Immediate implants at fresh extraction sockets: from myth to reality

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1 Periodontology 2000, Vol. 66, 2014, John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Printed in Singapore. All rights reserved PERIODONTOLOGY 2000 Immediate implants at fresh extraction sockets: from myth to reality FABIO VIGNOLETTI &MARIANO SANZ It is well accepted by the scientific community that physiological dimensional changes occur in the alveolar ridge after tooth extraction (47, 57, 59) and that most of these changes will occur within the first 3 months of socket healing (67). These height (apicocoronal) and width (bucco-lingual) alterations in the alveolar ridge may therefore influence subsequent implant placement. In the Third International Team for Implantology (ITI) Consensus Conference (43), three basic protocols for implant placement were defined according to the time between tooth extraction and implant installation. In the type-1 protocol (immediate implant installation), implants are placed in fresh extraction sockets, with the aim to engage the remaining socket walls with the implant. In the type-2 protocol (early implant placement), implants are placed approximately 4 8 weeks after tooth extraction. The main objective of this protocol is to ensure the lack of pathology when placing the implant and, at the same time, to optimize the availability of soft tissues for primary healing and probable lateral bone augmentation. It also aims to improve the availability of crestal bone for implant placement because, within this short interval from tooth extraction, part of the socket bone walls should still be preserved. In the type-3 protocol (early-delayed implant placement) the implants are placed once most of the dimensional changes in the alveolar ridge have occurred (12 16 weeks). Immediate implant placement after tooth extraction (i.e. the type-1 implant-placement protocol) has become a common surgical protocol in clinical practice. This therapeutic concept was introduced in 1976 (68) as an alternative protocol to the classical delayed implant surgical protocol proposed by Branemark (19). The proponents of this therapeutic concept claimed reduced exposure of patients to surgery, limited physiological bone resorption and hence better esthetic outcomes (53, 57). The first experimental studies using this therapeutic concept aimed to assess histologically whether the process of osseointegration, as described by Branemark (19), would occur in a similar manner at implants placed into fresh extraction sockets. Root analog implants were immediately placed after tooth extraction and demonstrated a similar histological pattern of osseointegration (51, 55). Subsequently, standard cylindrical endosseous titanium implants were used, demonstrating that, irrespective of the gap between the implant surface and the socket bone walls, osseointegration occurred both in humans (76) and in experimental animals (2, 10, 50). Furthermore, when the principles of guided tissue regeneration were applied together with immediate implant placement for attaining increased bone-to-implant contract, a tendency toward higher values of bone-to-implant contact was observed with the use of barrier membranes, although the results were mainly influenced by membrane exposure (75). Although osseointegration was demonstrated as a predictable outcome, no clear clinical and histological evidence was available on the possible influence of immediate implant placement on the physiologic process of crestal bone modeling and remodeling. This process was investigated in a series of experimental studies published by researchers from the University of Goteborg. These studies clearly demonstrated that the resorptive changes in the alveolar ridge occur independently of the timing of implant installation and, in fact, significant dimensional alterations in the buccal bone wall, both in apicocoronal and bucco-lingual directions, were reported 4 12 weeks after implant placement in fresh extraction sockets (6 8). This histological outcome was 132

2 Immediate implants in fresh extraction sockets further corroborated by human clinical trials reporting a reduction of up to 56% in the bucco-lingual dimension of the alveolar crest around immediately placed implants (18). In addition to these preliminary investigations, many studies have been published in the last 5 years, mostly agreeing that implant survival rates, the degree of osseointegration and the maintenance of interdental bone levels are not negatively affected by the immediate implant placement protocol, although only a few studies reported outcomes on peri-implant soft tissue health and esthetic results (27, 61). However, data on the amount and relevance of the resorptive osseous changes occurring at the buccal bone are conflicting in both experimental and clinical studies. Therefore, it is the objective of the present review to describe the critical factors in the healing process of the socket after tooth extraction and immediate implant placement and to analyse critically the evidence on the efficacy of this treatment concept from human clinical studies. The results from this review should help the reader to understand the most important patient-, site- and surgical-related factors that influence the healing of the fresh extraction sockets when using this therapeutic concept. Histological outcomes Basic knowledge of wound healing and of the changes taking place in the hard and soft tissues around immediate implants in fresh extraction sockets have been derived from experimental studies. Changes inside the alveolar socket The early phases of osseointegration after surgical insertion of endosseous titanium implants into healed crests have been evaluated histologically using the wound-chamber model (13). This model enables investigation of how bone heals within the space between two threads once the implants attain primary stability by engaging the walls of the drilled bone bed with the thread picks. In detail, the initially empty wound chamber became filled with a coagulum and a granulation tissue that was soon replaced by a provisional connective tissue matrix. The process of bone formation had already started within this matrix during the first week, first in contact with the parent bone by the appositional bone-formation bed, although bone was also formed in direct contact with the implant surface at a distance from the parent bone. This primary (or immature) bone was formed by woven bone that was soon remodeled into parallel-fibered and/or lamellar bone and marrow that filled the entire chamber. Histometrically, the percentage of bone-to-implant contact was 6.3% in the 4-day specimens, increasing to 24.8% after 1 week and gradually increasing further until reaching approximately 65% of the implant surface at the end of the study (12 weeks). Using a similar wound-chamber experimental model, osseointegration was studied at 4 h, and at 1, 2, 4 and 8 weeks after implant installation in a fresh extraction socket (72). After 4 h of healing the interior of the chamber was occupied with nonmineralized tissue, mainly composed of erythrocytes and bone remnants and debris resulting from drilling. Remnants of the periodontal ligament attached to the bundle bone were observed. After 1 week, the wound chamber was mainly filled with granulation tissue, which was rich in fibroblast-like cells within a fibrinlike extracellular matrix. At this time, bone modeling was absent, although abundant areas of bone remodeling were observed in the parent bone. However, after 2 weeks, bone modeling was manifest, with woven bone formation clearly identifiable. New bone formation was observed, both in intimate contact with the implant surface as well as adjacent to the parent bone. A marked angiogenesis that paralleled the osteoblastic activity was noticeable. At 4 and 8 weeks, both bone-modeling and bone-remodeling events were observed (Fig. 1). These histometric observations demonstrated that at day 0, bone implant contact was mostly limited to the thread-tip level and covered 10 15% of the implant surface. After 1 week of healing, bone implant contact decreased to approximately 5%, reached baseline values again at 2 weeks and thereafter showed a gradual increase, to approximately 45% of the implant surface, at 8 weeks (72) (Fig. 2). Comparison between both studies demonstrates that the processes of de-novo bone formation and osseointegration are similar, both quantitatively and qualitatively, However, in the immediate implant model a more pronounced osteoclastic remodeling phase was observed in the first 2 weeks, which translated to a decrease of approximately 10% of the boneto-implant contact between 4 h and 1 week after implant insertion. These findings, during early wound healing, are in line with the histological observations from studies on the spontaneous healing of the socket after tooth extraction, which reported an abundant osteoclastic phase during the first week of healing (5, 26). In light of these results, it may be hypothesized that the differences observed between 133

3 Vignoletti & Sanz A B C D E Fig. 1. Ground sections representing de-novo bone formation within the wound chamber. Toluidine-blue staining; original magnification x20. (A) Four hours. Erythrocytes are interposed between the implant surface and the parent bone. (B) One week. Provisional matrix of connective tissue cells with the first signs of bone formation and areas of bone remodeling observed in the parent bone. (C) Two weeks. Woven bone formation continuous with the parent bone and along the surface of the implant. (D) Four weeks. Woven bone is replaced with parallelfibered bone in contact with the implant surface. (E) Eight weeks. Mature lamellar bone is observed in intimate contact with the implant surface and occupies most of the wound chamber. Fig. 2. Diagram showing the degree of osseointegration (i.e. the percentage of bone implant contact) from 4 h to 8 weeks following use of implants with a surface characterized by discrete crystalline depositions (DCDs) of nanometer-scale calcium phosphate (CaP) particles on a dual acid-etched implant surface (DCD nano-particles, Nanotite TM Biomet 3i). Bone to implant contact (BIC). Source: Vignoletti et al. (73). the two surgical protocols may be a result of the superimposition of the initial remodeling phase of the socket after tooth extraction with the normal healing process of the implant. Dimensional alterations of the alveolar bone crest The dimensional changes occurring in alveolar crestal bone after tooth extraction and immediate implant placement have been investigated by several authors. The early healing of the buccal and lingual bone crests from 4 h to 8 weeks was described in experimental studies (72). At 4 h, depending on its thickness, the buccal bone plate was mainly composed of bundle bone in thin crests or by a combination of bundle and lamellar bone in thicker crests. The lingual plate was always thicker and more coronally situated (Fig. 3). Already at 1 week, although a connective tissue matrix rich in inflammatory cells 134

4 Immediate implants in fresh extraction sockets A B Fig. 3. Ground section representing the 4-h healing interval. (A) The buccal bone wall B is thinner and more apical than the lingual bone wall L. Toluidine-blue staining. Original magnification 310. (B) Highmagnification image of panel a. The buccal bone plate is composed only of bundle bone in its coronal aspect. Toluidine-blue staining; interference contrast; original magnification 320. filled the socket, numerous osteoclasts could be identified at the inner part of the buccal and lingual crests (Fig. 4). After 2 weeks, extensive new bone formation was observed at the inner part of the crest, whereas bundle bone was still undergoing resorption. After 4 weeks, bone modeling and remodeling were evident, whereas at 8 weeks the remnants of bundle bone could no longer be identified. Differences in the healing pattern between the buccal and lingual bone walls were described, with a resulting mean SD vertical resorption of mm in the buccal bone wall after 8 weeks of healing. This vertical buccal bone loss occurred mainly from baseline to 1 week ( mm), and from 1 week to the end of the study minimal vertical changes were observed. At the lingual counterpart, the bone crest was located 0.7 mm coronal to the implant shoulder, and this distance did not change throughout the study. Although varying degrees of vertical crestal bone resorption may occur in both crestal bone walls, they are mainly observed at the buccal bone wall. In a similar experimental study in dogs, the vertical dimensional changes of the buccal bone were and mm apical to the fixed landmark, after 4 and 12 weeks of healing, respectively (8). At the lingual counterpart, only minor changes were also observed (8). Furthermore, marked reductions of the thickness of the bone walls were observed between 4 and 12 weeks of healing, and these changes were also more pronounced at the buccal than at the lingual bone plate (7). The impact of immediate implant placement on the buccal bone has yielded heterogeneous results, ranging from mean buccal bone resorption of mm (Table 1). The reasons for this heterogeneity are probably very diverse, from lack of standardization in the preclinical models, use of different surgical protocols and implant systems and probably the inherent variability in the biological wound-healing process of the socket. Nevertheless, evidence from these animal experiments has highlighted some critical factors, such as the dimension of the gap between the implant surface and the inner socket wall, the implant position and the thickness of the buccal bone plate, all of which may play a significant role in the occurrence of these resorptive changes. However, it is unclear whether it is the bone-wall thickness or the A B Fig. 4. Ground section representing the 1-week healing interval. (A) Process of bone remodeling at the buccal bone plate. Toluidine-blue staining; original magnification 310. (B) High-magnification image of panel a. The osteoclasts are lined within Howsip lacunae on the top of the crest. Toluidine-blue staining; original magnification

5 Vignoletti & Sanz Table 1. Buccal bone loss reported in the literature Authors Model Healing time Socket Implant system (diameter, mm) Position/Surgical protocol Buccal bone loss (mm) Araujo et al. (3) 5 Beagle dogs 3 months 3/4 premolars Straumann (4.1) Center Araujo et al. (7) 6 Beagle dogs 1 and 3 months 4 premolars 1 molar Straumann (4.1) Center Araujo et al. (8) 7 Beagle dogs 0 and 1 year 2 months 3/4 premolars Straumann (4.1) Center Botticelli et al. (17) 6 Labrador dogs 2 and 4 months 3/4 premolars AstraTech (3.5) Center Blanco et al. (15) 5 Beagle dogs 3 months 3/4 premolars Straumann (3.3) Center/Flapped vs. flapless 1.33 (NA) 0.82 (NA) Vignoletti et al. (72) 16 Beagle dogs 0, 1, 2, 4 and 8 weeks 3/4 premolars 3i (3.25) Center Caneva et al. (21) 6 Labrador dogs 4 months 3 premolars Sweden & Martina (3.3) Center vs. 0.8 mm apical and lingual * Caneva et al. (22) 6 Labrador dogs 4 months 4 premolars Sweden & Martina (3.3 vs. 5.0) Center Caneva et al. (24) 6 Labrador dogs 4 months 2 premolars Sweden & Martina (3.3) Center/Flapped vs. flapless Caneva et al. (23) 6 Labrador dogs 4 months 3 premolars Sweden & Martina (3.3) Center/Collagen membrane vs. no membrane Submerged healing Araujo & Lindhe (4) 5 Beagle dogs 6 months 4 premolars Straumann (3.3) Center/Xenograft (deproteinized bovine bone mineral) vs. no graft Caneva et al. (20) 6 Labrador dogs 4 months 3 premolars Sweden & Martina (3.3) Center/Xenograft (deproteinized bovine bone mineral) vs. no graft Barone et al. (9) 5 Beagle dogs 2, 4 and 12 weeks 4 premolars 3i (3.25) Center/Graft (porcine collagenated bone) + collagen membrane vs. no guided bone regeneration Submerged healing

6 Immediate implants in fresh extraction sockets Table 1. (Continued) Authors Model Healing time Socket Implant system (diameter, mm) Position/Surgical protocol Buccal bone loss (mm) Beagle dogs 2, 4 and 12 weeks 1 molar 3i (3.25) Center/Graft (porcine collagenated bone) + collagen membrane vs. no guided bone regeneration Submerged healing Barone et al. (9) Labrador dogs 3 months 4 premolars Nobel Mark III (3.3) Lingual/Graft (deproteinized bovine bone mineral) + collagen membrane vs. no guided bone regeneration Nonsubmerged healing Favero et al. (40) Values are given as mean SD buccal bone loss reported in the literature. Negative values mean that the buccal bone crest is above the implant shoulder. *Relative bone loss (i.e. bone loss is measured from the implant shoulder that is placed 0.8 mm subcrestal). gap between the implant surface and the bone wall that is more relevant for the buccal crest resorption. The lack of bone resorption observed at the lingual aspect of the socket and the larger fraction of bundle bone that occupies the buccal bone of the socket wall, compared with the lingual side (6), suggests that the thickness of the residual cortical plate after the extraction plays a major role in this respect. Influence of the implant (surface, geometry, dimension and position) The possible influence of the implant surface was studied by Vignoletti et al. (73), when comparing the early healing of two implants with different surface microtopography after immediate insertion in fresh extraction sockets. The experimental implants had a modified surface consisting of a discrete crystalline deposition of calcium phosphate nanoparticles, whereas the control implants had a standard dual acid-etched surface. Evaluation of the dimensional changes of the crest did not reveal significant differences between the test and control implants, although there was a tendency for less buccal bone resorption in the experimental implants. The possible influence of the implant macrodesign was investigated in another experimental study by comparing the healing, 6 weeks after immediate implant installation, of four different implant systems based on their macroscopic design (Fig. 5). One of the systems Straumann â (Straumann AG, Basel, Switzerland) was a one-piece system with a conical internal connection, whereas the other three systems were two-piece cylindrical implants. Of these, Thommen â implants (Thommen Medical AG, Waldenburg, Switzerland) had a 1-mm machined collar; Astra â (Astra Tech, Molndal, Sweden) was a bone-level two-piece system with an internal conical connection; and the Biomet 3i â system (Biomet 3i, Palm Beach Gdns, FL, USA) was also a bone-level two-piece system but with an internal hexagonal connection. Six weeks after implant insertion, the alveolar ridge around the four types of implants showed marked resorption, with a mean buccal bone resorption of 2.5 mm, indicating that different geometry and macroscopic design do not affect the process of bone remodeling after tooth extraction (37). Caneva et al. (21) investigated, histologically, the influence of the implant position in the extraction sockets of Labrador dogs after 4 months of healing. In the control sites, 3.3-mm-diameter cylindrical implants were positioned in the center of the socket, whereas in the test sites, the implants were positioned 0.8 mm deeper and more lingually. 137

7 Vignoletti & Sanz A B C D Fig. 5. Ground sections representing the 6-week healing interval. Buccal bone remodeling at four types of implant systems: (A) 3.3 ITI Standard; (B) Thommen SPI Element 3.5; (C) 3i Osseotites Miniplant Certain straight; and (D) Astra 3.5 Micro Threads OsseoSpeeds. Levai Laczko staining; original magnification 320. Source: de Sanctis et al. (37). The results showed that the buccal crestal resorption was less pronounced at test sites, although this was not statistically significant. Furthermore, a similar experimental study from the same research group evaluated the influence of the implant diameter by comparing narrow cylindrical implants (3.3 mm) with a 0.8-mm polished collar with root-formed wide implants (5.0 mm). The wide implants occupying most of the socket did not prevent the bone-resorptive changes; in fact, they actually contributed to a more pronounced alveolar bone resorption (22) (Table 1). Influence of the socket anatomy The possible influence of both the width of the alveolus and the thickness of the buccal bone plate has been investigated by Araujo et al. (7) in the Beagle dog. The authors observed less bone-height reduction when placing 4.1-mm-diameter implants into molar sockets compared with placing the same implants into premolar sockets. They concluded that the wider the gap between the implant surface and the inner bone wall, the smaller the resorptive changes. These results were corroborated by a similar experimental investigation (73). The authors assessed whether the socket dimension influenced the morphological changes of the alveolar ridge when placing 3.25-mmdiameter cylindrical implants into the distal sockets of the third and fourth premolars in the Beagle dog. A minor vertical change of 0.3 mm was observed between baseline and 8 weeks at the buccal plate of the fourth premolar sites, whereas the corresponding change at the third premolar site was 1.1 mm, on average. The histometric measurements also demonstrated two different healing patterns at each socket site. At the distal socket of the third mandibular premolar, no vertical defect was observed at the marginal bone implant interface because of the pronounced resorption of the buccal plate, whereas at the fourth premolar site the vertical infrabony component of the defect was approximately mm. Influence of the surgical protocol The impact of raising a surgical flap and thus exposing the underlying bone has been investigated as a possible factor influencing the alveolar ridge resorptive changes. In an experimental study in dogs, Fickl et al. (42) reported that the elevation of mucosal flaps and the exposure of crestal bone caused more (about 14%) soft- and hard-tissue resorption than did a flapless tooth removal. Findings from a similar experiment performed by Araujo & Lindhe (6) failed to demonstrate any significant differences when comparing flapless with flap elevation. These heterogeneous results were also observed when using immediate implant protocols. A study in Beagle dogs that compared flap with flapless surgery when placing 3.3-mm-diameter implants into fresh extraction sockets reported higher resorption of the buccal bone wall (1.33 vs. 0.8 mm, respectively) (15). In contrast, 138

8 Immediate implants in fresh extraction sockets Caneva et al. (24) did not show any difference between the two surgical protocols. In summary, there is no clear demonstration that raising a flap significantly increases buccal bone resorption. Another important surgical consideration is whether the concomitant use of bone-regenerative techniques will counteract these described resorptive changes associated with immediate implant placement. Many studies have evaluated the placement of different biomaterials and bone-augmentation techniques simultaneously with immediate implant placement. Caneva et al. (23) evaluated the influence of the placement of a resorbable collagen barrier membrane over immediately placed implants in dogs. Although bone resorption occurred in both test and control sites (without membrane), the amount of bone resorbed was smaller in the test sites compared with the control sites (1.7 vs. 2.2 mm). Araujo & Lindhe (4) performed a series of experimental studies using different biomaterials placed in the gap between the implant surface and the buccal and lingual bone plates. When using a xenogeneic graft, healing at 6 months showed significantly less buccal bone resorption, both horizontally and vertically, compared with nongrafted controls. Similar results were reported using cancellous bone and a resorbable collagen membrane in a submerged healing environment (9). However, these results were not confirmed by a similar experimental investigation using a similar xenogeneic bone substitute (deproteinized bovine bone mineral) compared with nongrafted controls, as similar amounts of buccal bone resorption were observed in both groups ( vs mm, respectively) (20). The absence of a proper gap established when using the third mandibular premolar in the latter study, compared with the fourth mandibular premolar and the first molar of the two former studies, respectively, may be partly responsible for the differences in the results. Indeed, data from a recent study evaluating a guided boneregeneration approach combining a collagen membrane and deproteinized bovine bone mineral have shown that, under the same experimental conditions, the lingual positioning of the implant and the presence of a gap were more relevant than the regenerative technique regarding the vertical resorption occurring at the buccal bone plate (40). Morphogenesis of the peri-implant mucosa The morphogenesis and maturation of the periimplant mucosa, after implant placement into healed crests, have been described in detail from 2 h to 3 months of healing (12). The resulting histomorphometrical analysis demonstrated that a coagulum occupied the compartment between the mucosa and the implant during the initial phase of healing, and that the first signs of epithelial proliferation were observed after 1 2 weeks, with expansion of epithelium in a vertical dimension, 0.5 mm apically from the mucosal margin. After 6 8 weeks of healing, this epithelial dimension was mm and remained so for up to 12 weeks after surgery. Underneath this epithelial barrier, a connective tissue seal, consisting of collagen fibers running parallel to the implant surface, was formed after 4 6 weeks of healing. Using this standard implant protocol, soft-tissue attachment was established and became stable 4 6 weeks after implant installation. Using a similar experimental model, the early phases of formation and maturation of the biological width at implants placed in fresh extraction sockets were evaluated through histological and histometrical analyses (74). The most relevant difference was that, at the first week of healing, the oral epithelium was continuous with an already established barrier epithelium, of mm, which increased to mm after 2 weeks. Later, this epithelial dimension remained stable until the eighth week. However, the area of connective tissue contact with the implant surface showed a reduction, from mm at 1 week to mm at 12 weeks. Although the dimension of the connective tissue was similar to that reported when implants were placed in healed ridges, significant differences were observed in the junctional epithelium. In the immediate implant protocol an epithelial barrier was patent already at 1 week (Fig. 6) and remained about 1 mm larger during the whole healing process. It could be speculated that a tooth-dependent epithelium, which remains after extraction, may become incorporated during the morphogenesis of the peri-implant mucosa. In summary, this histometrical analysis (Fig. 7) revealed that the overall biological-width dimensions around immediately placed implants were and mm at the buccal and lingual sides, respectively, which is about 1 mm longer than the biological width described when implants are placed in healed alveolar crests (12). The finding of a longer epithelium around immediately placed implants was also reported by Rimondini et al. (63) in a similar experimental model in minipigs, but this result is in contrast with the results of other experimental studies in dogs, which have described biological width dimensions after 139

9 Vignoletti & Sanz A B C Fig. 6. Implant and surrounding tissue after 1 week of healing. A junctional epithelium is interposed between the implant surface (I) and the thin buccal bone crest (BC). Toluidine blue staining; original magnification 32.5 (B) High magnification image of panel A. The oral epithelium (OE) is continuous with the junctional epithelium (JE), which faces the implant abutment (I). Inflammatory cells are present. Toluidine blue staining; original magnification 310. (C) High magnification of panel A. Implant abutment interface. A microgap is present. The junctional epithelium and the connective tissue are infiltrated with inflammatory cells. Note the junctional epithelium in contact with the implant shoulder (arrow). Toluidine blue staining; original magnification 310. Note the osteoclasts on the buccal bone crest (yellow arrows). Toluidine blue staining; original magnification 310. Source: Vignoletti et al. (72). immediate implant placement similar to those reported when implants were placed in healed ridges (3, 7). Therefore, it remains to be proven whether a larger biological width consistently becomes established around immediate implants. Immediate implant placement vs. spontaneous healing of the socket There is limited evidence in the literature comparing the healing of fresh extraction sockets with and without implant placement. One study (3) reported that the amount of buccal bone height reduction after 3 months of healing was about 2.2 mm, being similar at implant sites and edentulous sites in contralateral jaws. More recently, another study compared the dimensional alterations of the alveolar ridge that occurred 6 weeks after immediate implant placement or following undisturbed healing. The evaluation of the histometric measurements showed that a marked bone resorption occurred at both sites. Nevertheless, this dimensional change was consistently more pronounced at implant sites. While the mean vertical difference between the buccal and lingual bone crests at the sockets with spontaneous healing was mm, the vertical bone loss was mm in the sockets where immediate implants were installed and these differences were statistically significant (P < 0.05) (71). These experimental studies clearly demonstrate that immediate implant placement fails to prevent the resorptive crestal changes described after tooth extraction. These results were recently corroborated in a preclinical experiment that evaluated the impact of immediate implant placement (test) on vertical and horizontal bone remodeling in comparison with adjacent sockets left to heal spontaneously (control) at five different healing times. The results from histometric measurements demonstrated that after 2 weeks of healing, the mean vertical difference between the buccal and lingual bone crests was and mm for test and control sites, respectively, whereas the corresponding values after 8 weeks of healing were and 140

10 Immediate implants in fresh extraction sockets A B C D Fig. 7. Ground sections representing the formation and maturation of the biological width at immediate implants, at: (A) 1 week; (B) 2 weeks; (C) 4 weeks; and (D) 8 weeks. At the right of the figure a histogram is shown representing the mucosal height through the study period: epithelial (red) and connective tissue (blue) dimensions are shown. Toluidine blue staining; original magnification 310. Source: Vignoletti et al. (74). Fig. 8. Ground sections representing buccal bone remodeling after 4 h, 1, 2, 4 and 8 weeks at a socket healed spontaneously (upper row of images) and at immediate implants (lower row of images). Toluidine blue staining , respectively, which were statistically significant (38). The finding that two to three times more vertical resorption occurred at the immediate implant sites than at the adjacent spontaneously healed sites (Fig. 8) suggests that the placement of an implant in a fresh extraction socket may jeopardize its spontaneous healing, fostering the process of bone remodeling, at least during the early phases of bone healing. Clinical outcomes Clinical studies in humans have evaluated, at different time periods, the outcomes of immediately placed dental implants into fresh extraction sockets (Table 2). Survival rates Survival rates, reported in the literature as the main efficacy outcome of immediate implant protocols, 141

11 Vignoletti & Sanz Table 2. Vertical and horizontal bone resorption and midfacial recession of selected clinical studies Authors Study design Follow-up No. of patients No. of implants Implant system Loading protocol Surgical protocol Biotype/ Buccal bone thickness (mm)/ implant position Vertical buccal bone loss at re-entry [mm (SD)] Horizontal bone loss at re-entry [% original dimension (SD)] Mid-facial recession [mm (SD)] Mid-facial recession% (n) Bianchi & Sanfilippo (14) Case series 1 9 years Straumann Delayed Submerged Not available Not available Not available Not available 0 corticocancellous porcine bone Semisubmerged Not available Not available Not available 80 Chen et al. (28) Controlled clinical study 6 months 3 years Straumann Delayed Semisubmerged anorganic bovine bone mineral Not available 1.1 (1.2) 13.9 (16.7) Buccal Not available 33.3 (10) implants Semisubmerged anorganic bovine bone mineral+ collagen membrane Not available 1.0 (0.6) 23.8 (23.4) Buccal Semisubmerged Not available 1.3 (0.9) 48.3 (9.5) Buccal Botticelli et al. (18) Case series 1 year Straumann Delayed Semisubmerged 1.4 (0.4) 0.3 (0.6) 56 Buccal Not available Not available 30 Palatal Botticelli et al. (16) Case series 5 years Straumann Delayed Semisubmerged 1.4 (0.4) Not available Not available 0.2 (1) Buccal Not available maxillary 1.2 (1.8) Buccal mandibular Not available 0.4 (0.1) Lingual maxillary Not available 0.9 (0.3) Lingual mandibular Not available Pooled data 0.4 Buccal Not available 0.5 Lingual 142

12 Immediate implants in fresh extraction sockets Table 2. (Continued) Authors Study design Follow-up No. of patients No. of implants Implant system Loading protocol Surgical protocol Biotype/ Buccal bone thickness (mm)/ implant position Vertical buccal bone loss at re-entry [mm (SD)] Horizontal bone loss at re-entry [% original dimension (SD)] Mid-facial recession [mm (SD)] Mid-facial recession% (n) Evans & Chen (39) Case series 6 50 months i/Straumann Delayed Semisubmerged/ Submerged Thin Not available Not available 1 (0.7) 26.1 (11) Thick Not available Not available 0.7 (0.57) 14.2 (6) Buccal Not available Not available 1.8 (0.83) 14.2 (6) Palatal Not available Not available 0.6 (0.55) 21.4 (9) Pooled data 0.9 (0.79) 40.4 (17) Cordaro et al. (30) Randomized controlled trial 12 months Straumann Delayed Semisubmerged Thin Not available Not available 0.73 (0.7) 17.2 (5) Thick Not available Not available 10.3 (3) Submerged Thin Not available Not available 0.82 (0.67) 10.3 (3) Thick Not available Not available 20.6 (6) Pooled data Not available 58.6 (17) Canullo et al. (25) Randomized controlled trial 25 months Sweden & Martina Immediate Flapless/ Platform switching (Thin/Thick) Not available Not available (0.46) 0.9 (1)** difference not statistically significant Flapless/ Conventional (Thin/Thick) Not available Not available 0.45 (0.27) 72 (9)** difference not statistically significant De Rouck et al. (36) Randomized controlled trial 12 months Nobel Biocare Delayed Submerged anorganic bovine bone mineral + collagen membrane Normal Not available Not available 1.16 (0.76) Not available to thick Immediate Transmucosal Not available Not available 0.41 (0.75) Not available 1 stage healing 143

13 Vignoletti & Sanz Table 2. (Continued) Authors Study design Follow-up No. of patients No. of implants Implant system Loading protocol Surgical protocol Biotype/ Buccal bone thickness (mm)/ implant position Vertical buccal bone loss at re-entry [mm (SD)] Horizontal bone loss at re-entry [% original dimension (SD)] Mid-facial recession [mm (SD)] Mid-facial recession% (n) Sanz et al. (66) Randomized controlled trial 4 months Astra Tech Delayed Semisubmerged 1 (0.5) 1 (2) 36% (37) Not available Not available Buccal 14% (36) Palatal Ferrus et al. (41) Randomized controlled trial 4 months Astra Tech delayed Semisubmerged 1 (0.5) 1.4 (2.5) anterior 0.7 (1.4) posterior 42 (46) Buccal Not available Not available anterior 32 (29) Buccal posterior Cooper et al. (29) Controlled clinical study 1 year Astra Tech Immediate Transmucosal 1 stage healing/ delayed Intact Not available Not available (0.89) Not available buccal bone Pieri et al. (58) Randomized controlled trial 12 months Biospark Immediate Flapless/ Not available Not available Not available 0.73 (0.52) Not available Platform switching Flapless/ Conventional Not available Not available Not available 0.61 (0.54) Not available Raes et al. (62) Controlled clinical study 52 weeks Astra Tech Immediate Flapless Nonsignificant Not available Not available Mean Not available difference Flapped Nonsignificant Not available Not available Not available 0.89 Covani et al. (34) Case series 10 years Sweden & Martina Delayed Submerged Not available Not available Not available 0.7 (0.4) Not available autologous bone + corticocancellous porcine bone+ collagen membrane Submerged 1 (0.7) Not available Implants with recession after 6 months of healing and longer definite restorations in comparison with contralateral. Recession 1 mm. Recession > 1mm. Mean discrepancy from the emergence line of the mesial and distal closest tooth crowns > 1 mm. **Recession = 0.5 mm. Recession measured from definitive crown-restoration placement (approximately 8 10 weeks after implant placement) until 1 year of function. Positive values (+) mean recession reduction. 144

14 Immediate implants in fresh extraction sockets have been extensively reported in the literature, although data from long-term studies are still limited. Survival is usually defined as implants remaining in situ at the follow-up examinations, irrespective of the conditions of the surrounding tissues. In a recent systematic review (52), 46 studies were identified, providing data on 2908 implants with a mean follow-up time of 2.08 years following immediate implant placement. The estimated annual failure rate of the implants was 0.82% (95% confidence interval: %), yielding a 2-year survival rate of 98.4% ( %). When nine studies with a mean follow-up time of 3 years were analysed separately, the estimated 4- year implant-survival rate decreased to 97.5% ( %) (52). Five-year data were limited to four studies only, which also reported high cumulative survival rates (100%) (14, 16). The quoted systematic review analysed five factors that might influence the outcome of this protocol: the reason for extraction; use of antibiotics; position of implants (posterior vs. anterior and maxillary vs. mandibular); and the timing of the restoration. A tendency toward lower failure rates was observed when teeth were extracted for nonperiodontal reasons, when implants were placed in the anterior area and when implants were loaded with a delayed protocol, although most of these differences were not statistically significant. Longer-term followups were limited to one study (34) that reported a 10- year cumulative survival rate of 91.8% for single-unit immediate implants in conjunction with autogenous bone augmentation and guided bone regeneration, when the gap was larger than 2 mm. When these authors compared the implants with guided bone regeneration with those without, the cumulative survival rates were 94.1% vs. 87.9%, respectively. Furthermore, in another study evaluating immediately placed implants in high-risk sites (chronic peri-apical infected sites), the reported 1-year survival rate was 92% (54). Hard-tissue changes Different studies have evaluated the changes occurring in the bone around an immediately placed implant by raising a flap and undertaking direct bone measurements, thus comparing the bone architecture at implant installation and at the second-stage surgery (usually 4 months later). In general, these studies have reported very similar outcomes to the histological descriptions from experimental studies because they have shown significant horizontal and vertical bone-dimensional changes occurring mainly in the buccal bone plate. Botticelli et al. (18) reported significant horizontal resorption in both the buccal and palatal bone plates (56% and 30%, respectively) after placing single-unit immediate implants in the upper maxilla. Similar outcomes were reported in a clinical trial comparing cylindrically and conically shaped implants immediately placed in fresh extraction sockets of the upper jaw. Both implant designs rendered similar outcomes in terms of horizontal changes of the alveolar bone crest, with 36% and 14% resorption at the buccal and palatal bone walls, respectively (66). In this clinical trial, mean vertical bone resorption of approximately 1 mm of the buccal bone plate was also reported 4 months after immediate implant installation, which was accentuated more when this buccal bone was thinner ( mm) and in the anterior maxillary teeth ( mm; Figs 9 12) (41). Using a multilevel multivariate analysis, the relevant factors influencing these resorptive changes were investigated. For horizontal bone-resorptive changes, the most relevant factor was the thickness of the buccal bone wall, whereas for vertical changes, both the implant position and the thickness of the buccal bone wall significantly influenced the amount of vertical bone change. In regards to the spontaneous filling of the gap between the implant surface and the inner bone plates, the most relevant factors were the implant (significantly better in cylindrical implants compared with the conical implants), the thickness of the buccal bone plate and the patient (smokers performed significantly worse) (70). With the goal of counteracting these changes, different treatment strategies have been proposed and tested, most of which involved the combination of immediate implant placement with the use of different grafting materials and barrier membranes. In a randomized clinical trial, Chen et al. (28) evaluated the outcome of immediate implants in the maxilla by comparing three treatment groups, one in which the gap between the implant surface and the bone was left unfilled (control), and the other two in which the A Fig. 9. Tooth 2.4. Extraction required for periodontal reasons. (A, B) Clinical photographs before the extraction. B 145

15 Vignoletti & Sanz A B C Fig. 10. Tooth 2.4. Intrasurgical aspect of the socket: (A) after tooth extraction; (B) after immediate implant placement; and (C) after 4 months, at the re-entry procedure. Please note the horizontal resorption of buccal bone crest and the partial fill of the gap. Fig. 11. Tooth 2.4. Definitive restoration. gaps were filled either with deproteinized bovine bone mineral only or with the combination of deproteinized bovine bone mineral and resorbable collagen membrane. Both experimental groups showed similar outcomes, demonstrating a significant reduction (of around 25%) in the extent of horizontal bone resorption compared with the control group. Regarding the extent of vertical resorption, the differences among the groups were not significant and the extent of resorption depended more on the thickness of the buccal bone than on the treatment group, thus corroborating the previously reported results. Interproximal hard-tissue changes Several authors have used, as outcomes, interproximal crestal bone levels (by assessing peri-apical radiographs) and clinical attachment levels (by periimplant probing). In a recent systematic review, Lang et al. (52) identified seven studies (11, 14, 16, 33, 45, 56, 60), with a mean follow-up time of 3 years, that evaluated the marginal bone level changes. With the exception of the study by Botticelli et al. (16), which reported a mean radiographic bone-level gain of 0.23 mm, the studies reported marginal bone loss, although within a limited range that fulfilled the success criteria stated by Albrektsson et al. (1) (annual vertical bone loss not exceeding 0.2 mm after the first year of service). Botticelli et al. (16) reported, in detail, the outcomes of maxillary and mandibular immediate implants after 5 years of function and showed that 29% of the implants exhibited radiographic marginal bone loss (mean mm), whereas the remaining implants gained bone (mean mm). In a recent long-term clinical trial (10 years of follow-up), comparing immediate implants with guided bone regeneration with immediate implants alone (34), there were no significant differences regarding changes in clinical attachment levels or radiographic interproximal bone levels. Independently of the treatment group, 98% of the implants experienced bone loss of 1.5 mm at the end of the study. The addition of soft-tissue grafts to the immediate implant protocol provides better outcomes, as dem- A B Fig. 12. Tooth 2.4. Clinical (A) and radiological (B) conditions of the implant-supported prosthesis after 1 year of function. 146

16 Immediate implants in fresh extraction sockets onstrated in a clinical trial, when compared with the same implant protocol without connective tissue grafts (14). After a follow-up period of 6 9 years, the number of implants demonstrating clinical attachment loss (> 2.5 mm) or radiographic bone loss (> 3.5 mm) was significantly lower in those in which a connective tissue graft had been added at implant installation. Soft-tissue healing/esthetic outcomes One of the most frequently reported complications with the use of immediately placed dental implants in areas of esthetic concern is the occurrence of marginal tissue recession and loss of the buccal maxillary contour. In the systematic review mentioned previously (52), the evaluation of studies with observation periods of 3 years or more showing recession ( 1 mm of midfacial marginal tissue recession) reported that this outcome occurred in about 20% of patients. The most important factors related to this finding were the position of the implant and the gingival biotype. Chen et al. (28) evaluated the changes in the buccal soft-tissue margin retrospectively in immediately placed implant-supported restorations, with a mean follow up of 18 months, reporting the occurrence of marginal tissue recession ( 1 mm) in one-third of the sites (33.3%). In this study, the position of the implant shoulder in relation to the buccal bone plate was significantly associated with the occurrence of marginal recession. In fact, recession occurred in only 16.7% of the implants placed lingually, in contrast to 58.3% of the buccally placed implants. These data are consistent with the results reported by Evans & Chen (39) of a mean change in crown height at the end of the study of mm in the buccally placed implants compared with only mm in those inserted lingually. Kan et al. (49) reported that this marginal recession occurred soon after implant installation and the placement of the restoration. These authors reported a mean facial mucosal recession of 0.55 mm at 1 year compared with 1.13 mm at the end of the study period (mean follow-up time of 4 years). In this study, the apical displacement of the marginal mucosa was significantly more pronounced in patients with a thin gingival biotype compared with those with a thicker gingival biotype (1.50 vs mm, respectively). Cordaro et al. (30) compared the clinical outcomes of submerged with nonsubmerged immediate implants placed in fresh extraction sockets. The results, after 1 year, showed a mean mucosal midfacial recession of 0.82 and 0.73 mm, respectively, with more than 50% of the patients in both groups showing buccal mucosal recession ( 1 mm). Botticelli et al. (16) reported, after 5 years of follow-up, that the observed recession was more marked in the lower jaw than in the upper jaw ( vs mm, respectively). In contrast to these publications, other studies have reported recession of < 1 mm after immediate implant placement and immediate provisionalization. Cooper et al. (29) reported that the mucosal zenith was stable or moved coronally in 83.7% of immediately placed and restored implants during the time interval from definitive crown placement to 1 year of function, although from implant placement a slight recession was observed. Similar results were reported by De Bruyn et al. (35) after 3 years of follow up. De Rouck et al. (36) evaluated the soft-tissue marginal changes using two different restorative protocols after immediate implant installation either the immediate connection of a temporary crown (test) or submerging the implants and having the patients wear a removable partial denture (control). The results after 1 year demonstrated that immediately restored implants had significantly less midfacial recession of the marginal mucosa compared with the controls ( vs mm, respectively). Several authors have investigated the possible influence of the surgical protocol on the stability of the soft-tissue margin. Covani et al. (34) compared the long-term outcomes (10 years) of immediate implants in combination with guided bone regeneration with immediate implants without guided bone regeneration. The overall mean recession was mm, with significantly more recession in the group without guided bone regeneration compared with the group with guided bone regeneration ( vs mm, respectively). The added value of a connective tissue graft in conjunction with immediate implant installation has been studied by Bianchi & Sanfilippo (14). They measured the buccal level of the mucosal margin when installing the final restoration and compared this margin with that of the mesial and distal adjacent teeth. They reported complete success (< 1 mm of a discrepancy) after 3 years in the group of patients who received immediate implant placement and simultaneous connective tissue grafting, whereas this outcome was achieved in only 80% of patients treated with immediate implants only. The influence of flapless surgery and the use of implant systems with a discrepancy in diameter between the implant and the abutment (platform-switching concept) has also 147

17 Vignoletti & Sanz been studied. Canullo et al. (25), using a flapless approach for placing immediate single-unit maxillary implants, compared the use of a horizontal mismatch of 0.85 mm at the implant abutment interface with matching components in a randomized controlled clinical trial. They reported statistically significant less recession of the midfacial mucosa when the platform-switching concept was applied. However, these differences were not confirmed in another randomized controlled clinical trial (58). Raes et al. (68) evaluated the influence of a flapless approach on buccal recession in a prospective case series, reporting more recession when a flap was elevated (a mean difference of 0.74 mm). Interdental papillae When studies evaluated the papilla fill according to the papilla index proposed by Jemt (46), there was a consistent finding that a gradual fill of the interproximal spaces will occur during a 1-year observation period in most cases (48), whereas papilla loss (> 1 mm) was found only in 4% and 16% of mesial and distal papillae, respectively (32). These results are in agreement with a long-term study recently published by Kan et al. (49). These authors reported mesial and distal papillae loss of 0.59 mm and 0.39 mm, respectively, at the 1-year observation, whereas the corresponding measurements at the end of the study were 0.22 and 0.21 mm, respectively. Similarly, Covani et al. (34) reported that 27% of the implant sites had a score of 1, 57% of the sites had a score of 2% and 13% of the implant sites had interproximal papillae filling the entire proximal space (i.e. a score of 3). Biological complications Only a few studies have evaluated the biological complications related to immediate implant placement. Bianchi & Sanfilippo (14) evaluated both bleeding on probing and probing depth. The evaluation of bleeding on probing in the control group (no soft-tissue graft) demonstrated that about 70% of the checked points had a bleeding on probing score of 0, 20% had a bleeding on probing score of 1% and 9% had a bleeding on probing score of 2. In the test groups (soft-tissue graft), around 69% of the sites had a bleeding on probing score of 0, 26% had a bleeding on probing score of 1% and 4% had a bleeding on probing score of 2. Furthermore, in both procedures, a small increase in probing depth, from 2.5 mm to about 3.5 mm, was encountered during the first year. In the following years, probing depth still increased in the control group, up to mean values of around 4 mm, whereas in the test group, this was not observed. In detail, 45% of the control sites presented a probing depth of > 3 mm compared with 27% in the test group. More recently, a 5-year prospective cohort comparative study evaluated the biological complications, as well as the clinical and radiological outcomes, of immediately placed implants (group II) compared with similar implants installed with a delayed protocol (group DI) in the same patients. Biological complications were defined as mucositis when implant sites demonstrated a peri-implant probing depth of 4 mm that bled on probing without significant bone loss. Peri-implantitis sites had to demonstrate peri-implant probing depth of 4 mm and bleeding on probing plus significant bone loss. During the follow-up period a tendency towards more biological complications was observed in the immediate implant group: mucositis was observed at six (17.6%) implants and peri-implantitis at three (8.8%) implants. The corresponding values in the DI group were 20.5% and 2.9%, respectively (64). The scarcity of data on biological complications using this surgical protocol may be a result of the lack of long-term studies because peri-implantitis usually occurs after a function time of 5 years (77). When direct bone measurements have been used to evaluate the outcomes of this surgical protocol, vertical bone loss always occurred in the buccal bone plate, mostly in anterior sites and when the buccal bone plate was thin (41, 66). This buccal bone dehiscence does not necessarily lead to marginal recession, and the soft-tissue collar around these implants may be stable (34). What is not clear is whether these sites might be more vulnerable for soft-tissue inflammation. When Schwarz et al. (69) evaluated the influence of residual bone marginal dehiscence after guided bone regeneration on peri-implant health, they reported that implants exhibiting dehiscence of 1 mm were at higher risk of presenting clinical attachment loss, marginal recession and deepened probing depth, 4 years after treatment. There may be a similar problem with immediately placed implants, although no direct evidence is available. Recommendations for clinical practice When considering which implant protocol might be most appropriate, the clinician must take into consid- 148

18 Immediate implants in fresh extraction sockets eration different factors: the patient; the location; and the surgical protocol. As for any other surgical implant protocol, the patient should be free from oral infections and all previous oral conditions should be treated before surgical implant placement. Patients should have good oral hygiene and should be advised to refrain from smoking. In patients affected by systemic diseases influencing wound healing after implant surgery, such as diabetes, their systemic status must be controlled before implant installation. In terms of the location, the factors of major concern when using the immediate implant protocol are the thickness and the integrity of the socket bone walls, mainly the buccal crest, as well as the gingival biotype (Fig. 13). Epidemiological data have shown that most of the sites in the upper anterior maxilla have thin buccal ridges (mean: 0.8 mm in teeth from cuspid to cuspid vs. 1.1 mm in the premolar region). A B Fig. 13. Fresh extraction socket of tooth 2.4. (A) Adequate thickness and integrity of the socket bone walls. (B) Detailed image of panel a. Bundle bone is present in the inner part of the socket. Note that the blood vessels which normally pass from the alveolar bone proper to the periodontal ligament are damaged and bleed through the Volkmann canals. In this anterior maxillary region, 87% of the buccal bone walls presented a width of 1 mm, and only 3% of the walls were 2 mm wide (44). On the other hand, the integrity of the socket bone walls will largely depend on the reason for tooth extraction and the underlying pathology, as well as the possible trauma during the extraction procedure. These factors may account for the unlikely presence of intact sockets in most of the extractions. These factors were discussed in a review publication focusing on the frequency of advanced recession in patients treated with immediate single implants (31). The authors concluded that a lower risk (< 10%) for gingival recession was found in patients with an intact buccal bone wall and thick gingival biotypes. From a surgical point of view, the implant design and implant position may be the factors of major concern. Hence, when using the immediate placement protocol, the buccal positioning of the implant and the use of implants that are too congruent with the socket anatomy (tapered implants) should be avoided. Implant placement must therefore be guided by the ideal prosthetic position as well as by the assurance of primary stability in the apical portion of the socket and the creation of an adequate gap dimension (> 2 mm) between the implant surface and the inner buccal bone plate in the coronal portion, to allow for adequate bone healing. In a vertical dimension, it is important that the final position of the implant rim is placed at least 1 mm apical to the buccal ridge, in order to compensate for the expected vertical resorption. In order to compensate for the expected horizontal bone resorption of the buccal plate, the use of bone substitutes, with a low resorption rate, to fill the gap has been shown to reduce this resorption significantly and therefore their use should be advocated when the esthetic demands are high (Fig. 14). A B C Fig. 14. Immediate implant placement in the socket of tooth 2.4. (A) Biologically and prosthetically driven implant position to allow the creation of a proper gap at a distance from the buccal bone plate. (B) A xenograft (a blend of granules of deproteinized bovine bone (90%) and porcine collagen fibers (10%); Bio- Oss collagen; Geistlich) is used to fill the gap. (C) Four months re-entry procedure. Remodeling has occurred despite the use of xenograft bone. 149

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