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Int. J. Oral Maxillofac. Surg. 2022; 51: 1345–1354 
https://doi.org/10.1016/j.ijom.2022.03.057, available online at https://www.sciencedirect.com 
Meta Analysis 
Dental Implants 
Long-term clinical outcomes of 
immediate loading versus 
non-immediate loading in 
single-implant restorations: a 
systematic review and 
meta-analysis 
G. Zhao, Y. Zhou, S. Shi, X. Liu, S. Zhang, Y. Song: Long-term clinical outcomes 
of immediate loading versus non-immediate loading in single-implant restorations: 
a systematic review and meta-analysis. Int. J. Oral Maxillofac. Surg. 2022; 51: 
1345–1354. © 2022 International Association of Oral and Maxillofacial 
Surgeons. Published by Elsevier Inc. All rights reserved. 
Abstract. Dental implant restoration is a predictable treatment option for 
replacing missing or damaged teeth. Conventional loading requires a prolonged 
treatment period and second surgical interventions. The aim of this study was to 
compare the clinical outcomes between immediate and non-immediate (early or 
conventional) loading in single-implant restorations. A literature search of the 
PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov 
databases was performed in January 2020. Only randomized clinical trials 
(RCTs) were included. The overall risk ratios (RRs), mean differences (MDs), 
and 95% confidence intervals (CIs) were used in the analyses. A total of 10 RCTs 
reporting on 423 patients were included. There was no significant difference in 
any of the outcomes of interest between the immediate and non-immediate 
loading cases: implant failure at the patient level (RR 1.29, 95% CI 0.35 to 4.78, 
P = 0.71), implant failure at the implant level (RR 1.19, 95% CI 0.40 to 3.51, P = 
0.75), marginal bone loss (MD −0.04, 95% CI −0.16 to 0.08, P = 0.54). 
Subgroup analyses showed similar results. Immediate loading had predictable 
long-term clinical outcomes if the indicated patients were carefully selected. The 
influences of several technical factors need to be confirmed in additional clinical 
trials. 
G. Zhaoa, Y. Zhoub, S. Shia, X. Liua, 
S. Zhanga, Y. Songa 
aState Key Laboratory of Military Stomatology 
and National Clinical Research Center for 
Oral Diseases and Shaanxi Engineering 
Research Center for Dental Materials and 
Advanced Manufacture, Department of Oral 
Implantology, School of Stomatology, The 
Fourth Military Medical University, Shaanxi, 
PR China; bLintong Rehabilitation and 
Convalescent Center of PLA Joint Logistic 
Support Force, Huaqing Road No.26, Xi’an, 
China, 710600 
Keywords: dental implants; single-tooth dental 
implants; immediate dental implant loading; 
dental restoration failure; randomized con-
trolled trials as topic. 
Accepted for publication 23 March 2022 
Available online 13 April 2022 
0901-5027/511345 + 10 © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved. 
https://doi.org/10.1016/j.ijom.2022.03.057
https://doi.org/10.1016/j.ijom.2022.03.057
http://www.sciencedirect.com/science/journal/09015027
https://doi.org/10.1016/j.ijom.2022.03.057
Conventionally, a non-disturbed healing 
period of at least 3 months without any 
loading on the implants after implanta-
tion surgery is needed to achieve com-
plete and successful osseointegration. 
This loading protocol is termed ‘con-
ventional loading’ (CL) or ‘delayed 
loading’.1–11 However, this traditional 
protocol requires a prolonged treatment 
period and an additional surgical inter-
vention,3,8 and patients usually have a 
strong desire to obtain their prosthesis 
as soon as possible.2,12,13 ‘Early loading’ 
(EL), which is defined as implant 
loading at least 48 hours but no later 
than 3 months after implant surgery, 
can shorten the treatment period. 
However, patients still need a second 
surgery and have to endure tooth loss 
for several weeks.14,15 Therefore, the 
concept of ‘immediate loading’ (IL) has 
been proposed. IL, which is defined as a 
prosthetic restoration performed within 
48 hours after the implantation proce-
dure,6,13,15–20 provides the clinician with 
the possibility of further improving the 
effect of dental implantation.6,16–19 
Compared with CL and EL, IL not 
only reduces the total treatment period 
and simplifies the surgical interventions 
but also protects the healing extraction 
socket and provides a platform to 
promote soft tissue healing, which 
contributes to aesthetics.16,21–25 Nu-
merous clinical trials have suggested 
that IL is a practical and predictable 
treatment option when sufficient pri-
mary stability of the implants can be 
achieved.9,14,17,19,26–36 Histological stu-
dies have also suggested that IL on 
implants does not influence the os-
seointegration process.37 Several sys-
tematic reviews and meta-analyses have 
shown that IL has comparable clinical 
outcomes to non-immediate loading 
(non-IL, i.e. EL or CL) over short-term 
follow-up.15,20,38 
Although IL has many advantages 
over non-IL, there is still controversy 
about this issue since some reviews 
have reported higher implant failure in 
IL cases compared with non-IL 
cases.20,39 Moreover, only a limited 
number of systematic reviews have re-
ported long-term clinical outcomes of 
IL compared with non-IL in single- 
implant restorations. A recent review 
suggested that more than 21% of im-
plant failures occur within 2 years of 
implant placement,40 which means that 
the analysis of the long-term results 
from IL implants requires a follow-up 
period of at least 2 years. 
The aim of this systematic review and 
meta-analysis was to compare the clinical 
and radiographic outcomes between IL 
and non-IL (EL or CL) in single-implant 
restorations using the indexes of the im-
plant failure rate and marginal bone loss 
(MBL). Moreover, the influences of sev-
eral technical factors were also in-
vestigated, including the type of non-IL 
(EL or CL), implant location (maxilla or 
mandible), implant placement time (im-
mediate or delayed implantation), 
loading concept (occlusal or non-occlusal 
contact), and prosthesis retention pattern 
(screw-retained or cement-retained). This 
study presents a more detailed and in- 
depth analysis to explore the influence of 
the different loading types (IL vs non-IL) 
on long-term clinical outcomes in single- 
implant restorations. 
Materials and methods 
The meta-analysis was performed 
based on the standard methodology 
outlined in the Cochrane Handbook 
and the findings are reported in ac-
cordance with the Preferred Reporting 
Items for Systematic Reviews and 
Meta-analyses (PRISMA) guidelines.41 
Search strategy 
The PICOS strategy was used to con-
struct the research question, and the 
PICO question for this research in-
cluded four aspect: P (patients or po-
pulation), patients in need of a single 
tooth replacement; I (intervention), 
treatment with a dental implant (placed 
immediately, early, or late) with im-
mediate prosthetic loading; C (com-
parator or control group), compared 
with treatment with a dental implant 
(placed immediately, early, or late) with 
conventional prosthetic loading; O 
(outcomes), implant failure and MBL. 
The search strategies to allow repeat-
ability of this study are provided in 
Supplementary Material Table S1. 
Screening of records and assessment of 
eligibility 
Two reviewers selected the studies in-
dependently by screening the titles and 
abstracts of the search results according 
to the following inclusion criteria: (1) 
the study type was a randomized clinical 
trial (RCT); (2) participants were pa-
tients with one or more missing teeth 
and undergoing IL or non-IL for single- 
implant restorations after implant 
placement; (3) a comparison between IL 
and non-IL was performed; (4) the 
duration of follow-up was at least 2 
years; (5) outcomes included implant 
failure (at the patient and implant levels) 
and MBL; and (6) publication in 
English. The exclusion criteria were as 
follows: (1) articles with inadequateavailable data (implant failure or MBL); 
and (2) reviews, case reports or case 
series, letters or comments. In addition, 
there was no limitation on the location 
of the implants in this study (maxilla or 
mandible; anterior or posterior loca-
tions). A third author resolved any dis-
agreement between the two reviewers. 
A full-text assessment was performed 
for those studies that the authors con-
sidered relevant and also those for 
which eligibility was uncertain; dis-
agreements were resolved by further 
discussion or an additional author’s 
evaluation. Regarding agreement be-
tween the reviewers, a kappa value be-
tween 0.40 and 0.59 was considered fair 
agreement, a value between 0.60 and 
0.74 was considered good agreement, 
and a value of 0.75 or more was 
considered excellent agreement. Dis- 
agreement regarding inclusion was re-
solved by discussion. When multiple 
articles reported the same trial, the 
most recent one with complete data was 
included. 
Data extraction 
Data from the studies were extracted by 
two investigators independently. The re-
corded data included general informa-
tion (first author’s name, year of 
publication, and region of the study), 
study design (loading location, types of 
non-IL, duration of follow-up, and 
sample size), characteristics of the parti-
cipants (sex and age), retention patterns 
of the prostheses, and clinical or radio-
graphic outcomes (implant failure, MBL, 
etc.). In this study, implant failure was 
defined as the presence of any mobility, 
pain, infection, or implant loss during the 
observation period, and implant failure 
rates were assessed at the patient level 
(percentage of patients with implant 
failure among all of the patients) and 
implant level (percentage of failed im-
plants among all of the implants). 
Quality assessment 
Two authors independently assessed 
the risk of bias in the included studies. 
The Cochrane Collaboration tool for 
1346 Zhao et al. 
assessing risk of bias in randomized 
trials was used,42 which includes six 
domains: selection bias, performance 
bias, detection bias, attrition bias, re-
porting bias, and other bias. Studies 
were classified as at low risk if all cri-
teria were met, as at moderate risk if 
one criterion was not met, and as at 
high risk if two or more criteria were 
not met. A third author resolved any 
disagreement between the two re-
viewers regarding the risk of bias as-
sessment. GRADEpro was used to 
perform the certainty assessment of the 
included study outcomes. 
Statistical analysis 
The data were analysed using RevMan 
v.5.3 software (Cochrane Collaboration). 
The overall risk ratios (RRs) or mean 
differences (MDs) as well as the 95% 
confidence intervals (CIs) were calculated 
with a fixed-effects model (Mantel– 
Haenszel method) or random-effects 
model (DerSimonian–Laird method). 
For dichotomous outcomes (implant 
survival), the estimate of the effect of the 
intervention on the survival rate was 
presented as the RR with a 95% CI.15 
For continuous outcomes (MBL), the 
estimate of the effect of the intervention 
was presented as the MD ± standard 
deviation with a 95% CI. The I2 statistic 
was used to present the heterogeneity of 
the studies: values ≤25% were classified as 
indicating low heterogeneity, values of 
25–50% indicated moderate hetero-
geneity, and values ≥50% indicated high 
heterogeneity.15 When significant het-
erogeneity was found (I2 > 50%), the 
random-effects model was used to pool 
the data. Otherwise, the fixed-effects 
model was applied. 
In addition, subgroup analyses based 
on the type of non-IL (EL or CL), im-
plant location (mandible or maxilla), 
implant placement time (immediate im-
plant placement or delayed implant pla-
cement), loading concept (occlusal 
contact or not), and type of prosthesis 
retention (screw-retained or cement-re-
tained) were performed. 
A sensitivity analysis was conducted 
by omitting one study at a time to ex-
amine the influence of individual stu-
dies on the overall results. Publication 
bias was explored using Egger’s test, 
with P–d
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1348 Zhao et al. 
analyses (Table 2). Most of the sub-
group analyses showed high hetero-
geneity, except those stratified by 
specific factors, including the subgroup 
analyses for mandible implant location 
(P = 0.18, I2 = 44%), implant placement 
time of delayed implant insertion (P = 
0.52, I2 = 0%), screw-retained pros-
thesis retention (P = 0.39, I2 = 3%), and 
loading concept of non-occlusal contact 
(P = 0.39, I2 = 3%). These results in-
dicate that the implant placement time, 
type of prosthesis retention, and the 
loading concept may be factors that 
affect the results. In addition, the sen-
sitivity analysis showed that none of the 
included studies had a high risk of bias; 
none of the included studies had a large 
effect on the pooled MD. 
Publication bias and assessment of the 
quality of evidence 
There was no significant publication 
bias, as evidenced by Egger’s test 
(P > 0.05). The GRADEpro results are 
shown in Supplementary Material Fig. 
S1; all of the outcomes analysed had 
high certainty. 
Discussion 
With the benefits of reducing the 
treatment period, avoiding a second 
surgical intervention, and better aes-
thetic outcomes,16,22–25,30 IL has been a 
topic of interest for years. However, 
previous studies have demonstrated the 
continuing controversy regarding the 
clinical outcomes of IL, and only a 
limited number of meta-analyses have 
focused on long-term outcomes. This 
Fig. 2. Risk of bias summary. 
Fig. 3. Risk of bias graph. 
Immediate vs non-immediate single implant loading 1349 
controversy prompted the present 
meta-analysis, which aimed to further 
investigate the predictability of IL 
compared with EL and CL in terms of 
long-term clinical outcomes and to ex-
plore factors that influence the ther-
apeutic effect of IL. The overall results 
showed that there was no significant 
difference in implant failure or MBL 
between IL and non-IL, and the sub-
group analyses showed similar results 
to those of the overall analyses. These 
findings indicate that IL is a predictable 
and reliable treatment protocol for 
single-implant restorations over long- 
term follow-up. 
All studies included in the analysis 
had strict inclusion criteria for patient 
selection, such as good clinical health, 
non-smoking status, a minimum bone 
height of 10–12 mm, a minimum bone 
width of 5–6 mm, at least 5 mm of 
keratinized gingiva crestal,1,44,46,48 and 
missing teeth with adjacent natural 
teeth.13,47 Patients with an active in-
fection or periodontal disease at the 
sites intended for implant placement, as 
well as those with chronic systemic 
diseases or poor oral hygiene, were ex-
cluded.43,45,49,50 These strict inclusion 
criteria indicate that IL is a procedure 
with high technique sensitivity; hence 
more clinical trials are needed to ex-
pand on its indication and application 
in intractable cases. Most of the in-
cluded studies considered an insertion 
torque of 30–35 N∙cm to be acceptable, 
because adequate primary stability 
usually means better loading tolerance 
and thus is regarded as an important 
condition to be satisfied when IL is to 
be used.1,43,44,46,47,49 
In the subgroup analyses for MBL, 
only the subgroup analyses by mand-
ible implant location, implant place-
ment time of delayed implant insertion, 
screw-retained prosthesis retention, and 
loading concept of non-occlusal contact 
did not present high heterogeneity, in-
dicating that these factors may affect 
the final prognosis. The difference in 
heterogeneity between the subgroups of 
implant location – maxilla or mandible 
– may be due to the difference in bone 
quality between the maxilla and 
mandible. The higher bone density of 
the mandible could lead to less bone 
remodelling and higher primary im-
plant stability. Regarding the type of 
prosthesis retention, the provisional 
restoration can be screw-retained or 
cement-retained. When the provisional 
restoration is cemented, there is a 
higher risk of gingival inflammation at 
the abutment–cement–restoration in-
terface, as well as cement debonding.51 
A recent review suggested that screw- 
retained single-implant restorations 
have several advantages over cement- 
retained restorations, including better 
clinical outcomes, more predictable re-
tention and retrievability, fewer biolo-
gical consequences associated with 
residual cement, and a simpler re-
storative process.52 Regarding the 
loading protocol, immediate restora-
tion without occlusal contact achieves a 
significantly higher implant survival 
Fig. 4. Forest plot for implant failure at the patient level. IL: immediate loading; EL: early loading; CL: conventional loading. 
Fig. 5. Forest plot for implant failure at the implant level. IL: immediate loading; EL: early loading; CL: conventional loading. 
1350 Zhao et al. 
T
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0.
98
 
0%
 
0.
97
 
1.
02
 (
0.
21
, 
4.
93
) 
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on
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cc
lu
sa
l 
co
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t 
5 
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37
 
0%
 
0.
94
 
2.
77
 (
0.
30
, 
25
.5
9)
 
P
ro
to
co
l 
fo
r 
no
n-
im
m
ed
ia
te
 l
oa
di
ng
 
IL
 v
s 
E
L
 
1 
0.
96
 
N
A
 
N
A
 
1.
07
 (
0.
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, 
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1)
 
IL
 v
s 
C
L
 
9 
0.
75
 
0%
 
0.
81
 
1.
21
 (
0.
37
, 
3.
95
) 
M
B
L
 
Im
pl
an
t 
lo
ca
ti
on
 
M
ax
ill
a 
6 
0.
73
 
60
%
 
0.
03
 
0.
03
 (
−
0.
15
, 
0.
22
) 
M
an
di
bl
e 
2 
0.
06
 
44
%
 
0.
18
 
−
0.
25
 (
−
0.
81
, 
0.
01
) 
Im
pl
an
t 
pl
ac
em
en
t 
ti
m
e 
Im
m
ed
ia
te
 
4 
0.
28
 
72
%
 
0.
01
 
−
0.
10
 (
−
0.
28
, 
0.
08
) 
D
el
ay
ed
 
6 
0.
54
 
0%
 
0.
52
 
0.
02
 (
−
0.
11
, 
0.
15
) 
T
yp
e 
of
 p
ro
st
he
si
s 
re
te
nt
io
n 
Sc
re
w
-r
et
ai
ne
d 
5 
0.
37
 
3%
 
0.
39
 
0.
04
 (
−
0.
10
, 
0.
18
) 
C
em
en
t-
re
ta
in
ed
 
4 
0.
11
 
58
%
 
0.
07
 
−
0.
13
 (
−
0.
29
, 
0.
03
) 
L
oa
di
ng
 c
on
ce
pt
 
O
cc
lu
sa
l 
co
nt
ac
t 
3 
0.
73
 
79
%
 
0.
01
 
−
0.
05
 (
−
0.
33
, 
0.
23
) 
N
on
-o
cc
lu
sa
l 
co
nt
ac
t 
5 
0.
52
 
3%
 
0.
39
 
0.
04
 (
−
0.
13
, 
0.
21
) 
P
ro
to
co
l 
fo
r 
no
n-
im
m
ed
ia
te
 l
oa
di
ng
 
IL
 v
s 
E
L
 
1 
0.
53
 
N
A
 
N
A
 
0.
 0
6 
(−
0.
13
, 
0.
25
) 
IL
 v
s 
C
L
 
9 
0.
43
 
53
%
 
0.
03
 
−
0.
05
 (
−
0.
18
, 
0.
08
) 
R
R
, 
ri
sk
 r
at
io
; 
M
D
, 
m
ea
n 
di
ff
er
en
ce
; 
C
I,
 c
on
fid
en
ce
 i
nt
er
va
l; 
N
A
, 
no
t 
ap
pl
ic
ab
le
; 
IL
, 
im
m
ed
ia
te
 l
oa
di
ng
; 
E
L
, 
ea
rl
y 
lo
ad
in
g;
 C
L
, 
co
nv
en
ti
on
al
 l
oa
di
ng
; 
M
B
L
, 
m
ar
gi
na
l 
bo
ne
 l
os
s.
 
Immediate vs non-immediate single implant loading 1351 
rate compared to restoration with oc-
clusal contact,23 since there is reduced 
interference with osseointegration of 
the implant. Therefore, it is concluded 
that the screw-retained type of pros-
thesis retention, a mandible location, 
and non-occlusal contact may be ben-
eficial and enhance the prognosis of IL 
in single-implant restorations. How-
ever, more clinical trials are needed to 
confirm the effects of these factors. 
Some of the included studies com-
bined immediate implant placement 
with IL43,45,47,49 to reduce the treatment 
period and replace the damaged tooth 
immediately. Recent clinical studies 
and reviews have suggested that IL of 
immediate dental implants is a reliable 
treatment option for dental rehabilita-
tion,28,53,54 but others have argued that 
immediate implants may be at higher 
risk of implant failure than delayed 
implants.15 In the present study, the 
analysis of MBL for IL versus non-IL 
showed high heterogeneity, while the 
heterogeneity in the subgroup analysis 
for MBL according to a delayed im-
plant placement time was not sig-
nificant. Therefore, it seems that IL has 
a more predictable prognosis when 
combined with delayed implant place-
ment than immediate implant place-
ment. Clinical studies have suggested 
that most of the reduction in alveolar 
bone mass after the extraction of nat-
ural teeth occurs within the first 6 
months to 2 years.12 This indicates that 
unpredictable MBL in IL of an im-
mediately placed implant might occur 
due to post-extraction bone remodel-
ling of the alveolar bone, so the influ-
ence of IL is still controversial. 
This study has some advantages 
when compared to previous meta-ana-
lyses.15,20,38–40,55 First, this study ana-
lysed the long-term follow-up clinical 
outcomes of IL compared with non-IL, 
including EL and CL, in single-implant 
restorations. Second, subgroup ana-
lyses were performed to further in-
vestigate factors influencing the final 
prognosis, including the type of non-IL 
(EL or CL), implant location (mandible 
or maxilla), implant placement time 
(immediate implant placement or de-
layed implant placement), loading 
concept (occlusal or non-occlusal con-
tact), and type of prosthesis retention 
(screw-retained or cement-retained). 
The controversy regarding the long- 
term effects of IL as reported in pre-
vious studies may have been caused by 
the factors mentioned above. For ex-
ample, according to this meta-analysis, 
better outcomes a more likely to be 
achieved with a screw-retained pros-
thesis, for implants located in the 
mandible, and for implants with non- 
occlusal contact. 
The main limitation of this study was 
the inability to perform all of the sub-
group analyses due to small sample 
sizes. Although multiple databases were 
searched, the number of included stu-
dies was still small, and for some cases, 
such as implant failure, there was rela-
tively low power to show any differ-
ences between IL and EL/CL for these 
outcomes. Thus, more clinical trials are 
still needed to investigate the effects of 
these factors on the prognosis of IL. 
In conclusion, IL shows predictable 
and reliable clinical outcomes at long- 
term follow-up when applied to single- 
implant restorations in carefully selected 
cases. An insertion torque of 30–35 N∙cm 
is acceptable for the use of IL for a single 
implant. A screw-retained prosthesis re-
tention type, implant location in the 
mandible, and implant with non-occlusal 
contact may be important to ensure the 
prognosis of IL of a single implant. 
Funding 
This study was supported by the 
National Natural Science Foundation 
of China (No. 81771107); the School of 
Stomatology, Fourth Military Medical 
University. The funding of this study 
supported the analysis, interpretation 
of the data, and the decision to submit 
the article for publication. 
Ethical approval 
Not required. 
Patient consent 
Not required. 
Data availability 
The data used to support the findings 
of this study are available from the 
corresponding author upon request. 
Acknowledgements. The authors thank 
Wei Ma, Chao Xie, and Yan Liu for 
their contributions and valuable assis-
tance in the research. 
Competing interests 
None. 
Appendix A. Supporting 
information 
Supplementary data associated with 
this article can be found in the online 
version at doi:10.1016/j.ijom.2022. 
03.057. 
Fig. 6. Forest plot for marginal bone loss. IL: immediate loading; EL: early loading; CL: conventional loading. 
1352 Zhao et al. 
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Correspondence to: State Key Laboratory 
of Military Stomatology and National 
Clinical Research Center for Oral Diseases 
and Shaanxi Engineering Research Center 
for Dental Materials and Advanced 
Manufacture 
Department of Oral implantology 
School of Stomatology 
The Fourth Military Medical University 
Shaanxi 710032 
PR China. 
Tel:+86 029 84776454. 
E-mail: songyingliang@163.com 
1354 Zhao et al. 
	Long-term clinical outcomes of immediate loading versus non-immediate loading in single-implant restorations: a systematic r...
	Materials and methods
	Search strategy
	Screening of records and assessment of eligibility
	Data extraction
	Quality assessment
	Statistical analysis
	Results
	Study selection
	Characteristics of the included studies
	Meta-analyses for implant failure
	Meta-analysis for marginal bone loss (MBL)
	Publication bias and assessment of the quality of evidence
	Discussion
	Funding
	Ethical approval
	Patient consent
	Data availability
	Acknowledgements
	Competing interests
	Appendix A. Supporting information
	References