Early dental implant failure

Braz J Oral Sci. October/December 2002 - Vol. 1 - Number 3

Early dental implant failure: A review of the literature M. C. L. G. Santos1, M. I. G. Campos1 S. R. P. Line1 Department of Morphology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil 1

Recebimento: 07/11/02 Aceite: 02/12/02

Abstract Osseointegrated dental implants have been considered the most esthetical and functional alternative to missing teeth. However, the treatment is not always successful resulting in the implant loss. The implant failure can be classified as early failure (the osseointegration is not established) and late failure (involving a breakdown of the established osseointegration). The implant loss can be attributed to factors such as biological, microbiological and biomechanical, but the cause and mechanism of the early implant failure are still obscure. The cluster phenomenon, multiple implant failures in the same subject, supports the evidence that individual characteristics play an important role in the early failure process. However, little is known about the influence of genetic susceptibility on osseointegration. The aim of this article was to present an evaluation of the literature regarding mechanism, epidemiology, histopathologic observations, role of inflammatory mediators and factors associated with early implant failures. Key Words: early implant failure, osseointegration, host factors

Correspondence to: Maria Cristina Leme Godoy dos Santos Faculdade de Odontologia de Piracicaba-UNICAMP Av. Limeira 901. Cx Postal 52 13414-900 Piracicaba- SP - Brazil e-mail: [email protected]

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Introduction The clinical evidence of osseointegration effectiveness revolutionized the implanthology, making implant replacement of missing natural teeth a viable alternative to the treatment of different edentulism situations. Osseointegration implants present predictable, reproducible and durable results. Despite the long-term success shown by longitudinal, multicenter studies1,2, failure is inevitable. Implant losses can arbitrarily be divided into early, when osseointegration fails to occur, and late, when the achieved osseointegration is lost after a period of function3. One way to discriminate between early and late losses is to include all failures occurring before prosthesis placement in the early group and those occurring after functional loading in the late group, if implants are not immediately loaded. Obviously, this subdivision has limitations, since it remains clinically difficult to determine to what extent an implant is actually osseointegrated 4. Excessive occlusal stress in conjunction with host characteristics and bacterial-induced marginal bone loss (peri-implantitis) seem to be the major etiologic factors for late losses. On the other hand, excessive surgical trauma, impaired healing, bacterial contamination and premature overloading may be the most common causes of implant failure at an early stage after implant placement 5. The epidemiology of early losses has been described in relation to different implant systems, anatomic locations and other aspects3. However, no hard evidence of the mechanisms for early failures has been reported. The knowledge of etiologies and factors associated with implant failure would help to develop adequate treatment and prevention strategies. Therefore, the aim of the present review was to discuss some topics related to early failure of osseointegrated oral implants. Biological aspects of the oral implant failure The mechanism of interaction between bone tissue and implant surface is clearly the key to implant success. The concept of osseointegration was developed by Branemark in the middle 1960s6 and led to the predictable long-term success of oral implants. Osseointegration has been defined from various viewpoints, including the description of longterm clinical results, a numeric evaluation of interfacial mechanical capacity and the morphological appearance of the tissue-implant interface. From a viewpoint of macro and microscopic biology, Branemark (1996) 7 defined osseointegration as the close apposition of new and reformed bone in congruence with the fixture, so that there is no interposition of connective or fibrous tissue at light microscopic level. Thus, a direct structural and functional connection, capable of carrying normal physiological loads without excessive deformation and without initiating rejecting mechanisms, is established.

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Early dental implant failure: A review of the literature

1.1 Osseointegration mechanism The Branemark system is screw-shape and made of commercially pure titanium. It was developed as a result of basic research on bone biology performed by Branemark during the fifties and sixties at the Universities of Lund and Gothenburg. The implant design and its surface characteristics have not been modified over more than a quarter century of clinical use, following the successful animal experiments8. After alveolus is prepared into the bone, using relatively slow speed drills and tapping, implant insertion is done at a very slow speed (20 rpm), and copious cooling fluid is used to avoid any increase in bone temperature. Very close contact is obtained between the implant surface and the bone. A healing time of 3-4 months is allowed for the lower jaw and 56 months for the upper jaw. This healing time, during which there is relative immobility at the implant/bone interface, allows the ingrowth of bone towards the grooved implant surface. Following, a titanium abutment is screwed onto the top of the implant, to which the prosthesis should be attached as soon as possible. Upper/lower and full/partial edentulism can be treated employing such system. The Branemark system, a commercially available product, was named after Branemark’s concept8. The osseointegration mechanism is very similar to the primary bone healing. Thus, after surgical trauma, there is an inflammatory process, in which a mediator cascade promotes hematoma as well as circulatory alteration. Following, regeneration is developed and, consequently, the wound is replaced by bone tissue. Subsequently, wound maturation takes place by means of a remodeling mechanism, which is influenced by occlusion pressure 9. When an adequate regeneration occurs, there is a direct contact between the metal surface and bone tissue. Other types of peri-implant response can occur, like the presence of a collagen layer observed between bone and implant surfaces 10 . Fairly prominent, this connective tissue zone consists of both parallel collagen fibers and supporting blood vascular elements, consistent with the anatomical organization of collagenous ligament11,12. This tissue response interface is called “fibro-osseous integration” 13 , however, it is physiologically well tolerated. The implant failure can be characterized by a connective tissue capsule that involves the implant14. This capsule forms when the repair process occurs instead of regeneration. After injury, fibroblasts and vascular endothelial cells proliferate, a granulation tissue is formed, and is mainly characterized by its histological features ¾ angiogenesis and the presence of fibroblasts. Migration of fibroblasts to the injury site and their consecutive proliferation are undoubtedly triggered by cytokines, such as transforming growth factor-b (TGF-b), platelet-derived factor (PDGF), interleukins (ILs) and tumor necrosis factor-a (TNF-a)15. As the repair process progresses,


the number of proliferating endothelial cells and fibroblasts reduces. Fibroblasts secrete increasing quantities of extracellular matrix (ECM). Some regulator factors of fibroblasts proliferation also stimulate the ECM synthesis. Finally, the granulation tissue framework is substituted by an avascular and colorless scar composed by fusiform fibroblasts, dense collagen, fragments of elastic tissue and other ECM components16. In the early failures, a repair process substitutes bone regeneration, resulting in a soft tissue capsule that surrounds the implant and promotes its mobility. After the implant removal, this capsule can be macroscopically observed9. 1.2 Epidemiology of early oral implant failures The epidemiology and factors associated with oral implant failures have recently been reviewed after analysis of a large number of clinical follow-up studies using the Branemark system3,5. Biological implant failures with the Branemark system are relativity rare: 7.7% over a 5 year period, excluding bone grafts. Implants in patients perform better than in fully edentulous patients in terms of early rates, 2% and 3.8%, and total failure rates, 3.4% and 7.6%, respectively. The higher success rates in partially edentulous might be partly explained by a more accurate patient selection in terms of age, health and anatomical conditions, together with a more favorable load distribution, since molar areas are excluded. The general trend of maxillas to have almost 3 times more implant losses than mandibles was confined to both early and late failures, with the exception of the partially edentulous situation, in which no difference can be observed. Higher failure rates, concerning early and total number of losses, 5.9% and 12.8%, respectively, have been significantly observed for overdenture. The prevalence of failed implants performed in bone grafts is higher (14.9%) than that observed in other situations, probably due to the complexity and risk of this procedure 3. 1.3 Histopathologic and clinical observation on early oral implant failures The microscopical aspects are of extreme importance in identifying the causal determinants of an implant failure. Several histological studies have been conduced with this objective4,17-20. ESPOSITO et al. (1999a)4 reported microscopical features of 20 cases having early implant failure. Asymptomatic implants with mobility at abutment connection revealed a lack of osseointegration and formation of a fibrous capsule. Bone was absent from all these implants, but two different histological features were observed, which may represent different phases of the failure process. In one of them, a dense connective tissue capsule rich in fibroblasts and collagen bundles aligned parallel to the implant surface, together with


few inflammatory cells surrounding some of these implants, indicating that the host was unable to regenerate new bone around the implant. The other histological feature was characterized by a soft tissue capsule heavily infiltrated by a large number of inflammatory cells4. Implants that failed after abutment connection and before prosthesis placement were histologically characterized by a heterogeneous interface, with areas of highly vascularized connective tissue and portions of bone with evidence of detachment from the implant surface, indicating that the degree of osseointegration achieved would be unable to withstand the stresses induced by the prosthetic procedures. Other implants presenting infection, often in the absence of clinical implant mobility, were associated with complicated surgical procedures. The histological features promoted a strong inflammatory response and possibly epithelial proliferation4. In a previous study, PIATTELLI et al. (1998a)17 observed that the mobility of the implants occurred in late failures after a mean period of 4 years. These implants showed connective tissue without inflammatory cells or bacteria. However, the early failure was associated with peri-implantitis, and, from a histological point, there was a gap between implant and bone filled by lymphocytes and plasma cells. Many bacteria surrounded the necrotic bone and no newly regenerated bone was observed. It was suggested that the overheating of the bone during implant insertion might be the reason for these failures. Nevertheless, the presence of bacterial cells in these specimens could indict the infection as a possible cause in place of overheating18,19. It was observed that an implant with poor primary retention presented early failure clinically classified as mobility and pain at the placement of the cover screw. The microscopical examination showed the presence of a fibrous connective tissue with no evidence of inflammatory infiltrate. A vital bone with many osteocytic lacunae was present on the external sides of this tissue. Many capillaries were present, and a rim of osteoblasts was observed on the bone margins20. Therefore, the surrounding tissue analyses of failed implants may provide important information that could help clarify the causes of implant failure. Different histological features reported suggest different reasons, such as infection and surgical trauma. But some early implant failures remain with no explication and seem to be associated with individual host characteristics of impaired healing. 1.4 Role of inflammatory mediators in tissue destruction It is known that implant materials, thought to be inert, can produce elevated levels of cytokines, such as IL-1b, TGF-b and TNF-a21-23. In order to clarify the possible implant failure mechanisms, several studies 24-31 investigating the tissues surrounding unsuccessful dental implants were conducted. An abnormal immune response involving different cell types such as macrophages, polymorphonuclear neutrophils, T and

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B lymphocytes, endothelial cells, fibroblasts, keratinocytes, osteoclasts and osteoblasts can destroy the peri-implant and periodontal tissues32-34. If activated, these cells can synthesize and release cytokines35-41 and lipid mediators42, which mediate both the inflammatory and the osteolytic processes. In an attempt to establish diagnostic markers for monitoring implant health status, levels of interleukins24-27 and proteolytic enzymes29 have been measured in diseased implant sites. Levels of IL-1b were higher in diseased implant sites when compared to healthy ones24,26,27,29. However, levels of other cytokines, such as TNF-a 27, have no correlation with the disease around implants. SALCETTI et al. (1997)25 believed that inflammatory mediators, such as IL-1b and PGE2, are associated with implant failure; however, the authors suggested that the systemic levels seem to be more relevant than local levels. Proteolytic enzymes, known as matrix metalloproteinases (MMPs), also contribute to the degradation and removal of collagen from damaged tissue and are secreted by inflammatory cells in response to stimuli such as lipopolysaccharide and cytokines43. Previous studies44,45 have also shown that proteinases (collagenases, gelatinases, elastase) are present in peri-implant sulcular fluid. TERONEM et al. (1997)30 observed collagenase levels were clearly higher in the peri-implant sulcular fluid of loose dental implants compared to well-fixed implants. Overall, collagenase is likely to cause increased proteolytic tissue destruction in periprosthetic tissue. Nevertheless, it was observed in a previous study29, that high levels of MMPs might appear only at the beginning of the inflammatory process and then decrease with time. The platelet-activating factor (PAF) is a phospholipid mediator produced by inflammatory and endothelial cells46 and capable of activating osteoclastic resorption47. It was demonstrated that the concentration of PAF is increased in gingival tissue around failed dental implants, suggesting that an enhanced local production of PAF might be associated with implant failures. In addition, PAF was correlated with both vessel density and inflammation evidence. This mediator might have a role in the onset and continuation of peri-implant tissue destruction. It may also occur as a consequence of a local cascade of inflammatory mediators involved in the destructive tissue process, initiated by upstream pathogenic factors48. Since elevated levels of inflammatory mediators are present in diseased implant sites, their analysis may provide an effective monitoring of the disease around dental implants. Factors associated with the failure of dental implants Implant failure is defined as the total failure of the implant to fulfill its purpose (functional, esthetic or phonetic) because of mechanical or biological reasons3. Dental implants may fail for different factors with a range that differentiates between a failure and a complication49. It is important to

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distinguish between failed and failing implants. The failed implant reaches an irreversible state and has to be removed because of different reasons, such as inability to osseointegrate, progressive infection, loss of support, pain, paraesthesia, etc. On the other hand, the failing implant is associated with assorted complications, which are either of temporary significance or amenable to treatment3,50. There are no established causes and mechanisms for the early implant failure, but this kind of failure tend to concentrate on few individuals. This situation is known as clustering phenomenon, indicating the importance of certain factors in determining whether a particular patient will be able to tolerate implants50,51 Among the different implant failure classifications proposed in the literature37,49,52, the most didactical divides factors into exogenous and endogenous. However, the boundaries of this subdivision are obviously difficult to distinguish as several of these conditions may overlap, rendering any kind of classification too simplified5. 2.1 Exogenous factors Didactically the exogenous causes can be divided into operator-related and biomaterial-related factors5. 2.1.1 Operator-related factors It has been suggested that higher failure rates might be associated with the operator experience50,54-57. Surgeons who had placed fewer than 50 implants had early failure rates twice as high as those who had placed 50 or more implants55. Surgical experience might also have played a role in early implant failures observed in type 1 bone57. According to ESPOSITO et al. (1998b)5, the experienced operator may directly avoid failure implants by selecting more accurately patients and sites. The adequate operator technique, which includes minimal surgical trauma and bacterial contamination, plays an important role in avoiding implant failures. It has been speculated that traumatic surgery can lead to soft tissue encapsulation of the implants58. The histological analysis of early failed implants has indicated that bone overheating might be the most probable cause for these failures17-20. It is known that the presence of bacteria can interfere with the healing process of an implant, determining its loss. Nevertheless, bacterial infection does not seem to be a common reason for early implant losses, if stringent aseptic surgical protocols are followed5. 2.1.2 Biomaterial-related factors A foreign material implanted in bone always promotes an inflammatory response, which may subside after a few days or end in total rejection of the implant. Many different metals are used in implantology, but in recent years there has been a clear trend towards titanium, because of its high degree of biocompatibility59,60. Almost all metal implants are now made of titanium in a myriad of shapes and surface modifications. Basically, titanium is a non-noble metal, protected by a


passive layer of titanium dioxide that forms spontaneously when exposed to air or water. This protective oxide layer is considered biologically inert61 and responsible for the minimal degradation of titanium62. If this oxide layer is damaged, it regenerates within a few seconds. Chemically, the oxide layer consists of various oxides (TiO2, TiO, Ti2O5), but the TiO2 type appears to predominate62. The contaminants released from implant surface were hypothesized to be associated with an enhanced and prolonged inflammatory response, thus altering the healing process and possibly provoking the dissolution of Ti 63-68. However, no significant changes in the oxide layer composition or thickness were observed in early failed implants69. 2.2 Local endogenous factors 2.2.1 Bone Quality The early implant stabilization is one of the prerequisites for obtaining successful osseointegration. For secure anchoring of endosteal implants, not only adequate bone quantity but also density is necessary. A gross estimation of bone quality can be obtained from radiographs; however, it is certainly determined only during the surgical procedure62. The most commonly used classification describes four types of bone70. The type IV bone, which is more commonly found in maxilla and posterior segments of mandible, offers little cortex and minimal internal strength 71. Some studies have reported increased failure rates with implants placed in type IV bone72,73. The negative effect of poor bone quality on the primary stabilization of the implant can be compensated by increasing the number and diameter of fixtures52,74. 2.2.2 Local immune response There is still no evidence that failures of titanium implants have occurred due to immunological reasons5, although host resistance aspects might influence implant maintenance75. KRONSTROM et al. (2000)76 observed that IgG antibody titers against Staphylococcus aureus and Bacteroides forsythus were significantly higher in subjects with successful titanium dental implants than in those with early failure, suggesting that humoral immunity factors relative to these bacteria might explain why osseointegration of implants fail to occur. In addition, KRONSTROM et al. (2000)76 have proposed that the assay sera for antibody titers might identify subjects at risk and predict early implant failure. 2.2.3 Irradiation therapy Irradiation therapy, used in the treatment of oral tumors, provokes chronic changes in bone, such as cell death, increased susceptibility to infection, delayed and impaired bone healing77-79. Besides, the extent of cellular damage seems to be dose dependent 80,81. Thus, irradiated tissues are hypocellular, hypovascular and hypoxic, with reduced reparative response to surgical trauma82. These conditions, making the implant treatment more complex, should not be


considered an absolute contraindication 5 . A previous experimental study has reported that the implant therapy should be performed at least 1 year after irradiation to promote revascularization and partial recuperation of tissues77. 2.3 Systemic endogenous factors 2.3.1 Age The mineral composition, the collagen and the morphogenetic protein content of the bone change with time. Conformation of the bone and fracture healing tend to be delayed83,84. A previous study investigating implant osseointegration in rats has observed a decreased rate and quantity of regenerated bone with increasing age, suggesting that in older patient bone healing may be slower and failure rates may be increased85. Clinical investigations, however, have showed no significant differences in osseointegration between young and old patients86,87. 2.3.2 Smoking Increase in plaque accumulation 88,89, higher incidence of gingivitis and periodontitis 90-92, increased resorption of alveolar ridge93,94 and higher rate of tooth loss95 are commonly observed for smoking patients. In relation to implant failure, the reduced vascularity of bone is considered the predominant mechanism for losses in smokers96. Therefore, the impact of smoking may be more important to long-term implants than to early implant failure97-99. In order to improve the blood flow and platelet adhesion, a strict cessation protocol is recommended before surgical procedure. The smoke cessation should continue for the minimal of two months after implant surgery to prevent tobacco derivatives from influencing the initial osseointegration phase 100. 2.3.3 General health Systemic diseases, having a negative influence on implant survival, can alter the remodulation of the bone, a very active metabolic tissue75,101. Diabetes mellitus and osteoporosis are prevalent chronic diseases, and consequently more commonly studied in relation to implant failure. Diabetes mellitus is a metabolic disease, which can influence wound healing. This disease leads to vascular alterations, disturbing the circulation at the implanted site. Furthermore, the chemotactic and phagocytic function of neutrophils is reduced, resulting in an increased susceptibility to infections102,103. There is an increase in early implant failure rates in diabetic patients104,105. It has been demonstrated that type 2 diabetic individuals tend to have more failures than non-diabetic ones 106 . However, successful rates of osseointegrated implants in diabetic patients indicate that diabetes mellitus is no longer considered to be an absolute contraindication for implant-supported prostheses, since the patient’s blood sugar is under control, and that there is motivation for oral hygiene procedures75,107. Osteoporosis has been considered a risk factor in the

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treatment of implants, particularly in postmenopausal women (type I osteoporosis), because the decreased bone density and mass can negatively and substantially affect the implantbone contact 108. On the other hand, BRYANT (1998) 71 observed that patients with osteoporosis could be successfully treated using osseointegrated implants. There is so far no conclusive evidences to include osteoporosis among the risk factors for osseointegrated dental implants109. 2.3.4 Genetic factors Several factors can be associated with osseointegrated implant failure; however, many points remain to be clarified, especially in relation to the early failure. The cluster phenomenon, in which the same patient suffers multiple implant failures, supports the evidence that specific characteristics of each individual influence the early failure process. The genetic influence on the severity of periodontitis has been widely studied 110-117. Like age, sex, race, stress and smoking118-121, genetic polymorphisms seem to be risk factors in the onset and pathogenesis of periodontal diseases. Gene polymorphism is a mechanism by which individuals may exhibit variations within the range of what is considered biologically normal 122 . Polymorphisms in certain hostresponse genes have been related to the hypersecretion of several cytokines upon microbiological challenge123,124 . In the Brazilian population, polymorphisms in the IL-6125, IL4 126 and MMP-1 127 genes have been associated with susceptibility to chronic periodontitis in Caucasians, confirming the role of genetic factors in chronic periodontitis. Since the inflammatory reaction is associated with bone resorption, which is the most important event in the genesis of implant failure, further studies are needed for evaluating the relationship between early implant failure and polymorphisms in genes of inflammatory mediators. WILSON & NUNN (1999) 99 failed to demonstrate an association between polymorphisms in the IL-1 genes and implant loss. Nevertheless, the presence of smokers in their study group might have possibly masked a genetic influence, since it is known that smoking is a strong risk factor in early implant failures. ROGERS et al. (2002)128, evaluating late implant failures, found no significant association between the composite IL-1 genotype and dental implant loss, but it was not clear whether the implant loss occurred because of biological or mechanical reasons. The discovery of genetic markers related to early implant failure could be clinically invaluable to identify individuals susceptible to implant loss. Moreover, further individual therapeutics could be developed in order to improve successful implant rates. References 1.

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