Systemic risk factors for peri-implant bone loss: a systematic review and meta-analysis


The aim of this study was to determine the influence of patient-related systemic risk factors (systemic disease, genetic traits, chronic drug or alcohol consumption, and smoking status) on peri-implant bone loss at least 1 year after implant installation and prosthetic loading. An electronic search was performed of MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials up to January 2012. One thousand seven hundred and sixty-three studies were identified. After applying a three-stage screening process, 17 articles were included in the qualitative analysis, but only 13 in the quantitative analysis, since smoking was a common exposure. The meta-analysis of these 13 studies (478 smokers and 1207 non-smokers) revealed a high level of heterogeneity and that smoking increases the annual rate of bone loss by 0.164 mm/year. Exposure to smoking had a harmful effect on peri-implant bone loss. However, the level of evidence for oral implant therapy in patients with systemic conditions is very low. Future studies should be improved in order to provide more robust data for clinical application.

The achievement of osseointegration is a biological concept already adopted in implant dentistry. The long-term maintenance of bone around an osseointegrated implant is paramount to clinical success, and peri-implant bone remodelling has commonly been expressed in terms of survival rates. It is believed that several factors may affect peri-implant bone resorption: local, surgical, implant, post-restorative, and patient-related risk factors, which include systemic diseases, genetic traits, chronic drug or alcohol consumption, and smoking status. Nevertheless, there is uncertainty around some factors. As an example, the results of a number of in vitro studies that aimed to investigate the association between specific interleukin 1 (IL-1) gene polymorphisms and peri-implant diseases were unclear ; this later generated further methodological problems. On the other hand, other factors have been identified as a risk. It has been observed that smokers have a higher risk of dental implant failure than non-smokers, with an increased risk for patients with a history of treated periodontitis.

Diabetes is considered a relative contraindication for dental implant treatment. The success rates improve by 85–95% with the eradication of co-morbidities (poor oral hygiene, cigarette smoking, and periodontitis), stabilization of glycaemic control (glycated haemoglobin (HbA1c) around 7%), and preventive measures against infection. Implant failure in patients using oral/intravenous bisphosphonates to treat osteoporosis is a subject that remains controversial. In a recent systematic review, only two out of 10 selected papers demonstrated a negative impact of bisphosphonates on implant success. Moreover, no scientific data are available to sufficiently support any specific treatment protocol for the management of bisphosphonate-related osteonecrosis of the jaws (BRONJ). Finally, although the ravages of cancer therapy are well-known, implants can osseointegrate and remain functionally stable in oral cancer patients who have undergone radiotherapy and chemotherapy.

Nevertheless, the current goals of implant therapy include long-term function, the capability to maintain good oral hygiene at home (even in posterior areas of the oral cavity), and overall aesthetics. In cases of implant survival, it is very important to address how much bone is lost over time radiographically. Furthermore, there is a lack of results on peri-implant soft tissue outcomes (bleeding on probing, plaque index, gingival recession, and width of keratinized tissues).

The aim of the present study was to review, in a systematic manner, the influence of systemic risk factors on peri-implant bone loss.

Materials and methods

Study protocol

The recommendations of the PRISMA statement were followed for the review process.

Focused question

The question in focus was ‘In patients undergoing dental implant treatment, what is the influence of systemic risk factors (systemic disease, genetic traits, chronic drug or alcohol consumption, and smoking status) on the occurrence of peri-implant bone loss at least 1 year after implant installation and prosthetic loading?’

Eligibility criteria

The following inclusion criteria were applied: (1) English language publications; (2) randomized controlled clinical trials, controlled clinical trials, cohort studies, case–control studies, and case series with at least five patients (in order to include as many studies as possible); (3) human subjects presenting systemic risk factors (systemic disease, genetic traits, chronic drug or alcohol consumption, and smoking status); (4) intervention involving dental implants and/or immediate loading of dental implants; (5) studies reporting on radiographic peri-implant bone level changes assessed by means of intraoral or panoramic X-rays; and (6) follow-up of at least 1 year after implant placement and prosthetic loading (to avoid the risk of false-positive measurements of peri-implant bone loss due to bone remodelling in the first 3–6 months after implant placement, or early implant loss due to surgical procedures).

The following were exclusion criteria: (1) letters, reviews, and unpublished data; (2) patients with acute medical conditions that could contraindicate implant therapy (acute infection, severe bronchitis or emphysema, severe anaemia, uncontrolled diabetes, uncontrolled hypertension, abnormal liver function, nephritis, severe psychiatric disease, conditions with a severe risk of haemorrhage, endocarditis, and myocardial infarction); and (3) studies reporting only implant failure, survival, and/or success rates.

Study selection

Information sources and the search strategy are available in the Supplementary Material, available online.

A three-stage screening process was performed independently by two reviewers (MC and PHOR). Initially, all titles were screened to eliminate non-related publications and reviews. During the second stage, all selected abstracts were analyzed and the full-text articles were consequently retrieved. Then, all reference lists of the selected studies, relevant reviews, and studies from the ‘grey literature’ were screened for additional papers that might meet the eligibility criteria of this systematic review. In the third stage, selected articles were analyzed. Any disagreements between the two reviewers were resolved after additional discussion with a third reviewer (LC). The inter-reviewer reliability of the data extraction was calculated by determining the percentage of agreement and the correlation coefficient (kappa, 5% level of significance). In addition, study authors were contacted for incomplete or missing data when necessary.

Heterogeneity of the outcome

In order to evaluate the heterogeneity of the outcome between the selected studies, the following factors were recorded: (1) study design; (2) duration of follow-up; (3) number, mean age (range), and gender of subjects; (4) numbers and types of dental implants; (5) type of prosthetic unit; (6) systemic risk factor affecting the study population; (7) measurement of bone level changes (in mm); and (8) peri-implant soft tissue outcomes (bleeding on probing, plaque index, gingival recession, and width of keratinized tissues).

Risk of bias

Two reviewers (MC and PHOR) assessed the methodological quality using the forms ‘quality assessment of a cohort study’ and ‘quality assessment of a randomized clinical trial’, combining the proposed criteria of the MOOSE statement, STROBE statement, and PRISMA. These two validity tools consist of eight and nine items, respectively, which have to be scored with a plus, a minus, or a question mark. In accordance with Telleman et al., it was decided that studies scoring four or more plusses were methodologically acceptable. The two observers, who were blinded to the author, institute, and journal, independently generated a score for the articles. Any disagreement was resolved with a third reviewer (LC).

Data analysis and synthesis

The meta-analysis was based on the DerSimonian and Laird method. The weighted mean difference (WMD) was expressed for bone loss under a randomized effects model. WMD estimations were accompanied by the 95% confidence interval (95% CI) of the standard error and the P -value of the distinction of a null effect of the smoking factor (WMD = 0) for the solution of the meta-analysis, including the statistical value of association Q A . The statistical Q H value for heterogeneity and the relative P -value for the χ 2 test were both included. At the same time, the index I 2 was also calculated, considered as representative of the total variation due to heterogeneity. A forest plot was obtained for better visualization of the results, and a funnel plot was drawn to assess potential publication bias. The software used to perform this meta-analysis was Sinergy 3.2 (Biometrics Department, GlaxoSmithKline). All analyses were conducted with a 5% level of significance.


Study selection

The search identified 1763 references up to January 2012. A further 160 references were retrieved from other sources and cross-checked references, giving a total 1923 studies. After duplicates were removed, 1824 references were available for screening. Of these, 254 publications fulfilled the eligibility criteria; however a further 237 studies were excluded, as most of them did not report on peri-implant bone loss. After qualitative assessment of the 17 selected studies (16 cohort studies and one randomized controlled trial (RCT)), only 13 studies were included in the quantitative synthesis (meta-analysis) ( Fig. 1 ). Agreement in study selection between the reviewers was 89.53% (kappa value = 0.46).

Fig. 1
Study selection process for the meta-analysis.
(Based on the flow chart adapted from Ref. ).

Study characteristics

Table 1 gives a detailed description of the studies included, which were published from 1996 to 2011; most reported between 2 and 5 years of follow-up (range 6 months to 20 years ). A total of 1883 patients and 5730 implants were analyzed. Cigarette and tobacco smoking were the most prevalent exposures (identified as single factors in 11 studies). The others were osteoporosis, IL-1 gene polymorphisms, diabetes, endocrine diseases, cardiac diseases, and arthritis, and Sjögren’s syndrome. Radiographic bone loss was evaluated by means of intraoral apical X-rays in 11 studies, panoramic X-rays in four studies, and both methods were used in two studies. Only a few studies reported soft tissue outcomes (bleeding on probing, plaque index, gingival recession, and width of keratinized tissues). Bleeding on probing was considered in one study, the plaque index in three studies, and the pocket probing depth in three studies. No study reported data for peri-implant gingival recession or width of keratinized tissues.

Table 1
Characteristics of the selected studies.
Author, year (Ref.) Title Design/setting Follow-up time Number of patients Number of implants Single or multiple prosthetic unit Systemic factor Peri-implant bone loss (mm) Soft tissue outcomes
Haas et al., 1996 The relationship of smoking on peri-implant tissue: a retrospective study Retrospective
Smokers with dental implants
Non-smokers with dental implants
BS, IMZ implants (both groups)
S = 22.4 months
NS = 21.9 months
S = 107
NS = 314
S = 366
NS = 1000
FPD, OD (both groups) Cigarette smoking Mean values (peri-apical)
S = 3.95 Max, 1.97 Mand
NS = 1.64 Max, 1.32 Mand
Mean values (Max/Mand):
S: PI 0.96/1.12; BI 1.75/0.70; PPD 4.32/2.31; MI 1.0/0.46
NS: PI 0.60/1.1; BI 0.85/0.89; PPD 2.78/2.37; MI 0.38/0.47
Isidor et al., 1999 Outcome of treatment with implant-retained dental prostheses in patients with Sjögren syndrome Case series
BS dental implants (6 per patient)
Dental arches with poor denture retention/stability
4 years 8 54 Multiple
OD, complete, FSP
Sjögren’s syndrome Mean radiographic bone loss (peri-apical) < 1.0 (0–4 years) PI (1 year): 0.4
PI (4 years): 0.3
Carlsson et al., 2000 Long-term marginal peri-implant bone loss in edentulous patients Prospective
Duplicated data from Lindquist et al. (1996 and 1997)
15 years 44 273 FxMd prostheses (15 mm = bilateral cantilever) Cigarette smoking Mean values (peri-apical), Max/Mand
S = 1.0/1.25
NS = 0.7/0.63
No report
Geurs et al., 2001 Retrospective radiographic analysis of sinus graft and implant placement procedures from the Academy of Osseointegration Consensus Conference on Sinus Grafts Retrospective
Sinus grafts (7 types) and implant placement
Selected patients, digitized panoramic radiographs
3 years 100 (145 sinus grafts) S = 55
NS = 266
No report Tobacco smoking Mean loss in sinus graft height on panoramic radiographs
S = 1.75
NS = 1.36
Not possible (only radiographs were analyzed)
von Wowern and Gotfredsen, 2001 Implant-supported overdentures, a prevention of bone loss in edentulous mandibles? A 5-year follow-up study Prospective follow-up
AST, two-stage implant placement
Mandibular OD
11 patients (bar attachment)
11 patients (ball attachment)
5 years 22 (18 women)
OP: S = 2, NS = 5
NOP: S = 6, NS = 5
44 (2 per patient) OD Osteoporosis
Cigarette smoking
MBL (standard, peri-apical radiographs)
OP = 0.47
NOP = 0.01
GI: OP = 0.29, NOP = 0.57
PI: OP = 0.07, NOP = 0.20
Feloutzis et al., 2003 IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a well-maintained population Retrospective
Heavy smokers, moderate smokers, previous smokers, non-smokers
IL-1A (+4845) and IL-1B (+3954)
5.6 years HS = 14
MS = 14
FS = 23
NS = 39
119 IL-1-neg
56 IL-1-pos
No report IL-1 polymorphisms
Cigarette smoking
ABL: IL-1-neg = 0.45; IL-1-pos = 0.215
Peri-apical, long-cone
ABL (median values):
HS = 1.98; MS = ?; FS = 0.24; NS = 0.18; NS = 0.07 IL-1-pos, 0.36 IL-1-neg
Reported, but not divided by smoking groups
Gruica et al., 2004 Impact of IL-1 genotype and smoking status on the prognosis of osseointegrated implants Retrospective
Smokers (light, heavy), non-smokers, former light smoker, former heavy smoker
IL-1A (+4845) and IL-1B (+3954)
8 years 53
(64 = IL-1-pos)
292 No description IL-1 polymorphisms
Cigarette smoking
Mean change (1–8 years) (peri-apical radiographs)
NS = 0.21; FLS = 0.13; FHS = −0.014; LS = 0.38; HS = 0.08
No report
Peñarrocha et al., 2004 Radiologic study of marginal bone loss around 108 dental implants and its relationship to smoking, implant location, and morphology Retrospective
Single or partial tooth loss in maxilla and mandible
Solid ITI dental implants (SLA)
1 year 42 (total)
S = 16
NS = 26
S = 47 (total)
G1: n = 18
G2: n = 18
G3: n = 11
NS = 61
Single and multiple prosthetic units Cigarette smoking Mean bone loss (peri-apical radiographs)
G1: 1–10 cig/day, 0.59
G2: 11–20 cig/day, 0.91
G3: >20 cig/day, 0.89
NS = not reported
No report
Galindo-Moreno et al., 2005 Influence of alcohol and tobacco habits on peri-implant marginal bone loss: a prospective study Prospective
BS, IMTEC (TPS), Calciteck (HA)
3 years 185
S = 63
NS = 122
S = ?
NS = ?
Fixed prosthesis, OD, single crowns Tobacco smoking MBL (digital panoramic radiographs)
S = 1.36
NS = 1.25
No report
Nitzan et al., 2005 Impact of smoking on marginal bone loss Retrospective
Different implants used
S = 42.9 months
NS = 48.4 months
S = 59
NS = 102
S = 271
NS = 375
No report Cigarette smoking MBL (panoramic radiographs)
S = 0.15
NS = 0.047
No report
DeLuca and Zarb, 2006 The effect of smoking on osseointegrated dental implants. Part II: peri-implant bone loss Retrospective
Consecutive complete or partially edentulous patients
BS implants
20 years 235 767 Single, multiple, and OD Endocrine diseases, cardiac diseases, and arthritis
Cigarette smoking
Mean bone loss (peri-apical), following the first year of clinical loading
S2 = 0.07
NS2 = 0.04
No report
Norton, 2006 Multiple single-tooth implant restorations in the posterior jaws: maintenance of marginal bone levels with reference to the implant–abutment microgap Retrospective
Missing posterior teeth, some cases with sinus grafts
AST dental implants
3 years S = 7
NS = 47
S = ?
NS = ?
Multiple, freestanding prostheses Smoking Mean bone loss (peri-apical)
S = 0.77 (0.1–1.6)
NS = 0.63 (0–2.7)
Purulent exudate (1 implant)
Apical infection (2 implants)
Herzberg et al., 2006 Implant marginal bone loss in maxillary sinus grafts Retrospective
Patients with the need of a dental implant and maxillary sinus grafts
cpTi and HA-coated dental implants
6–56.5 months (mean 21.7 months) 60 S = 56
NS = 104
No report Cigarette smoking Mean bone loss (panoramic or intraoral)
S = 0.24/year
NS = 0.09/year
Two patients with swelling and sinus membrane perforations
Sanna et al., 2007 Immediately-loaded CAD–CAM manufactured fixed complete dentures using flapless implant placement procedures: a cohort study of consecutive patients Prospective
At least 1 completely edentulous arch
BS (TiUnite) immediately loaded dental implants
5 years (mean 2.2 years) S = 13
NS = 17
212 Multiple
Complete, fixed supported prostheses
Cigarette smoking Mean bone loss after 4 years (digital panoramic radiographs)
S = 2.6 (25 implants)
NS = 1.3 (22 implants)
No report
Tandlich et al., 2007 Removable prostheses may enhance marginal bone loss around dental implants: a long-term retrospective analysis Retrospective
BioCom, rough-surface dental implant
≥30 months S = 17
NS = 65
265 Single ( n = 63); multiple ( n = 52); OD (ball) ( n = 22) Osteoporosis
Cigarette smoking
BLRate (panoramic or peri-apical):
S = 0.065
NS = 0.05
No report
Sánchez-Pérez et al., 2007 Tobacco as a risk factor for survival of dental implants Retrospective
Consecutive patients
Screw-taped, sandblasted, acid-etched dental implants (Bis)
5 years S = 40
NS = 26
S = 95
NS = 70
No report Cigarette smoking Retroalveolar radiographs, parallel technique
MBL1: S = 2.7; NS = 2.78
MBL2: S = 2.41; NS = 3.13
S = 3.0
NS = 2.5
Stoker et al., 2012 Long-term outcomes of three types of implant-supported mandibular overdentures in smokers Randomized controlled clinical trial
36 patients (2IBA group)
37 patients (2ISB group)
37 patients (4ITB group)
One-stage ITI/Bonefit dental implants
8.3 years 110 baseline
103 for analysis after follow-up
256 OD Smoking Mean bone loss (long-cone)
S: 2IBA = 1.53; 2ISB = 1.17; 4ITB = 2.46
NS: 2IBA = 0.7; 2ISB = 0.83; 4ITB = 1.24
PPD (overall)
2IBA: 3.1
2ISB: 3.5
4ITB: 3.6
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Jan 21, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Systemic risk factors for peri-implant bone loss: a systematic review and meta-analysis
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