or more
Main inclusion criteria (Chiapasco 2001; Payne 2002; Tawse-Smith 2002).
• 10 mm of residual anterior mandibular bone or more
• Completely edentulous mandible (Chiapasco 2001; Payne
(Romeo 2002).
2002; Romeo 2002; Tawse-Smith 2002; Assad 2007; Turkyilmaz
• Elderly participants (55 to 80 years) (Payne 2002;
2007; Cannizzaro 2008a; Enkling 2010).
Tawse-Smith 2002).
• Completely edentulous maxilla able to harbour at least five
• Sufficient bone to allow placement of two 15 mm long
implants (Fischer 2004; Cannizzaro 2008b).
implants (Turkyilmaz 2007).
• Partially edentulous participants (both mandibles and
• Sufficient bone to allow placement of two 9.5 mm long
maxillae) (Cannizzaro 2003; Testori 2007; Merli 2008).
implants with a diameter of 4 mm (Enkling 2010).
• Partially edentulous participants (both mandibles and
• Sufficient bone to allow placement of at least 13 mm long
maxillae) in the posterior jaws (premolar and molar areas)
implants and with a diameter of 3.7 mm (Cannizzaro 2003;
allowing the placement of at least 8 mm long implants, and the
Assad 2007; Crespi 2008).
bone thickness at implant sites had to be of at least 6 mm
• Sufficient bone to allow placement of 11.5 mm long
(Zöllner 2008).
implants with a diameter of 4 mm (Güncü 2008).
• Bilaterally missing first mandibular molars (Güncü 2008;
• Sufficient bone to allow placement of at least 10 mm long
Meloni 2012).
implants and with a diameter of 3.7 mm (Cannizzaro 2008a;
• Missing one first or second mandibular molar allowing the
Cannizzaro 2008b).
placement of one at least 8.5 mm long implant, and the bone
• Sufficient bone to allow placement of at least 9.5 mm long
thickness at implant site had to be of at least 7 mm (Schincaglia
implants, and the bone thickness at implant sites had to be of at
2008).
least 5.5 mm (Merli 2008).
• Missing one single tooth in the anterior (premolar to
• Residual bone height of at least 10 mm and thickness of at
premolar) maxilla, with adjacent teeth present, allowing the
least 6 mm (Meloni 2012).
placement of at least 10 mm long implants with a 2.5 mm
• Minimal insertion torque of 45/48 Ncm to be immediately
diameter (Hall 2006).
loaded (Cannizzaro 2003; Cannizzaro 2008a; Cannizzaro
• Missing one single tooth in the anterior (premolar to
2008b; den Hartog 2011).
premolar) maxilla, allowing the placement of at least 10 mm
• Minimal insertion torque of 40 Ncm to be immediately
long implants with a 3.7 mm diameter with a flapless procedure
loaded (Cannizzaro 2008d; Merli 2008).
(Oh 2006).
• Minimal insertion torque of 35 Ncm to be immediately
• Missing one single tooth in the anterior (first premolar to
loaded (De Rouck 2009; Cannizzaro 2010; Enkling 2010;
first premolar) maxilla with adjacent natural teeth, allowing the
Meloni 2012).
placement of at least 13 mm long implant with a diameter of 3.5
• Minimal insertion torque of 30 Ncm for single implants
mm (den Hartog 2011).
(Lindeboom 2006; Testori 2007), and 20 Ncm for splinted 2008), and 6 months (Güncü 2008).
implants (Testori 2007). • If primary implant stability could not be achieved (Hall
• Minimal insertion torque of 25 Ncm and primary implant 2006; Zöllner 2008).
stability ISQ > 60 to be immediately loaded (Crespi 2008). • Previous history of failed implants (Hall 2006).
• Minimal primary implant stability of 20 Ncm to be • Less than 4 mm (Merli 2008), or 5 mm (Meloni 2012), of
immediately loaded (Donati 2008; Schincaglia 2008). keratinised mucosa.
• Presence of dehiscence or fenestrations of the post-
Main exclusion criteria
extractive sites (Crespi 2008; De Rouck 2009).
• Presence of peri-apical lesions or any other abnormalities in
• Any evidence of current or previous smoking (Payne 2002;
the maxillary anterior region as determined on radiographs (den
Tawse-Smith 2002).
Hartog 2011).
• Smoking (Lindeboom 2006; Güncü 2008; den Hartog
• Unknown exclusion criteria (Oh 2006; Assad 2007;
2011).
Enkling 2010).
• Smoking more than 10 cigarettes per day (Chiapasco 2001;
Cannizzaro 2003; Fischer 2004; Crespi 2008; Zöllner 2008; De
Rouck 2009; Meloni 2012). Sample size
• Smoking more than 20 cigarettes per day (Romeo 2002; A priori sample size calculation was performed in eight trials
Hall 2006). (Lindeboom 2006; Testori 2007; Cannizzaro 2008a; Cannizzaro
• Any systemic disease likely to compromise implant surgery 2008b; Cannizzaro 2008d; Merli 2008; Schincaglia 2008; den
(Chiapasco 2001; Payne 2002; Romeo 2002; Tawse-Smith 2002; Hartog 2011). The sample size of one trial was calculated assum-
Cannizzaro 2003; Fischer 2004; Lindeboom 2006; Assad 2007; ing that treatment modalities were equivalent (Lindeboom 2006):
Testori 2007; Turkyilmaz 2007; Cannizzaro 2008a; Cannizzaro 21 implants were needed in each group to reject the null hypoth-
2008b; Cannizzaro 2008d; Crespi 2008; Donati 2008; Güncü esis that the treatments were not equivalent with a power of 80%
2008; Merli 2008; Zöllner 2008; De Rouck 2009; Cannizzaro and a type I error rate of 0.05. Non-equivalence was defined as
2010; Meloni 2012). a difference in implant stability quotient (ISQ) values measured
• Presence of severe systemic conditions (ASA III) with Osstell of 10 or more. Twenty-five implants (24 participants)
(Schincaglia 2008; den Hartog 2011). were included in each group. Calculations of three trials (Testori
• Previously bone grafted bone jaws (Payne 2002; 2007; Cannizzaro 2008d; Merli 2008) were based on the outcome
Tawse-Smith 2002; Fischer 2004; Hall 2006; Turkyilmaz 2007; (implant failure) of another RCT of similar design (Ottoni 2005),
Cannizzaro 2008a; Cannizzaro 2008b). and it was calculated that 26 participants per group were needed
• In need of tissue augmentation procedures (Güncü 2008; to complete the trial. Unfortunately, because of an independent
Schincaglia 2008; Meloni 2012). decision of the clinicians in violation of the research protocol, only
• Previously irradiated jaws (Chiapasco 2001; Payne 2002; 25 participants were included in the immediately loaded group in
Romeo 2002; Tawse-Smith 2002; Cannizzaro 2003; Testori one trial (Testori 2007). The other two trials achieved the planned
2007; Turkyilmaz 2007; Cannizzaro 2010; den Hartog 2011; sample size (Cannizzaro 2008d; Merli 2008). The sample size cal-
Meloni 2012), or jaws irradiated less than 1 year before culation for the other two trials was based on a theoretical esti-
(Cannizzaro 2008a; Cannizzaro 2008b; Cannizzaro 2008d; mate of implant failures and 286 participants should have been
Merli 2008). included in each group (Cannizzaro 2008a; Cannizzaro 2008b).
• Bone quality type IV (very soft bone) according to the The sample size could not be achieved and the number of failures
classification of Lekholm 1985 detected at the time of surgery which actually occurred were much less than those estimated in
(Chiapasco 2001; Payne 2002; Romeo 2002; Tawse-Smith 2002; the calculations, therefore the number of participants to be in-
Cannizzaro 2003; Cannizzaro 2010), or on radiographs (Hall cluded to detect a difference should have been much greater. An-
2006). other trial calculated the sample size on a peri-implant marginal
• History of bruxism (Payne 2002; Tawse-Smith 2002). bone level change difference of 0.3 mm among immediately ver-
• Severe clenching or bruxism (Chiapasco 2001; Romeo sus conventionally loaded implants based on an error of 5% and
2002; Cannizzaro 2003; Hall 2006; Lindeboom 2006; Testori a power of 80% (Schincaglia 2008): 14 participants were needed
2007; Cannizzaro 2008d; Crespi 2008; Güncü 2008; Merli in each group and 15 participants per group were enrolled. For
2008; Zöllner 2008; De Rouck 2009; Cannizzaro 2010; Meloni another trial (De Rouck 2009), calculations were based on data
2012). from a previous cohort study on immediate single implants. A
• Severe maxillo-mandibular skeletal discrepancy (Chiapasco difference in soft tissue dimensions of 0.5 mm between the groups
2001; Romeo 2002; Cannizzaro 2003; Lindeboom 2006). was defined as clinically relevant. Based on standard deviations
• Extraction sockets with healing less than 3 months (Donati (SD) of 0.7 mm for both groups, an a error level of 5% and statis-
2008; den Hartog 2011), 4 months (Schincaglia 2008; Zöllner tical power of 80%, a sample size of 24 participants per group was
calculated. In this study 26 participants per group were recruited. versus osteotomes). Ten participants were treated according to a
Cannizzaro 2010 calculated the sample size for the primary out- split-mouth design and were excluded.
come measure (implant failure) based on the findings of another Güncü 2008 and Meloni 2012, in split-mouth design trials, com-
similar trial. A two group continuity corrected Chi² test with a pared one single mandibular implant in the first molar site loaded
0.05 two-sided significance level will have 90% power to detect the same day with one single contralateral implant loaded after 3
the difference between a proportion of 0.999 and a proportion months.
of 0.920 for participants experiencing at least one implant failure Schincaglia 2008 compared one single implant loaded within 24
(odds ratio of 0.0012) when the sample size in each group is 154. hours with one implant loaded after 3 months in the first or second
It was originally decided to recruit 80 participants in each group, mandibular molar site.
each centre recruiting 10 participants, however, only 40 partici- Enkling 2010 compared two interforaminal immediately loaded
pants were recruited, 20 per group. den Hartog 2011 used non- implants with two implants loaded after 3 months supporting
inferiority analysis defined as 0.5 mm mean marginal bone loss. mandibular overdentures.
It was assumed that a mean marginal bone loss of 1 mm (SD 0.6) De Rouck 2009 compared one single immediate post-extractive
would occur from implant placement to 18 months thereafter for implant loaded the same day with one implant loaded after 3
implants restored according to a conventional protocol. With a months between second to second upper premolars.
one-sided significance level of 5% and a power of 90%, a mini- den Hartog 2011 compared one single implant loaded within 24
mum of 26 participants per group was required. The number of hours with one implant loaded after 3 months between second to
participants per group was set at 31 to deal with withdrawal. second upper premolars.
(2) Early versus conventional loading

Characteristics of interventions
Early loading was compared with conventional loading in three
trials (Payne 2002; Tawse-Smith 2002; Fischer 2004).
Payne 2002 and Tawse-Smith 2002 compared two implants in
(1) Immediate versus conventional loading fully edentulous mandibles early loaded at 6 weeks or convention-
ally loaded at 12 weeks.
Immediate loading was compared with conventional loading in Fischer 2004 compared five to six implants in fully edentulous
15 trials (Chiapasco 2001; Romeo 2002; Cannizzaro 2003; Hall maxillae early loaded (9 to 18 days) or conventionally loaded (2.5
2006; Oh 2006; Assad 2007; Turkyilmaz 2007; Crespi 2008; to 5.1 months).
Donati 2008; Güncü 2008; Schincaglia 2008; De Rouck 2009;
Enkling 2010; den Hartog 2011; Meloni 2012).
Chiapasco 2001; Romeo 2002; Assad 2007 and Turkyilmaz 2007 (3) Immediate versus early loading
compared four implants in each edentulous mandible immedi- Immediate loading was compared with early loading in six trials
ately loaded after insertion (2 to 7 days) with four implants con- (Testori 2007; Cannizzaro 2008a; Cannizzaro 2008b; Cannizzaro
ventionally loaded after 3 to 8 months. 2008d; Merli 2008; Zöllner 2008).
Cannizzaro 2003 compared one or more implants in partially Testori 2007 compared implants in both mandibles and maxillae of
edentulous participants in both mandibles and maxillae loaded partially edentulous participants, immediately but non-occlusally
the same day with implants conventionally loaded (3.5 months loaded (when possible) within 48 hours with implants early loaded
for mandibles and 4.5 months for maxillae). at 2 months.
Hall 2006 compared one single implant loaded the same day with Cannizzaro 2008a compared two implants in fully edentulous
one single implant conventionally loaded at 6 months in the an- mandibles loaded the same day or early loaded at 6 weeks.
terior maxilla (between premolars). Cannizzaro 2008b compared five to eight implants, placed flapless,
Oh 2006 compared one single implant loaded the same day with in fully edentulous maxillae loaded the same day or early loaded
one single implant conventionally loaded at 4 months placed with at 2 months.
a flapless procedure in the anterior maxilla (between premolars). Cannizzaro 2008d, in a split-mouth design, compared one single
Crespi 2008 compared one single implant in fresh extraction sock- 7 mm long implant, placed flapless, occlusally loaded the same
ets in the maxillary aesthetic zone immediately occlusally loaded day with one implant early loaded at 6 weeks.
the same day with one single implant conventionally loaded at 3 Merli 2008 compared implants, placed flapless, in both mandibles
months. and maxillae of partially edentulous participants, immediately but
Donati 2008 compared one single implant immediately loaded non-occlusally loaded (when possible) within 72 hours with im-
within 24 hours with one single implant conventionally loaded plants early non-occlusally loaded at 6 weeks.
at 3 months in area 15 to 25 and 35 to 45. Immediately loaded Zöllner 2008 compared one to four implants in both posterior
sites were treated with two different preparation techniques (drills mandibles and maxillae of partially edentulous participants, im-
mediately but non-occlusally loaded the same day with implants 13. Steri-Oss® (Steri-Oss, Yorba Linda, California, USA) HL
early non-occlusally loaded at 1 month. series, 3.8 mm in diameter acid-etched titanium grade 4 screws
(Tawse-Smith 2002).
14. Thommen® (SPI®Element System; Thommen Medical
(4) Occlusal versus non-occlusal loading
AG, Waldenburg, Switzerland) sand-blasted acid-etched screws.
Occlusal loading was compared with non-occlusal loading in two In some of the post-extraction sites SPI®Contact troncoconical
trials (Lindeboom 2006; Cannizzaro 2010). screws were used (Merli 2008).
Lindeboom 2006 compared immediately occlusally loaded single 15. Zimmer® tapered SwissPlus (Zimmer Dental, Carlsbad,
implants with immediately non-occlusally loaded implants within California, USA) implants (Cannizzaro 2008a; Cannizzaro
1 day in the anterior and premolar region of the maxilla. 2008b).
Cannizzaro 2010 compared immediately occlusally loaded single 16. Zimmer® Spline Twist MTX (Zimmer Dental, Carlsbad,
implants with immediately non-occlusally loaded implants the day California, USA) HA-blasted and acid-etched titanium screws
of placement. (Cannizzaro 2003).
17. Zimmer® unknown type (Zimmer Dental, Carlsbad,
California, USA) dental implants (Oh 2006).
(5) Progressive loading
18. Zimmer® Screw-Vent® (but described as Paragon, Core-
No trial could be included. Vent Corporation, Las Vegas, USA) titanium screws (Assad
2007).
Implant systems 19. Z-Look3® (Z-System, Oensingen, Switzerland) one-piece
zirconia sand-blasted screws (Cannizzaro 2010).
Nineteen different implant systems were used in the trials in this
Early and conventionally loaded implants were used according
review.
to a submerged (two-stage) procedure, i.e. the implants were
1. 3i® Osseotite FNT (3i Biomet, Palm Beach, Florida, USA)
covered by the mucosa during the healing phase, thus a sec-
titanium tapered screws (Testori 2007).
ond surgical intervention was necessary to connect the abut-
2. 3i® Nanotite (3i Biomet, Palm Beach, Florida, USA)
ments to the implants (Chiapasco 2001; Hall 2006; Assad 2007;
titanium grade 5 cylindrical screws (Cannizzaro 2008d).
Crespi 2008; Donati 2008; De Rouck 2009; Enkling 2010; den
3. Astra OsseoSpeed® (Astra Tech Dental, Mölndal, Sweden)
Hartog 2011), or according to a non-submerged (one-stage) pro-
titanium grade 1 screws (Donati 2008).
tocol, i.e. the abutments were directly connected to the implants,
4. BioComp® (BioComp Industries BV, Vught, The
thus a second operation was avoided (Payne 2002; Romeo 2002;
Netherlands) tapered titanium plasma sprayed (TPS) screws
Tawse-Smith 2002; Cannizzaro 2003; Fischer 2004; Oh 2006;
(Lindeboom 2006).
Testori 2007; Turkyilmaz 2007; Cannizzaro 2008a; Cannizzaro
5. Brånemark® (Nobel Biocare AB, Göteborg, Sweden) Mark
2008b; Cannizzaro 2008d; Güncü 2008; Merli 2008; Schincaglia
II type turned titanium grade 1 screws (Chiapasco 2001).
2008; Zöllner 2008; Cannizzaro 2010; Meloni 2012). More
6. Brånemark® (Nobel Biocare AB, Göteborg, Sweden)
specifically the Z-Look3 one-piece zirconia implants used by
TiUnite Mark III type titanium grade 1 screws (Turkyilmaz
Cannizzaro 2010 could only be inserted according a non-sub-
2007; Güncü 2008), wide body (Schincaglia 2008).
merged technique.
7. ITI® SLA (Institut Straumann AG, Waldenburg,
• Removable overdentures were retained by clip attachments
Switzerland) solid sand-blasted large-grit acid-etched titanium
to a bar supported by four implants (Chiapasco 2001; Romeo
grade 4 screws (Payne 2002; Romeo 2002; Fischer 2004).
2002; Assad 2007), or two implants (Cannizzaro 2008a; Enkling
8. ITI® SLA active (Institut Straumann AG, Waldenburg,
2010), or were retained by two unsplinted ball attachments
Switzerland) solid sand-blasted large-grit acid-etched titanium
(Payne 2002; Tawse-Smith 2002; Turkyilmaz 2007).
grade 4 screws, three standard plus implants were also used
• Fixed maxillary full-arch prostheses, without using
(Zöllner 2008).
provisional ones, were connected to the implant in one trial
9. NobelReplace Tapered Groovy (Nobel Biocare AB,
(Fischer 2004). In another trial provisional cemented metal
Göteborg, Sweden) TiUnite titanium grade 4 screws (De Rouck
reinforced acrylic full-arch maxillary prostheses were replaced by
2009; den Hartog 2011; Meloni 2012).
metal ceramic or metal resin full-arch prostheses after 2 to 3
10. Outlink (Sweden & Martina, Padova, Italy) titanium
months (Cannizzaro 2008b).
plasma-sprayed cylindrical screws (Crespi 2008).
• Temporary resin bridges/crowns were fabricated and then
11. SICace® (SIC invent AG, Basel, Switzerland) titanium
replaced by final restorations in 13 trials (Cannizzaro 2003; Hall
screws (Enkling 2010).
2006; Lindeboom 2006; Testori 2007; Cannizzaro 2008d;
12. Southern® (Southern Implants Irene, South Africa) sand-
Crespi 2008; Donati 2008; Güncü 2008; Merli 2008; Zöllner
blasted acid-etched titanium grade 4 screws (Tawse-Smith 2002;
2008; De Rouck 2009; Cannizzaro 2010; den Hartog 2011). In
Hall 2006).
nine of these studies, only single crowns were used (Hall 2006; Cannizzaro 2008d; Schincaglia 2008; Donati 2008; Zöllner 2008;
Lindeboom 2006; Cannizzaro 2008d; Crespi 2008; Donati Merli 2008; Cannizzaro 2008a; Cannizzaro 2008b; De Rouck
2008; Güncü 2008; De Rouck 2009; Cannizzaro 2010; den 2009; Cannizzaro 2010; den Hartog 2011; Meloni 2012). One
Hartog 2011). study described randomisation by drawing lots till one group was
• Temporary resin crowns were fabricated and then replaced “full” and then simply putting all the rest into the other group,
by definitive metal-ceramic crowns in the immediately loaded a process we assessed at high risk of selection bias (Chiapasco
group, whereas permanent metal-ceramic crowns were delivered 2001). For the other eight studies, the risk of bias for this domain
in the conventionally loaded group in three trials (Oh 2006; was unclear because insufficient detail on the method of sequence
Schincaglia 2008; Meloni 2012). generation was available either from the report or from emails with
the author.
Occlusal or non-occlusal immediate loading
Allocation concealment
In 17 trials, the prostheses were put in full occlusion (Chiapasco
2001; Payne 2002; Romeo 2002; Tawse-Smith 2002; Cannizzaro Allocation concealment was reported as being done adequately in
2003; Fischer 2004; Oh 2006; Assad 2007; Turkyilmaz 2007; 12 (46%) of the included studies (Cannizzaro 2003; Fischer 2004;
Cannizzaro 2008a; Cannizzaro 2008b; Cannizzaro 2008d; Crespi Lindeboom 2006; Testori 2007; Cannizzaro 2008a; Cannizzaro
2008; Donati 2008; Güncü 2008; Schincaglia 2008; Enkling 2008b; Cannizzaro 2008d; Merli 2008; Zöllner 2008; Cannizzaro
2010). 2010; den Hartog 2011; Meloni 2012). In nine studies, it was
In seven trials, the prostheses were not put in full static or dynamic unclear from the report and communication with authors whether
occlusion for 2 months (Hall 2006; Testori 2007), 3 months ( allocation had been adequately concealed, and these studies were
Meloni 2012), 5 months (Zöllner 2008), or 6 months (Merli 2008; assessed at unclear risk of bias for this domain (Payne 2002;
De Rouck 2009; den Hartog 2011). Tawse-Smith 2002; Hall 2006; Oh 2006; Assad 2007; Crespi
In two trials (Lindeboom 2006; Cannizzaro 2010), single crowns 2008; Donati 2008; De Rouck 2009; Enkling 2010). In the re-
were randomised into full occlusion or not for 4 to 5 months maining five studies, the method of randomisation undertaken by
(Cannizzaro 2010), or 6 months (Lindeboom 2006). the authors was such that allocation concealment was not possible
and these trials were assessed at high risk of bias for this domain.
Overall less than half of the included studies (42%) are at
Characteristics of outcome measures low risk of selection bias (Cannizzaro 2003; Cannizzaro 2008a;
• Prosthesis failures (all trials with the exception of Zöllner Cannizzaro 2008b; Cannizzaro 2008d; Cannizzaro 2010; den
2008, for which the number of prosthetic failures was assumed Hartog 2011; Lindeboom 2006; Meloni 2012; Merli 2008; Testori
to be identical to the number of implant failures). 2007; Zöllner 2008).
• Implant failures (all trials).
• Radiographic bone level changes were assessed in all trials Blinding
with two exceptions (Oh 2006; Cannizzaro 2008a). However,
Blinding of operators and trial participants to the loading time is
the peri-implant bone level measurements of eight trials were not
not possible in these trials. We acknowledge that this introduces
included in the present analyses because they were performed on
a potential risk of performance bias in all of the included studies,
panoramic radiographs (Chiapasco 2001; Romeo 2002), because
but we have not assessed each included study for this domain.
data were presented in a way we could not use (Fischer 2004;
However, blinding of outcome assessment is possible and we
Assad 2007; Donati 2008; Zöllner 2008; De Rouck 2009), or
assessed this in the included studies. Blinded outcome assess-
because they just related to the 3-year follow-up (Merli 2008).
ment was reported in 13 studies (Chiapasco 2001; Payne 2002;
Romeo 2002; Tawse-Smith 2002; Cannizzaro 2003; Lindeboom
2006; Hall 2006; Oh 2006; Cannizzaro 2008d; Güncü 2008;
Risk of bias in included studies Cannizzaro 2008a; Cannizzaro 2008b; Enkling 2010), and was
not done in three studies (Fischer 2004; Turkyilmaz 2007; den
Hartog 2011). In the remaining 10 studies it was unclear whether
Allocation
outcome assessment was conducted by examiners blinded to allo-
cated treatment and these studies were assessed at unclear risk of
Sequence generation detection bias.
Seventeen (65%) of the included studies described an adequate
method of sequence generation and were assessed as being at low Incomplete outcome data
risk of bias for this domain (Payne 2002; Romeo 2002; Tawse- Two studies were assessed at high risk of attrition bias due to
Smith 2002; Cannizzaro 2003; Lindeboom 2006; Testori 2007; missing outcome data which was unequally missing from each
group (Hall 2006; Zöllner 2008). With the low event rate in these two different types of implants used in this trial, factors which
studies missing outcome data is a likely source of bias. In the were assessed as introducing a high risk of bias to this study. Sim-
remaining 24 included studies all randomised participants were ilarly in three other studies there were other differences between
included in the outcome assessments and risk of attrition bias was the groups besides loading time: Lindeboom 2006, in which more
low. larger diameter implants were used in the immediately occlusally
loaded group; Testori 2007, in which more early loaded implants
were placed in maxillae; Cannizzaro 2008b, in which more im-
Selective reporting
mediately loaded implants were placed in fresh extraction sockets
We assessed all of the trials included in this review to be at low risk compared to the early loaded group. The clinical significance, if
of selective reporting bias because all studies reported the main any, of these findings is difficult to interpret, so these three studies
outcomes of this review. were assessed as being at unclear risk of other bias. For six trials, the
baseline participant characteristics were not described in sufficient
Other potential sources of bias detail to enable an assessment to be made (Assad 2007; Turkyilmaz
2007; Crespi 2008; Donati 2008; Enkling 2010; Meloni 2012).
An additional source of bias was identified in seven included stud-
The overall risk of bias assessment after having incorporated the
ies (Tawse-Smith 2002; Lindeboom 2006; Testori 2007; Merli
additional information, kindly provided by the authors of the in-
2008; Cannizzaro 2008b; De Rouck 2009; den Hartog 2011).
cluded trials, is summarised in Figure 1 and Figure 2. Summaris-
Different radiographic assessment techniques were used in each
ing the risk of bias for each study, three trials were judged to be at
group in the study by De Rouck 2009, which introduced a high
low risk of bias (Cannizzaro 2003; Cannizzaro 2008a; Cannizzaro
risk of bias. A high rate of protocol violations occurred in the early
2008d), 11 trials were judged to be at an unclear risk of bias (Payne
loading group in the trial by Merli 2008, which introduced a high
2002; Lindeboom 2006; Oh 2006; Testori 2007; Assad 2007;
risk of bias. In den Hartog 2011 there was an imbalance in gender
Crespi 2008; Donati 2008; Cannizzaro 2008b; Cannizzaro 2010;
in each group at baseline which suggests that the allocation to treat-
Enkling 2010; Meloni 2012), whereas 12 trials were judged to be
ment may not have been truly random, so this trial was assessed
at high risk of bias (Chiapasco 2001; Romeo 2002; Tawse-Smith
at unclear risk of other bias. In the study by Tawse-Smith 2002,
2002; Fischer 2004; Hall 2006; Turkyilmaz 2007; Güncü 2008;
there was a very different distribution of the length of the implants
Schincaglia 2008; Zöllner 2008; Merli 2008; De Rouck 2009; den
between the groups with different loading times together with dif-
Hartog 2011).
ferent levels of operator skill associated with the placement of the
Figure 1. Risk of bias graph: review authors’ judgements about each risk of bias item presented as
percentages across all included studies.
Figure 2. Risk of bias summary: review authors’ judgements about each risk of bias item for each included
study.
Effects of interventions
See: Summary of findings for the main comparison; Summary
of findings 2; Summary of findings 3
In total 2120 implants were originally placed in 1217 participants.
The numbers of participants and implants for each comparison
are shown below.
Comparison Test Group 1 Test Group 2

participants* (implants) participants (implants)
Immediate versus conventional All (15 trials) 299 (432) 236 (401)
Mandible (8 trials) 98 (199) 66 (199)
Maxilla (6 trials) 187 (187) 156 (156)
Both (1 trial) 14 (46) 14 (46)
Early versus conventional All (3 trials) 52 (167) 44 (119)
Mandible (2 trials) 36 (72) 36 (72)
Maxilla (1 trial) 16 (95) 8 (47)
Immediate versus early All (6 trials) 268 (464) 230 (449)
Mandible (1 trials) 30 (30) (30)
Maxilla (1 trials) 15 (90) 15 (87)
Both (4 trial) 223 (314) 185 (302)
Occlusal versus non-occlusal All (2 trials) 44 (44) 44 (44)
Maxilla (1 trials) 24 (24) 24 (24)
Both (1 trial) 20 (20) 20 (20)
* Participants from the split-mouth trials are only included once
in the ’Test Group 1’ column. five (12.5%) immediately loaded single crowns failed in another
During the follow-up considered in this review (1 year of function trial (Cannizzaro 2010).
for all trials with the exception of Oh 2006 and Cannizzaro 2008d, The meta-analyses for prosthesis failures, implant failures and mar-
for which we could only use the 6 and 9 months data, respectively), ginal bone level changes at 1 year, with the exception of Oh 2006
57 implants failed. Twenty-nine of the failed implants were im- (6 months data used), Cannizzaro 2008d (6 months data used for
mediately loaded, 20 were early loaded and eight conventionally radiographs and 9 months data for prosthesis and implant failures),
loaded. Of the 990 planned/placed restorations (unknown num- Crespi 2008 (2 years data used for radiographs), and Lindeboom
ber of prostheses placed in Zöllner 2008, we assumed that for each 2006 (18 months data used for radiographs), are presented in Data
implant failure corresponded one prosthesis failure), 45 (or 43 de- and analyses ’Comparisons 1 to 4’.
pending on the success criteria adopted) failed: 22 in the imme-
diately loaded group, 14 (or 12 depending on the success criteria (1) Immediate versus conventional loading after 1
adopted) in the early loaded group, and 4 in the conventionally year of function (Comparison 1)
loaded group. The majority of prosthesis failures occurred in four Fifteen trials were included (Chiapasco 2001; Romeo 2002;
trials: six prostheses failed in one trial (Tawse-Smith 2002): five Cannizzaro 2003; Hall 2006; Oh 2006; Turkyilmaz 2007; Assad
(42%) of those (or three (25%) depending on the success crite- 2007; Crespi 2008; Güncü 2008; Schincaglia 2008; Donati 2008;
ria adopted) were early loaded. Three (25%) immediately loaded De Rouck 2009; Enkling 2010; den Hartog 2011; Meloni 2012).
prostheses failed in one trial (Oh 2006); five (10%) immediately Data on the numbers of participants, and the number of prosthetic
loaded single crowns failed in one trial (Lindeboom 2006) and and implant failures are given in the table below.
Design Prosthetic failures Implant failures

(immediate loading first) (immediate loading first)
Chiapasco 2001 Parallel No failures 1/10, 1/10
Romeo 2002 Parallel No failures 0/10, 1/10
Cannizzaro 2003 Parallel 0/14, 1/14 0/14, 1/14
Hall 2006 Parallel 1/13, 0/12 1/13, 0/12
Oh 2006 Parallel 3/12, 0/12 3/12, 0/12
Assad 2007 Parallel No failures (n = 5) No failures (n = 5)
Turkyilmaz 2007 Parallel No failures (n = 10) No failures (n = 10)
Crespi 2008 Parallel No failures (n = 20) No failures (n = 20)
Donati 2008 Parallel 3/84, 0/53 3/84, 0/53
Güncü 2008 Split-mouth 1/13, 0/13 1/13, 0/13
Schincaglia 2008 Parallel 1/15, 0/15 1/15, 0/15
De Rouck 2009 Parallel 1/25, 2/24 1/25, 2/24
Enkling 2010 Parallel No failures (n = 15) No failures (n = 15)
den Hartog 2011 Parallel 1/31, 0/31 1/31, 0/31
(Continued)
Meloni 2012 Split-mouth No failures (n = 20) No failures (n = 20)
Chiapasco 2001 (parallel group design) compared four immedi-

ately loaded (2 to 3 days) Brånemark implants with four conven- apparent baseline differences for sex, age, bone quality, soft tis-
tionally loaded (4 to 8 months) implants supporting bar-retained sue thickness, and implant position between the two groups. No
overdentures in totally edentulous mandibles of adequate shape withdrawals at 1 year. Three prostheses/implants failed in the im-
and quality for 2 years. Ten participants were originally included mediately loaded group.
in each group. No baseline differences were apparent for sex, age, Assad 2007 (parallel group design) compared four immediately
and length of the implants used between the two groups. No with- loaded (within 4 days) Screw-Vent implants with four conven-
drawals at 1 year. One implant failed in each group. tionally loaded (4 months) implants supporting bar-retained over-
Romeo 2002 (parallel group design) compared four immediately dentures in totally edentulous mandibles of adequate shape for 2
loaded (2 days) ITI SLA implants with four conventionally loaded years. Ten participants were originally included in each group. It
(3 to 4 months) implants supporting bar-retained overdentures in was unclear whether there were baseline differences between the
totally edentulous mandibles of adequate shape and quality for 2 two groups. No withdrawals at 1 year. No implant failed.
years. Ten participants were originally included in each group. It Turkyilmaz 2007 (parallel group design) compared two unsplinted
was unclear whether there were baseline differences between the immediately loaded (1 week) Brånemark TiUnite implants with
two groups. No withdrawals at 1 year. One implant failed for peri- two unsplinted conventionally loaded (3 months) implants sup-
implantitis in the conventionally loaded group. porting overdentures in totally edentulous mandibles of adequate
Cannizzaro 2003 (parallel group design) compared single crowns/ shape for 2 years. Ten participants were originally included in each
bridges immediately loaded (same day) Zimmer Spline twist im- group. It was unclear whether there were baseline differences be-
plants with conventionally loaded implants (3.5 and 4.5 months tween the two groups. No withdrawals at 1 year. No implant failed.
in mandibles and maxillae respectively) in partially edentulous Crespi 2008 (parallel group design) compared single Outlink Swe-
participants for 2 years. Fourteen participants were originally in- den & Martina 13 mm long implants placed in fresh extraction
cluded in each group. There were no apparent baseline differ- sockets immediately loaded (same day) with identical implants
ences with respect to sex, age, bone quality, implant position and conventionally loaded at 3 months in maxillae (premolar to pre-
length between the two groups. No withdrawals at 1 year. One molar area) for 2 years. Twenty participants were originally in-
prosthesis/implant failed at abutment connection in the conven- cluded in each group. There were no baseline differences in im-
tionally loaded group. There was no statistically significant dif- plant diameter and position between the two groups. No with-
ference in prosthesis failures, implant failures and marginal bone drawals at 1 year. No implant failed.
level changes between the different loading strategies (Analysis 1.1; Donati 2008 (parallel group design) compared one immediately
Analysis 1.2; Analysis 1.3). loaded (within 1 day) Astra OsseoSpeed implant with one conven-
Hall 2006 (parallel group design) compared single immediately tionally loaded (3 months) implant replacing a tooth in position
non-occlusally loaded (same day) Southern tapered implants with 15 to 25 and 35 to 45 for 1 year. Three groups were formed: two
conventionally loaded implants (6 months) in the anterior maxilla groups had implants immediately loaded. The immediately loaded
(premolar to premolar) for 1 year. Fourteen participants were orig- groups differed in the preparation of the implant site: a conven-
inally included in each group. There were no apparent baseline tional preparation with drills (44 participants), and a preparation
differences for sex, age, bone quality, bone quantity and implant with osteotomes (42 participants). We considered these two groups
length between the two groups. One participant emigrated from as a single group. The control group consisted of 53 participants
the immediately loaded group (the implant was in function) ver- who had implant sites conventionally prepared and loaded. Ten
sus two participants who emigrated to Australia from the conven- participants who were treated according to a split-mouth design
tionally loaded group at 1 year. One prosthesis/implant failed at had to be excluded from the analyses. It was unclear whether there
abutment connection in the immediately loaded group. were baseline differences between the three groups. There were
Oh 2006 (parallel group design) compared single immediately two withdrawals at 1 year from the conventionally loaded group
loaded (same day) Zimmer implants with conventionally loaded because of poor health conditions. Three crowns/implants failed
implants (4 months) in the anterior maxilla (premolar to premo- from the immediately loaded groups: one from the conventionally
lar), placed with a flapless technique, for 6 months. Twelve par- prepared sites and two from the osteotomes prepared sites.
ticipants were originally included in each group. There were no Güncü 2008 (split-mouth design) compared one immediately
loaded (same day) Brånemark TiUnite implant with one con- crown/implant failed from the immediately loaded group.
tralateral conventionally loaded (3 months) implant replacing first Meloni 2012 (split-mouth design) compared one immediately
mandibular molars for 1 year. Thirteen participants were orig- loaded (within 1 day) NobelReplace Tapered Groovy TiUnite im-
inally included. No baseline differences were apparent between plant with one contralateral conventionally loaded (3 months) im-
the contralateral sites. No withdrawals at 1 year. One implant/ plant replacing first mandibular molars for 1 year. Twenty partic-
crown failed in the immediately loaded group. There was no sta- ipants were originally included. It was unclear whether there were
tistically significant difference in prosthesis, implant failures and baseline differences between the two groups. No withdrawals at 1
marginal bone level changes between the different loading strate- year. No implant failed.
gies (Analysis 1.1; Analysis 1.2; Analysis 1.3).
Summary of Effects of Interventions - immediate versus
Schincaglia 2008 (parallel group design) compared one immedi-
conventional loading
ately loaded (within 1 day) Brånemark TiUnite implant with one
conventionally loaded (3 to 4 months) implant replacing first or For the outcome of prosthesis failures, the meta-analysis of eight
second mandibular molars for 1 year. Fifteen participants were trials (381 participants) (Cannizzaro 2003; Hall 2006; Oh 2006;
originally included in each group. There were no apparent base- Donati 2008; Güncü 2008; Schincaglia 2008; De Rouck 2009;
line differences in implant position and insertion torque between den Hartog 2011) found no evidence of a difference, risk ratio
the two groups. However, the implants of the immediately loaded (RR) 1.87 (95% confidence interval (CI) 0.70 to 5.01) random-
group were longer than those in the conventionally loaded group. effects, with no heterogeneity (Analysis 1.1). The meta-analysis
No withdrawals at 1 year. One implant/crown failed in the imme- was based only on eight trials because there were no prosthesis
diately loaded group. failures in the other seven trials (110 participants) and therefore
De Rouck 2009 (parallel group design) compared single NobelRe- the risk ratios for these trials could not be calculated. Of the eight
place Tapered Groovy TiUnite implants placed in fresh extraction trials included in the meta-analysis, one trial was at low risk of bias
sockets immediately loaded (same day) with identical implants (Cannizzaro 2003), five trials were at high risk of bias (Hall 2006;
conventionally loaded at 3 months in anterior maxillae (premolar Güncü 2008; Schincaglia 2008; De Rouck 2009; den Hartog
to premolar area) for 1 year. Twenty-six participants were origi- 2011), and two trials were at unclear risk of bias (Oh 2006; Donati
nally included in each group, however, two participants from the 2008).
conventional loading and one from the immediate loading groups For implant failures, the meta-analysis of 10 trials (Chiapasco
were excluded because loss of buccal wall at extractions (conven- 2001; Romeo 2002; Cannizzaro 2003; Hall 2006; Oh 2006;
tional loading) and insufficient primary implant stability (20 Ncm; Donati 2008; Güncü 2008; Schincaglia 2008; De Rouck 2009;
immediate loading). The implant-bone gap was grafted with gran- den Hartog 2011) found no evidence of a difference, RR 1.65
ules of anorganic bovine bone. There were no baseline differences (95% CI 0.68 to 3.98) random-effects, with no heterogeneity
in age, gender, implant length, diameter and position between the (Analysis 1.2). In a further five trials (total 70 participants) there
two groups. No further withdrawals at 1 year. One immediately were no implant failures in either group, so risk ratios could not
loaded and two conventionally loaded implants failed. be calculated and they could not be included in the meta-analysis.
Enkling 2010 (parallel group design) compared two immediately Of the 10 trials included in the meta-analysis, one trial was at
loaded interforaminal implants with two conventionally loaded (3 low risk of bias (Cannizzaro 2003), seven trials were at high risk
months) implants supporting bar-retained overdentures in totally of bias (Chiapasco 2001; Romeo 2002; Hall 2006; Güncü 2008;
edentulous mandibles for 1 year. Sixteen participants were origi- Schincaglia 2008; De Rouck 2009; den Hartog 2011) and two
nally included in each group. It was unclear whether there were trials were at unclear risk of bias (Oh 2006; Donati 2008).
baseline differences between the two groups. The outcome of two For marginal bone level changes, the meta-analysis of nine tri-
participants (one from each group) was not provided. No implant als (Cannizzaro 2003; Hall 2006; Turkyilmaz 2007; Crespi 2008;
failed. Güncü 2008; Schincaglia 2008; Enkling 2010; den Hartog 2011;
den Hartog 2011 (parallel group design) compared one immedi- Meloni 2012) found reduced bone loss associated with immedi-
ately loaded (within 1 day) NobelReplace Tapered Groovy TiUnite ately loaded implants, MD -0.10 mm (95% CI -0.20 to -0.01;
implant with one conventionally loaded (3 months) implant re- P = 0.03) random-effects, with some heterogeneity (Tau² = 0.01;
placing a tooth in position 14 to 24 for 18 months post-insertion. Chi² = 14.37, df = 8 (P = 0.07); I² = 44%) (Analysis 1.3). This is
Thirty-one participants were originally included in each group. based on one trial at low risk of bias (Cannizzaro 2003), five trials
There were no apparent baseline differences in reason for tooth at high risk of bias (Hall 2006; Turkyilmaz 2007; Güncü 2008;
loss, implant position, length, diameter and bone augmentation Schincaglia 2008; den Hartog 2011), and three at unclear risk of
between the two groups. When needed sites where augmented bias (Crespi 2008; Enkling 2010; Meloni 2012).
with a mixture of autogenous bone and anorganic bovine bone
and resorbable collagen barriers both before implant placement (2) Early versus conventional loading after 1 year of
and at implant placement. No withdrawals at 18 months. One function (Comparison 2)
Three trials were included (Payne 2002; Tawse-Smith 2002;
Fischer 2004).
Data on the numbers of participants experiencing at least one
prosthetic and implant failure are given in the table below.

(early loading first) (early loading first)
Payne 2002 Parallel No failures No failures
Tawse-Smith 2002 Parallel 5/24, 1/24 5/24, 1/24
Fischer 2004 Parallel No failures 1/16, 2/8
Payne 2002 (parallel group design) compared two unsplinted early

loaded (6 weeks) ITI SLA implants with two unsplinted conven- ventionally loaded group. There were no apparent baseline dif-
tionally loaded (12 weeks) implants supporting overdentures in ferences in implant length and cantilever length between the two
totally edentulous mandibles of adequate shape and quality for 2 groups. No withdrawals at 1 year. No prosthesis failures. One im-
years. Twelve participants were originally included in each group. plant failed in the early loaded group versus two implants in two
There were no apparent baseline differences in gender, bone qual- participants in the conventionally loaded group.
ity and quantity between the two groups. Two withdrawals oc- Summary of Effects of Interventions - early versus
curred from the conventionally loaded group at 1 year. No implant conventional loading
failed.
For the outcome of prosthesis failure, one trial (Tawse-Smith 2002)
Tawse-Smith 2002 (parallel group design) compared two un-
at high risk of bias found no difference between early and con-
splinted early loaded (6 weeks) Southern or Steri-Oss implants
ventional loading Analysis 2.1, and two further trials (one at high
with two unsplinted conventionally loaded (12 weeks) implants
risk of bias and the other at unclear risk of bias) had no prosthe-
supporting overdentures in totally edentulous mandibles of ad-
sis failures in either group in the first year. There is insufficient
equate shape and quality for 2 years. Twelve participants were
evidence from these three trials to determine whether there is a
originally included in each of the four groups (Southern early
clinically important difference between early loading and conven-
loaded, Steri-Oss early loaded, Southern conventionally loaded,
tional loading with regard to the outcome of prosthesis failure.
Steri-Oss conventionally loaded). There were no apparent base-
For the outcome of implant failure, the meta-analysis of two trials
line differences in bone quality and quantity between the two
(Tawse-Smith 2002; Fischer 2004), both at high risk of bias, found
groups. However, the implants of both the Steri-Oss and Southern
insufficient evidence to determine whether there was a difference
early loaded groups were shorter than those in the convention-
between early and conventional loading with regard to implant
ally loaded groups, and we were unable to determine the reasons
failure in the first year, RR 1.55 (95% CI 0.46 to 5.18) fixed-
for this. In the article Steri-Oss implants were described as hav-
effect, with no evident heterogeneity (Analysis 2.2).
ing a turned surface, but after having analysed the surface of one
For marginal bone level changes, the meta-analysis of two trials
implant, kindly provided by the authors, it was realised that the
(Payne 2002; Tawse-Smith 2002), one at high and the other at un-
implant surface was chemically treated. No withdrawals at 1 year.
clear risk of bias, found insufficient evidence to determine whether
Seven Steri-Oss implants failed in five participants of the early
there was a difference in bone loss associated with early or con-
loaded group versus one Steri-Oss implant in the conventionally
ventional loading of implants, MD -0.04 (95% CI -0.15 to 0.07)
loaded group. No implants failed in the Southern groups. Most
fixed-effect, with no evident heterogeneity (Analysis 2.3).
of the failed implants were placed by a surgeon who only placed
some Steri-Oss implants.
Fischer 2004 (parallel group design) compared five to six early (3) Immediate versus early loading after 1 year of
loaded (9 to 18 days) ITI SLA implants with five to six conven- function (Comparison 3)
tionally loaded (2.5 to 5.1 months) ITI EstheticPlus implants sup- Six trials were included (Testori 2007; Cannizzaro 2008a;
porting fixed maxillary cross-arch bridges for 5 years. Sixteen par- Cannizzaro 2008b; Cannizzaro 2008d; Merli 2008; Zöllner 2008)
ticipants were originally included in the early and eight in the con- in this comparison.
Data on the numbers of participants experiencing at least one
prosthetic and implant failure are given in the table below.

(immediate loading first) (immediate loading first)
Testori 2007 Parallel 1/25, 0/27 1/25, 0/27
Cannizzaro 2008a Parallel 0/30, 2/30 0/30, 2/30
Cannizzaro 2008b Parallel No failures 1/15, 2/15
Cannizzaro 2008d Split-mouth 1/30, 1/30 1/30, 1/30
Merli 2008 Parallel No failures No failures
Zöllner 2008 Parallel 4/138, 6/128 4/138, 6/128
Testori 2007 (parallel group design) compared immediately non-

occlusally loaded 3i FNT implants (within 48 hours) with early two groups, though more immediate post-extractive implants were
loaded implants (2 months) supporting single crowns/partial placed in the early loaded group. Four implants were immediately
bridges for 4 years. Twenty-five participants were originally in- replaced with larger diameter ones to obtain the implant insertion
cluded in the immediately loaded group and 27 in the early loaded torque (> 48 Ncm) required. No withdrawals at 1 year. No pros-
group. There were no baseline differences with respect to sex, age, thesis failures. One implant did not achieve a sufficient primary
bone quality, implant length and number between the two groups, stability and was immediately removed and not replaced. Four im-
however, more implants of the early loaded group were placed in plants failed: one in the immediately loaded group and three in
maxillae than those of the immediately loaded group. No with- two participants of the early loaded group.
drawals at 1 year. One single implant and its related provisional Cannizzaro 2008d (split-mouth design) compared single Biomet
crown failed after 2 months in the immediately loaded group. 3i Nanotite 6.5 mm long cylindrical implants, placed with a flap-
Cannizzaro 2008a (parallel group design) compared two immedi- less technique, immediately occlusally loaded (same day) with
ately loaded Zimmer SwissPlus implants (within 12 hours) with identical implants early loaded (6 weeks) for 5 years. Thirty partic-
two early loaded implants (6 weeks), placed with a flapless tech- ipants were originally included. There were no baseline differences
nique, supporting mandibular bar-retained overdentures for 1 in the number of post-extractive sites, bone quality, implant di-
year. Thirty participants were included in each group. There were ameter and position between the two groups. Eight implants were
no apparent baseline differences for sex, age, smoking habits, num- immediately replaced with larger diameter ones to obtain the im-
ber of maxillary dentures, number of immediate post-extractive plant insertion torque (> 40 Ncm) required. The randomisation
implants, and implant length between the two groups. Two im- of one implant of the immediately loaded group was subverted:
plants were immediately replaced with larger diameter ones to ob- the implant was early loaded according to the research protocol
tain the implant insertion torque (> 48 Ncm) required. No with- since a sufficient implant insertion torque (> 40 Ncm) could not
drawals at 1 year. Two implants failed in two participants of the be obtained. No withdrawals at 1 year. One implant and its related
early loaded group which determined the failure of the overden- crown failed from each group.
tures, however both implants were successfully replaced. Merli 2008 (parallel group design) compared immediately non-
Cannizzaro 2008b (parallel group design) compared five to eight occlusally loaded Thommen implants (within 72 hours) with early
immediately loaded Zimmer SwissPlus implants (within 12 hours) non-occlusally loaded implants (6 weeks), placed with a flapless
with five to eight early loaded implants (2 months), placed with technique, supporting single crowns/partial bridges for 1 year.
a flapless technique, supporting fixed maxillary cross-arch bridges Thirty participants were included in the immediately loaded group
for 1 year. Fifteen participants were included in each group. There and 30 in the early loaded group. The randomisation of two par-
were no apparent baseline differences for sex, age, smoking habits, ticipants in each group was subverted: two participants of the im-
number of mandibular dentures, and implant length between the mediately loaded group were treated as early loaded participants
according to the research protocol since a sufficient implant in- 2008) found insufficient evidence to determine whether there
sertion torque (> 40 Ncm) could not be obtained, whereas two is a difference between immediate and early loading, RR 0.68
participants of the early loaded group were immediately loaded by (95% CI 0.25 to 1.86) random-effects, with no evident hetero-
mistake. Five additional participants of the early loaded group were geneity (Analysis 3.1). Two of these trials were at low risk of
actually conventionally loaded. There were no apparent baseline bias (Cannizzaro 2008a; Cannizzaro 2008d), one at unclear risk
differences with respect to sex, age, bone quality, implant length (Testori 2007) and the other at high risk of bias (Zöllner 2008).
and number between the two groups. No withdrawals at 1 year. For the outcome of implant failure, the meta-analysis of five trials
No prosthesis or implant failures. (Testori 2007; Cannizzaro 2008a; Cannizzaro 2008b; Cannizzaro
Zöllner 2008 (parallel group design) compared immediately non- 2008d; Zöllner 2008) (two low, two unclear and one at high risk
occlusally loaded implants (the same day) with early non-occlusally of bias) found insufficient evidence to determine whether there is
loaded implants (1 month), placed in posterior jaws (premolar a difference between immediate and early loading, RR 0.65 (95%
and molars areas) supporting single crowns/partial bridges for 1 CI 0.26 to 1.63) random-effects, with no evident heterogeneity
year. One-hundred-and-thirty-eight participants were treated in (Analysis 3.2).
the immediately loaded group and 128 in the early loaded group. For the outcome of radiographic bone levels, the meta-analysis of
There were no apparent baseline differences in bone quality, im- three trials (Testori 2007; Cannizzaro 2008b; Cannizzaro 2008d)
plant length, number and position between the two groups. Un- (one low and two at unclear risk of bias) there was insufficient
clear whether five withdrawals occurred in the immediately loaded evidence to determine whether there is a difference in bone loss
group and one in the early loaded group prior to implant place- between immediate and early loading of implants, MD -0.06 (95%
ment or during a 5-month follow-up period and it is unclear how CI -0.16 to 0.03) random-effects, with no evident heterogeneity
many drop-outs occurred at 1 year. Four implants failed in the (Analysis 3.3).
immediately loaded group versus six in the early loaded group. We
assumed that an equal number of prostheses were lost, since we
were not able to obtain this information from the authors. (4) Occlusal versus non-occlusal loading (Comparison
4)
Summary of Effects of Interventions - immediate versus
Two trials were included (Lindeboom 2006; Cannizzaro 2010) in
early loading
this comparison.
For the outcome of prosthesis failure, the meta-analysis of four tri- Data on the numbers of participants experiencing at least one
als (Testori 2007; Cannizzaro 2008a; Cannizzaro 2008d; Zöllner prosthetic and implant failure are given in the table below.

(occlusal loading first) (occlusal loading first)
Lindeboom 2006 Parallel 2/24, 3/24 2/24, 3/24
Cannizzaro 2010 Parallel 3/20, 2/20 3/20, 2/20
Lindeboom 2006 (parallel group design) compared immediately

occlusally loaded with immediately non-occlusally loaded single pants were included in each group. There were no apparent base-
BioComp implants for 1 year. Twenty-four participants (25 im- line differences in sex, age, bone quality, implant position and im-
plants) were included in each group. There were no apparent base- plant sizes between the two groups. No withdrawals at 1 year. Five
line differences in sex, age, previously grafted sites, and implant crowns/implants failed in five participants: three in the occlusally
position between the two groups, though more larger diameter loaded group and two in the non-occlusally loaded group.
implants were used in the occlusally loaded group. No withdrawals Summary of Effects of Interventions - occlusal versus non
at 1 year. Five crowns/implants failed in five participants: two in occlusal loading
the occlusally loaded group and three in the non-occlusally loaded
group. The meta-analysis of two trials (Lindeboom 2006; Cannizzaro
Cannizzaro 2010 (parallel group design) compared immediately 2010), both at unclear risk of bias, found insufficient evidence
occlusally loaded with immediately non-occlusally loaded single to determine whether there is a difference between immediate
one-piece Z-Look3 zirconia implants for 1 year. Twenty partici- occlusal and non-occlusal loading, with regard to prosthesis failure,
RR 1.00 (95% CI 0.31 to 3.22) fixed-effect, with no evident
heterogeneity (Analysis 4.1), implant failure, RR 1.00 (95% CI
0.31 to 3.22) fixed-effect, with no evident heterogeneity (Analysis
4.2), or bone loss, MD 0.03 (95% CI -0.10 to 0.15) fixed-effect,
with no evident heterogeneity (Analysis 4.3).
(5) Progressive loading

No trial could be included.
Subgroup analyses
No subgroup analysis was conducted as the maximum number of
trials within any meta-analysis was 10 (Analysis 1.2), and there
was no evidence of heterogeneity.
A D D I T I O N A L S U M M A R Y O F F I N D I N G S [Explanation]
Conventional compared with early loading of dental implants

Intervention: early loading
Comparison: conventional loading
Conventional Early
Prosthesis failure Low risk population RR 5.00 (0.63 to 39.67) 48 +OOO

at 1 year (1) very low
10 per 10001 50 per 1000
(6 to 397)
100 per 1000 241 per 1000
(63 to 1000)

2. only one small study at high risk of bias
RR = risk ratio
Moderate quality (+++O): Further research is likely to have an important impact on our confidence in the estimate of effect and may
25
26
Early compared with immediate loading of dental implants

Intervention: immediate loading
Comparison: early loading
Early Immediate
Prosthesis failure Low risk population RR 0.68 (0.25 to 1.86) 408 +++O2 As the incidence of fail-
at 1 year (4) moderate ure is so low future stud-
50 per 10001 34 per 1000 ies are unlikely to in-
(13 to 93) crease the precision sub-
stantially
240 per 1000 163 per 1000
(60 to 446)

2. One trial high, one unclear and two at low risk of bias
RR = risk ratio
Moderate quality (+++O): Further research is likely to have an important impact on our confidence in the estimate of effect and may
27
28
DISCUSSION
Although this review has included 26 RCTs, the low failure rate of
both implants and prostheses in these trials means that there is still
Summary of main results insufficient evidence to support definitive conclusions. However,
The question of whether implants could be immediately or early research suggests that thousands of participants would need to
loaded after their insertion has relevant clinical implications since be included in randomised trials in order to produce conclusive
the treatment period could be drastically reduced for the patients’ evidence (Thorlund 2011), and this is unlikely to occur, at least
benefit. The main outcome for this type of study is the success in the short term.
of the prosthesis since implant loss may not always jeopardise The risk of implant failure can be substantially minimised by
prosthesis success. It was decided to consider only a relatively short proper patient selection and well-trained operators. It could make
follow-up (4 months to 1 year) since it was felt that such follow- more clinical sense to load an implant immediately if the implant
ups would be sufficient to understand the role of loading on the was inserted with a sufficient torque and if there are not other
establishment of osseointegration. factors believed to negatively influence its prognosis. In the case of
The 26 trials included in this update of the review were divided poor primary implant stability or other suspected negative prog-
into four groups based on the comparison being evaluated. nostic variables, it might be preferable to wait for a conventional
• Comparison 1: Immediate versus conventional loading healing period.
(after 3 months): From 15 randomised controlled trials (RCTs), It is possible that some specific factors might have played a de-
there was no evidence of a difference in either prosthesis failure terminant role in the final outcome in some of the trials. Factors
(risk ratio (RR) 1.87, 95% confidence interval (CI) 0.70 to 5.01) such as the surgical skill of the operators, or the flapless place-
or implant failure (RR 1.65, 95% CI 0.68 to 3.98) in the first ment of dental implants, which is technically demanding, might
year, but there is some evidence of a small reduction in bone loss have contributed to the sub-optimal success rates of immediately
favouring immediate loading (MD -0.10 mm, 95% CI -0.20 to - loaded implants. Insertion torque is another factor which may be
0.01; P = 0.03), with some heterogeneity (Tau² = 0.01; Chi² = associated with subsequent implant failure, but there is no con-
14.37, df = 8 (P = 0.07); I² = 44%). clusive evidence as to the minimum insertion torque required to
• Comparison 2: Early (6 weeks) versus conventional loading: prevent failure. More recently, an RCT compared success rates of
From three RCTs there is insufficient evidence to determine immediately loaded single implants placed according to a split-
whether or not there is a clinically important difference in mouth design with insertion torques between 25 and 35 Ncm or
prosthesis failure, implant failure or bone loss. superior to 80 Ncm in 50 participants (Cannizzaro 2012). Seven
• Comparison 3: Immediate versus early loading: From the of the implants placed with 25 to 35 Ncm torque failed versus
six RCTs in this group there is insufficient evidence to determine none of the implants placed with more than 80 Ncm. In addi-
whether or not there is a clinically important difference in tion, since RCTs reporting excellent success rates for immediately
prosthesis failure, implant failure or bone loss between or early loaded implants used techniques to insert the implants
immediate and early loaded implants with high insertion torques, it can be concluded that a high de-
• Comparison 4: Occlusal versus non-occlusal loading: From gree of primary stability at implant insertion is a key prerequisite
the two trials in this group there is insufficient evidence to for successful immediate or early loading procedures. What is the
determine whether there is a clinically important difference in ideal insertion torque? A very accurate answer cannot be given yet,
the outcomes of prosthesis failure, implant failure or bone loss but for single implants insertion torques superior to 35 Ncm are
between occlusal and non-occlusal loading. mandatory in order to obtain predictable success rates.
Another important question is how difficult is it to obtain a suf-
Despite including 26 trials with over 1200 patients, the low fail- ficiently high insertion torque? In a few trials, the number of
ure rate of both prostheses and implants in all the included tri- implants which were immediately replaced in order to obtain
als means there is still insufficient information to draw definitive the required insertion torque was reported (Cannizzaro 2008a;
conclusions. The only statistically significant difference was a very Cannizzaro 2008b; Cannizzaro 2008d; Merli 2008). It is interest-
small reduction in bone loss associated with immediate loading ing to observe that in one study, eight out of 60 placed implants
compared to conventional loading, MD -0.10 mm (95% CI -0.20 (13%) were immediately replaced by larger diameter ones to ob-
to -0.01; P = 0.03) but this difference may be too small to be clin- tain an insertion torque > 40 Ncm (Cannizzaro 2008d). While
ically important. There was insufficient evidence from the smaller this appears to be a costly procedure, the following observations
number of trials in comparisons 2 to 4 to determine whether or should be made: (1) all implants were only 6.5 mm long and were
not there was a difference in bone loss. placed according to a flapless procedure some even in fresh ex-
traction sites (30%), therefore it is understandable that is not easy
to achieve high insertion torques; (2) this was a clinical trial and
Overall completeness and applicability of it was decided at protocol level that the operator could replace
evidence the implants with larger diameter ones in order to conduct the
study in the most appropriate way. In everyday clinical practice, The present review update unfortunately has not brought a great
the loading of those implants, which could not be inserted with deal of new evidence. In fact, despite the updated search identify-
the desired torque, could be delayed to allow osseointegration to ing 14 new RCTs, too many of these trials had to be excluded. The
take place. most common reason for study exclusion was that some of these
It is debated whether immediate ’non-occluding’ loading (i.e. a trials were not actually randomised as described in the original ar-
provisional restoration is placed on the implants but not in contact ticles. In addition, we have to say that some of the RCTs currently
with the opposite dentition, also called ’immediate provisionali- included in the present review may not be actually randomised.
sation’), as opposed to ’occlusal’ loading (the restoration is in full How to explain this recent explosion of ’fake’ RCTs? Authors now
occlusal contact with the opposite dentition), could be consid- are starting to be aware that the most reliable study design to eval-
ered as a real immediate loading procedure. From a patient’s point uate effectiveness of therapy interventions is the RCT, but instead
of view, this difference may not be very significant since patients of conducting truly randomised controlled trials, in some cases,
do prefer to have their new teeth as soon as possible (Schropp a simple controlled trial (sometimes even a retrospective study) is
2004). In addition, non-occluding restorations are actually func- described as randomised, despite the fact that no robust prospec-
tionally used when chewing. There are only two RCTs included in tive randomised allocation of participants to treatment ever took
this review that investigated whether it is better to avoid static or place. These ’RCTs’ may even be published in peer-reviewed jour-
dynamic occlusal contacts at implants immediately restored with nals, which means that the peer-review process has failed, in some
single provisional crowns (Lindeboom 2006; Cannizzaro 2010). cases, to detect this issue. There is still a long way to go in order
Their meta-analyses did not find any statistically significant dif- to determine the best interventions for our patients, and if too
ference comparing immediate direct occlusal loading versus non- ’easy’ or expedient shortcuts are taken in order to have articles
occlusal loading, because the combined sample size was too small more easily published or cited, there is a serious risk of providing
to reach definitive conclusions. Substantial implant failure rates misleading information to clinicians and patients, which is exactly
(10% in Lindeboom 2006 and 12.5% in Cannizzaro 2010) were the opposite of what we need.
reported In both trials, however, it is difficult to find a reliable Sometimes the evaluation of the included trials was complex and
explanation for this observation. may be not completely reliable due to the insufficient information
In this review update we added the objective to determine whether presented in the articles. For instance, there are two large multi-
loading implants progressively, when compared to directly, either centre sponsored trials which could only be included thanks to the
immediately, early or conventionally could provide additional ben- kindness of the main authors who provided us with a lot of ad-
eficial effects. We were unable to include any trial evaluating this ditional relevant information which was not included in the trial
technique. The only trial that was identified compared progres- reports (Donati 2008; Zöllner 2008). While it is recognised that
sive versus direct loading after a healing period of 5 months and running large multicentre clinical trials is not an easy task, more
included only five participants (Appleton 2005). It was excluded efforts should be made at protocol level to decrease the risk of bias,
also because it was judged not to be randomised. However, from for instance by randomising participants after implant placement,
the general results of the current review it is highly unlikely that to have good allocation concealment, to select centres able to con-
progressive loading could provide any clinical benefit; on the conduct clinical research, to clearly report drop-outs and exclusions
trary it would make loading procedures more time-consuming and and their reasons, and moreover to report results according to in-
expensive. ternational standards (www.consort-statement.org). In particular,
The generalisation from the results of the included trials in this the power of one trial was decreased by having two groups test-
review to ordinary clinical practice should be made with extreme ing different techniques for installing implants to be immediately
caution. In the majority of the included trials, the inclusion cri- loaded, and by having 10 participants treated according to a split-
teria were strict and only patients known to be ideal candidates mouth design, despite the study being designed with parallel arms
for implant treatment were recruited. In general, operators were (Donati 2008). There was no report of drop-outs for the other
highly experienced, and it is important to observe that in those trial (Zöllner 2008), meaning that it was unknown how many par-
trials with less experienced operators, prosthetic failure rates were ticipants completed the trial after 1 year, and it was also unclear
higher, ranging from 25% to 42% (depending on the success cri- how many prostheses were delivered. Interestingly, it was acknowl-
teria adopted) (Tawse-Smith 2002), and 44% (Ottoni 2005). On edged that the lack of allocation concealment possibly resulted in
the other hand, it has been shown that in selected patients it is participants being treated differently (implants in the immediate
possible to load dental implants immediately with excellent suc- loaded group were placed deeper probably in the attempt to in-
cess rates. crease insertion torques). While the authors attributed no clinical
significance to this observation, we have noted the high risk of
attrition bias in our assessment of this trial (Zöllner 2008).
Quality of the evidence
Potential biases in the review process AUTHORS’ CONCLUSIONS
We conducted a sensitive search of electronic databases and made
extensive efforts to obtain information about both published and
Implications for practice
unpublished trials from researchers and manufacturers of im- Overall there was no convincing evidence of a clinically important
plants. However, we have had to exclude some potentially relevant difference in either implant failure, prosthesis failure, or bone loss
trials because we could not be sure that allocation was randomised associated with different loading times of implants. A high degree
and we were unable to obtain this information from the authors. of primary implant stability (high value of insertion torque) seems
We also suspect that there is some publication bias, underestimat- to be one of the prerequisites for a successful procedure.
ing failures of immediately loaded implants as suggested by a se-
ries of published abstracts (Polson 2000), and the information of Implications for research
a trial aborted in the UK due to excessive implant failures. Un-
More well-designed randomised controlled trials (RCTs) are
fortunately, despite our request, the information was not made
needed to understand how reliable the protocols for immediate
available to us.
and early loading are. Such trials should be correctly designed and
reported according to the Consolidated Standards of Reporting
Trials (CONSORT) guidelines (www.consort-statement.org). It
is suggested that priority should be given to trials assessing the ef-
Agreements and disagreements with other fectiveness of immediately versus early implant loading to improve
studies or reviews patient satisfaction and decrease treatment time.
One of the problems associated with evaluating the outcomes fol-

lowing implant placement and loading is the lack of information
on long-term outcomes. There are many variables which are likely
ACKNOWLEDGEMENTS
to affect the success of implants, including but not limited to bone
quality and quantity, clinician skill and experience, diameter and We wish to thank Anne Littlewood and Joanne Leese (Cochrane
length of implant and nature and time of loading. Many of these Oral Health Group) for their assistance with literature searching
factors interact. and obtaining copies of the studies respectively; Luisa Fernan-
Our review has included all of the randomised trials available to dez Mauleffinch and Philip Riley (Cochrane Oral Health Group)
date, but the low failure rate of implants in all of these trials means for their help with the preparation of this review; Peter Thom-
that statistically it is not possible to determine whether there is any sen and Mark Willings, Hubert Achille, and Paul Coulthard for
important difference between different loading times. Other pub- contributing as co-authors to previous versions of this review;
lished reviews, less rigorous than Cochrane reviews, have reached and Gioacchino Cannizzaro, Matteo Chiapasco, Mauro Donati,
similar conclusions (Alsabeeha 2010; Romanos 2010; Chung Norbert Enkling, Kerstin Fischer, Baris Güncü, Michael Hotze,
2011). In these non-Cochrane reviews, clinician judgement based Jerome Lindeboom, Silvio Meloni, Mauro Merli, Judith Maria
on adequate alveolar bone levels and primary implant stability Pinheiro Ottoni, Alan Payne, George Romanos, Eugenio Romeo,
(Javed 2010), and patient preference are factors in the choice of Andrew Tawse-Smith, Ilser Turkyilmaz and Axel Zöllner for pro-
loading time. Where clinical judgement is that immediate loading viding us with information on their trials. We would also like to
is appropriate, and patient desire to shorten the treatment period thank the following referees: Matteo Chiapasco, Kerstin Fischer,
and avoid an extended period of edentulism is expressed, immedi- Anne-Marie Glenny, Lee Hooper, Jerome Lindeboom, David R
ate loading of dental implants is an acceptable alternative to con- Moles, Ian Needleman, Michele Nieri, Alan Payne, and Andrew
ventional protocols. Tawse-Smith.
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stage restoration of small-diameter implants for a single (AADR Abstracts):211 (Abstract No 1405).
missing maxillary lateral incisor: a 3-year randomized Polson AM, Sharkey D, Minsk L, Lee I, Polson AP, Salama
clinical trial. Journal of Periodontology 2009;80(9):1393–8. H, et al.Two year alveolar bone levels of dental implants
Degidi 2010 {published data only (unpublished sought but not used)} after immediate loading. Journal of Dental Research 2000;79
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Degidi M, Nardi D, Piattelli A. A comparison between (IADR Abstracts):337 (Abstract No 1550).
immediate loading and immediate restoration in cases Polson AM, Sharkey D, Polson AP, Salama H, Minsk L,
of partial posterior mandibular edentulism: a 3-year Rose L, et al.Four year clinical status of dental implants
randomized clinical trial. Clinical Oral implants Research after immediate loading. Journal of Dental Research 2002;81
2010;21(7):682–7. (Spec Issue A):A-101 (Abstract No 0616).
Göthberg 2007 {unpublished data only}
∗
Göthberg C, Slotte C, Bergendal T, Thomsen P, Suska Roccuzzo 2001 {published data only}
F, Zoric N, et al.Tissue reactions around implants in Roccuzzo M, Aglietta M, Bunino M, Bonino L. Early
fixed partial dentures and evaluation of healing times. A loading of sandblasted and acid-etched implants: a
prospective, randomized, controlled study. Ongoing trial. randomized-controlled double-blind split-mouth study.
Five-year results. Clinical Oral Implants Research 2008;19
Jokstad 2011 {published data only}
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Roccuzzo M, Bunino M, Prioglio F, Bianchi SD. Early
early loading protocols in full arch reconstructions in the
loading of sandblasted and acid-etched (SLA) implants: a
edentulous maxilla using the Cresco prosthetic system:
prospective split-mouth comparative study. Clinical Oral
a three-arm parallel group randomized-controlled trial.
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Clinical Oral Implants Research 2011;22(5):455–63.
Kim 2011 {published data only} Romanos 2006 {published and unpublished data}
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Kim YK, Kim SG, Park JY, Yi YJ, Bae JH. Comparison Romanos GE. Immediate loading in the posterior mandible.
of clinical outcomes of sinus bone graft with simultaneous A clinical study. Clinical Oral Implants Research 2002;13
implant placement: 4-month and 6-month final prosthetic (4):xxi (Abstract No 52).
loading. Oral Surgery, Oral Medicine, Oral Pathotology, Oral ∗
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Radiology, and Endodontics 2011;111(2):164–9. functional loading of implants in the posterior mandible:
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Mackie A, Lyons K, Thomson WM, Payne AG. Mandibular The International Journal of Periodontics and Restorative
two-implant overdentures: prosthodontic maintenance Dentistry in press.
Salvi 2004 {published data only} Alsabeeha 2010
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Salvi GE, Gallini G, Lang NP. Early loading (2 or 6 weeks) Alsabeeha N, Atieh M, Payne AG. Loading protocols for
of sandblasted and acid-etched (SLA) ITI(R) implants in mandibular implant overdentures: a systematic review with
the posterior mandible. Clinical Oral Implants Research meta-analysis. Clinical Implant Dentistry and Related
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Implants with Immediate Loading vs. Conventional Trachtenberg DI. The influence of functional use of
Loading: 1-Year Randomized Clinical Trial. Clinical endosseous dental implants on the tissue-implant interface.
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Drago C, Pera P. Immediate versus delayed loading of dental Brånemark PI, Engstrand P, Öhrnell LO, Gröndahl K,
implants in edentulous maxillae: a 36-month prospective Nilsson P, Hagberg K, et al.Brånemark Novum: a new
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vs. early loading in partially edentulous patients. Practical Cannizzaro G, Leone M, Ferri V, Viola P, Federico G,
Procedures and Aesthetic Dentistry 2003;15(10):787–94. Esposito M. Immediate loading of single implants inserted
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Research 2006;17(5):501–5. combining parallel and cross-over clinical trials. II: Binary
Turkyilmaz I, Tözüm TF, Tumer C, Ozbek EN. A 2-year outcomes. Statistics in Medicine 2002;21(15):2145–59.
clinical report of patients treated with two loading protocols Del Fabbro 2006
for mandibular overdentures: early versus conventional Del Fabbro M, Testori T, Francetti L, Taschieri S, Weinstein
loading. Journal of Periodontology 2006;77(12):1998–2004. R. Systematic review of survival rates for immediately loaded
Van de Velde 2010 {published data only} dental implants. The International Journal of Periodontics
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teeth: different types of dental implants. Cochrane Database Sennerby 2008
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14651858.CD003815.pub3] early loading of dental implants. A literature review of
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Ioannidou 2005
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CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by year of study]
Chiapasco 2001
Methods Trial design: randomised, parallel group trial

Location: Milan, Italy
Number of centres: one (University of Milan Dental clinic)
Recruitment period: 1996 to 1997
Funding source: Z systems partially supported this trial
Participants Inclusion criteria: patients that have been edentulous in the mandible for at least 3
months. Mandibles allowing the placement of 4 implants at least 13 mm long
Exclusion criteria: patients with type IV bone quality (very soft bone) according to
the Lekholm and Zarb classification detected at implant insertion (none), previously
irradiated jaws, severe bruxism, smoking habits (more than 10 cigarettes a day) and any
systemic diseases likely to compromise implant surgery
Age at baseline: mean age 58.4 years, (44 to 73)
Gender: M5/F15
Number randomised: 20
Number evaluated: 20
Interventions Comparison: Immediate versus conventional loading

Gp A (n = 10) Immediate loading: 4 implants immediately loaded (within 3 days of
insertion)
Gp B (n = 10) Conventional loading: 4 implants supporting a bar and an overdenture
conventionally loaded 4 to 8 months later
Brånemark (Nobel Biocare AB, Göteborg, Sweden) submerged turned titanium MKII
screws were used
Duration of follow-up: 2 years
Outcomes Prosthesis/implant failures, Periotest, marginal bone level changes on panoramic radio-
graphs, plaque accumulation, modified bleeding index, probing pocket depth 1-year
data used
Notes Sample size calculation: not reported
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection High risk Reported in the article: “Patients were ran-
bias) domly assigned to 1 of 2 treatment groups:
immediate loading (test group, n=10) or
delayed loading (control group, n=10)”
Author replied that “a drawing lot was used,
however since there was a numeric imbal-
ance between the 2 groups, once a group
was completed the remaining patients were
Chiapasco 2001 (Continued)
allocated to the other group”
Allocation concealment (selection bias) High risk Nothing reported in the article
Reviewer comments: with the methods of
randomisation used by the author it is not
possible to ensure a proper allocation con-
cealment
Blinding of outcome assessment (detection Low risk Nothing reported in the article
bias) Author replied that “measurements were
All outcomes made by a blinded post-graduate training
specialist”
Incomplete outcome data (attrition bias) Low risk All data presented
All outcomes
Selective reporting (reporting bias) Low risk All outcomes appear to be presented
Other bias Low risk None detected
Payne 2002

Location: Dunedin, New Zealand
Number of centres: one (University of Otago dental clinic, Dunedin, New Zealand)
Recruitment period: not stated
Funding source: study was supported by ITI Research Foundation (Research Grant #
203/2000 RCL), Institut Straumann AG (Waldenburg, Switzerland, Ivovclar Vivadent
(Auckland New Zealand), Radiographic Supplies (Christchurch New Zealand) & Col-
gate Oral Care, New Zealand
Participants Inclusion criteria: elderly patients with edentulous mandibles having 13 to 15 mm of

residual anterior bone height
bone-grafted or irradiated jaws, history of bruxism, any evidence of current or previous
smoking and any systemic diseases likely to compromise implant surgery
Age at baseline: range 55-80 years
Gender: M12/F12
Number evaluated: 22 (2 withdrawals at 1 year from the conventionally loaded group
for emigration)
Interventions Comparison: Early versus conventional loading

Gp A (n = 12) Early loading: 2 unsplinted implants with ball attachments early loaded
at 6 weeks
Gp B (n = 12) Conventional loading: 2 unsplinted implants with ball attachments
supporting an overdenture conventionally loaded at 12 weeks
ITI (Institut Straumann AG, Waldenburg, Switzerland) SLA non-submerged solid tita-
Payne 2002 (Continued)
nium screws were used

Outcomes Prosthesis/implant failures, Periotest, Osstell, marginal bone level changes on standard-
ised intraoral radiographs, plaque accumulation, modified sulcus bleeding index, prob-
ing pocket depth, width of the keratinised mucosa
1-year data used
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “Using a table of
bias) random numbers participants were ran-
domly allocated, with maximum allocation
concealment (Esposito et al. 2001), to two
treatment groups, each with 12 partici-
pants”
Allocation concealment (selection bias) Unclear risk Reported in the article: “Using a table of
random numbers participants were ran-
domly allocated, with maximum allocation
concealment (Esposito et al. 2001), to two
treatment groups, each with 12 partici-
pants”
No clarifying reply to letter
All outcomes made by calibrated blinded outcome asses-
sors”
All outcomes
Romeo 2002

Number of centres: one (dental clinic of the University of Milan, Italy)
Recruitment period: 1997-1999
Funding source: not stated
Participants Inclusion criteria: patients that have been edentulous in the mandible for at least 3
months. Mandibles allowing the placement of 4 implants of at least 10 mm length
irradiated jaws, severe bruxism, smoking habits (more than 20 cigarettes a day) and any
Age at baseline: mean 63.2 (range 42-73 years)
Gender: M8/F12
Number evaluated: 20 (no withdrawals at 1 year)

Gp A (n = 10) Immediate loading: 4 implants immediately loaded (within 2 days from
insertion)
conventionally loaded (3 to 4 months)
ITI (Institut Straumann AG, Waldenburg, Switzerland) SLA non-submerged solid tita-
nium screws were used
Outcomes
Notes Sample size calculation: not reported but trial authors note that small sample size was a
limitation of this study
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “Patients were ran-
bias) domly attributed to the test (immediate
loading) or control (delayed loading), each
one made up of 10 patients”
Author replied that “a drawing lot was
used”
randomisation used by the author it is
unlikely to have 2 numerically balanced
groups
Author replied that “the operator knew pa-
tient allocation the day of intervention”
Romeo 2002 (Continued)

randomisation used by the author it is not
possible to ensure a proper allocation con-
cealment
All outcomes made by a calibrated blinded outcome as-
sessor”
All outcomes
Tawse-Smith 2002

Number of centres: one (university dental clinic of the University of Otago, Dunedin,
New Zealand)
Participants Inclusion criteria: patients with edentulous mandibles having 13 to 15 mm of residual

anterior bone height
bone-grafted or irradiated jaws, history of bruxism, any evidence of current or previous
smoking and any systemic diseases likely to compromise implant surgery
Age at baseline: range 55-80 years
Gender: not reported
Number randomised: 48 (4 groups, 2 groups evaluated each implant system)

Gp A (n = 12) Early loading: 2 unsplinted implants with ball attachments loaded at 6
weeks
Gp B (n = 12) Conventional loading: 2 unsplinted implants with ball attachments
supporting an overdenture loaded at 12 weeks
Patients in groups A&B used Steri-Oss® (Steri-Oss, Yorba Linda, California, USA) non-
submerged acid-etched titanium screws HL series, 3.8 mm in diameter
Gp C (n = 12) Early loading: 2 unsplinted implants with ball attachments loaded at 6
weeks
Gp D (n = 12) Conventional loading: 2 unsplinted implants with ball attachments
supporting an overdenture loaded at 12 weeks
Patients in groups C&D used Southern (Southern Implants Ltd, Irene, South Africa)
Tawse-Smith 2002 (Continued)
non-submerged sand-blasted acid-etched titanium screws

Outcomes Prosthesis/implant failures, Periotest, marginal bone level changes on standardised intrao-
ral radiographs, plaque accumulation, modified sulcus bleeding index, probing pocket
depth, width of the keratinised mucosa
1-year data used

Most of the failed implants were placed by a surgeon who placed only Steri-Oss implants
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “Participants were
bias) randomly allocated to either the Sterioss
system or the Southern Implant system on
a one-by-one basis. For each system, par-
ticipants were further allocated with max-
imum concealment into 2 subgroups (12
participants), in whom mandibular im-
plant overdentures and their respective ma-
trices were inserted following the standard
12-week healing period, or the test group
(12 participants), in whom a 6-week heal-
ing period was followed by loading in a sim-
ilar manner”
Author replied that “Table of random num-
bers were used to randomly allocated par-
ticipants”
Allocation concealment (selection bias) Unclear risk Reported in the article: “participants were
randomly allocated to either the Sterioss
system or the Southern Implant system on
a one-by-one basis. For each system, par-
ticipants were further allocated with max-
imum concealment into 2 subgroups (12
participants), in whom mandibular im-
plant overdentures and their respective ma-
trices were inserted following the standard
12-week healing period, or the test group
(12 participants), in whom a 6-week heal-
ing period was followed by loading in a sim-
ilar manner”
No clarifying reply to letter
Tawse-Smith 2002 (Continued)
All outcomes made by calibrated blinded outcome asses-
sors”
All outcomes
Other bias High risk It appears that implants were not placed in
a balanced way by different operators but
that one inexperienced operator, placing
preferentially one type of implants, might
have biased the success rates
Cannizzaro 2003

Location: Pavia, Italy (private practice)
Number of centres: one
Participants Inclusion criteria: partially edentulous patients (both mandibles and maxillae) allowing
the placement of at least 13 mm long implants with a diameter of 3.7 mm. For implants
to be immediately loaded, a primary implant stability of 45 Ncm had to be achieved at
insertion
Exclusion criteria: patients with type IV bone quality (very soft bone) according to the
Lekholm and Zarb classification detected at implant insertion, less than 3 years irradiated
jaws, severe bruxism, smoking habits (more than 10 cigarettes per day), substance abusers,
pregnancy, uncontrolled diabetes, and any systemic diseases likely to compromise implant
surgery
Age at baseline: 18 to 72 years, Group 1 mean 37.1 years, Group 2 mean 38.6 years
Gender: 14M/14F
Number evaluated: 28 (at 1 year)

Gp A (n = 14) Immediate loading: One or more adjacent implants restored first with
acrylic restorations in full occlusion and then with cemented metal-ceramic prostheses,
loaded the same day
Gp B (n = 14) Conventional loading: One or more adjacent implants restored first with
acrylic restorations in full occlusion and then with cemented metal-ceramic prostheses,
loaded after 3.4 months (mandibles) or 4.5 months (maxillae)
Zimmer (Zimmer, Carlsbad, Ca, USA) Spline Twist MTX titanium screws were used
Cannizzaro 2003 (Continued)
Outcomes Prosthesis/implant failures, Periotest, Osstell, marginal bone level changes on standard-
ised intraoral radiographs, plaque accumulation, probing pocket depth
1-year data used
Risk of bias
Random sequence generation (selection Low risk Nothing reported in the article
bias) Author replied that “random number ta-
bles were used”
Allocation concealment (selection bias) Low risk Nothing reported in the article
Author replied that “just before the in-
tervention the operator was informed of
which therapy to deliver”
Blinding of outcome assessment (detection Low risk Reported in the article: “A member of the
bias) treatment team recorded the following pa-
All outcomes rameters 1 month after prosthesis seating
(baseline) and every 6 months until con-
clusion of the study in June 2001”
Author replied that: “3 blinded outcome
assessors were used: Dr Fontana S. for ra-
diographic evaluation, Dr Ignaccolo S. for
Periotest evaluation, and Dr Leone M. for
periodontal indexes evaluation”
All outcomes
Fischer 2004

Location: Falun, Sweden
Number of centres: one (County Hospital, Falun, Sweden)
Recruitment period: April 1999 to September 2000
Funding source: Institut Straumann supported this study
Participants Inclusion criteria: patients with edentulous maxillae allowing the placement of 5 to 6
implants
Exclusion criteria: smoking habits (more than 10 cigarettes a day), use of augmentation
Fischer 2004 (Continued)
procedures at the implanted sites, and any systemic diseases likely to compromise implant
surgery
Age at baseline: mean 64 years
Gender: immediate M6/F10; conventional M2/F6

Gp A (n = 16) Immediate loading: 5-6 implants per patient restored directly with defini-
tive full-arch titanium-resin prosthesis with cantilevers (7-11 mm long) at 9-18 days. ITI
SLA (Institut Straumann AG, Waldenburg, Switzerland) non-submerged solid titanium
screw type implants were used
Gp B (n = 8) Conventional loading 5-6 implants per patient restored directly with
definitive full-arch titanium-resin prosthesis with cantilevers (7-11 mm long) after 2.5-
5.1 months. Submerged ITI EstheticPlus implants in the conventionally loaded group
(except for one patient)
Outcomes Prosthesis/implant failures, marginal bone level changes on standardised intraoral radio-
graphs, plaque index, sulcus bleeding index, width of the keratinised mucosa 1-year data
used
Risk of bias
Random sequence generation (selection Unclear risk Reported in the article: “Patients were ran-
bias) domized and consecutively enrolled in the
study according to predefined inclusion
and exclusion criteria”
Reviewer comments: patients were ran-
domised with a 2 to 1 ratio, i.e. 16 in the
early loading group and 8 in the conven-
tional loading group. There are no advan-
tages by doing this and authors had further
reduced their already small sample size
Author replied that “When patient had
signed the informed consent form a
sealed treatment code envelope was opened
through which patient was allocated to ei-
ther the test or the control group”
Blinding of outcome assessment (detection High risk Nothing reported in the article
bias) Author replied that “outcome assessors
All outcomes were not blinded”
Fischer 2004 (Continued)
All outcomes
Lindeboom 2006

Location: Amsterdam, the Netherlands
Number of centres: one (Oral and Maxillofacial Surgery Department of the Academic
Medical Center of the University of Amsterdam, The Netherlands)
Participants Inclusion criteria: healthy (ASA I) patients missing single teeth in anterior maxilla (pre-
molar to premolar), allowing the placement with no fenestration of a at least 8 mm long
implant with a diameter of 3.4 mm placed with an insertion torque of at least 30 Ncm
Exclusion criteria: patients with smoking habits, parafunctional habits, drug or alcohol
abuse, lack of a stable occlusion, lack of adequate proper oral hygiene and compliance
and any systemic diseases likely to compromise implant surgery
Age at baseline: 42.3 years ± 13.1 (range 19-78)
Gender: M17/F31
Interventions Comparison: Occlusal versus non-occlusal immediate loading

Gp A (n = 24) Immediate loading occlusal: Single implants immediately restored within
1 day with acrylic single crowns in occlusion
Gp B (n = 24) Immediate loading non occlusal: Single implants immediately restored
within 1 day with acrylic single crowns not in occlusion
Permanent ceramic crowns were provided to both groups after 6 months
BioComp® (BioComp Industries BV, Vught, The Netherlands) tapered TPS screws
were used
Duration of follow-up :1 year
Outcomes Prosthesis/implant failures, Osstell, marginal bone level changes on intraoral radiographs,
Papilla Index by Jemt 1997 and midbuccal gingival levels
1-year data used
Notes Sample size calculation:Not reported, but authors note that small sample size in this
study was the reason that “no definite conclusions could be drawn”
Risk of bias
Lindeboom 2006 (Continued)
Random sequence generation (selection Low risk Reported in the article: “Patients were allo-
bias) cated to either immediate loading or imme-
diate provisionalization groups by means of
computer generated randomization”
Author replied that “The treatment allo-
cation (after computer randomization) was
presented at placement of the provisional.
so that the patient was treated with an im-
plant, and after that was moved to the next
room with an impression post for provi-
sional fabrication. At that point a cal was
received from the Clinical Epidemiology
Unit (performing randomization)”
All outcomes were blinded”
All outcomes
Other bias Unclear risk The distribution of small and larger diam-
eter implants is different in the two groups.
There are more large diameter implants in
the immediate loading group
Hall 2006

Number of centres: one (University of Otago Dental Clinic, Dunedin, New Zealand)
Funding source: Southern Implants (Irene, south Africa) and Radiographic Supplies
(Christchurch, New Zealand, supported this trial
Participants Inclusion criteria: patients missing a single tooth in anterior maxilla (premolar to premo-
lar) with adjacent teeth present, allowing the placement of at least 10 mm long implant
with a diameter of 2.5 mm
Exclusion criteria: patients with type IV bone quality (very soft bone) according to the
Lekholm and Zarb classification detected on radiographs, severe bruxism, smoking habits
(more than 20 cigarettes per day), previous history of failed implants, and sites requiring
augmentation surgery
Age at baseline: mean 43.25 range 23 to 71 years
Gender: not stated
Hall 2006 (Continued)
Number evaluated: 25 (3 withdrawals at 1 year, 1 for the immediately loaded group and
2 from the conventionally loaded group for emigration)

Gp A (n = 14) Immediate loading non-occlusal - single implants restored first with acrylic
restorations (not in occlusion), then by screw-connected metal-ceramic crowns
Gp B (n = 14) Conventional loading Single implants had screw-retained provisional
crowns placed after 6 months
Definitive screw-retained metal ceramic crowns were placed into occlusion for all par-
ticipants 8 weeks after provisionalisation
Southern (Southern Implants Ltd, Irene, South Africa) tapered sand-blasted acid-etched
titanium screws were used
Duration of follow-up: 1 year
Outcomes Prosthesis/implant failures, Periotest, marginal bone level changes on standardised in-
traoral radiographs, plaque accumulation, sulcus bleeding index, unspecified peri-im-
plant soft tissues and prosthetic outcomes measures including the Papilla Index by Jemt
1997
1-year data used
Notes
Risk of bias
Random sequence generation (selection Unclear risk Reported in the article: “Participants.....
bias) were randomly allocated using sealed en-
velopes to the conventional loading....”
The reply of the author failed to clarified
the issue
Allocation concealment (selection bias) Unclear risk Nothing reported in the article
The reply of the author failed to clarified
the issue
All outcomes were blinded”
Incomplete outcome data (attrition bias) High risk All data presented. 3 withdrawals at 1
All outcomes year, 1 for the immediately loaded group
(included in outcome based on email re-
sponses) and 2 from the conventionally
loaded group for emigration
Hall 2006 (Continued)
Oh 2006

Location: Ann Arbor, USA
Number of centres: one (University of Michigan dental clinic, Ann Arbor, USA)
Participants Inclusion criteria: 2 single teeth missing in the anterior maxilla (premolar to premolar)
allowing the placement of at least 10 mm long implants with a diameter of 3.8 mm
Exclusion criteria: none specified
Age at baseline: immediate 45.2 ±13.2; delayed 47.3 ±17.8
Gender: immediate M8/F4; delayed M2/F10

Gp A (n = 12) Immediate loading: Single implants placed with a flapless technique and
restored first with acrylic restorations and then 10-14 days later replaced with cemented
metal-ceramic crowns
Gp B (n = 12) Conventional loading: Single implants placed with a flapless technique
and restored with cemented metal-ceramic crowns after 4 months
Zimmer (Zimmer, Carlsbad, Ca, USA) non-submerged implants were used
Duration of follow-up: 6 months
Outcomes Prosthesis/implant failures, probing pocket depths, plaque index, sulcus bleeding index,
marginal level of soft tissues, soft tissue thickness, width of the keratinised mucosa,
Papilla Index by Jemt 1997
6-month data used
Notes Sample size calculation: not reported but small sample size noted by the authors as a
limitation of this study
Risk of bias
Random sequence generation (selection Unclear risk Reported in the article: “The subjects were
bias) randomly assigned to one of two groups:
IL (12 patients) or DL (12 patients)”
No reply to letter
No reply to letter
Oh 2006 (Continued)
Blinding of outcome assessment (detection Low risk Reported in the article: “All of the clinical
bias) measurements were performed by one cal-
All outcomes ibrated blind examiner at baseline (at the
time of implant loading) and at 2, 4, and 6
months after implant loading”
All outcomes
Assad 2007
Methods Trial design: parallel group RCT

Location: Prosthodontic Department, Al Zahraa University Hospital, Egypt
Participants Inclusion criteria: patients with edentulous mandibles allowing the placement of 4 12
mm long and 3.7 mm wide implants
Exclusion criteria: any systemic or local disease that might contraindicate implant place-
ment
Age at baseline: 48 to 63 years
Gender: all male
Number randomised: 10 patients, 4 implants per patient
Number evaluated: 10 patients, 4 implants per patient

Gp A (n = 5) Immediate loading: 4 implants immediately loaded (within 4 days of
insertion)
conventionally loaded (4 months after placement)
Screw-Vent (Paragon, Core-Vent Corporation, Las Vegas, NV, USA) submerged titanium
screws were used on all patients. “All patients received maxillary conventional complete
dentures and mandibular bar retained dentures”
Outcomes Prosthesis/implant failures, implant percussion, marginal bone level changes on stan-
dardised intraoral radiographs, gingival index, plaque index, probing pocket depth re-
ported at baseline, 6,12,18 & 24 months
Risk of bias
Assad 2007 (Continued)
Random sequence generation (selection Unclear risk Reported in the article: “Patients partic-
bias) ipating in this study were randomly di-
vided into 2 equal groups, each containing
5 edentulous patients”
No reply to letter
No reply to letter
Blinding of outcome assessment (detection Unclear risk Nothing reported in the article
bias) No reply to letter
All outcomes
All outcomes
Turkyilmaz 2007
Methods Trial Design: randomised, parallel group trial

Location: Ankara, Turkey
Number of centres: one (Faculty of Dentistry, Hecettepe University, Ankara, Turkey)
Participants Inclusion criteria: patients with edentulous mandibles allowing the placement of 2 x 15
mm long implants
Exclusion criteria: patients with previously bone-grafted or irradiated jaws, and any
Age at baseline: immediate 62.4 ± 8.6 years); delayed 62.3 ± 7.1 years
Gender: M8/F12

Gp A (n = 5) Immediate loading: 2 unsplinted implants with ball attachments supporting
an overdenture immediately loaded at 1 week
Gp B (n = 5) Conventional loading: 2 unsplinted implants with ball attachments con-
ventionally loaded at 3 months
Brånemark® (Nobel Biocare AB, Göteborg, Sweden) non-submerged TiUnite Mark III
type titanium screws were used
Turkyilmaz 2007 (Continued)
Outcomes Prosthesis/implant failures, Osstell, marginal bone level changes on standardised intraoral
radiographs, complications
1-year data used
Risk of bias
Random sequence generation (selection Unclear risk Reported in the article: “The patients ran-
bias) domly allocated into two groups pre-oper-
atively”
Author replied that “We actually toss a coin
(heads or tails) and created groups ran-
domly”
Reviewer comment: “it is possible but
highly unlikely to create 2 groups with
identical number of patients by tossing a
coin”
Author replied that “The surgeon did not
know the groups before implant place-
ment”
Blinding of outcome assessment (detection High risk Nothing reported in the article
bias) Author replied that “the outcome assessor
All outcomes was not blinded”
All outcomes
Testori 2007
Methods Trial design: multicenter, randomised, parallel group trial

Location: Italy
Number of centres: five (private practices in Italy)
Recruitment period: prior to May 2005
the placement of at least 8.5 mm long implants with a diameter of 4 mm. For implants to
be immediately loaded, a primary implant stability of 20 or 30 Ncm had to be achieved at
Testori 2007 (Continued)
insertion for implants which were going to be splinted and single implants, respectively
Exclusion criteria: patients irradiated in the head and neck area, severe bruxism, substance
abusers, pregnancy, uncontrolled diabetes, and any systemic diseases likely to compromise
implant surgery, lack of opposing occluding dentition, need for augmentation procedures
Age at baseline: immediate 51.6 (range 27-74 years); delayed 51.3 (range 34-73 years)
Interventions Comparison: Immediate versus early loading

Gp A (n = 25) Immediate loading: 1 or more implants restored first with acrylic restora-
tions (not in occlusion) and then with cemented metal-ceramic crowns, within 48 hours
Gp B (n = 27) Early loading: 1 or more implants restored first with acrylic restorations
(not in occlusion) and then with cemented metal-ceramic crowns, after 2 months
3i (3i Biomet , Palm Beach, FL, USA) Osseotite FNT tapered titanium screws were used;
1 of the centres used some other similar prototypes in both groups
Duration of follow-up :4 years
Outcomes Prosthesis/implant failures, marginal bone level changes on intraoral radiographs, buccal
peri-implant marginal soft tissue levels
1-year data used
Notes Sample size calculation: reported that 26 patients per group would be required
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “A manually gener-
bias) ated restricted randomization list was used
to create two groups with equal number of
patients”
Allocation concealment (selection bias) Low risk Reported in the article: “Only one of the
investigators, not involved in the selec-
tion and treatment of the patients, was
aware of the randomization sequence and
could have access to the randomization list
stored in a pass-word protected portable
computer. The randomized codes were en-
closed in sequentially numbered, identi-
cal, opaque, sealed envelopes. Envelopes
were opened sequentially only after the im-
plants to be included in the trial were in-
serted, therefore treatment allocation was
concealed to the investigator in charge of
enrolling and treating the patients included
in the trial”
Testori 2007 (Continued)
Blinding of outcome assessment (detection Unclear risk Reported in the article: “Prosthesis and im-
bias) plant failures were assessed by the treating
All outcomes clinicians who were therefore not blinded.
...Radiographic bone level and height the
clinical crown changes and outcome mea-
sures were assessed by 2 independent,
blinded, calibrated outcome assessors. One
measured all radiographs and the other the
clinical crown height on plaster models. All
radiographs were coded so that the out-
come assessor was blinded to which group
the implants belonged to, nor was the asses-
sor informed of the aims of the study. Since
the assessor did not know which crown
(s) to measure on the plaster models, the
implant-supported crown(s) were marked
with a black spot. The outcome assessors
did not know the dates that either the ra-
diographs or the plaster models were cre-
ated”
All outcomes
Selective reporting (reporting bias) Low risk All outcomes were presented
Other bias Unclear risk There was a difference between the groups
in the number of implants placed in
the maxillae (14/52 in immediate loading
group vs 31/52 in early loading group)
Zöllner 2008
Methods Trial Design: multicentre randomised, parallel group trial

Location: 10 countries
Number of centres: 19
Funding source: sponsor
Participants Inclusion criteria: patients missing teeth in premolar and molar areas allowing the place-
ment of 8 mm long and 4.1 mm large single implant
Exclusion criteria: post-extractive implants (at least 4 months healing was required),
lack of primary implant stability, opposing fixed dentition, smoking > 10 cigarettes per
day, severe bruxism/clenching, and any systemic diseases likely to compromise implant
surgery
Age at baseline: 46.3 ± 12.8 years
Gender: not stated
Zöllner 2008 (Continued)
Number evaluated: unclear. Possibly 5 withdrawals from the immediately loaded group
(3 subjects withdrew consent and 2 could not be located) and 1 from the early loaded
group (withdrew consent) at 5 months (it is unclear whether patients were lost prior to
or after implant placement) and unknown number of withdrawals at 1 year

Gp A (n = 138) Immediate loading: temporary acrylic restoration out of occlusal contact,
placed on the day of surgery, with permanent occluding restoration (either single crown
or 2-4 unit fixed prosthesis cemented or screw-retained restorations made of porcelain,
acrylic resin or gold) placed 20-23 weeks after surgery
Gp B (n = 128) Early loading: temporary acrylic restoration out of occlusal contact, placed
28-34 days after surgery, with permanent occluding restoration (either single crown or 2-
4 unit fixed prosthesis cemented or screw-retained restorations made of porcelain, acrylic
resin or gold) placed 20-23 weeks after surgery
ITI® SLA active (Institut Straumann AG, Waldenburg, Switzerland) solid sand-blasted
large-grit acid-etched titanium grade 4 screws, 3 standard plus implants were also used
Duration of follow-up: 1 year (interim analysis)
graphs
1-year data used
Notes Sample size calculation: reported that 35 patients per group would be required to detect
a difference of 0.3 mm in bone loss
Risk of bias
Random sequence generation (selection Low risk Reported in the first article: “This is an
bias) ongoing prospective randomized study in
which patients receive between one and
four implants in the posterior maxilla or
mandible.... Patients were randomized into
immediate or early loading arms”
Reported in the second article: “The ran-
domization list was generated for each cen-
ter by an independent statistician using
block sizes of 10; randomization numbers
were sequential, and each group (immedi-
ate or early) had an equal number in each
block”
Author replied that: “Patients were ran-
domized into two loading arms according
to a master randomization list to receive
a temporary restoration (single crown or
2-4 unit fixed partial denture) out of oc-
clusal contact. A randomization list defined
which patient is treated within the immedi-

ate or early loading arms. The randomiza-
tion list was generated by an independent
statistician for each of the 19 centers using
2 block sizes of 10 for each center, with each
center having its own unique center num-
ber and sequential randomization number,
and an equal number (i.e. 5 each) within
each block randomized to either group im-
mediate or early”
Allocation concealment (selection bias) Low risk Nothing reported in the first article
Reported in the second article: “The
sequential randomization was placed in
sealed envelopes for each center, which
were opened before surgery after obtaining
signed informed consent from the patient”
Author replied that: “The sequential ran-
domization for each center was placed in
a sealed envelope, which the investigator
was allowed to open at least one to 5 days
prior to the planned surgery and only after
signed informed consent from the patient
had been obtained. Patients were consecu-
tively enrolled into the study and had the
sealed treatment code envelope that corre-
sponded to their time of entry, patient 1 re-
ceived envelope 1, the 2nd patient received
envelope 2 and so on for each center. Mas-
ter copies of the randomization lists were
held by the sponsor and the organization
who performed the randomization”
bias) Author replied that: “The analysis of bone
All outcomes level change was performed by an indepen-
dent expert who was blinded to the alloca-
tion of the treatment group. Secondary ob-
jective were to evaluate the effectiveness in
terms of implant survival, implant success
and patient satisfaction at month 5. Sec-
ondary parameters were assessed by each
clinician. They were not blinded in respect
of treatment groups”
Incomplete outcome data (attrition bias) High risk Possibly 5 withdrawals from the immedi-
All outcomes ately loaded group (3 subjects withdrew
consent and 2 could not be located) and
1 from the early loaded group (withdrew
consent) at 5 months (it is unclear whether

patients were lost prior to or after implant
placement) and unknown number of with-
drawals at 1 year
Crespi 2008

Number of centres: one (“Vita Salute” University, San Rafaele Hospital)
Participants Inclusion criteria: patients rehabilitated with single implants in maxillary (premolar to
premolar) fresh extraction sockets with 4 bony walls and at least 4 mm of bone beyond
the root apex and the presence of adjacent teeth
Exclusion criteria: presence of dehiscence or fenestration of the residual bony walls, signs
of acute infection around the alveolar bone at the implant site, bruxism, patients smoking
more than 10 cigarettes a day, uncontrolled diabetes, coagulation disorders, alcohol or
drug abuse
Age at baseline: mean 47.21 years (24-68 years)
Gender: M16/F24

Gp A (n = 20) Immediate loading: 13 mm long single implants loaded immediately (the
same day)
Gp B (n = 20) Conventional loading: 13 mm long single implants loaded conventionally
at 3 months
Outlink (Sweden & Martina, Padova, Italy) titanium solid screws were used
Outcomes Prosthesis/implant failures, marginal bone level changes on periapical radiographs

1-year data used
Risk of bias
Crespi 2008 (Continued)
Random sequence generation (selection Unclear risk Reported in the article: “All patients re-
bias) quired a single-tooth extraction for root
fractures, caries or endodontic reasons, or
periapical disease and were randomly as-
signed to the test or control group”
No reply to letter
No reply to letter
All outcomes
All outcomes
Merli 2008

Location: Rimini, Italy
Number of centres: one (private practice)
Funding source: partial support for this study was provided by Thommen Medical AG,
Wldenburg, Switzerland
the placement of at least 9.5 mm long implants and the bone thickness at implant sites
had to be of at least 5.5 mm. For implants to be immediately loaded, a primary implant
stability of 40 Ncm had to be achieved at implant insertion
Exclusion criteria: patients irradiated in the head and neck area within the previous year,
severe bruxism, substance abusers, pregnancy, uncontrolled diabetes, and any systemic
diseases likely to compromise implant surgery, lack of opposing occluding dentition,
a need for bone-augmentation procedures with exception of Bio-Oss granules in post-
extractive sites, presence of less than 4 mm of keratinised mucosa
Age at baseline: immediate 50.3 (28 to 72 years); early 48.7 (19 to 68 years)
Gender: immediate M10/F20; early M12/F18

Gp A (n = 30 patients, 35 implants) Immediate loading: 1 or more implants placed
with a flapless technique and restored with non-occluding acrylic restorations, within
72 hours
Merli 2008 (Continued)
Gp B (n = 30 patients, 34 implants) Early loading: 1 or more implants placed with a

flapless technique and restored with non-occluding acrylic restorations after 6 weeks
For all patients permanent restoration with occluding cemented metal-ceramic crowns
was performed after 6 months
SPI®Element System (Thommen Medical AG, Waldenburg, Switzerland) sand-blasted
acid-etched screws, and in some of the post-extraction sites SPI®Contact troncoconical
screws were used
Outcomes Prosthesis/implant failures and complications

1-year data used
Notes Sample size calculation: reported that 26 patients per group would be required to show
a difference in proportion of failures from 39% to 4%
Risk of bias
Random sequence generation (selection Low risk Reported in the first article: “A manually
bias) generated restricted randomization list was
used to create two groups with equal num-
bers of patients. Only one of the investi-
gators, not involved in the selection and
treatment of the patients, was aware of the
randomization sequence and had access to
the randomization list stored in a password-
protected portable computer”
Allocation concealment (selection bias) Low risk Reported in the first article: “The ran-
domized codes were enclosed in sequen-
tially numbered, identical, opaque, sealed
envelopes. Envelopes were opened sequen-
tially only after the implants to be included
in the trial were inserted, therefore treat-
ment allocation was concealed to the inves-
tigator in charge of enrolling and treating
the patients included in the trial”
Blinding of outcome assessment (detection Unclear risk Reported in the first article: “These out-
bias) come measures (prosthetic failures, implant
All outcomes failures and complications) were assessed by
an independent assessor (FB), who was not
blinded to the interventions”
Reported in the third article: “Although pa-
tients and the surgeon were aware of the
allocated arm, radiographic outcome asses-
sor (G. Mariotti) was kept blinded to the
allocation. Prosthesis failure, implant fail-
Merli 2008 (Continued)
ure and complications were assessed by an

independent assessor (M. Moscatelli), who
was not blinded to the intervention”
All outcomes
Other bias High risk A substantial rate of protocol deviations

were present, for instance of the 30 patients
allocated to the early loading group, 5 were
conventionally loaded and 2 immediately
loaded
Donati 2008
Methods Trial design: multicenter, randomised, parallel group trial with 3 arms
Location: Italy
Number of centres: eight (private practices in Italy)
Funding source: “This study was supported by grants from Astra Tech Dental”
Participants Inclusion criteria: patients missing a single tooth in area 15-25 and 35-45 allowing the
placement of 8 mm long and 4 mm large single implant
Exclusion criteria: post-extractive implants (at least 3 months healing was required),
insertion torque < 20 Ncm, and any systemic diseases likely to compromise implant
surgery
Age at baseline: M mean age 46.7 (SD18.3); F Mean age 44.2 (SD 12.9)
Gender: M70/F81
Number randomised: 139 (151 patients were randomised (57, 50, 54 tooth sites), how-
ever, 10 of these patients had 2 tooth sites treated according to a split mouth design and
their data were excluded from this systematic review)
Number evaluated: 137 patients (2 withdrawals from conventionally loaded group due
to poor health)

Gp A (n = 42) Immediate loading: Standard preparation procedure for implant placement
and immediate functional loading
Gp B (n = 42) Immediate loading: Modified preparation procedure with osteotomies,
followed by immediate functional loading
Gp C (n = 53) Conventional loading: Single implants restored after 3 months with
occluding screw-retained acrylic crowns, replaced after 6 months by cemented or screw-
retained metal-ceramic crowns
Astra OsseoSpeed® (Astra Tech Dental, Mölndal, Sweden) titanium grade 1 screws were
used
Donati 2008 (Continued)
graphs, plaque accumulation, mucositis, probing pocket depth, changes in papilla height
and width of the keratinised mucosa
1-year data used

10 patients who were treated according to a split-mouth design, and their data were
excluded from this systematic review
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “A randomization
bias) protocol was produced from a computer-
generated list for the distribution of sub-
jects in the three treatment groups”
Author replied failed to clarify the matter
Blinding of outcome assessment (detection Unclear risk Reported in the article: “The radiographs
bias) were analyzed by an experienced radiologist
All outcomes who was blinded with regard to treatment
groups”
Author replied that “the outcome assessor
for the clinical outcomes was not blinded”
Incomplete outcome data (attrition bias) Low risk All data presented after clarification by the
All outcomes author
Schincaglia 2008

Location: Bologna, Italy
Number of centres: one (School of Dentistry, University of Bologna, Italy)
Recruitment period: 2002-2004
Participants Inclusion criteria: patients missing 1 mandibular first or second molar allowing the
placement of a single implant at least 8.5 mm long and 5 mm wide with a minimal
insertion torque of 20 Ncm
Exclusion criteria: severe systemic conditions (ASA III), in need of bone augmentation,
and if the tooth was extracted less than 4 months before
Schincaglia 2008 (Continued)
Age at baseline: immediate 51.87 (range 31-75 years); delayed 49.2 (range 35-68 years)

Gp A (n = 15) Immediate loading: Single implants restored the same day with occluding
screw-retained acrylic crowns, replaced after 3 to 4 months by cemented or screw-retained
metal-ceramic crowns
Gp B (n = 15) Conventional loading: Single implants were initially connected to a healing
abutment and directly restored after 3-4 months with cemented or screw-retained metal-
ceramic crowns
Wide-Platform type titanium screws were used
Outcomes Prosthesis/implant failures, marginal bone level changes on intraoral radiographs, buccal
peri-implant marginal soft tissue levels
1-year data used
Notes Sample size calculation: reported that 14 implants in each group were required to give
80% power detect a difference of 0.3 mm (SD 0.4 mm)
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “Patients were al-
bias) located to either the immediate loading or
in the delayed loading group using a ran-
domization table”
Author replied that: “The patients were
consecutively assigned to test and control
groups according to a predetermined ran-
domization table”
Author replied that: “the surgeon was not
blinded in relation to the type of treatment
before the implant placement”
Blinding of outcome assessment (detection Unclear risk Reported in the article: “A blinded exam-
bias) iner made the bone height measurements”
All outcomes The author reply to our request of clarifica-
tion implied that the other clinical outcome
measures were not assessed by a blinded
outcome assessor
Schincaglia 2008 (Continued)
All outcomes
Cannizzaro 2008b

Recruitment period: November 2004 to November 2005
Funding source: “No commercial support of any form has been received by the investi-
gators”
Participants Inclusion criteria: patients with edentulous maxillae allowing the placement of 5 to
8 implants at least 10 mm long and with a diameter of 3.7 mm. For implants to be
immediately loaded, a primary implant stability of 48 Ncm had to be achieved at insertion
Exclusion criteria: irradiated head & neck less than 1 year previously, substance abusers,
pregnancy or lactation, uncontrolled diabetes, and any systemic diseases likely to com-
promise implant surgery, need for augmentation procedures, lack of opposite occluding
dentition/prosthesis, psychiatric problems
Age at baseline: immediate 62 (45-75); early 56 (42-69)
Gender: M15/F15

Gp A (n = 15) Immediate loading: 5-8 implants, placed with a flapless procedure,
immediately (same day) restored with metal reinforced acrylic provisional prostheses
replaced 2 to 3 months after by full-arch metal ceramic or metal resin prostheses with
short cantilevers
Gp B (n = 15) Early loading: 5-8 implants, placed with a flapless procedure, restored after
2 months with metal reinforced acrylic provisional prostheses replaced 2 to 3 months
after by full-arch metal ceramic or metal resin prostheses with short cantilevers
Zimmer SwissPlus (Zimmer, Carlsbad, Ca, USA) non-submerged solid titanium screws
were used
Duration of follow-up: 1-year
patient satisfaction, complications
1-year data used
Notes Sample size calculation: not reported, but authors note that the actual sample size was
insufficient to detect a statistically significant difference in prosthesis/implant failures
Risk of bias
Cannizzaro 2008b (Continued)
Random sequence generation (selection Low risk Reported in the article: “A computer gener-
bias) ated restricted randomisation list was used
to create two groups with equal numbers of
patients by one of the authors who was not
involved in patient recruitment or treat-
ment and had access to the randomisation
list stored in a password-protected portable
computer (Dr Marco Esposito)”
Allocation concealment (selection bias) Low risk Reported in the article: “The randomised
codes were enclosed in sequentially num-
bered, identical, opaque, sealed envelopes.
Envelopes were opened sequentially only
after all the implants were inserted, there-
fore treatment allocation was concealed to
the investigator in charge of enrolling and
treating the patients included in the trial”
Blinding of outcome assessment (detection Low risk Reported in the article: “Complications
bias) were assessed by the treating dentist (Dr
All outcomes Gioacchino Cannizzaro), who was not
blinded. Independent dentists who were
not aware of patient allocation evaluated
implant stability, including ISQ values (Dr
Michele Leone) and marginal bone levels
changes (Dr Cinzia Torchio)”
All outcomes
Other bias Unclear risk More implants (n = 22) were placed in fresh
extraction sockets in the early loaded group
compared to the immediate loading group
(n = 12 implants placed in fres extraction
sockets)
Güncü 2008
Methods Trial design: randomised, split-mouth group trial

Location: Ankara Turkey
Number of centres: one (Faculty of Dentistry, Hecettepe University, Ankara, Turkey)
Recruitment period: November 2004 to August 2005
Funding source: not reported
Participants Inclusion criteria: patients missing both mandibular first molars allowing the placement
of 11.5 mm long and 4 mm large single implants with an implant to crown length ratio
1/1
Exclusion criteria: smoking, osteoporosis, severe parafunctional habits, post-extractive
implants, untreated periodontal disease, poor oral hygiene, drug or alcohol abuse, need
of augmentation procedures at the implanted sites, and any systemic diseases likely to
compromise implant surgery
Age at baseline: 41.09 years (± 8.46) range 30-55
Gender: M4/F8

Gp A (n = 12) Immediate loading: Single implants restored the same day with acrylic
crown and after 1 week with occluding cemented metal-ceramic crowns
Gp B (n = 12) Conventional loading: Single implants restored after 3 months with
occluding cemented metal-ceramic crowns
type titanium screws were used
plaque index, gingival index, probing depths, bleeding time index
1-year data used
Risk of bias
Random sequence generation (selection Unclear risk Reported in the article: “Randomization
bias) for IL and CL selection was performed by
coin toss”
Author replied that: “Coin toss was per-
formed before implant placement during
surgery for each patient. Group allocation
was concealed to the investigators”
Reviewers comment: if the coin was tossed
before implant placement obviously alloca-
tion could not be concealed
Güncü 2008 (Continued)
bias) Author replied that “the outcome assessor
All outcomes was blinded”
Incomplete outcome data (attrition bias) Low risk All data presented after clarification by the
All outcomes author
Cannizzaro 2008d
Methods Trial Design: randomised, split-mouth group trial

Recruitment period: September to November 2007
Funding source: implants and prosthetic components were donated by Biomax and
Biomet 3i
Participants Inclusion criteria: partially edentulous patients needing 2 x 7 mm long single implants
in bone at least 5.5 wide. For implants to be immediately loaded, a primary implant
stability of 40 Ncm had to be achieved at insertion
Exclusion criteria: irradiated in the head and/or neck less than 1 year previously, sub-
stance abusers, pregnancy or lactation, uncontrolled diabetes, severe bruxism or clench-
ing, and any systemic diseases likely to compromise implant surgery, need for augmenta-
tion procedures with exception of Bio-Oss in fresh extractions sockets, lack of opposite
occluding dentition/prosthesis, psychiatric problems
Age at baseline: 35 years (18-57)
Gender: M15/F15

Gp A (n = 15) Immediate loading: 2 single implants, planned to be placed with a flapless
procedure, immediately (same day) loaded with acrylic crowns replaced by metal-ceramic
crowns after 9 weeks
Gp B (n = 15) Early loading: 2 single implants, planned to be placed with a flapless
procedure, early loaded after 6 weeks with acrylic crowns replaced by metal-ceramic
crowns after 3 weeks
7 mm* long Biomet 3i (Palm Beach, Florida, USA) Nanotite cylindrical titanium-alloy
implants non-submerged were used
Outcomes Prosthesis/implant failures, marginal bone level changes on intraoral radiographs, patient
satisfaction, complications
9-month data used
Cannizzaro 2008d (Continued)
Notes Sample size calculation: reported that 26 patients were required to show a change in
failure rate from 39% to 4%, so the trial recruited 30 participants to allow for drop-outs
* In the first paper (Cannizzaro 2008d) with follow-up data 9 months after loading,
these implants were described as 6.5 mm because the implant height without the external
hexagon is 6.5 mm. In the subsequent paper(Cannizzaro 2012) the same implants are
described as 7 mm - a measure which included the external hexagon
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “A computer-gen-
bias) erated restricted randomisation list was
used to create two groups with equal num-
bers of patients by Dr Marco Esposito, who
was not involved in patient recruitment or
treatment and had access to the randomi-
sation list stored in a password-protected
portable computer”
after the two implants were inserted, there-
the investigator (GC) in charge of enrolling
and treating the patients included in the
trial”
bias) were assessed by the treating dentist (GC),
All outcomes who was not blinded, but implant stability
and ISQ values were recorded by an inde-
pendent dentist who was not aware of pa-
tient allocation (ML)”
All outcomes
Cannizzaro 2008a

Location: Pavia,Italy (private practice)
Recruitment period: November 2004 to December 2005
Funding source: “No commercial support was received by the investigators”
Participants Inclusion criteria: patients with edentulous mandibles allowing the placement of 2 im-
plants at least 10 mm long and with a diameter of 3.7 mm. For implants to be immedi-
ately loaded, a primary implant stability of 48 Ncm had to be achieved at insertion
Exclusion criteria: general contraindications to implant surgery, poor oral hygiene and
motivation, substance abuse, pregnancy or lactation, uncontrolled diabetes, and any sys-
temic diseases likely to compromise implant surgery, need for augmentation procedures,
lack of opposite occluding dentition/prosthesis, psychiatric problems
Age at baseline: immediate 62 (44-72); early 61 (36-80)
Gender: M25/F35
Number evaluated: 60 (after 1 year)

Gp A (n = 30) Immediate loading: 2 implants, placed with a flapless procedure, sup-
porting a bar and an overdenture immediately (same day)
Gp B (n = 30) Early loading: 2 implants, placed with a flapless procedure, supporting a
bar and an overdenture loaded early (6 weeks)
Zimmer SwissPlus (Zimmer, Carlsbad, Ca, USA) non-submerged solid titanium screws
were used
Duration of follow-up: 1-year
Outcomes Prosthesis/implant failures, Osstell, patient satisfaction, complications

1-year data used
Notes Sample size calculation: authors suggest that a “sample size of 300 patients pre group
may be needed to detect a difference in prosthesis or implant failures”
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “The operator
bias) coded the selected implants sites on the
forms as site number 1 and site number 2.
..... A computer generated restricted ran-
domization list was created by one of the
authors who was not involved in patient re-
cruitment or treatment, and had access to
the random list stored in a password-pro-
tected portable computer (Dr Marco Es-
posito)”
Cannizzaro 2008a (Continued)
Allocation concealment (selection bias) Low risk Reported in the article: “The randomized
after both implants were placed, there-
the investigator in charge of enrolling and
treating the patients included in the trial”
bias) were assessed by the treating dentist (Dr
All outcomes Gioacchino Cannizzaro) who was not
blinded. Two independent dentists (Dr
Michele Leone and Dr Cinzia Torchio) not
aware of patient allocation evaluated im-
plant stability and peri-implant marginal
bone levels changes on periapical radio-
graphs, respectively”
All outcomes
De Rouck 2009

Location: Bruxelles, Belgium
Number of centres: one (Dental Clinic of the Free University)
Participants Inclusion criteria: patients requiring the immediate replacement of a single tooth in the
anterior maxilla (15-25) having both neighbouring teeth and at least 5 mm of bone
height apical to the alveolus of the failing tooth to allow implant placement with a
minimal insertion torque of 35 Ncm
Exclusion criteria: systemic diseases, smoking more than 10 cigarettes a day, bruxism,
lack of posterior occlusion, non-treated periodontal diseases, presence of active infection
(pus, fistula) around the hopeless tooth, loss of the labial crest after extraction of the
failing tooth
Age at baseline: immediate 55 years (SD 13); conventional 52 years (SD 12)
De Rouck 2009 (Continued)

Gp A (n = 26) Immediate loading: Single immediate post-extractive implants restored
the same day with non-occluding screw-retained acrylic crowns, replaced after 6 months
by permanent metal-ceramic crowns
Gp B (n = 26) Conventional loading: Implants were conventionally loaded and restored
after 3 months with screw-retained acrylic crowns, replaced after 3 months by permanent
metal-ceramic crowns. A collagen membrane (Bio-Gide, Geistlich Biomaterials) covered
the implant prior to crown placement
The implant-bone gap was grafted with granules of anorganic bovine bone
Nobelreplace Tapered Groovy (Nobel Biocare AB, Göteborg, Sweden) TiUnite titanium
screws were used
Outcomes Prosthesis/implant failures, marginal bone level changes on intraoral radiographs, plaque,
bleeding on probing, probing pocket depths, papilla levels, midfacial mucosal levels,
patient’s esthetic satisfaction
1-year data used
Notes Sample size calculation: paper states that 24 patients per group were required to show a
difference in soft tissue dimensions of 0.5 mm
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “This was per-
bias) formed by means of a computer-generated
randomization scheme”
Allocation concealment (selection bias) Unclear risk Reported in the article: “After screening
for recruitment, impressions were made
to fabricate an acrylic stent for recording
purposes. Thereupon, patients were ran-
domly allocated to the ‘immediate restora-
tion group’ (IRG) or the ‘delayed restora-
tion group’ (DRG)”. Allocation conceal-
ment not mentioned
All outcomes
Incomplete outcome data (attrition bias) Low risk Reported in the article: “From the 52 pa-
All outcomes tients that had been recruited (actually ran-
domised), 49 were included in the study
[IRG: 24 patients, DRG: 25 patients]. In
two patients the labial crest was partially
lost following tooth removal. Another pa-
tient listed for immediate restoration was
De Rouck 2009 (Continued)
excluded as the insertion torque was only

20 Ncm”
Other bias High risk The author used different baseline radio-
graphic assessment making the 2 groups ac-
tually non-comparable
Enkling 2010

Location: not reported
Number of centres: not reported
Recruitment period: not reported
Funding source: not reported
Participants Inclusion criteria: patients with edentulous mandibles allowing the placement of 2 in-
terforaminal implants 9.5 mm long and wit 4 mm in diameter with an insertion torque
of at least 35 Ncm. Patients were dissatisfied with the retention of their dentures after
having wore them for at least 2 months
Exclusion criteria: not reported
Age at baseline: not reported
Gender: not reported
Number evaluated: 30 (due to missing data)

Gp A (n = 16) Immediate loading: overdentures on 2 mandibular interforaminal implants
using a prefabricated bar (SFI-Bar®, C+M, Biel, Switzerland)
Gp B (n = 16) Conventional loading: (3 months) loading of overdentures on 2 mandibu-
lar interforaminal implants using a prefabricated bar (SFI-Bar®, C+M, Biel, Switzer-
land)
SICace® (SIC invent AG, Basel, Switzerland) titanium screws were used
Outcomes Prosthesis/implant failures, marginal bone levels, complications, oral-health-related-

quality-of life (OHRQoL), plaque index, probing pocket depth, bleeding on probing,
sounding depth
1-year data used
Risk of bias
Enkling 2010 (Continued)
Random sequence generation (selection Unclear risk No information provided in the abstract
bias) Author replied that: “We recruited pairs of
patients regarding the parameters age and
gender. In each pair the allocation to the
immediate or delayed loading group was
randomized by a computer generated list”
Allocation concealment (selection bias) Unclear risk No information provided in the abstract
No reply to this question
Blinding of outcome assessment (detection Low risk No information provided in the abstract
bias) Author replied that: “The clinical assessors
All outcomes as well as the assessors for the x-rays (post-
graduate students) were blinded and were
independent of the surgical and prosthetic
team”
Incomplete outcome data (attrition bias) Low risk No information provided in the abstract
All outcomes Author replied that: “After the first year,
we had two drop-outs as two paired female
patients died due to age reasons”
The problem is that the data at 1 year for
one patient per group is missing
Cannizzaro 2010
Methods Trial design: multicenter, randomised, parallel group trial

Location: Italy
Number of centres: four (private dental practices)
Recruitment period: February to November 2008
Funding source: Z systems partially supported this trial
Participants Inclusion criteria: patients missing a single tooth with residual bone height of at least 10
mm and width of at least 5 mm allowing implant placement with an insertion torque of
at least 35 Ncm
Exclusion criteria: general contraindications to implant surgery, lack of opposite occlud-
ing dentition in the area intended for implant placement, acute infection in the area
intended for implant placement, immunosuppression or immunodepression, untreated
periodontitis, poor oral hygiene and motivation, irradiation in the head or neck area,
bruxism, under treatment or past treatment with intravenous amino-bisphosphonates,
uncontrolled diabetes, pregnant or lactating, substance abuse, psychiatric disorders or
unrealistic expectations, participation in other clinical trials interfering with present pro-
tocol, having been referred only for implant placement or unable to be followed for
at least one year, requiring the use of a membrane at implant placement, implant sites
subjectively evaluated as being characterised by soft bone quality

Age at baseline: occlusal 38 (918-54); non-occlusal 39 (26-55)
Gender: M17/F23
Interventions Comparison: Occlusal versus non-occlusal immediate loading

Gp A (n = 20) Immediate loading: (Occlusal) Single implants immediately restored the
same day with acrylic single crowns in occlusion
Gp B (n = 20) Immediate loading: (Non-occlusal) Single implants immediately restored
the same day with acrylic single crowns not in occlusion
Permanent ceramic crowns were cemented after 4 to 5 months in both groups
Z-Look3® (Z-System, Oensingen, Switzerland) one-piece zirconia sand-blasted screws
were used
Outcomes Prosthesis/implant failures, marginal bone levels, complications

1-year data used
Notes Sample size calculation: sample size calculation reported and states that the original
intention was to recruit 80 patients in each group to detect a difference between a
proportion of 0.999 and 0.920 (patients experiencing at least one implant failure)
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “A computer gen-
bias) erated restricted randomisation list was cre-
ated. Only one investigator (ME), who was
not involved in the selection and treatment
of the patients, knew the randomization
sequence and had access to the random-
ization list stored in a pass-word protected
portable computer”
codes were enclosed in sequentially-num-
Flap closure was obtained with vicryl 4.0
and the envelope containing the randomi-
sation code was opened to disclose patient
allocation........ Envelopes were opened se-
quentially after the implants were placed.
Therefore, treatment allocation was con-
cealed to the investigators in charge of en-
rolling and treating the patients”
Blinding of outcome assessment (detection Unclear risk Reported in the article: “One dentist (CT)
bias) who treated 10 patients performed all ra-
All outcomes diographic assessments without knowing
group allocation for the patients of the
other 3 centres, therefore the outcome as-
sessor was blinded for 30 out of 40 patients.
....... ”
Author replied that: “implant success was
assessed by blinded outcome assessors at
each centers”
All outcomes
den Hartog 2011

Location: Groningen, The Netherlands
Number of centres: one (University of Groningen, The Netherlands)
Recruitment period: January 2005 to February 2008
Funding source: study was funded by Nobel Biocare AB, Goteborg, Sweden (grant #
2004-288)
Participants Inclusion criteria: patients missing a maxillary single tooth from first to first premolars
allowing the placement of a single implant at least 13 mm long and 3.5 mm wide with
a minimal insertion torque of 45 Ncm
Exclusion criteria: severe systemic conditions (ASA III), presence of periodontal disease,
previous irradiation, smoking, presence of peri-apical lesions or any other abnormalities
in the maxillary anterior region, and missing tooth extracted less than 3 months before
study start
Age at baseline: immediate 38.4 (± 14.0); conventional 40.1 (± 14.4)

Gp A (n = 31) Immediate loading: implants were restored within 24 hours with pro-
visional non-occluding acrylic crowns, replaced after 6 months by cemented or screw-
retained metal-ceramic crowns
Gp B (n = 31) Conventional loading implants were also restored after 3 months with
provisional occluding acrylic crowns, replaced after 3 months by cemented or screw-
retained occluding metal-ceramic crowns
Nobel Replace Tapered Groovy (Nobel Biocare AB, Göteborg, Sweden) submerged TiU-
nite titanium screws were used
den Hartog 2011 (Continued)
Duration of follow-up: 18 months
Outcomes Crown and implant success, marginal bone levels, recession, various aesthetic indexes,
patient satisfaction
1-year data used for crown/implant success and 18 months form marginal bone level
changes
Notes Sample size calculation: paper states that “sample size was too small to demonstrate
whether immediate loading was non-inferior to conventional loading with respect to
implant survival”
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “A specifically de-
bias) signed locked computer software program
was used to randomly assign patients to
one of two study groups.... Randomization
by minimization (Altman 1991) was used
to balance possible prognostic variables be-
tween the treatment groups. Minimization
was used for the variables age (<30 years,
>31 <60 years, >60 years), location of the
implant site (central or lateral incisor, ca-
nine or first premolar)and whether or not
a pre-implant augmentation procedure was
indicated based on a clinical and diagnostic
cast assessment”
Allocation concealment (selection bias) Low risk Reported in the article: “The allocation re-
sult was kept in a locked computer file
that was not accessible for the examiner
and the practitioners. The surgeon who in-
serted the implants was informed about the
allocation on the day of surgery, before im-
plant surgery was started”
Blinding of outcome assessment (detection High risk Reported in the article: “The examiner was
bias) blinded to the photographs and the ra-
All outcomes diographs taken at T6m and T18m. The
radiographic examination could not be
blinded to the radiographs collected after
implant placement (baseline, T0), as the
study group could be deduced from these
radiographs.... The examiner was blinded
for the protocol that was applied for a par-
ticular patient (for clinical measurements).
....The examiner was blinded to the group
den Hartog 2011 (Continued)
allocation (for the aesthetic outcome assess-

ment”
Reviewer comment: “it was possible to take
baseline radiograph not showing group al-
location”
All outcomes
Other bias Unclear risk There was an imbalance in gender between

the groups at baseline which may have in-
troduced a bias to this study
Meloni 2012
Methods Trial design: multicenter, randomised, split-mouth trial

Location: Sassari, Italy
Number of centres: three (University of Sassari and in two private practices in Sassari,
Italy)
Participants Inclusion criteria: patients missing 2 bilateral mandibular first molars allowing the place-
ment of a single implant at least 8 mm long and 4.3 mm wide with a minimal insertion
torque of 35 Ncm
Exclusion criteria: bone height < 10 mm, bone thickness < 6 mm, < 5 mm of keratinised
gingiva, general contraindications to implant surgery; lack of occluding dentition in
the area intended for immediate loading, periodontitis, bruxism, immunosuppression,
previous history of irradiation of the head and neck area, uncontrolled diabetes, smoking
>10 cigarettes/day, poor oral hygiene, current or past treatment with bisphosphonates,
substance abuse, psychiatric disorder, need of bone augmentation, pregnancy or lactation
Age at baseline: not stated
Gender: not stated

Gp A (n = 5) Immediate loading: implants restored within 24 hours with provisional
non-occluding acrylic crowns, replaced after 4 months by cemented definitive zirconia-
ceramic or metal-ceramic crowns on individualised titanium-zirconia abutments
Gp B (n = 5) Conventional loading: implants restored after 4 months with cemented
definitive zirconia-ceramic or metal-ceramic crowns on individualised titanium-zirconia
abutments
NobelReplace Tapered Groovy (Nobel Biocare AB, Göteborg, Sweden) non-submerged
TiUnite titanium screws were used
Meloni 2012 (Continued)
Outcomes Crown and implant success, complications, marginal bone levels, probing pocket depth
(PPD) and bleeding on probing (BOP)
1-year data used
Risk of bias
Random sequence generation (selection Low risk Reported in the article: “In each eligible
bias) patient, the mandibular right or left molar
was randomly selected to receive either an
immediate or delayed provisional crown;
the randomisation code was assigned by an
independent operator not involved in the
trial, and was placed in envelopes with a
code done by a dedicated computer pro-
gramme combining a sequence of numbers
with the two different procedures”
Allocation concealment (selection bias) Low risk Reported in the article: “The envelope con-
taining a randomisation code to assign the
immediate and the delayed site was opened
only in this moment (after implant place-
ment) by a blinded independent medical
doctor and the immediate loading site was
assigned”
Blinding of outcome assessment (detection Unclear risk Reported in the article: “A blinded radiolo-
bias) gist (F.G.), unaffiliated with the study cen-
All outcomes tre, interpreted all radiographs”
Author replied that: “all outcomes were as-
sessed by blinded assessors with the excep-
tions of implant stability that was assessed
by the surgeon”
All outcomes
Characteristics of excluded studies [ordered by year of study]
Study Reason for exclusion
Polson 2000 Trial comparing immediate versus conventional loading. Insufficient data presented. No reply to letter
Roccuzzo 2001 Trial comparing early versus conventional loading of different implant types
Testori 2003 Trial comparing immediate non-occluding loading versus conventional loading but at the same time patients
were also randomised to 2 different implant types
Salvi 2004 Trial comparing 2 early loading procedures (2 versus 6 weeks). Such comparison does not fit within this review
Appleton 2005 Trial comparing progressive versus direct loading after an healing period of 5 months. It was unclear whether
the trial was actually randomised, there was a mixed study design parallel and split-mouth and implants with
problems not accounted for biasing the results. No replay to letter
Ottoni 2005 Trial comparing immediate versus conventional loading. The author informed us that the study was not a
randomised controlled trial
Turkyilmaz 2006 Trial comparing early versus conventional loading. The author informed us that the study was not a randomised
controlled trial
Romanos 2006 Trial comparing immediate versus conventional loading. The author informed us that the study was not a
randomised controlled trial
Göthberg 2007 Ongoing trial comparing immediate versus early loading in partially edentulous patients. Patients are subse-
quently randomised again to 3 different abutment solutions (no abutment, abutment with a rough surface and
abutment with a machined surface)
Cannizzaro 2008c Trial comparing flapless surgery + modified implant installation technique + immediate loading versus conven-
tional surgery and loading
Degidi 2009 Trial comparing immediate versus conventional loading, judged not to be randomised. No reply to letter
Degidi 2010 Trial comparing immediate occlusal versus non-occlusal loading, judged not to be randomised. No reply to
letter
Shibly 2010 Trial comparing immediate (the same day) loading with delayed loading (3 months) of single post-extractive
implants. Author stated in both publications that 1 immediately loaded implants and 2 delayed loading implants
failed. However in the table the presented the opposite results. In addition one patient dropped out but it was
not possible to understand from which group. No reply to letter
Van de Velde 2010 Trial comparing immediate versus early loading. Groups not comparable at baseline since implants were placed
with flapless-guide surgery only in the immediately loaded group
Kim 2011 Trial comparing 2 conventional loading after 4 months versus conventional loading after 6 months. Such
comparison does not fit within this review
(Continued)
Tealdo 2011 Trial comparing immediate versus conventional loading. It is not a randomised controlled trial
Mackie 2011 Trial comparing early loading at 2 weeks with early loading at 6 weeks with conventional loading at 12 weeks.
A ’posthumous cocktail’ of different RCTs, some of them already included in this review
Jokstad 2011 Trial comparing 2 early loading procedures (10 days versus 6-8 weeks). Such comparison does not fit within
this review
Barewal 2012 Trial comparing immediate versus early versus conventional loading. The ’stratified’ randomisation method
used by the authors inevitably generated 3 non-comparable groups, in fact the trial is not randomised
DATA AND ANALYSES
Comparison 1. Immediate versus conventional loading
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Patients with prosthesis failures 8 381 Risk Ratio (Random, 95% CI) 1.87 [0.70, 5.01]
2 Patients with implant failures 10 421 Risk Ratio (Random, 95% CI) 1.65 [0.68, 3.98]
3 Marginal bone level changes 9 293 Mean Difference (Random, 95% CI) -0.10 [-0.20, -0.01]
Comparison 2. Early versus conventional loading
No. of No. of
1 Patients with prosthesis failures 1 48 Risk Ratio (M-H, Fixed, 95% CI) 5.0 [0.63, 39.67]
2 Patients with implant failures 2 72 Risk Ratio (M-H, Fixed, 95% CI) 1.55 [0.46, 5.18]
3 Marginal bone level changes 2 70 Mean Difference (IV, Fixed, 95% CI) -0.04 [-0.15, 0.07]
Comparison 3. Immediate versus early loading
No. of No. of
1 Patients with prosthesis failures 4 438 Risk Ratio (Random, 95% CI) 0.68 [0.25, 1.86]
2 Patients with implant failures 5 468 Risk Ratio (Random, 95% CI) 0.65 [0.26, 1.63]
3 Marginal bone level changes 3 136 Mean Difference (Random, 95% CI) -0.06 [-0.16, 0.03]
Comparison 4. Occlusal versus non-occlusal loading
No. of No. of
1 Patients with prosthesis failures 2 88 Risk Ratio (M-H, Fixed, 95% CI) 1.0 [0.31, 3.22]
2 Patients with implant failures 2 88 Risk Ratio (M-H, Fixed, 95% CI) 1.0 [0.31, 3.22]
3 Marginal bone level changes 2 78 Mean Difference (IV, Fixed, 95% CI) 0.03 [-0.10, 0.15]
Analysis 1.1. Comparison 1 Immediate versus conventional loading, Outcome 1 Patients with prosthesis
failures.
Review: Interventions for replacing missing teeth: different times for loading dental implants
Comparison: 1 Immediate versus conventional loading
Outcome: 1 Patients with prosthesis failures
Study or subgroup Immediate loading Conventional loading log [Risk Ratio] Risk Ratio Weight Risk Ratio
N N (SE) IV,Random,95% CI IV,Random,95% CI
Cannizzaro 2003 14 14 -1.1 (1.6) 9.8 % 0.33 [ 0.01, 7.66 ]
Hall 2006 13 12 0.995 (1.645) 9.3 % 2.70 [ 0.11, 67.98 ]
Oh 2006 12 12 1.955 (1.48) 11.5 % 7.06 [ 0.39, 128.48 ]
Güncü 2008 13 13 0.7673 (1.093) 21.0 % 2.15 [ 0.25, 18.35 ]
Schincaglia 2008 15 15 1.099 (1.6) 9.8 % 3.00 [ 0.13, 69.06 ]
Donati 2008 84 53 1.43 (1.5) 11.2 % 4.18 [ 0.22, 79.04 ]
De Rouck 2009 24 25 -0.652 (1.191) 17.7 % 0.52 [ 0.05, 5.38 ]
den Hartog 2011 31 31 1.1 (1.614) 9.7 % 3.00 [ 0.13, 71.05 ]
Total (95% CI) 100.0 % 1.87 [ 0.70, 5.01 ]

Heterogeneity: Tau2 = 0.0; Chi2 = 3.65, df = 7 (P = 0.82); I2 =0.0%
Test for overall effect: Z = 1.25 (P = 0.21)
Test for subgroup differences: Not applicable
0.2 0.5 1 2 5
Favours immediate Favours conventional
Analysis 1.2. Comparison 1 Immediate versus conventional loading, Outcome 2 Patients with implant
failures.
Outcome: 2 Patients with implant failures
Study or subgroup Immediate loading Conventional loading log [Risk Ratio] Risk Ratio Weight Risk Ratio
Chiapasco 2001 10 10 0 (1.342) 11.3 % 1.00 [ 0.07, 13.88 ]
Romeo 2002 10 10 -0.1086 (1.6) 7.9 % 0.90 [ 0.04, 20.64 ]
Cannizzaro 2003 14 14 -1.1 (1.6) 7.9 % 0.33 [ 0.01, 7.66 ]
Hall 2006 13 12 0.995 (1.645) 7.5 % 2.70 [ 0.11, 67.98 ]
Oh 2006 12 12 1.955 (1.48) 9.3 % 7.06 [ 0.39, 128.48 ]
Güncü 2008 13 13 0.7673 (1.093) 17.0 % 2.15 [ 0.25, 18.35 ]
Schincaglia 2008 15 15 1.099 (1.6) 7.9 % 3.00 [ 0.13, 69.06 ]
Donati 2008 84 53 1.43 (1.5) 9.0 % 4.18 [ 0.22, 79.04 ]
De Rouck 2009 25 24 -0.652 (1.191) 14.3 % 0.52 [ 0.05, 5.38 ]
den Hartog 2011 31 31 1.1 (1.614) 7.8 % 3.00 [ 0.13, 71.05 ]
Total (95% CI) 100.0 % 1.65 [ 0.68, 3.98 ]

0.001 0.01 0.1 1 10 100 1000

Analysis 1.3. Comparison 1 Immediate versus conventional loading, Outcome 3 Marginal bone level
changes.
Outcome: 3 Marginal bone level changes
Mean Mean
Study or subgroup Immediate loading Conventional loading Mean Difference (SE) Difference Weight Difference
N N IV,Random,95% CI IV,Random,95% CI
Cannizzaro 2003 14 13 0.02 (0.047) 25.4 % 0.02 [ -0.07, 0.11 ]
Hall 2006 12 12 -0.14 (0.568) 0.7 % -0.14 [ -1.25, 0.97 ]
Turkyilmaz 2007 10 10 0 (0.114) 11.7 % 0.0 [ -0.22, 0.22 ]
Güncü 2008 11 11 -0.23 (0.1484) 8.0 % -0.23 [ -0.52, 0.06 ]
Crespi 2008 20 20 -0.14 (0.164) 6.9 % -0.14 [ -0.46, 0.18 ]
Schincaglia 2008 14 15 -0.43 (0.1777) 6.0 % -0.43 [ -0.78, -0.08 ]
Enkling 2010 15 15 -0.41 (0.18) 5.9 % -0.41 [ -0.76, -0.06 ]
den Hartog 2011 30 31 0.01 (0.151) 7.8 % 0.01 [ -0.29, 0.31 ]
Meloni 2012 20 20 -0.11 (0.0387) 27.5 % -0.11 [ -0.19, -0.03 ]
Total (95% CI) 100.0 % -0.10 [ -0.20, -0.01 ]

Heterogeneity: Tau2 = 0.01; Chi2 = 14.37, df = 8 (P = 0.07); I2 =44%
-2 -1 0 1 2
Analysis 2.1. Comparison 2 Early versus conventional loading, Outcome 1 Patients with prosthesis failures.
Comparison: 2 Early versus conventional loading
Study or subgroup Early loading Conventional loading Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Tawse-Smith 2002 5/24 1/24 100.0 % 5.00 [ 0.63, 39.67 ]
Total (95% CI) 24 24 100.0 % 5.00 [ 0.63, 39.67 ]

Total events: 5 (Early loading), 1 (Conventional loading)
Heterogeneity: not applicable
0.001 0.01 0.1 1 10 100 1000

Favours early Favours conventional
Analysis 2.2. Comparison 2 Early versus conventional loading, Outcome 2 Patients with implant failures.
Study or subgroup Early loading Conventional loading Risk Ratio Weight Risk Ratio
Tawse-Smith 2002 5/24 1/24 27.3 % 5.00 [ 0.63, 39.67 ]
Fischer 2004 1/16 2/8 72.7 % 0.25 [ 0.03, 2.36 ]
Total (95% CI) 40 32 100.0 % 1.55 [ 0.46, 5.18 ]

Total events: 6 (Early loading), 3 (Conventional loading)
Heterogeneity: Chi2 = 3.76, df = 1 (P = 0.05); I2 =73%
0.001 0.01 0.1 1 10 100 1000

Analysis 2.3. Comparison 2 Early versus conventional loading, Outcome 3 Marginal bone level changes.
Mean Mean
Study or subgroup Early loading Conventional loading Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Tawse-Smith 2002 24 0.12 (0.19) 24 0.13 (0.29) 60.1 % -0.01 [ -0.15, 0.13 ]
Payne 2002 12 0.27 (0.18) 10 0.35 (0.22) 39.9 % -0.08 [ -0.25, 0.09 ]
Total (95% CI) 36 34 100.0 % -0.04 [ -0.15, 0.07 ]

Heterogeneity: Chi2 = 0.39, df = 1 (P = 0.53); I2 =0.0%
-1 -0.5 0 0.5 1
Analysis 3.1. Comparison 3 Immediate versus early loading, Outcome 1 Patients with prosthesis failures.
Comparison: 3 Immediate versus early loading
Study or subgroup Immediate Early log [Risk Ratio] Risk Ratio Weight Risk Ratio
Testori 2007 25 27 1.172 (1.61) 10.1 % 3.23 [ 0.14, 75.76 ]
Zöllner 2008 138 128 -0.478 (0.63) 65.9 % 0.62 [ 0.18, 2.13 ]
Cannizzaro 2008d 30 30 0 (1.45) 12.4 % 1.00 [ 0.06, 17.15 ]
Cannizzaro 2008a 30 30 -1.609 (1.5) 11.6 % 0.20 [ 0.01, 3.78 ]
Total (95% CI) 100.0 % 0.68 [ 0.25, 1.86 ]

0.01 0.1 1 10 100

Favours immediate Favours early
Analysis 3.2. Comparison 3 Immediate versus early loading, Outcome 2 Patients with implant failures.
Study or subgroup Immediate Early log [Risk Ratio] Risk Ratio Weight Risk Ratio
Testori 2007 25 27 1.172 (1.61) 8.5 % 3.23 [ 0.14, 75.76 ]
Cannizzaro 2008d 30 30 0 (1.45) 10.5 % 1.00 [ 0.06, 17.15 ]
Cannizzaro 2008a 30 30 -1.609 (1.5) 9.8 % 0.20 [ 0.01, 3.78 ]
Cannizzaro 2008b 15 15 -0.693 (1.2) 15.4 % 0.50 [ 0.05, 5.25 ]
Zöllner 2008 138 128 -0.478 (0.63) 55.7 % 0.62 [ 0.18, 2.13 ]
Total (95% CI) 100.0 % 0.65 [ 0.26, 1.63 ]

0.01 0.1 1 10 100

Analysis 3.3. Comparison 3 Immediate versus early loading, Outcome 3 Marginal bone level changes.
Mean Mean
Study or subgroup Immediate Early Mean Difference (SE) Difference Weight Difference
N N IV,Random,95% CI IV,Random,95% CI
Testori 2007 24 24 -0.04 (0.157) 9.8 % -0.04 [ -0.35, 0.27 ]
Cannizzaro 2008b 15 15 -0.1 (0.071) 48.1 % -0.10 [ -0.24, 0.04 ]
Cannizzaro 2008d 29 29 -0.03 (0.076) 42.0 % -0.03 [ -0.18, 0.12 ]
Total (95% CI) 100.0 % -0.06 [ -0.16, 0.03 ]

-1 -0.5 0 0.5 1
Analysis 4.1. Comparison 4 Occlusal versus non-occlusal loading, Outcome 1 Patients with prosthesis
failures.
Comparison: 4 Occlusal versus non-occlusal loading
Study or subgroup Occlusal loading Non-occlusal loading Risk Ratio Weight Risk Ratio
Lindeboom 2006 2/24 3/24 60.0 % 0.67 [ 0.12, 3.64 ]
Cannizzaro 2010 3/20 2/20 40.0 % 1.50 [ 0.28, 8.04 ]
Total (95% CI) 44 44 100.0 % 1.00 [ 0.31, 3.22 ]

Total events: 5 (Occlusal loading), 5 (Non-occlusal loading)
0.001 0.01 0.1 1 10 100 1000

Favours occlusal Favours non-occlusal
Analysis 4.2. Comparison 4 Occlusal versus non-occlusal loading, Outcome 2 Patients with implant failures.
Study or subgroup Occlusal loading Non-occlusal loading Risk Ratio Weight Risk Ratio
Lindeboom 2006 2/24 3/24 60.0 % 0.67 [ 0.12, 3.64 ]
Cannizzaro 2010 3/20 2/20 40.0 % 1.50 [ 0.28, 8.04 ]
Total (95% CI) 44 44 100.0 % 1.00 [ 0.31, 3.22 ]

Total events: 5 (Occlusal loading), 5 (Non-occlusal loading)
0.001 0.01 0.1 1 10 100 1000

Analysis 4.3. Comparison 4 Occlusal versus non-occlusal loading, Outcome 3 Marginal bone level changes.
Mean Mean
Study or subgroup Occlusal loading Non-occlusal loading Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Lindeboom 2006 22 0.15 (0.21) 21 0.15 (0.24) 86.0 % 0.01 [ -0.13, 0.14 ]
Cannizzaro 2010 17 0.9 (0.41) 18 0.72 (0.59) 14.0 % 0.18 [ -0.16, 0.52 ]
Total (95% CI) 39 39 100.0 % 0.03 [ -0.10, 0.15 ]

-1 -0.5 0 0.5 1
APPENDICES
Appendix 1. MEDLINE (OVID) Search Strategy

1. exp Dental Implants/
2. exp Dental Implantation/ or dental implantation
3. exp Dental Prosthesis, Implant-Supported/
4. ((osseointegrated adj implant$) and (dental or oral))
5. dental implant$
6. (implant$ adj5 dent$)
7. (((overdenture$ or crown$ or bridge$ or prosthesis or restoration$) adj5 (Dental or oral)) and implant$)
8. “implant supported dental prosthesis”
9. (“blade implant$” and (dental or oral))
10. ((endosseous adj5 implant$) and (dental or oral))
11. ((dental or oral) adj5 implant$)
12. OR/1-11
The above subject search was linked to the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomized trials in
MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 6.4.11.1 and detailed in box 6.4.c of The Cochrane
Handbook for Systematic Reviews of Interventions, Version 5.1.0 [updated March 2011].
1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. drug therapy.fs.
6. randomly.ab.
7. trial.ab.
8. groups.ab.
9. or/1-8
10. exp animals/ not humans.sh.
11. 9 not 10
Appendix 2. The Cochrane Oral Health Group Register Search Strategy

(dental-implants OR “dental implant*” OR “oral implant*” OR dental-implantation OR dental-prosthesis-implant-supported OR
“implant supported” OR “implant supported prosthesis” OR dental-implantation-endosseous-endodontic OR “endosseous implant*”
OR blade-implantation OR “blade implant*” OR (implant* AND (oral OR dental)) or dental-implantation-subperiosteal OR “sub-
periosteal implant” OR (implant* AND overdenture*) OR ((overdenture* OR crown* OR bridge* OR prosthesis OR prostheses OR
restoration*) AND (“dental implant*” OR “Oral implant” OR (zygoma* AND implant*))))
Appendix 3. Cochrane Central Register of Controlled Clinical Trials (CENTRAL) Search Strategy
#1 DENTAL IMPLANTS explode all trees (MeSH)
#2 DENTAL IMPLANTATION explode all trees (MeSH)
#3 DENTAL PROSTHESIS IMPLANT-SUPPORTED single term (MeSH)
#4 ((osseointegrat* near implant*) and (dental* or oral*))
#5 (dental next implant*)
#6 (implant* near dent*)
#7 dental-implant*
#8 ((overdenture* near dental*) and implant*)
#9 ((overdenture* near oral*) and implant*)
#10 ((crown* near dental*) and implant*)
#11 ((crown* near oral*) and implant*)
#12 ((bridge* near dental*) and implant*)
#13 ((bridge* near oral*) and implant*)
#14 ((prosthesis near dental*) and implant*)
#15 ((prosthesis near oral*) and implant*)
#16 ((prostheses near dental*) and implant*)
#17 ((prostheses near oral*) and implant*)
#18 ((restoration* near dental*) and implant*)
#19 ((restoration* near oral*) and implant*)
#20 (implant next supported next dental next prosthesis)
#21 (blade next implant*)
#22 ((endosseous near implant*) and dental)
#23 ((endosseous near implant*) and oral*)
#24 ((dental* near implant*) or (oral* near implant*))
#25 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #
20 or #21 or #22 or #23 or #24)
Appendix 4. EMBASE (OVID) Search Strategy
1. tooth implantation/
2. ((implant-supported or implant$) adj support$).mp.
3. ((osseointegrated adj implant$) and (dental or oral)).mp.
4. ((dental implant$ or dental-implant or implant$) adj (dent$ or oral or tooth)).mp.
5. (((overdenture$ or crown$ or bridge$ or prosthesis or prostheses or restoration$) adj5 (dental or oral)) and implant$).mp.
6. “implant supported dental prosthesis”.mp.
7. (“blade implant$” and (dental or oral or tooth or teeth)).mp.
8. ((endosseous adj5 implant$) and (dental or oral or tooth or teeth)).mp.
9. ((dental or oral or tooth or teeth) and implant$).mp.
10. or/1-9
The above subject search was linked to the Cochrane Oral Health Group filter for EMBASE via OVID:
1. random$.ti,ab.
2. factorial$.ti,ab.
3. (crossover$ or cross over$ or cross-over$).ti,ab.
4. placebo$.ti,ab.
5. (doubl$ adj blind$).ti,ab.
6. (singl$ adj blind$).ti,ab.
7. assign$.ti,ab.
8. allocat$.ti,ab.
9. volunteer$.ti,ab.
10. CROSSOVER PROCEDURE.sh.
11. DOUBLE-BLIND PROCEDURE.sh.
12. RANDOMIZED CONTROLLED TRIAL.sh.
13. SINGLE BLIND PROCEDURE.sh.
14. or/1-13
15. ANIMAL/ or NONHUMAN/ or ANIMAL EXPERIMENT/
16. HUMAN/
17. 16 and 15
18. 15 not 17
19. 14 not 18
WHAT’S NEW
Last assessed as up-to-date: 20 February 2013.
Date Event Description
20 February 2013 New search has been performed Searches updates to 8 June 2012.
20 February 2013 New citation required but conclusions have not Methods updated. One previously included study now
changed excluded. Five new included studies. No change to the
conclusions of the review. New co-author
HISTORY
Protocol first published: Issue 4, 2002
Review first published: Issue 1, 2003
Date Event Description
31 October 2008 New citation required and conclusions have changed Change of authorship.
We have added a secondary hypothesis, previously de-
scribed in the subgroup analyses.
We have updated the review adding 11 new included
studies (Lindeboom 2006 (previously excluded); Assad
2007; Turkyilmaz 2007; Cannizzaro 2008a; Canniz-
zaro 2008b; Cannizzaro 2008d; Crespi 2008; Donati
2008; Güncü 2008; Schincaglia 2008; Zöllner 2008)
and additional data from two previously included stud-
ies (Merli 2007; Testori 2007).
Conclusions slightly changed.
31 October 2008 New search has been performed The searches were updated in June 2008.
10 June 2008 Amended Converted to new review format.
15 February 2007 New citation required and conclusions have changed Change of authorship. We have updated the review
adding seven new included studies (Cannizzaro 2003
(previously excluded); Fischer 2004; Hall 2006; Oh
2006; Romanos 2006; Merli 2007; Testori 2007), and
excluding eight new trials.
We also included studies with a minimum follow up of
6 months in function. Conclusions slightly changed
15 February 2007 New search has been performed The searches were updated in February 2007.
15 March 2004 New citation required and conclusions have changed Change of authorship. We have updated the review and
added three new included studies (Payne 2002; Romeo
2002; Romanos in press). We have added to the methods
of the review section the following possible subgroup
analyses to be conducted in the future if appropriate
data become available:
(1) Whether implants were placed in mandibles or max-
illae
(2) Whether implants were placed in partially or fully
edentulous jaws
(3) Whether implants were placed in the anterior or
posterior jaw
(4) Different number of inserted implants (for instance
overdentures supported by two versus overdentures sup-
ported by four implants)
(5) Whether turned (machined) or implants with a
(Continued)
roughened surface were used

(6) Whether the trial was supported by implant manu-
facturer(s) or not
15 March 2004 New search has been performed The searches were updated in March 2004.
CONTRIBUTIONS OF AUTHORS
Conceiving, designing and co-ordinating the review (Marco Esposito (ME)).
Developing search strategy and undertaking searches (ME).
Screening search results and retrieved papers against inclusion criteria (ME, Maria Gabriella Grusovin (GG), Hassan Maghaireh (HM).
Appraising quality and extracting data from papers (ME, GG, HM).
Writing to authors for additional information (ME, GG, Helen Worthington (HW)).
Data management for the review and entering data into RevMan (HW, ME).
Analysis and interpretation of data (ME, HW).
Writing the review (ME).
Providing general advice on the review (GG, HM).
Performing previous work that was the foundation of current study (ME, HW).
DECLARATIONS OF INTEREST
Marco Esposito is among the authors of six of the included, and one of the excluded studies, however, he was not involved in the quality
assessment of these trials. Marco Esposito is working as independent methodological consultant for various implant related projects
for some of the companies whose implants were used both in the included and excluded trials, however, in this review, implant brands
were not under evaluation.
SOURCES OF SUPPORT
Internal sources
• School of Dentistry, The University of Manchester, UK.
• MAHSC, UK.
The Cochrane Oral Health Group is supported by the Manchester Academic Health Sciences Centre (MAHSC) and the NIHR
Manchester Biomedical Research Centre.
External sources
• Cochrane Oral Health Group Global Alliance, UK.
All reviews in the Cochrane Oral Health Group are supported by Global Alliance member organisations (British Orthodontic Society,
UK; British Society of Paediatric Dentistry, UK; National Center for Dental Hygiene Research & Practice, USA and New York
University College of Dentistry, USA) providing funding for the editorial process (http://ohg.cochrane.org).
• National Institute for Health Research (NIHR), UK.
All reviews in the Cochrane Oral Health Group are supported by NIHR Systematic Reviews Programme infrastructure funding.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

The new aim of evaluating progressive loading has been added, though no study could be included.
INDEX TERMS
Medical Subject Headings (MeSH)

∗ Dental Implantation, Endosseous; Bone Density; Dental Implants; Mandible [physiology]; Materials Testing; Randomized Controlled
Trials as Topic; Time Factors; Tooth Loss [∗ surgery]
MeSH check words

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Interventions for replacing missing teeth: different times for

loading dental implants (Review)

Esposito M, Grusovin MG, Maghaireh H, Worthington HV

Interventions for replacing missing teeth: different times for

Marco Esposito1 , Maria Gabriella Grusovin2 , Hassan Maghaireh3 , Helen V Worthington1

Editorial group: Cochrane Oral Health Group.

PLAIN LANGUAGE SUMMARY

Conventional compared with immediate loading of dental implants

Patient or population: patients requiring dental implants

Assumed risk Corresponding risk

1. the prosthetic failure rate in the conventional loading group is 1.2%

3. To determine the effects of osseointegrated dental implants

Types of outcome measures

Risk of bias Interpretation Within a study Across studies

Assessment of reporting biases Sensitivity analysis

(2) Early versus conventional loading

Comparison Test Group 1 Test Group 2

Mandible (8 trials) 98 (199) 66 (199)

Maxilla (6 trials) 187 (187) 156 (156)

Both (1 trial) 14 (46) 14 (46)

Early versus conventional All (3 trials) 52 (167) 44 (119)

Mandible (2 trials) 36 (72) 36 (72)

Maxilla (1 trial) 16 (95) 8 (47)

Immediate versus early All (6 trials) 268 (464) 230 (449)

Mandible (1 trials) 30 (30) (30)

Maxilla (1 trials) 15 (90) 15 (87)

Both (4 trial) 223 (314) 185 (302)

Occlusal versus non-occlusal All (2 trials) 44 (44) 44 (44)

Maxilla (1 trials) 24 (24) 24 (24)

Both (1 trial) 20 (20) 20 (20)

Design Prosthetic failures Implant failures

Chiapasco 2001 Parallel No failures 1/10, 1/10

Romeo 2002 Parallel No failures 0/10, 1/10

Cannizzaro 2003 Parallel 0/14, 1/14 0/14, 1/14

Hall 2006 Parallel 1/13, 0/12 1/13, 0/12

Oh 2006 Parallel 3/12, 0/12 3/12, 0/12

Assad 2007 Parallel No failures (n = 5) No failures (n = 5)

Turkyilmaz 2007 Parallel No failures (n = 10) No failures (n = 10)

Crespi 2008 Parallel No failures (n = 20) No failures (n = 20)

Donati 2008 Parallel 3/84, 0/53 3/84, 0/53

Güncü 2008 Split-mouth 1/13, 0/13 1/13, 0/13

Schincaglia 2008 Parallel 1/15, 0/15 1/15, 0/15

De Rouck 2009 Parallel 1/25, 2/24 1/25, 2/24

Enkling 2010 Parallel No failures (n = 15) No failures (n = 15)

den Hartog 2011 Parallel 1/31, 0/31 1/31, 0/31

Meloni 2012 Split-mouth No failures (n = 20) No failures (n = 20)

Chiapasco 2001 (parallel group design) compared four immedi-

Design Prosthetic failures Implant failures

Payne 2002 Parallel No failures No failures

Tawse-Smith 2002 Parallel 5/24, 1/24 5/24, 1/24

Fischer 2004 Parallel No failures 1/16, 2/8

Payne 2002 (parallel group design) compared two unsplinted early

Design Prosthetic failures Implant failures

Testori 2007 Parallel 1/25, 0/27 1/25, 0/27

Cannizzaro 2008a Parallel 0/30, 2/30 0/30, 2/30

Cannizzaro 2008b Parallel No failures 1/15, 2/15

Cannizzaro 2008d Split-mouth 1/30, 1/30 1/30, 1/30

Merli 2008 Parallel No failures No failures

Zöllner 2008 Parallel 4/138, 6/128 4/138, 6/128

Testori 2007 (parallel group design) compared immediately non-