Successfully osseointegrated endosteal dental implants have a good long-term rate of success; but despite careful patient selection, careful treatment planning, and careful insertion by skilled and experienced surgeons, complications of implant treatment can arise.1,2 Implant periapical bone loss usually with symptoms such as pain, tenderness, swelling, and perhaps the development of a sinus tract, is one such complication3,4 that if left untreated, may be progressive and can result in implant failure3,5–9 (Fig. 1).
A radiolucent inflammatory implant periapical lesion can be defined as a symptomatic zone of bone destruction at the apex of an endosteal implant.8,10 These lesions are sometimes referred to in the literature as “apical periimplantitis,”6,7,11 or as “retrograde periimplantitis.”1,5,8,12–14 Data on the incidence and etiopathogenesis of this lesion are scanty and has been gleaned from individual case reports and from limited retrospective studies.15 The reported incidence ranges from 0.26% to 7.8%.5,10,16 In a review of published case reports and retrospective studies, Romanos et al,17 found that about 70% of such lesions were detected before implant exposure, about 20% at the time of implant loading, and the remaining 10% sometime after loading.
Little is known about the etiopathogenesis of radiolucent inflammatory implant periapical lesions.11,15 It has been proposed that multiple factors may be implicated (Table 1),2,4 but the role of some of the suggested etiological factors is not supported by scientific data.17 Symptomatic inflammatory implant periapical radiolucencies as discussed above should be distinguished from noninflammatory asymptomatic implant periapical radiolucencies, which may be caused by an osteotomy that is deeper than the length of the implant. Such a suspicious radiolucency should disappear as the bone heals, unless infections supervene from any of the sources to be discussed below.2,4
It is the purpose of this article to critically evaluate factors that have the capacity to cause inflammatory implant periapical bone loss (Table 1), to discuss the terminology used, the etiopathogenesis, and the treatment options for this condition, and to argue that this condition is not a unique pathological entity, but rather either a granuloma or an abscess occurring at the apex of an implant,9 analogous to granulomas and abscesses around the apices of nonvital natural teeth.
Radiolucent inflammatory periapical lesions have previously been referred to in the literature as active implant periapical lesions, retrograde periimplantitis, or symptomatic implant periapical radiolucencies.14 All these terms seem inappropriate because they do not clearly reflect the pathological features of the condition. We will argue that inflammatory implant periapical radiolucent lesions consist of granulation tissue with varying degrees of fibrosis and with varying intensities of inflammation. Acute exacerbations with abscess formation may occasionally occur. Because there is no evidence that the inflammatory implant periapical lesion is a unique pathological entity, and based on its histopathological features, it should be termed periapical granuloma/abscess9 (Fig. 2).
Results of histopathological examination of soft tissue samples from radiolucent inflammatory implant periapical lesions have been reported in only a few studies,3,7,9,18 and it is therefore not possible with certainty to draw conclusions regarding the histopathological nature of the lesions. Penarrocha-Diago et al,7 reported that all 7 cases they investigated exhibited acute inflammatory cell infiltrates. Balshi et al,3 reported that in 37 of their 39 cases, there was a stroma of immature connective tissue, with numerous dilated capillaries and with an inflammatory cell infiltrate predominantly of lymphocytes and plasma cells. Chan et al,13 reported 2 cases of radiolucent inflammatory implant periapical lesions. One case had a mixed acute and chronic inflammatory cell infiltrate on a background of immature granulation tissue and the other had a chronic mixed inflammatory cell infiltrate with lymphocytes predominating on a background of relatively dense connective tissue. These variations are, of course, consistent with granulomata at different stages of maturity (Fig. 2).
Although it is impossible to prove, it seems that bacterial contamination of the apical portion of an implant after its insertion can be caused by residual bacteria in the apical portion of the osteotomy. These bacteria may be residual from periapical infections of endodontic origin, from periodontal disease, or from infected residual root fragments of an extracted tooth4,8,9,12,14,17,19 (Fig. 3). The bacteria have the capacity to survive in colonies in the bone, escaping immune surveillance and constituting subclinical infection.11 Changes in the cytokine milieu of the bone microenvironment in response to the preparation of the osteotomy and to the presence of the implant in situ or as part of the process of wound healing of the osteotomy may activate this latent bacterial infection, resulting in bone destruction and manifesting radiographically as a chronic implant periapical radiolucency and histopathologically either as a granuloma or as an abscess.5,11,19
Circumstantial evidence supporting this view is the fact that many implants that developed radiolucent inflammatory periapical lesions had been placed in bone that had previously supported teeth with a known history of endodontic or periodontal disease.8,10–13,17,19 However, these findings should be interpreted with caution because most implants are placed in bone that previously surrounded endodontically or periodontally diseased teeth, yet they do not develop periapical bone destruction. The question therefore is what factors contribute to the formation of radiolucent inflammatory implant periapical lesions in a manifestly small number of patients.
Bone destruction around the apical portion of an implant can occur by contiguous spread of infection from a nonvital tooth with a periapical infection in close proximity to it or even from an apparently successfully endodontically treated tooth with a history of septic pulpitis5,8,10,18 (Fig. 3). In a study of endodontically treated teeth in cadavers, Green et al,20 reported that on histopathological examination, all the periapical radiolucent lesions showed inflammatory cell infiltrates of varying degrees and 26% of endodontically treated teeth without periapical radiolucencies, regardless of the quality of the endodontic treatment, showed histopathological features of periapical inflammation. In studies in living subjects, periapical tissues of asymptomatic successfully endodontically treated teeth not infrequently show inflammatory cell infiltrates on histopathological examination.21,22
It is therefore possible that bacteria, bacterial endotoxins, inflammatory cells, or inflammatory cytokines from the periapex of a clinically asymptomatic endodontically treated tooth or from an untreated nonvital tooth, with or without a periapical radiolucency, may involve the periapex of a close adjacent implant by direct extension.23–27 This manifestation is undoubtedly very uncommon; but when it occurs, exacerbation may give rise to a periapical granuloma or to an abscess around the apical portion of the implant. As a corollary, it has been reported that if an implant is placed with its apex closer than 2 mm to the apex of an endodontically treated tooth or to a tooth in which endodontic treatment had been completed in less than 4 weeks before insertion of the implant, the likelihood of implant periapical bone destruction occurring is increased.5
Bacterial contamination of an implant surface during its insertion can occur, but it is then likely that the infection will bring about complete failure of integration, rather than causing merely inflammatory bone destruction at the apex of the implant.
Although it is reasonable to assume that implant periapical granulomas are infective in origin, bacteriological evidence of this is not available, so any association between an inflammatory implant periapical lesion and bacterial infection is yet to be proven.
Implanted Foreign Material
Foreign body reactions induced by the starch on powdered surgical gloves are uncommon. Unintentionally implanted, starch particles at a surgical site may induce either a localized simple chronic foreign body granuloma or a delayed hypersensitivity response.28
In support of this rare etiopathological sequence of events, Nedir et al15 reported that histopathological examination of a tissue sample from a single inflammatory implant periapical lesion showed fibrous connective tissue with a dense chronic inflammatory cell infiltrate of lymphocytes, plasma cells, and occasional macrophages and with numerous foreign bodies, which were identified by Fourier transform infrared microscopy as starch particles.
It has been demonstrated that if autologous gingiva is implanted in the mandibles of experimental animals, implantation cysts will develop.29 The likelihood of unintentional implantation of oral epithelium into an osteotomy site during mucosal flap surgery must be very low; and there are no reports of implantation cysts at implant sites even after flapless implant surgery. Nevertheless, although there are no reports in the literature documenting the presence of epithelial cells, far less of epithelial implantation cysts within radiolucent implant periapical lesions, the latter cannot be ruled out as a cause of radiolucent periapical lesions.
Compression and Overheating of Bone
In response to the drilling of a hole in the bone, there is an immediate local diminution in blood flow because of direct damage to the blood vessels and of thermal precipitation of proteins in the microvessel caused by the drilling, leaving proteinaceous deposits occluding the microvessels. This brings about ischemia and bone necrosis immediately surrounding the osteotomy site.30 If operative trauma and heat generation are minimized by careful surgical technique, the zone of necrosis around the osteotomy site will be small, will be readily repaired by bone remodeling, and osseointegration of the implant will occur. However, heavy-handed surgery with undue heat generation and pressure while preparing the osteotomy site and further frictional heat generation and excessive compression during insertion of an implant may produce a zone of bone necrosis exceeding the bone repair capacity and consequent nonintegration of the implant.
Osteocytes will react to microdamage to bone by pressure and heating, initiating bone remodeling.31 Osteocytes lying within the substance of bone in lacunae, have long slender cytoplasmic processes in a network of interconnected canaliculi allowing the osteocytes, through gap junctions, to communicate with one another and with osteoblasts.32 Within this 3-dimensional lacuno-canalicular network, the osteocytes and their processes are bathed in fluid, the fluctuating flow of which transports nutrients, cellular waste products, and signaling molecules, thus supporting metabolic function and the viability of the entire system.31–35
This ebb and flow of fluid within the lacuno-canalicular network is determined by differentials of hydraulic pressure related to the blood circulatory pressure and to responses to functional variations in mechanical loading.35,36 Physiological loading or traumatogenic loading of bone will cause stress-related alterations in the flow within the lacuna-canalicular system with generation of flow potentials and secondarily of electromagnetic fields all of which affect bone cells.37 Osteocytes are presumed to be the primary bone cells, which respond to this whole complex of stimuli32,33,38 and then through their cytoplasmic processes and intercellular gap junctions they “cross-talk” to one another and to osteoblasts, transmitting and amplifying the detected biophysical signals, thus initiating, promoting, and mediating bone remodeling.37,38
Changes in fluid flow can generate shear stresses at the osteocytic and osteoblastic cell membranes, activating intracellular transduction pathways that consequently induce expression of specific genes participating in bone remodeling.39 Changes in the fluid flow within the lacuno-canalicular network after microdamage to bone may stimulate osteocytes to secrete biological mediators such as nitric oxide, prostaglandin E2, and transforming growth factor β, which likewise may initiate bone remodeling.34 Bone repair and remodeling is thus a complex but orderly sequence of events comprising detection of bone damage, recruitment, and activation of osteoclasts to remove the damaged bone and of osteoblasts to lay down new bone.36
However, if the bone microdamage is more severe as from excessive loading, surgical, or thermal trauma, many osteocytes may be destroyed, and many others may undergo apoptosis with a corresponding increase in the number of empty lacunae, disruption of the lacuno-canalicular network, and alterations in fluid flow.40 It is possible that apoptosis of osteocytes may also be brought about not only by direct physical injury, but also indirectly by alterations in the fluid flow consequent upon damage by physical factors, with activation of intracellular apoptotic pathways, or by disruption of the nutritional supply.31,36
It has been suggested that DNA fragmentation products resulting from apoptosis of osteocytes may provide the signals necessary for recruitment of osteoclasts to the zone of microdamaged bone, and that their subsequent activation may initiate focal bone remodeling. Local release of cytokines and proteases consequent to the bone microdamage further promotes osteoclastic bone resorption, which must precede the process of new bone formation.40 In the context of bone microdamage, the death of osteocytes as evidenced by empty lacunae has been demonstrated to coincide with osteoclastic bone resorption,31 supporting the veracity of the sequence of events as described above.
Bone Compression at the Apex of the Implant
It has been suggested that lateral bone compression owing to excessive tightening of an implant may cause implant failure,10 and when there is excessive bone compression at the apical portion of the implant, it may cause ischemia and necrosis of the bone at the apex of the implant.17,41,42 Osteoclast resorption of the necrotic bone and its replacement by granulation tissue may occur, and this may or may not be followed by reossification depending on whether there is low-grade infection present10,17,41,42 so that an implant periapical radiolucency may or may not ensue.
Animal studies have shown that when implants are placed using the osteotome technique with lateral compression of the trabecular bone, on the one hand, the density of the bone immediately around the osteotomy site is beneficially increased; but on the other hand, the bone marrow spaces are collapsed with microfractures of the trabecular bone and disruption of the lacuno-canalicular network and of the local blood supply, which may be detrimental.43,44 When an implant is inserted, the advantage of increased density of the periimplant bone may or may not therefore be outweighed by the disturbance to neoangiogenesis and osteogenesis caused by the compression of bone.45
The additional lateral compression of bone from the use of the osteotome technique may bring about a delay in local bone regeneration or even failure of regeneration with bone resorption so that the periimplant bone is replaced by connective tissue leading to total implant failure.10
In summary, excessive lateral compression of bone at the periphery of the osteotomy either from the use of the osteotomy technique or from excessive tightening of the implant may result in replacement of bone by connective tissue and failure of the implant to osseointegrate. Similarly, by driving an implant beyond the depth of the osteotomy site, the bone at the apex of the implant will be compressed, causing microfractures and apoptosis of osteocytes. If this microdamage exceeds the capacity of bone remodeling, a periapical granuloma may develop.
Heat-Induced Bone Damage
Drilling a hole in bone generates frictional heat, and bone necrosis may ensue if the temperature of the bone exceeds 47°C for >60 seconds. If an implant is then inserted at that site, implant failure may occur.46 The frictional heat generated at the cutting tip of the drill is dissipated along a thermal gradient into the surrounding bone and into the drill.47 Because the metal of the drill has a better heat capacity than does bone, it will absorb most of the thermal energy.48
The degree of heat generated during drilling of bone depends on a complex of factors, including the heat capacity, thermal conductivity, and mineral density/hardness of the particular bone site and the rotation speed of the drill, its diameter, and the force applied to it. Equally important factors are the hardness of the metal of the drill, its sharpness, the efficacy of the coolant irrigation system, which may be a factor of the drilling depth, and the duration of the drilling and the temperature of the irrigant.47,49
Drilling in cancelous bone generates less heat than drilling in dense compact bone because there is less friction, the drilling is faster, and the heat is dissipated more rapidly within the bone.48 Increasing the force applied to the drill, and its rotational speed will reduce the time of drilling and may minimize overheating.48
Thermal-induced bone necrosis is characterized by disruption of the local microvasculature, causing local ischemia, by an inflammatory reaction in response to tissue damage, and later, by death of osteocytes as is evident from the presence of empty lacunae and the inactivity of oxidative enzymes in the immediately adjacent bone. However, microscopic evidence of empty lacunae as an indicator of bone necrosis may underestimate the extent of the necrosis because many lacunae may still be occupied by nonvital osteocytes. Therefore, absence of enzymatic activity in the bone may be a more reliable indicator of heat-induced bone necrosis.50 If the thermal injury is severe, the necrotic bone will in time be replaced by fibrous connective tissue with consequent nonintegration of the implant,50 but if it is less severe, bone healing will be retarded and osseointegration will be delayed.51,52
It is possible that signals generated by those osteocytes undergoing heat-induced apoptosis and by heat-induced disturbances in the flow of the fluid within the lacuno-canalicular system will increase osteoclastic bone resorption, and in the absence of normal osteoblastic activity owing to the heat-induced trauma, a net bone loss will occur.
As a result of minimally traumatic bone drilling, there is a release of growth factors from bone matrix and from the injured blood vessels and recruitment of bone progenitor cells from tissues surrounding the osteotomy,53 this probably being the manifestation of the regional acceleratory phenomenon described by Frost54 in 1983. However, if heat-induced bone necrosis occurs, these growth factors and cells will not be available, compromising bone healing and implant integration.
In drilling for implant insertion, as the drill passes through the cortex of the bone transiently, there is greater generation of heat than when the drill enters and passes through cancelous bone.55,56 However, if the osteotomy is prepared in predominantly dense bone, the deeper the osteotomy, the greater will be the accumulation of frictional heat at the depth of the osteotomy,47 and the cooling effect of the irrigant will diminish as the depth increases.56
Therefore, after deep drilling in dense bone, sometimes aseptic bone necrosis may occur at the greatest depth of the osteotomy. Gradually, osteoclastic resorption of the necrotic bone with replacement of soft tissue will give rise to implant periapical granuloma. If bacterial contamination had occurred at any stage, the result may be an implant periapical abscess.
Premature Loading or Overloading of an Implant in Relation to Implant Periapical Bone Destruction
It has often been stated that radiolucent implant periapical lesions may be initiated by either premature loading or by excessive loading of an implant.11,57 It is the opinion of the authors that these factors do not play any role in the etiology of implant periapical granuloma/abscess. If the magnitude of the strain within the bone in response to occlusal stresses exceeds the elastic limit of the bone, either microcracks or dystrophic changes of the crestal bone will occur. If the damage to the bone exceeds the repair capacity of the bone, crestal bone resorption will occur.58
Excessive occlusal force does not induce localized bone resorption at the apex of an implant because most of the force distribution from implant to bone occurs near the crest of the bone.59 Similarly, excessive immediate or early occlusal loading of an implant with good primary stability is much more likely to cause either crestal bone resorption or complete failure of osseointegration, but it is very unlikely to cause only a discrete implant periapical bone destruction.60
Implant periapical granuloma/abscess should be treated without delay to forestall implant failure.9 If there is an endodontic infection of the adjacent tooth, this should be treated. The implant periapical granuloma/abscess should be removed, and the affected apical portion of the implant be mechanically cleaned and chemically detoxified, with appropriate antibiotic support.7,12,19,61 If there is no adequate access for the cleaning and detoxifying procedures, the apex of the implant should be resected.1,12 Some authors recommend that this should be followed by guided bone regeneration to improve the likelihood of reosseointegration of the denuded portion of the implant.1,3,8,10,13,27,62
The denuded apical portion of the implant can be cleaned mechanically with rotary instruments, with ultrasonic debridement, air powder abrasion, or with plastic or metal curettes; chemically with various agents (chlorhexidine, citric acid, hydrogen peroxide, metronidazole gel); or with lasers or photodynamic measures.63–67 It seems that none of these methods including Er:YAG laser (2940 nm) and diode laser (660 nm) methods are demonstrably superior in decontaminating the denuded implant surface,64,65,68 but without regenerative procedures, there will be no reosseointegration.65,68
Approximately 75% of implants with periapical granuloma/abscess have reportedly survived for follow-up times of 4 months to 7 years after treatment.17 However, this should be interpreted with caution for several reasons: first, this survival rate has been deduced by a review of case reports and retrospective studies; second, the characteristics of the implants and of the periapical bone lesions varied from case to case; third, circumstances bringing about the implant periapical lesions varied; and last, the treatment modalities were not the same in all cases reported.17
From this literature review, it seems that implant inflammatory periapical lesions are either granulomas or abscesses, analogous to granulomas or abscesses around the apices of natural teeth.
There is strong circumstantial evidence that most implant periapical granulomas or abscesses are infective from bacterial contamination of the apex of the implant either from residual infection from a tooth at that site or from a periapical infection of endodontic origin of an adjacent tooth. Overheating and excessive compression of bone during implant surgery may sometimes give rise to aseptic bone necrosis at the greatest depth of the osteotomy. Gradually, osteoclastic resorption of the necrotic bone with its replacement by soft tissue may result in an implant periapical granuloma. In the presence of residual subclinical infection, the granuloma may become symptomatic with pain, tenderness, swelling, or sinus tract.
The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.
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