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Histological features of peri-implant bone subjected to overload
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Histological features of peri-implant bone subjected to overload Gaia Pellegrini a,b,∗ , Luigi Canullo c , Claudia Dellavia a a
Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy. Research Center for Oral Implantology (CRIO), IRCCS Galeazzi Orthopaedic Institute, Milan, Italy. c Private Practice, Rome, Italy. b
a r t i c l e
i n f o
Article history: Received 4 December 2014 Received in revised form 13 January 2015 Accepted 11 February 2015 Available online xxx Keywords: Overloading Peri-implantitis Histology Animal study Dental implant
a b s t r a c t Purpose: The aim of this review has been to investigate the histological findings of bone structure surrounding implants subjected to excessive load. Materials and methods: Clinical and pre-clinical histological studies that observed overloaded intraoral implants were included. Results: All included studies (n = 15) were conducted on animals. Most of them failed to find pathological alteration in the microstructure of bone surrounding overloaded implants. Overload and infection alone may induce bone loss, but related lesions have different and peculiar features. Conclusions: The different histological features observed around implants subjected to overload or to ligature-induced peri-implantitis may indicate a specific pathogenetic mechanism for overload or infection-induced loss of osseointegration. The clinical significance of these findings should be confirmed in human studies. © 2015 Elsevier GmbH. All rights reserved.
Contents 1. 2.
3.
4. 5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Types of studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Type of intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Outcome measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5. Information sources and search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7. Data extraction and management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Static overload . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Dynamic overload . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Loading the bone tissue during physiologic masticatory function regulates the remodeling of peri-implant tissue (Greenstein et al., 2013). When the applied force has the potential to cause permanent
∗ Corresponding author at: Via Mangiagalli, 31 20133 Milano, Italy. Tel.: +39 0250315405; fax: +39 0250315387; mobile: +39 347 5923198. E-mail address: [email protected] (G. Pellegrini).
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deformation or damage to the structure or its support, overloading occurs (Laney et al., 2007). In implant dentistry, the effect of occlusal overloading on the loss of osseointegration is still a controversial issue. Some recent reviews were designed to examine the role of excessive and adverse masticatory load in peri-implant bone loss (Naert et al., 2012; Chambrone et al., 2010; Chang et al., 2013). These studies did not resolve this issue since the available data in the literature were too limited. Therefore, the question of whether the occlusal overloading by itself is able to induce peri-implant bone loss and
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Please cite this article in press as: Pellegrini, G., et al., Histological features of peri-implant bone subjected to overload. Ann. Anatomy (2015), http://dx.doi.org/10.1016/j.aanat.2015.02.011
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thus implant failure still remains. Histological evidence may help to answer this question, since it contributes to understanding of the pathogenetic mechanism of bone resorption under excessive mechanical stress. The aim of the present review has been to describe bone histological features around implants subjected to overload. 2. Materials and methods This review was performed according to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and MetaAnalyses). 2.1. Types of studies Clinical trials, randomized controlled clinical trials, case series as well as animal experimental trials, which had performed histological analysis and were published in English were included. No narrative or systematic reviews were considered. 2.2. Type of intervention Clinical or pre-clinical studies that applied overload to osseointegrated implants placed in maxillary or mandibular bone were included. 2.3. Study selection In this review, clinical and pre-clinical studies presenting histological descriptions of the peri-implant bone features after static and dynamic overload on osseointegrated implants were included. All types of histological assessments were included. No publication status was imposed. For clinical trials a follow-up of at least 6 months was required, including a measure of the occlusal overload and the assessment of overload as aetiological factor of the periimplantal bone loss. All studies evaluating factors that increase the load transmitted to the implant–bone interface such as single vs. splinted implants, short vs. long cantilevers, small vs. large crownimplant ratios, misfitting prosthesis were also included. For the animal studies, only intra-oral experimental sites were considered. No unpublished data were included. No narrative or systematic reviews were considered. In vitro studies, studies on immediately loaded implants, not measuring the overload and not assessing histologically the peri-implant bone status as consequence of the occlusal overload were excluded. 2.4. Outcome measures The primary outcome was the histological assessment of static or dynamic overload on bone structure surrounding the osseointegrated implants. Overload was defined as the application of forces that presumably exceed the physiological range in terms of intensity, direction or timing. 2.5. Information sources and search Studies were identified by the Medline (Pubmed) electronic databases and the search was performed on articles published from the 1st January 1975 to the 22nd of June 2014. Hand search by scanning reference lists of articles and consultation with experts in the field were performed. Authors were contacted in order to acquire missing information. To perform the research, the following key terms were applied to the database: oral OR dental AND implant$ AND (load OR overload OR excessive
load OR force$ OR bruxism) AND (bone loss OR bone resorption OR implant failure$). 2.6. Study selection One independent reviewer (GP) firstly excluded irrelevant records by their title and abstract. To be included in the review, the full-text of each remaining paper was evaluated by two independent reviewers (CD and GP); disagreements between reviewers were resolved by consensus. 2.7. Data extraction and management To perform a statistical comparison between articles, studies that used similar protocols were selected and comparable data were extracted. 3. Results A total of 3222 studies were identified in the database. After removing duplicates and records that did not fit the inclusion criteria, only 15 articles remained (see Fig. 1) (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002; Hürzeler et al., 1998; Miyata et al., 1998, 2000, 2002; Ogiso et al., 1994; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007; Nagasawa et al., 2013; Isidor, 1997a,b). All included studies were performed on animals (seven on dogs) (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002; HeitzMayfield et al., 2004; Kozlovsky et al., 2007), seven on monkeys (Hürzeler et al., 1998; Miyata et al., 1998, 2000, 2002; Ogiso et al., 1994; Isidor, 1997a,b), one on rats (Nagasawa et al., 2013) and had variable periods of observation from 1 week to 18 months as reported in Table 1. The included studies analyzed the bone response after static and dynamic overload, in healthy conditions or after experimental plaque induced peri-implant inflammation. Data from the studies were reported separately considering the type of load and the control or not of peri-implant inflammation. Most of the studies reported quantitative histological parameters such as: bone-implant-contact (BIC), bone density (BD), bone level and other histomorphometric measurements of the peri-implant defect (i.e. inflammatory connective tissue are, ICT) (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002; Hürzeler et al., 1998; Miyata et al., 1998, 2000, 2002; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007; Nagasawa et al., 2013; Isidor, 1997a,b). Furthermore, few studies reported microscopic morphological aspects of peri-implant bone (Hürzeler et al., 1998; Miyata et al., 1998, 2000; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007; Nagasawa et al., 2013; Isidor, 1997a,b), and few studies evaluated the bone metabolism by means of fluorochromes (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002).Due to the heterogeneity of data reported from the included studies, no meta-analysis was performed. 3.1. Static overload In a dog model, 12 implants after 24 weeks of overload had similar peri-implant histological features, bone level, even greater bone density (from 70% to 76%) and bone-to-implant contact (66–67%) than unloaded sites (bone density 58%, BIC 59%) (Gotfredsen et al., 2001a). In a further study performed on 5 dogs, for a total of 20 implants loaded for 12 weeks and 10 unloaded implants, similar bone density was found in overloaded implants with mucositis (69.1%) and overloaded implants with ligature induced peri-implantitis (75.7%); on the contrary unloaded implants with ligature-induced peri-implantitis showed lower bone density (59%) and bone activity (Gotfredsen et al., 2002). Implants with experimental peri-implantitis had greater bone loss than those affected
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Table 1 Characteristics of the included studies. Article
Experimental model
Implant number (time of loading or observation)
Load mode
Type of loading
Histological assessments
Histological results
Miyamoto et al. (2008)
12 dogs/mandible
12 UI (24 w)
Cantilever-type superstructure
Static
BIC, bone level, flourochrome
Expansion screw (0.0 mm, 0.2 mm, 0.4 mm, 0.6 mm of expansion)
Static
BIC, BD, flourochrome, marginal bone level
Overload cause time-depending changes LI 4 w: higher remodeling activity than UI and LI 12 w. Higher ratio of fluorescence-labeled bone is in the inner thread region of LI 4 w than of LI 12 w (p < 0.05). Lower marginal bone loss in UI and LI 4 w than LI 12 w (p < 0.05). Higher BIC in LI 4 w than UI (p < 0.05). BIC = UI: 56–61%. LI 4 w 74–77%, LI 12 w 63%. Higher BD and BIC around LI than around UI. Respectively (BD: 70–79%; BIC: 66–67%, and BD: 58%; BIC: 59%).
Expansion screw (0.6 mm of expansion)
Static
BIC, BD, flourochrome
Expansion screw (0.6 mm of expansion)
Static
BIC, BD, flourochrome
Expansion screw (1.6 mm of expansion)
Static
BD, flourochrome, histometric measurements (ICT)
Orthodontic springs
Dynamic horizontal
BIC (length and percentage)
Supra occlusal contact of 100 m
Dynamic, lateral
Quantity of bone resorption
Supra occlusal contact of 100 m, 180 m and 250 m
Dynamic, lateral
Bone resorption
12 LI (12 w)
Gotfredsen et al. (2001a)
3 dogs/mandible
12 LI (4 w) 18 LI (24 w)
Gotfredsen et al. (2001b)
3 dogs/mandible
6 UI (24 w) 6 TPS LI (24 w)
6 machined LI (24 w)
Gotfredsen et al. (2001c)
3 dogs/mandible
9 LI (10 w)
Gotfredsen et al. (2002)
5 dogs/mandible
9 LI (46 w) 10 LI-mucositis (12 w) 10 UI-PI
Hürzeler et al. (1998)
5 monkeys/mandible
10 LI-PI (12 w) 10 UI (4 m) 10 LI (4 m) 10 UI-PI (4 m)
Miyata et al. (1998)
Miyata et al. (2000)
5 monkeys/mandible
4 monkeys/mandible
10 LI-PI (4 m) 2 UI 2 LI (1 w) 2 LI (2 w) 2 LI (3 w) 2 LI (4 w) 2 UI 2 LI/100 m (4 w)
2 LI/180 m (4 w) 2 LI/250 m (4 w)
Higher marginal bone level, BIC, BD in TPS than in machined BD: 73% in TPS and 63% in machined; BIC: 60% in TPS and 53% in machined Similar BD and BIC. 10 w = BD: 81%, BIC: 81%; 46 w = BD: 83%, BIC: 83%. Lower bone markers at 46 w than at 10 w Similar bone loss in LI-PI and UI-PI Higher BD and bone labels in LI-PI than UI-PI. BD respectively 75% and 59% (p > 0.05). BD in LI-mucositis was 69%. In LI-mucositis the ICT was small and localized; UI-PI and LI-PI had large ICT in the peri-implant mucosa and extended 0.5–1 mm apical to the JE No significant effects of load Lower BIC length and % in PI than in healthy sites Higher BIC in LI (57%) and UI (55%) than in LI-PI (36%) and UI-PI (43.8%) (p < 0.05) Absence of great bone loss in loaded sites
Bone resorption depending on IVD No bone resorption in LI/100 m and UI. In LI/180 m slight bone resorption to almost half of the implant. In LI/250 m vertical bone resorption reaching the apex of the implant, epithelial downgrowth.
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4 Table 1 (Continued) Article
Experimental model
Implant number (time of loading or observation)
Load mode
Type of loading
Histological assessments
Histological results
Miyata et al. (2002)
4 monkeys/mandible
2 LI-PI (8 w) (group P)
Supra occlusal contact of 250 m
Dynamic, lateral
Inflammatory cell infiltration
Supra occlusal contact; IVD: 4–5 mm
Dynamic, axial
Morphology
Supra occlusal contact; IVD: 3 mm
Dynamic, axial
BIC, linear measurements (alveolar bone height, bone levels)
Supra occlusal contact; IVD: 3 mm
Dynmic, axial.
BIC, histomorphometric measures
Cantilever-type superstructure
Dynamic, lateral
BIC
Supra occlusal contact with a lateral direction
Dynamic, lateral
BIC, BD
Supra occlusal contact with a lateral direction
Dynamic, lateral
Bone level
No difference in bone resorption. Irreversible changes in E. In N (NI): slight ICT. In P and E: bone resorption at apical third of the implant and massive ICT. Peri-implant bone progressively thickening and remodeling over the time No differences in bone height, bone level and BIC between LI and UI. BIC: LI = 73.9%, UI = 72.6%. 2 LI lost, 1 UI lost. Overloading without inflammation increased BIC and BIC%. Overloading + inflammation increased bone loss (LI: 0.12/0.5 mm, UI: 0.37/0.8 mm, LI-PI: −3.08/−3.28 mm, UI-PI: −2.5/−2.53 mm), but did not change BIC% (LI: 66%, UI: 53%, LI-PI: 67.53, UI-PI: 62.68%). Bone degeneration after loading UI 2 w: partial osseointegration. LI 2 w: two implants failed, active bone resorption, loss of osseointegration, microfractures of the bone adjacent to the implant surface. Higher BIC in UI. UI 4 w: established osseointegration. LI 4 w: relatively wide area of preserved osseointegration, active bone resorption in the remote areas of the implant after 15 d of loading. Differently from peri-implant infection, overload induces loss of osseointegration. LI: 6 out of 8 implants became mobile. BIC: 23–34%, BD: 55%. UI-PI: BIC: 64.3%, BD: 38%. Overload induces loss of osseointegration. Bone level: LI = −4.8 mm, UI-PI = −2.4 mm.
Ogiso et al. (1994)
6 monkey mandible/maxilla
2 NI (group N) 4 LI-PI for 4 w and then UI brushed for subsequent 4 w (group E) 12 LI (1–3 m)
Heitz-Mayfield et al. (2004)
6 dogs/mandible
Pristine bone as control 22 LI (8 m)
Kozlovsky et al. (2007)
4 dogs/mandible
23 UI (8 m) 8 LI (12 m)
Nagasawa et al. (2013)
40 rats/maxilla
8 UI (12 m) 8 LI-PI (12 m) 8 UI-PI (12 m) Abutment placed after 2 w of healing 16 UI
Isidor (1997a)
4 monkeys/mandible
8 LI (5 d) 8 LI (10 d) 8 LI (15 d) Abutment placed after 4 w of healing 16 UI 8 LI (5 d) 8 LI (10 d) 8 LI (15 d) 8 LI (18 m)
Isidor (1997b)
4 monkeys/mandible
12 UI-PI (18 m) 8 LI (18 m)
12 UI-PI (18 m)
TPS, titanium plasma spray; BD, bone density; BIC, bone-implant contact; LI, overloaded implants; UI, unloaded implants; NI, normal occlusion implants; PI, ligature induced peri-implantitis; ICT, inflammatory infiltrate connective tissue; JE, junctional epithelium; IVD, increased vertical dimension; w, weeks; d, days; m, months.
by mucositis (Gotfredsen et al., 2002). The authors demonstrated that lateral static load did not enhance bone loss at implants with experimental peri-implantitis (Gotfredsen et al., 2002). In only one study on dogs following 12 implants over different loading periods, was the static-oblique load (mesio-distal/coronalapical) induced by means of a cantilever-like superstructure (Miyamoto et al., 2008). The authors observed increased remodeling activity in the peri-implant bone after 4 weeks of loading compared to the unloaded control. However, at 12 weeks of loading,
the remodeling activity decreased and marginal bone loss was significantly greater than at 4 weeks (Miyamoto et al., 2008). 3.2. Dynamic overload All studies of this group compared overloaded implants to unloaded implants except Miyata et al. (2002) and Ogiso et al. (1994) that respectively chose normally loaded implants and pristine bone as control.
Please cite this article in press as: Pellegrini, G., et al., Histological features of peri-implant bone subjected to overload. Ann. Anatomy (2015), http://dx.doi.org/10.1016/j.aanat.2015.02.011
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Records idenfied through database searching (n = 3222)
5
Addional records idenfied through other sources (n = 0)
Records aer duplicates removed (n = 894 duplicates removed)
Records screened (n = 2328)
Records excluded (n = 2302)
Full-text arcles assessed for eligibility (n = 26)
Full-text arcles excluded, with reasons (n = 11)
Studies included in qualitave synthesis (n = 15)
Studies included in quantave synthesis (n = 0)
Fig. 1. PRISMA flow diagram.
In three studies the excessive occlusal load was produced by means of supra-occlusal contact provided by 3–5 mm vertical dimension increments (Ogiso et al., 1994; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007). Thus an axial direction of the occlusal load was mainly obtained (Ogiso et al., 1994; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007). At 1 month of loading, Ogiso et al. (1994) in 6 monkeys on 12 overloaded implants compared to pristine bone, a bone remodeling progressing along the loaded implants was found, with poorly differentiated bone without lamellar structure transforming into new highly stained lamellar bone. After 3 months of loading the authors observed thicker trabeculae and compact bone with several more osteons than after 1 month (Ogiso et al., 1994). Heitz-Mayfield et al. (2004) (6 dogs with a total of 45 implants followed for 8 months) did not observe differences between loaded and unloaded sites (respectively, BIC% was 74% and 73%). Kozlovsky et al. (2007) (4 dogs with 8 implants each, followed for 12 months) found a higher percentage of BIC in loaded (66%) than in unloaded (53%) in healthy sites. In sites with experimental peri-implantitis, overloading enhanced peri-implant intrabony vertical bone resorption, which resulted in a significant increase in bone loss (p < 0.05) (Kozlovsky et al., 2007). In a study on monkeys, sites were only submitted to a distalizing overload obtained with an orthodontic device when the animal opened its mouth (Hürzeler et al., 1998). After 4 months (10 implants per group), no inflamed peri-implant connective tissue was observed and collagen fibers were organized parallel to the implant surface and were similar to non-overloaded sites (Hürzeler et al., 1998). In the same study, detrimental effects on bone level were observed in sites with ligature-induced periimplantitis compared to healthy sites. In inflamed sites (with or
without overload) large inflammatory infiltrate moved from the peri-implant soft tissue toward the alveolar bone thus altering the structure of the peri-implant soft-tissue. In particular, apically extended pocket epithelium was found and no collagen fibers were observed between the junctional epithelium and the alveolar bone (Hürzeler et al., 1998). However, the addition of overload did not affect BIC and bone loss, but the remaining apical two-thirds of the implant were osseointegrated in compact alveolar bone (Hürzeler et al., 1998). Six studies produced supra-occlusal contacts with an oblique/lateral (mesio-distal or lingual-buccal) stress direction (Miyata et al., 1998, 2000, 2002; Nagasawa et al., 2013; Isidor, 1997a,b). Miyata showed increased bone resorption in four monkeys only when a 180 m or even more excessive height of the suprastructures was applied (two implants per group in a parallel group study) (Miyata et al., 2000) while in four monkeys (Miyata et al., 1998) no effect of a 100 m supra occlusal contact was observed at 1, 2, 3, and 4 weeks compared to unloaded implants (one monkey) (Miyata et al., 1998). Isidor (1997a) examined eight overloaded implants in four monkeys and six out of eight implants became mobile in a 18-month observation period. Nagasawa et al. (2013) reported on 40 rats with two implants each, one loaded at 2 weeks and one at 4 weeks and overall only two implants failed (at 15 days in 2 w group). In all, 16 implants were non-loaded and 24 overloaded. Observation times were 5, 10, and 15 days. Both studies reported degenerative changes in peri-implant bone subjected to excessive stress (Nagasawa et al., 2013; Isidor et al., 1997a). In particular, the authors observed a moderate inflammatory infiltrate within the supracrestal mucosa. At the coronal site of the implants the bone loss was evident, while at the apical part it was
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observed that the loss of bone-implant contact with active bone resorption was mediated by multinucleated cells. Furthermore, islands of bone appeared close to or in direct contact with the implant surface but they were isolated from the remaining bone by surrounding connective tissue (Nagasawa et al., 2013; Isidor et al., 1997a).
4. Discussion The detrimental effect of occlusal overload on bone-implant interface is still a controversial issue. Previous systematic reviews of literature, performed on pre-clinical studies, failed to find a close correlation between occlusal overload and implant failure, since only a few studies with several biases have been conducted to support the cause–effect relationship (Naert et al., 2012; Chambrone et al., 2010). Otherwise, clinical studies reported negative effects of bruxism on long-term prognosis of dental implants (Esposito et al., 1998). Due to ethical reasons, clinical control trials evaluating survival of overloaded or loaded implants have not been published. Assessment of pathogenic mechanism underlying the bone resorption induced by overload, may help to clear this issue. The present review was designed to describe the histological response of peri-implant bone tissue subjected to an excessive load, and, thus, to histologically define the failing peri-implant tissue and investigating the pathogenic mechanism of peri-implant bone resorption induced by excessive load. Depending on its intensity, load may have osteogenic properties or may induce bone damage. Frost reported that at about 1000–1500 microstrain the modeling usually promotes strengthening of the bone and at 3000 microstrain microscopic bone damage begins to accumulate without being repaired (Frost, 2004). These threshold strains may change depending on systemic factors such as hormones, drugs, and vitamins that modify the bone structure and its response to a mechanical stress (for review see Frost, 2004), and may also change depending on the type of load (Duyck and Vandamme, 2014). Implant position, masticatory function and habits, including the type of diet, the muscular biotype and the masticatory model (horizontal vs. vertical) may affect the load; however, studies did not analyze these parameters. Studies selected in the present review did not carefully measure and report the actual load transmitted to the bone-implant interface, different animal models were used with different time of loading and different follow-ups and for these reasons conflicting data emerges. Between selected studies, some reported bone resorption (Miyata et al., 2000, 2002; Nagasawa et al., 2013; Isidor, 1997a,b) as well as some observed increase in bone density in overloaded implants (Miyamoto et al., 2008; Gotfredsen et al., 2001a, 2002; Kozlovsky et al., 2007). It is not possible to demonstrate that the observed effect is directly related to the excessive force over the threshold strain. However, histological alterations on physiologic bone structure around osseointegrated overloaded implants were observed (Miyata et al., 2000; Nagasawa et al., 2013; Isidor, 1997a,b). Thus, a detrimental effect of the force over a threshold strain on the integrity of peri-implant bone may be accepted, but it is not possible to define which are the real masticatory dynamic or static situations that establish such bone damage. In order to characterize bone damage following overload, the histological features of peri-implant lesions were observed, and differences between plaque and overload induced peri-implant bone loss were found. The included studies observed only a minimal inflammatory infiltrate in the supracrestal connective tissue around overloaded implants (Miyata et al., 2000; Nagasawa et al., 2013; Isidor, 1997a). A narrow zone of fibrous tissue was interposed between the implant and the surrounding bone. Multinucleated cells were observed adjacent to the implant surface. Small pieces
of bone tissue appeared close to or in contact with the implant surface but separated from the remaining bone by dense fibrous connective tissue as result of microfractures (Nagasawa et al., 2013; Isidor, 1997a). In contrast, around implants with ligatureinduced peri-implantitis and without overload, the supracrestal connective tissue was densely infiltrated by inflammatory cells and osteoclastic activity appeared on the bone crest of these implants (Nagasawa et al., 2013). Bone resorption may be performed by several cells. Osteoclasts are the most important cells inducing bone remodeling in physiological status (Athanasou and Sabokbar, 1999). Monocytes/macrophages may intervene in bone resorption during pathological events, for example, in peri-prosthetic osteolysis, which is characterized by macrophage phagocytosis of particles of wear debris and formation of foreign body granulomas (Lassus et al., 1998; Koulouvaris et al., 2008; Purdue, 2008). Studies selected in this review seem to indicate that overload and ligature induced infection cause a different pattern of bone resorption with the involvement of different cells. However, studies did not define the gene profile of cellular population that intervened in these pathologic processes. Esposito et al. (1997) found only a minimal inflammatory infiltrate in supracrestal connective tissue and found (similarly to what happens in peri-prosthetic osteolysis) a large number of macrophages accumulated within the tissue adjacent to the implant surface. Piattelli et al. (2003) found the complete absence of bacteria in the most coronal portion of the implant, and a poorly cellular dense connective tissue with few inflammatory cells. However, in both these studies the overload as reason of implant failure was only deduced by the absence of bacteria and inflammation (Esposito et al., 1997; Piattelli et al., 2003). Although all studies included in this review were performed on animals, the reported experimental condition may be assimilated to some clinical situations. Static load resembles misfits of prostheses supported by multiple implant abutments; dynamic load may be assimilated to premature occlusal contact during chewing. Histological data reviewed in the present article does not resolve the issue of whether occlusal overload causes implant failure in humans. Several unclear aspects still exist, such as: which load conditions negatively affect the bone-implant interface, and what is the pathogenic mechanism? However, from data of this study it can be claimed that, to resolve this point, it is necessary to design human histological studies with an appropriate control, a defined load measure (in terms of intensity, direction and timing) and with the assessment of genic profile of cells involved in bone damage.
5. Conclusion Histologically the tissue around overloaded implants undergoing loss of osseointegration presented minimal inflammatory infiltrate in the supracrestal connective tissue. A narrow zone of fibrous tissue was interposed between the implant and the surrounding bone with multinucleated cells and small pieces of bone adjacent to the implant surface. The present review on histologic features of peri-implant bone subjected to overload was based only on various animal models with a range of overloading conditions and follow-up times, so it is not possible to draw conclusions that could be applied on humans. However the histopathological finding of a peculiar lesion that surrounds overloaded failing implant seems to support the evidence of a detrimental effect of excessive mechanical stress on the bone-implant interface, but this effect is not exactly defined in terms of the masticatory load model. It was clear that the histopathogenic process supporting such damage was different from peri-implantitis, which is an inflammatory plaque induced
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condition. From a clinical point of view, even if there is no sound evidence, it would be suggested to the clinician to adopt surgical and prosthetic protocols to reduce the overloading on implant supported restorations. Acknowledgements The authors thank Prof. Piattelli A., Dr. Calesini G., and Dr. Fernandez A. for reviewing the manuscript. References Athanasou, N.A., Sabokbar, A., 1999. Human osteoclastontogeny and pathological bone resorption. Histol. Histopathol. 14, 635–647. Chambrone, L., Chambrone, L.A., Lima, L.A., 2010. Effects of occlusal overload on peri-implant tissue health: a systematic review of animal-model studies. J. Periodontol. 81, 1367–1378. Chang, M., Chronopoulos, V., Mattheos, N., 2013. Impact of excessive occlusal load on successfully-osseointegrated dental implants: a literature review. J. Invest. Clin. Dent. 4, 142–150. Duyck, J., Vandamme, K., 2014. The effect of loading on peri-implant bone: a critical review of the literature. J. Oral Rehabil. 41, 783–794. Esposito, M., Thomsen, P., Mölne, J., Gretzer, C., Ericson, L.E., Lekholm, U., 1997. Immunohistochemistry of soft tissues surrounding late failures of Brånemark implants. Clin. Oral Implants Res. 8, 352–366. Esposito, M., Hirsch, J.M., Lekholm, U., Thomsen, P., 1998. Biological factors contributing to failures of osseointegrated oral implants. (I). Success criteria and epidemiology. Eur. J. Oral Sci. 106, 527–551. Frost, H.M., 2004. A 2003 update of bone physiology and Wolff’s law for clinicians. Angle Orthod. 74, 3–15. Gotfredsen, K., Berglundh, T., Lindhe, J., 2001a. Bone reactions adjacent to titanium implants subjected to static load. A study in the dog (I). Clin. Oral Implants Res. 12, 1–8. Gotfredsen, K., Berglundh, T., Lindhe, J., 2001b. Bone reactions adjacent to titanium implants with different surface characteristics subjected to static load. A study in the dog (II). Clin. Oral Implants Res. 12, 196–201. Gotfredsen, K., Berglundh, T., Lindhe, J., 2001c. Bone reactions adjacent to titanium implants subjected to static load of different duration. A study in the dog (III). Clin. Oral Implants Res. 12, 552–558. Gotfredsen, K., Berglundh, T., Lindhe, J., 2002. Bone reactions at implants subjected to experimental peri-implantitis and static load. A study in the dog. J. Clin. Periodontol. 29, 144–151. Greenstein, G., Cavallaro, J., Tarnow, D., 2013. Assessing bone’s adaptive capacity around dental implants: a literature review. J. Am. Dent. Assoc. 144, 362–368.
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Heitz-Mayfield, L.J., Schmid, B., Weigel, C., Gerber, S., Bosshardt, D.D., Jönsson, J., Lang, N.P., Jönsson, J., 2004. Does excessive occlusal load affect osseointegration? An experimental study in the dog. Clin. Oral Implants Res. 15, 259–268. ˜ Hürzeler, M.B., Quinones, C.R., Kohal, R.J., Rohde, M., Strub, J.R., Teuscher, U., Caffesse, R.G., 1998. Changes in peri-implant tissues subjected to orthodontic forces and ligature breakdown in monkeys. J. Periodontol. 69, 396–404. Isidor, F., 1997a. Histological evaluation of peri-implant bone at implants subjected to occlusal overload or plaque accumulation. Clin. Oral Implants Res. 8, 1–9. Isidor, F., 1997b. Clinical probing and radiographic assessment in relation to the histologic bone level at oral implants in monkeys. Clin. Oral Implants Res. 8, 255–264. Koulouvaris, P., Ly, K., Ivashkiv, L.B., Bostrom, M.P., Nestor, B.J., Sculco, T.P., Purdue, P.E., 2008. Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis. J. Orthop. Res. 26, 106–116. Kozlovsky, A., Tal, H., Laufer, B.Z., Leshem, R., Rohrer, M.D., Weinreb, M., Artzi, Z., 2007. Impact of implant overloading on the peri-implant bone in inflamed and non-inflamed peri-implant mucosa. Clin. Oral Implants Res. 18, 601–610. Laney, W.R., Broggini, N., Buser, D., Cochran, D.L., Garcia, L.T., Giannobile, W.V., Hjorting-Hansen, E., Taylor, T.D., 2007. Glossary of Oral and Maxillofacial Implants, 1st ed. Quintessence Publishing Co Ltd., Berlin, pp. 118. Lassus, J., Salo, J., Jiranek, W.A., Santavirta, S., Nevalainen, J., Matucci-Cerinic, M., Horák, P., Konttinen, Y., 1998. Macrophage activation results in bone resorption. Clin. Orthop. Relat. Res., 7–15. Miyamoto, Y., Koretake, K., Hirata, M., Kubo, T., Akagawa, Y., 2008. Influence of static overload on the bony interface around implants in dogs. Int. J. Prosthodont. 21, 437–444. Miyata, T., Kobayashi, Y., Araki, H., Motomura, Y., Shin, K., 1998. The influence of controlled occlusal overloadon peri-implant tissue: a histologic study in monkeys. Int. J. Oral Maxillofac. Implants 13, 677–683. Miyata, T., Kobayashi, Y., Araki, H., Ohto, T., Shin, K., 2000. The influence of controlled occlusal overloadon peri-implant tissue. Part 3: A histologic study in monkeys. Int. J. Oral Maxillofac. Implants 15, 425–431. Miyata, T., Kobayashi, Y., Araki, H., Ohto, T., Shin, K., 2002. The influence of controlled occlusal overload on peri-implant tissue. Part 4: A histologicstudy in monkeys. Int. J. Oral Maxillofac. Implants 17, 384–390. Naert, I., Duyck, J., Vandamme, K., 2012. Occlusal overload and bone/implant loss. Clin. Oral Implants Res. 23 (Suppl. 6), 95–107. Nagasawa, M., Takano, R., Maeda, T., Uoshima, K., 2013. Observation of the bone surrounding an overloaded implant in a novel rat model. Int. J. Oral Maxillofac. Implants 28, 109–116. Ogiso, M., Tabata, T., Kuo, P.T., Borgese, D., 1994. A histologic comparison of the functional loading capacity of an occluded dense apatite implant and the natural dentition. J. Prosthet. Dent. 71, 581–588. Piattelli, A., Scarano, A., Favero, L., Iezzi, G., Petrone, G., Favero, G.A., 2003. Clinical and histologic aspects of dental implants removed due to mobility. J. Periodontol. 74, 385–390. Purdue, P.E., 2008. Alternative macrophage activation in periprosthetic osteolysis. Autoimmunity 41, 212–217.
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Contents lists available at ScienceDirect
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Histological features of peri-implant bone subjected to overload Gaia Pellegrini a,b,∗ , Luigi Canullo c , Claudia Dellavia a a
Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy. Research Center for Oral Implantology (CRIO), IRCCS Galeazzi Orthopaedic Institute, Milan, Italy. c Private Practice, Rome, Italy. b
a r t i c l e
i n f o
Article history: Received 4 December 2014 Received in revised form 13 January 2015 Accepted 11 February 2015 Available online xxx Keywords: Overloading Peri-implantitis Histology Animal study Dental implant
a b s t r a c t Purpose: The aim of this review has been to investigate the histological findings of bone structure surrounding implants subjected to excessive load. Materials and methods: Clinical and pre-clinical histological studies that observed overloaded intraoral implants were included. Results: All included studies (n = 15) were conducted on animals. Most of them failed to find pathological alteration in the microstructure of bone surrounding overloaded implants. Overload and infection alone may induce bone loss, but related lesions have different and peculiar features. Conclusions: The different histological features observed around implants subjected to overload or to ligature-induced peri-implantitis may indicate a specific pathogenetic mechanism for overload or infection-induced loss of osseointegration. The clinical significance of these findings should be confirmed in human studies. © 2015 Elsevier GmbH. All rights reserved.
Contents 1. 2.
3.
4. 5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Types of studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Type of intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Outcome measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5. Information sources and search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7. Data extraction and management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Static overload . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Dynamic overload . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Loading the bone tissue during physiologic masticatory function regulates the remodeling of peri-implant tissue (Greenstein et al., 2013). When the applied force has the potential to cause permanent
∗ Corresponding author at: Via Mangiagalli, 31 20133 Milano, Italy. Tel.: +39 0250315405; fax: +39 0250315387; mobile: +39 347 5923198. E-mail address: [email protected] (G. Pellegrini).
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deformation or damage to the structure or its support, overloading occurs (Laney et al., 2007). In implant dentistry, the effect of occlusal overloading on the loss of osseointegration is still a controversial issue. Some recent reviews were designed to examine the role of excessive and adverse masticatory load in peri-implant bone loss (Naert et al., 2012; Chambrone et al., 2010; Chang et al., 2013). These studies did not resolve this issue since the available data in the literature were too limited. Therefore, the question of whether the occlusal overloading by itself is able to induce peri-implant bone loss and
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thus implant failure still remains. Histological evidence may help to answer this question, since it contributes to understanding of the pathogenetic mechanism of bone resorption under excessive mechanical stress. The aim of the present review has been to describe bone histological features around implants subjected to overload. 2. Materials and methods This review was performed according to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and MetaAnalyses). 2.1. Types of studies Clinical trials, randomized controlled clinical trials, case series as well as animal experimental trials, which had performed histological analysis and were published in English were included. No narrative or systematic reviews were considered. 2.2. Type of intervention Clinical or pre-clinical studies that applied overload to osseointegrated implants placed in maxillary or mandibular bone were included. 2.3. Study selection In this review, clinical and pre-clinical studies presenting histological descriptions of the peri-implant bone features after static and dynamic overload on osseointegrated implants were included. All types of histological assessments were included. No publication status was imposed. For clinical trials a follow-up of at least 6 months was required, including a measure of the occlusal overload and the assessment of overload as aetiological factor of the periimplantal bone loss. All studies evaluating factors that increase the load transmitted to the implant–bone interface such as single vs. splinted implants, short vs. long cantilevers, small vs. large crownimplant ratios, misfitting prosthesis were also included. For the animal studies, only intra-oral experimental sites were considered. No unpublished data were included. No narrative or systematic reviews were considered. In vitro studies, studies on immediately loaded implants, not measuring the overload and not assessing histologically the peri-implant bone status as consequence of the occlusal overload were excluded. 2.4. Outcome measures The primary outcome was the histological assessment of static or dynamic overload on bone structure surrounding the osseointegrated implants. Overload was defined as the application of forces that presumably exceed the physiological range in terms of intensity, direction or timing. 2.5. Information sources and search Studies were identified by the Medline (Pubmed) electronic databases and the search was performed on articles published from the 1st January 1975 to the 22nd of June 2014. Hand search by scanning reference lists of articles and consultation with experts in the field were performed. Authors were contacted in order to acquire missing information. To perform the research, the following key terms were applied to the database: oral OR dental AND implant$ AND (load OR overload OR excessive
load OR force$ OR bruxism) AND (bone loss OR bone resorption OR implant failure$). 2.6. Study selection One independent reviewer (GP) firstly excluded irrelevant records by their title and abstract. To be included in the review, the full-text of each remaining paper was evaluated by two independent reviewers (CD and GP); disagreements between reviewers were resolved by consensus. 2.7. Data extraction and management To perform a statistical comparison between articles, studies that used similar protocols were selected and comparable data were extracted. 3. Results A total of 3222 studies were identified in the database. After removing duplicates and records that did not fit the inclusion criteria, only 15 articles remained (see Fig. 1) (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002; Hürzeler et al., 1998; Miyata et al., 1998, 2000, 2002; Ogiso et al., 1994; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007; Nagasawa et al., 2013; Isidor, 1997a,b). All included studies were performed on animals (seven on dogs) (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002; HeitzMayfield et al., 2004; Kozlovsky et al., 2007), seven on monkeys (Hürzeler et al., 1998; Miyata et al., 1998, 2000, 2002; Ogiso et al., 1994; Isidor, 1997a,b), one on rats (Nagasawa et al., 2013) and had variable periods of observation from 1 week to 18 months as reported in Table 1. The included studies analyzed the bone response after static and dynamic overload, in healthy conditions or after experimental plaque induced peri-implant inflammation. Data from the studies were reported separately considering the type of load and the control or not of peri-implant inflammation. Most of the studies reported quantitative histological parameters such as: bone-implant-contact (BIC), bone density (BD), bone level and other histomorphometric measurements of the peri-implant defect (i.e. inflammatory connective tissue are, ICT) (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002; Hürzeler et al., 1998; Miyata et al., 1998, 2000, 2002; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007; Nagasawa et al., 2013; Isidor, 1997a,b). Furthermore, few studies reported microscopic morphological aspects of peri-implant bone (Hürzeler et al., 1998; Miyata et al., 1998, 2000; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007; Nagasawa et al., 2013; Isidor, 1997a,b), and few studies evaluated the bone metabolism by means of fluorochromes (Miyamoto et al., 2008; Gotfredsen et al., 2001a,b,c, 2002).Due to the heterogeneity of data reported from the included studies, no meta-analysis was performed. 3.1. Static overload In a dog model, 12 implants after 24 weeks of overload had similar peri-implant histological features, bone level, even greater bone density (from 70% to 76%) and bone-to-implant contact (66–67%) than unloaded sites (bone density 58%, BIC 59%) (Gotfredsen et al., 2001a). In a further study performed on 5 dogs, for a total of 20 implants loaded for 12 weeks and 10 unloaded implants, similar bone density was found in overloaded implants with mucositis (69.1%) and overloaded implants with ligature induced peri-implantitis (75.7%); on the contrary unloaded implants with ligature-induced peri-implantitis showed lower bone density (59%) and bone activity (Gotfredsen et al., 2002). Implants with experimental peri-implantitis had greater bone loss than those affected
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Table 1 Characteristics of the included studies. Article
Experimental model
Implant number (time of loading or observation)
Load mode
Type of loading
Histological assessments
Histological results
Miyamoto et al. (2008)
12 dogs/mandible
12 UI (24 w)
Cantilever-type superstructure
Static
BIC, bone level, flourochrome
Expansion screw (0.0 mm, 0.2 mm, 0.4 mm, 0.6 mm of expansion)
Static
BIC, BD, flourochrome, marginal bone level
Overload cause time-depending changes LI 4 w: higher remodeling activity than UI and LI 12 w. Higher ratio of fluorescence-labeled bone is in the inner thread region of LI 4 w than of LI 12 w (p < 0.05). Lower marginal bone loss in UI and LI 4 w than LI 12 w (p < 0.05). Higher BIC in LI 4 w than UI (p < 0.05). BIC = UI: 56–61%. LI 4 w 74–77%, LI 12 w 63%. Higher BD and BIC around LI than around UI. Respectively (BD: 70–79%; BIC: 66–67%, and BD: 58%; BIC: 59%).
Expansion screw (0.6 mm of expansion)
Static
BIC, BD, flourochrome
Expansion screw (0.6 mm of expansion)
Static
BIC, BD, flourochrome
Expansion screw (1.6 mm of expansion)
Static
BD, flourochrome, histometric measurements (ICT)
Orthodontic springs
Dynamic horizontal
BIC (length and percentage)
Supra occlusal contact of 100 m
Dynamic, lateral
Quantity of bone resorption
Supra occlusal contact of 100 m, 180 m and 250 m
Dynamic, lateral
Bone resorption
12 LI (12 w)
Gotfredsen et al. (2001a)
3 dogs/mandible
12 LI (4 w) 18 LI (24 w)
Gotfredsen et al. (2001b)
3 dogs/mandible
6 UI (24 w) 6 TPS LI (24 w)
6 machined LI (24 w)
Gotfredsen et al. (2001c)
3 dogs/mandible
9 LI (10 w)
Gotfredsen et al. (2002)
5 dogs/mandible
9 LI (46 w) 10 LI-mucositis (12 w) 10 UI-PI
Hürzeler et al. (1998)
5 monkeys/mandible
10 LI-PI (12 w) 10 UI (4 m) 10 LI (4 m) 10 UI-PI (4 m)
Miyata et al. (1998)
Miyata et al. (2000)
5 monkeys/mandible
4 monkeys/mandible
10 LI-PI (4 m) 2 UI 2 LI (1 w) 2 LI (2 w) 2 LI (3 w) 2 LI (4 w) 2 UI 2 LI/100 m (4 w)
2 LI/180 m (4 w) 2 LI/250 m (4 w)
Higher marginal bone level, BIC, BD in TPS than in machined BD: 73% in TPS and 63% in machined; BIC: 60% in TPS and 53% in machined Similar BD and BIC. 10 w = BD: 81%, BIC: 81%; 46 w = BD: 83%, BIC: 83%. Lower bone markers at 46 w than at 10 w Similar bone loss in LI-PI and UI-PI Higher BD and bone labels in LI-PI than UI-PI. BD respectively 75% and 59% (p > 0.05). BD in LI-mucositis was 69%. In LI-mucositis the ICT was small and localized; UI-PI and LI-PI had large ICT in the peri-implant mucosa and extended 0.5–1 mm apical to the JE No significant effects of load Lower BIC length and % in PI than in healthy sites Higher BIC in LI (57%) and UI (55%) than in LI-PI (36%) and UI-PI (43.8%) (p < 0.05) Absence of great bone loss in loaded sites
Bone resorption depending on IVD No bone resorption in LI/100 m and UI. In LI/180 m slight bone resorption to almost half of the implant. In LI/250 m vertical bone resorption reaching the apex of the implant, epithelial downgrowth.
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4 Table 1 (Continued) Article
Experimental model
Implant number (time of loading or observation)
Load mode
Type of loading
Histological assessments
Histological results
Miyata et al. (2002)
4 monkeys/mandible
2 LI-PI (8 w) (group P)
Supra occlusal contact of 250 m
Dynamic, lateral
Inflammatory cell infiltration
Supra occlusal contact; IVD: 4–5 mm
Dynamic, axial
Morphology
Supra occlusal contact; IVD: 3 mm
Dynamic, axial
BIC, linear measurements (alveolar bone height, bone levels)
Supra occlusal contact; IVD: 3 mm
Dynmic, axial.
BIC, histomorphometric measures
Cantilever-type superstructure
Dynamic, lateral
BIC
Supra occlusal contact with a lateral direction
Dynamic, lateral
BIC, BD
Supra occlusal contact with a lateral direction
Dynamic, lateral
Bone level
No difference in bone resorption. Irreversible changes in E. In N (NI): slight ICT. In P and E: bone resorption at apical third of the implant and massive ICT. Peri-implant bone progressively thickening and remodeling over the time No differences in bone height, bone level and BIC between LI and UI. BIC: LI = 73.9%, UI = 72.6%. 2 LI lost, 1 UI lost. Overloading without inflammation increased BIC and BIC%. Overloading + inflammation increased bone loss (LI: 0.12/0.5 mm, UI: 0.37/0.8 mm, LI-PI: −3.08/−3.28 mm, UI-PI: −2.5/−2.53 mm), but did not change BIC% (LI: 66%, UI: 53%, LI-PI: 67.53, UI-PI: 62.68%). Bone degeneration after loading UI 2 w: partial osseointegration. LI 2 w: two implants failed, active bone resorption, loss of osseointegration, microfractures of the bone adjacent to the implant surface. Higher BIC in UI. UI 4 w: established osseointegration. LI 4 w: relatively wide area of preserved osseointegration, active bone resorption in the remote areas of the implant after 15 d of loading. Differently from peri-implant infection, overload induces loss of osseointegration. LI: 6 out of 8 implants became mobile. BIC: 23–34%, BD: 55%. UI-PI: BIC: 64.3%, BD: 38%. Overload induces loss of osseointegration. Bone level: LI = −4.8 mm, UI-PI = −2.4 mm.
Ogiso et al. (1994)
6 monkey mandible/maxilla
2 NI (group N) 4 LI-PI for 4 w and then UI brushed for subsequent 4 w (group E) 12 LI (1–3 m)
Heitz-Mayfield et al. (2004)
6 dogs/mandible
Pristine bone as control 22 LI (8 m)
Kozlovsky et al. (2007)
4 dogs/mandible
23 UI (8 m) 8 LI (12 m)
Nagasawa et al. (2013)
40 rats/maxilla
8 UI (12 m) 8 LI-PI (12 m) 8 UI-PI (12 m) Abutment placed after 2 w of healing 16 UI
Isidor (1997a)
4 monkeys/mandible
8 LI (5 d) 8 LI (10 d) 8 LI (15 d) Abutment placed after 4 w of healing 16 UI 8 LI (5 d) 8 LI (10 d) 8 LI (15 d) 8 LI (18 m)
Isidor (1997b)
4 monkeys/mandible
12 UI-PI (18 m) 8 LI (18 m)
12 UI-PI (18 m)
TPS, titanium plasma spray; BD, bone density; BIC, bone-implant contact; LI, overloaded implants; UI, unloaded implants; NI, normal occlusion implants; PI, ligature induced peri-implantitis; ICT, inflammatory infiltrate connective tissue; JE, junctional epithelium; IVD, increased vertical dimension; w, weeks; d, days; m, months.
by mucositis (Gotfredsen et al., 2002). The authors demonstrated that lateral static load did not enhance bone loss at implants with experimental peri-implantitis (Gotfredsen et al., 2002). In only one study on dogs following 12 implants over different loading periods, was the static-oblique load (mesio-distal/coronalapical) induced by means of a cantilever-like superstructure (Miyamoto et al., 2008). The authors observed increased remodeling activity in the peri-implant bone after 4 weeks of loading compared to the unloaded control. However, at 12 weeks of loading,
the remodeling activity decreased and marginal bone loss was significantly greater than at 4 weeks (Miyamoto et al., 2008). 3.2. Dynamic overload All studies of this group compared overloaded implants to unloaded implants except Miyata et al. (2002) and Ogiso et al. (1994) that respectively chose normally loaded implants and pristine bone as control.
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Records idenfied through database searching (n = 3222)
5
Addional records idenfied through other sources (n = 0)
Records aer duplicates removed (n = 894 duplicates removed)
Records screened (n = 2328)
Records excluded (n = 2302)
Full-text arcles assessed for eligibility (n = 26)
Full-text arcles excluded, with reasons (n = 11)
Studies included in qualitave synthesis (n = 15)
Studies included in quantave synthesis (n = 0)
Fig. 1. PRISMA flow diagram.
In three studies the excessive occlusal load was produced by means of supra-occlusal contact provided by 3–5 mm vertical dimension increments (Ogiso et al., 1994; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007). Thus an axial direction of the occlusal load was mainly obtained (Ogiso et al., 1994; Heitz-Mayfield et al., 2004; Kozlovsky et al., 2007). At 1 month of loading, Ogiso et al. (1994) in 6 monkeys on 12 overloaded implants compared to pristine bone, a bone remodeling progressing along the loaded implants was found, with poorly differentiated bone without lamellar structure transforming into new highly stained lamellar bone. After 3 months of loading the authors observed thicker trabeculae and compact bone with several more osteons than after 1 month (Ogiso et al., 1994). Heitz-Mayfield et al. (2004) (6 dogs with a total of 45 implants followed for 8 months) did not observe differences between loaded and unloaded sites (respectively, BIC% was 74% and 73%). Kozlovsky et al. (2007) (4 dogs with 8 implants each, followed for 12 months) found a higher percentage of BIC in loaded (66%) than in unloaded (53%) in healthy sites. In sites with experimental peri-implantitis, overloading enhanced peri-implant intrabony vertical bone resorption, which resulted in a significant increase in bone loss (p < 0.05) (Kozlovsky et al., 2007). In a study on monkeys, sites were only submitted to a distalizing overload obtained with an orthodontic device when the animal opened its mouth (Hürzeler et al., 1998). After 4 months (10 implants per group), no inflamed peri-implant connective tissue was observed and collagen fibers were organized parallel to the implant surface and were similar to non-overloaded sites (Hürzeler et al., 1998). In the same study, detrimental effects on bone level were observed in sites with ligature-induced periimplantitis compared to healthy sites. In inflamed sites (with or
without overload) large inflammatory infiltrate moved from the peri-implant soft tissue toward the alveolar bone thus altering the structure of the peri-implant soft-tissue. In particular, apically extended pocket epithelium was found and no collagen fibers were observed between the junctional epithelium and the alveolar bone (Hürzeler et al., 1998). However, the addition of overload did not affect BIC and bone loss, but the remaining apical two-thirds of the implant were osseointegrated in compact alveolar bone (Hürzeler et al., 1998). Six studies produced supra-occlusal contacts with an oblique/lateral (mesio-distal or lingual-buccal) stress direction (Miyata et al., 1998, 2000, 2002; Nagasawa et al., 2013; Isidor, 1997a,b). Miyata showed increased bone resorption in four monkeys only when a 180 m or even more excessive height of the suprastructures was applied (two implants per group in a parallel group study) (Miyata et al., 2000) while in four monkeys (Miyata et al., 1998) no effect of a 100 m supra occlusal contact was observed at 1, 2, 3, and 4 weeks compared to unloaded implants (one monkey) (Miyata et al., 1998). Isidor (1997a) examined eight overloaded implants in four monkeys and six out of eight implants became mobile in a 18-month observation period. Nagasawa et al. (2013) reported on 40 rats with two implants each, one loaded at 2 weeks and one at 4 weeks and overall only two implants failed (at 15 days in 2 w group). In all, 16 implants were non-loaded and 24 overloaded. Observation times were 5, 10, and 15 days. Both studies reported degenerative changes in peri-implant bone subjected to excessive stress (Nagasawa et al., 2013; Isidor et al., 1997a). In particular, the authors observed a moderate inflammatory infiltrate within the supracrestal mucosa. At the coronal site of the implants the bone loss was evident, while at the apical part it was
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observed that the loss of bone-implant contact with active bone resorption was mediated by multinucleated cells. Furthermore, islands of bone appeared close to or in direct contact with the implant surface but they were isolated from the remaining bone by surrounding connective tissue (Nagasawa et al., 2013; Isidor et al., 1997a).
4. Discussion The detrimental effect of occlusal overload on bone-implant interface is still a controversial issue. Previous systematic reviews of literature, performed on pre-clinical studies, failed to find a close correlation between occlusal overload and implant failure, since only a few studies with several biases have been conducted to support the cause–effect relationship (Naert et al., 2012; Chambrone et al., 2010). Otherwise, clinical studies reported negative effects of bruxism on long-term prognosis of dental implants (Esposito et al., 1998). Due to ethical reasons, clinical control trials evaluating survival of overloaded or loaded implants have not been published. Assessment of pathogenic mechanism underlying the bone resorption induced by overload, may help to clear this issue. The present review was designed to describe the histological response of peri-implant bone tissue subjected to an excessive load, and, thus, to histologically define the failing peri-implant tissue and investigating the pathogenic mechanism of peri-implant bone resorption induced by excessive load. Depending on its intensity, load may have osteogenic properties or may induce bone damage. Frost reported that at about 1000–1500 microstrain the modeling usually promotes strengthening of the bone and at 3000 microstrain microscopic bone damage begins to accumulate without being repaired (Frost, 2004). These threshold strains may change depending on systemic factors such as hormones, drugs, and vitamins that modify the bone structure and its response to a mechanical stress (for review see Frost, 2004), and may also change depending on the type of load (Duyck and Vandamme, 2014). Implant position, masticatory function and habits, including the type of diet, the muscular biotype and the masticatory model (horizontal vs. vertical) may affect the load; however, studies did not analyze these parameters. Studies selected in the present review did not carefully measure and report the actual load transmitted to the bone-implant interface, different animal models were used with different time of loading and different follow-ups and for these reasons conflicting data emerges. Between selected studies, some reported bone resorption (Miyata et al., 2000, 2002; Nagasawa et al., 2013; Isidor, 1997a,b) as well as some observed increase in bone density in overloaded implants (Miyamoto et al., 2008; Gotfredsen et al., 2001a, 2002; Kozlovsky et al., 2007). It is not possible to demonstrate that the observed effect is directly related to the excessive force over the threshold strain. However, histological alterations on physiologic bone structure around osseointegrated overloaded implants were observed (Miyata et al., 2000; Nagasawa et al., 2013; Isidor, 1997a,b). Thus, a detrimental effect of the force over a threshold strain on the integrity of peri-implant bone may be accepted, but it is not possible to define which are the real masticatory dynamic or static situations that establish such bone damage. In order to characterize bone damage following overload, the histological features of peri-implant lesions were observed, and differences between plaque and overload induced peri-implant bone loss were found. The included studies observed only a minimal inflammatory infiltrate in the supracrestal connective tissue around overloaded implants (Miyata et al., 2000; Nagasawa et al., 2013; Isidor, 1997a). A narrow zone of fibrous tissue was interposed between the implant and the surrounding bone. Multinucleated cells were observed adjacent to the implant surface. Small pieces
of bone tissue appeared close to or in contact with the implant surface but separated from the remaining bone by dense fibrous connective tissue as result of microfractures (Nagasawa et al., 2013; Isidor, 1997a). In contrast, around implants with ligatureinduced peri-implantitis and without overload, the supracrestal connective tissue was densely infiltrated by inflammatory cells and osteoclastic activity appeared on the bone crest of these implants (Nagasawa et al., 2013). Bone resorption may be performed by several cells. Osteoclasts are the most important cells inducing bone remodeling in physiological status (Athanasou and Sabokbar, 1999). Monocytes/macrophages may intervene in bone resorption during pathological events, for example, in peri-prosthetic osteolysis, which is characterized by macrophage phagocytosis of particles of wear debris and formation of foreign body granulomas (Lassus et al., 1998; Koulouvaris et al., 2008; Purdue, 2008). Studies selected in this review seem to indicate that overload and ligature induced infection cause a different pattern of bone resorption with the involvement of different cells. However, studies did not define the gene profile of cellular population that intervened in these pathologic processes. Esposito et al. (1997) found only a minimal inflammatory infiltrate in supracrestal connective tissue and found (similarly to what happens in peri-prosthetic osteolysis) a large number of macrophages accumulated within the tissue adjacent to the implant surface. Piattelli et al. (2003) found the complete absence of bacteria in the most coronal portion of the implant, and a poorly cellular dense connective tissue with few inflammatory cells. However, in both these studies the overload as reason of implant failure was only deduced by the absence of bacteria and inflammation (Esposito et al., 1997; Piattelli et al., 2003). Although all studies included in this review were performed on animals, the reported experimental condition may be assimilated to some clinical situations. Static load resembles misfits of prostheses supported by multiple implant abutments; dynamic load may be assimilated to premature occlusal contact during chewing. Histological data reviewed in the present article does not resolve the issue of whether occlusal overload causes implant failure in humans. Several unclear aspects still exist, such as: which load conditions negatively affect the bone-implant interface, and what is the pathogenic mechanism? However, from data of this study it can be claimed that, to resolve this point, it is necessary to design human histological studies with an appropriate control, a defined load measure (in terms of intensity, direction and timing) and with the assessment of genic profile of cells involved in bone damage.
5. Conclusion Histologically the tissue around overloaded implants undergoing loss of osseointegration presented minimal inflammatory infiltrate in the supracrestal connective tissue. A narrow zone of fibrous tissue was interposed between the implant and the surrounding bone with multinucleated cells and small pieces of bone adjacent to the implant surface. The present review on histologic features of peri-implant bone subjected to overload was based only on various animal models with a range of overloading conditions and follow-up times, so it is not possible to draw conclusions that could be applied on humans. However the histopathological finding of a peculiar lesion that surrounds overloaded failing implant seems to support the evidence of a detrimental effect of excessive mechanical stress on the bone-implant interface, but this effect is not exactly defined in terms of the masticatory load model. It was clear that the histopathogenic process supporting such damage was different from peri-implantitis, which is an inflammatory plaque induced
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condition. From a clinical point of view, even if there is no sound evidence, it would be suggested to the clinician to adopt surgical and prosthetic protocols to reduce the overloading on implant supported restorations. Acknowledgements The authors thank Prof. Piattelli A., Dr. Calesini G., and Dr. Fernandez A. for reviewing the manuscript. References Athanasou, N.A., Sabokbar, A., 1999. Human osteoclastontogeny and pathological bone resorption. Histol. Histopathol. 14, 635–647. Chambrone, L., Chambrone, L.A., Lima, L.A., 2010. Effects of occlusal overload on peri-implant tissue health: a systematic review of animal-model studies. J. Periodontol. 81, 1367–1378. Chang, M., Chronopoulos, V., Mattheos, N., 2013. Impact of excessive occlusal load on successfully-osseointegrated dental implants: a literature review. J. Invest. Clin. Dent. 4, 142–150. Duyck, J., Vandamme, K., 2014. The effect of loading on peri-implant bone: a critical review of the literature. J. Oral Rehabil. 41, 783–794. Esposito, M., Thomsen, P., Mölne, J., Gretzer, C., Ericson, L.E., Lekholm, U., 1997. Immunohistochemistry of soft tissues surrounding late failures of Brånemark implants. Clin. Oral Implants Res. 8, 352–366. Esposito, M., Hirsch, J.M., Lekholm, U., Thomsen, P., 1998. Biological factors contributing to failures of osseointegrated oral implants. (I). Success criteria and epidemiology. Eur. J. Oral Sci. 106, 527–551. Frost, H.M., 2004. A 2003 update of bone physiology and Wolff’s law for clinicians. Angle Orthod. 74, 3–15. Gotfredsen, K., Berglundh, T., Lindhe, J., 2001a. Bone reactions adjacent to titanium implants subjected to static load. A study in the dog (I). Clin. Oral Implants Res. 12, 1–8. Gotfredsen, K., Berglundh, T., Lindhe, J., 2001b. Bone reactions adjacent to titanium implants with different surface characteristics subjected to static load. A study in the dog (II). Clin. Oral Implants Res. 12, 196–201. Gotfredsen, K., Berglundh, T., Lindhe, J., 2001c. Bone reactions adjacent to titanium implants subjected to static load of different duration. A study in the dog (III). Clin. Oral Implants Res. 12, 552–558. Gotfredsen, K., Berglundh, T., Lindhe, J., 2002. Bone reactions at implants subjected to experimental peri-implantitis and static load. A study in the dog. J. Clin. Periodontol. 29, 144–151. Greenstein, G., Cavallaro, J., Tarnow, D., 2013. Assessing bone’s adaptive capacity around dental implants: a literature review. J. Am. Dent. Assoc. 144, 362–368.
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