The role of systemic diseases and local conditions as risk factors
Henning Schliephake
Abstract
The integration and long-term success of dental implants exploit the unique biology of the oral cavity, which allows for osseous incorporation of a biomaterial and its long-term health within a bacteria-laden oral milieu.1 The delicate balance of defense and repair mechanisms underlying this unique environment may be challenged by various factors that can act both locally and/or systemically, thereby increasing the risk of implant loss and jeopardizing the long-term success of inserted implants. Local risk factors that are present in the oral cavity and systemic risk factors that have the potential to affect oral health on a systemic level can compromise implant treatment at all stages of treatment delivery by: (a) complicating surgical procedures and other invasive measures required during treatment; (b) compromising the process of tissue healing following implant insertion/increasing the risk of wound infection; and (c) contributing to the deterioration of long-term peri-implant health and tissue stability (Table 1). Reduced bone healing Reduced implant stability Reduced bone remodeling Reduced angiogenesis Reduced bone regeneration Acquired immunosuppression Hypovascularity Iatrogenic immunosuppression Reduced tissue regeneration Hypovascularity hypoxia Leukocyte dysfunction Conditions that interfere with invasive procedures, which include poor general health status (https://www.asahq.org/resources/clinical-information/asa-physical-status-classification-system) as a result of severe systemic disease, may impact upon implant surgery, healing, and maintenance. These are mostly cardiovascular conditions that can place the patient at high risk during surgery, irrespective of the nature of the intervention. Bleeding disorders, which may be innate or acquired, as well as attributable to the use of anticoagulants, may also complicate invasive measures. While the former are considered to be relatively rare, the latter may have a significant impact on daily implant treatment in an aging population. All these conditions can also have a negative impact on long-term peri-implant health and maintenance of peri-implant tissues as a result of compromised vascularity, as well as alterations in the immune defense or repair capacity of peri-implant tissues. The increasing patient demand for implant-based treatments in conjunction with a demographic shift of the patient population has resulted in a growing body of literature dealing with an increasing number of patients presenting with medical conditions. A recent cross-sectional analysis indicated that almost 90% of patients aged > 65 years were taking medication for underlying systemic diseases, which could jeopardize implant success.2 The advent of new treatment modalities, such as antiresorptive drugs or monoclonal antibody therapies, adds to the number of potential risk factors,3 leading to an increasing challenge for the provision of implant-based treatments in the future. The aim of this narrative review was therefore to analyze the importance of systemic and local conditions as risk factors for implant loss by critically evaluating the available evidence. During evaluation of the available literature, it was obvious that the term “implant loss” was used to a much lesser degree than “implant failure.” Very few reports clearly defined implant failure as implant loss, but the context in which this term has historically been used indicates that implant failure was synonymous for implant loss. It is only in the last decade or so that definitions of implant failure have been published, and not until the 2017 World Workshop on Periodontal and Peri-Implant Disease Classification was an international definition agreed upon.4 One of the major reasons for implant loss is the progressive loss of peri-implant bone support. Therefore, marginal bone loss was also included in the analysis. As progressive crestal bone loss around implants in the absence of clinical signs of soft tissue inflammation is rare,5 reported radiographic bone loss was considered in conjunction with clinical peri-implant parameters (where provided) in the individual reports in order to assess the prognostic relevance of the findings. The effect of cardiovascular conditions on implant treatment has been mostly analyzed in cross-sectional cohort studies. In these reports, 15.6%-37%6-8 of patients were affected by cardiovascular diseases. Two recent multivariate analyses of large cohorts consisting of > 6300 and > 22 000 patients did not identify cardiovascular conditions as significant risk factors for implant loss6 or peri-implant pathology.9 This is in line with other cross-sectional studies of smaller cohorts.10-13 Cardiovascular conditions may, however, be associated with the maintenance of long-term peri-implant tissue health. Patients with diseased implants have shown a higher likelihood of cardiovascular comorbidity,8 and a recent prospective study of 44 patients with fixed mandibular prostheses demonstrated an association between cardiovascular disease and increased radiographic peri-implant bone loss.14 The available evidence currently suggests that cardiovascular conditions are not a major risk factor for implant loss. Although the radiographic bone loss reported had not been classified as progressive, cardiovascular disease should be taken into account in maintenance protocols as a potential comorbidity15 that may affect long-term peri-implant tissue health. Bleeding disorders can be innate, such as hemophilia A/B and von Willebrand–Jürgens Syndrome, or acquired during end stage liver disease, with subsequent deterioration of coagulation factors and platelet counts. The placement of implants in patients with hemophilia is rarely documented in case reports.16, 17 In contrast to this, patients with iatrogenic bleeding disorders as a result of anticoagulation therapy have been studied more frequently. Depending on the underlying disease, anticoagulation therapy may encompass antiplatelet drugs, vitamin K antagonists, or direct oral anticoagulants. There is widespread agreement that anticoagulation therapy with antiplatelet drugs or vitamin K antagonists should not be discontinued for dental surgical procedures, as long as a single drug is used and the level of activity is within the therapeutic range (international normalized ratio 2.5-3.0).18, 19 Some uncertainty exists about the management of patients using direct oral anticoagulants, but it is assumed that no interruption of therapy is required; consulting with the hematologist responsible for the patient's care is always advisable.20 Implant surgery in patients undergoing anticoagulation therapy has been reported in a number of controlled clinical studies, albeit consisting of rather small cohorts.21-24 Follow-up included an immediate postoperative period of 8-10 days. All the authors agreed that implants could be safely placed in patients with anticoagulation therapy without interruption of medication of vitamin K antagonists or direct oral anticoagulants. An exception to this may be dual anticoagulation therapy using two antiplatelet drugs (acetylsalicylic acid and clopidogrel), as is commonly employed following stenting of the coronary arteries. In these cases, postoperative morbidity may occur as a result of the increased risk of postoperative bleeding (Figure 1). Implant surgery should therefore be postponed until dual antiplatelet therapy has returned to single antiplatelet drug use. Depending on the type of stent used, this period may vary from 6 weeks to 6 months. To date, no is available on implant in patients the immediate period of surgical wound The management of for soft tissue management or peri-implant has not been reported but may have an impact on the long-term of and should be taken into implants are for patients with anticoagulation it should be that the for anticoagulation therapy is commonly an underlying cardiovascular that to be and may anticoagulation therapy is used of a associated with an increased risk for is The for has been on a risk of during implant but to of is is by a loss of of bone and a in bone in an deterioration of bone of and of aged years are to be can of the loss of of in years in or of in general may also to Syndrome, or as a result of medication the is from dual of the and/or the a that the of bone of the patient in from the of A of is considered to be of has been a in implant from an stage in the of the A number of have the of bone is associated with bone in the or bone did not with documented dual bone to implants from patients did not a number of bone or To identify with bone such as the mandibular mandibular and the have been A recent review reported these as in patients with bone but did not to patients with a review the association between measures of bone and bone was to is associated with in the The of in the success of implant treatment and the stability of marginal bone has been in a number of studies. have no in implant between patients with and without ratio or a direct but effect of on dental implant loss ratio and case did not evidence for an association between bone and increased implant loss. to peri-implant bone loss, the of recent studies and case reported no in radiographic peri-implant bone loss between patients with and without cross-sectional study reported increased radiographic loss of marginal bone in patients All the patients in this study were of a maintenance with and conditions. in radiographic bone level have been to in bone remodeling in The relevance of these with to long-term implant to be While as such may not a in implant failure or loss of peri-implant used for therapy may interfere with and long-term maintenance of peri-implant health. The drugs are mostly or a monoclonal antibody the that is in the of both the activity of as well as the activity of in a The effect of the antiresorptive therapy is a in bone and remodeling activity of bone tissues. As remodeling is an of bone regeneration and has been the capacity of peri-implant bone to implants inserted clinical have reported implant of in patients taking oral and of for of studies the impact of on implant treatment that is evidence for a negative effect of on implant the effect on implant of the long-term use of antiresorptive is the risk of a of the of the can be by surgical and by from as well as from of the of of the during the of dental implants or the of peri-implant during antiresorptive medication is therefore a significant and rather invasive measures for management (Figure The of of the has been considered to in on the and of with oral presenting a risk for of the than recent that it is not the of but the of antiresorptive medication that the of of the The evidence reported for the of of the therapy with or is on case or case In these reports, the number of reported for of the in patients taking oral is almost as high as in patients or that it is not the of that is for the of of the a number of case reports and case on implant treatment with oral therapy did not of of the in the patients The level of evidence for an association between implant treatment and the of of the antiresorptive therapy and to be by controlled the number of reported of of the suggests that antiresorptive drugs to be considered as a risk and to to the of the as of the potential of of the implants can to the of of the for in patients antiresorptive drugs by from Therefore, factors to be considered to a on a patient with antiresorptive drugs is for implant therapy (Table the of these factors a to implant therapy may also be a in patients with antiresorptive oral surgical procedures are in patients with antiresorptive is The for of has not been A is for however, the and of postoperative of therapy to be to for the management of patients with antiresorptive medication is is by a of as a result of the loss of in the of the or by of the failure of to to the by in the This in in with which to of to end An level of end to increased and of for end These are present on and which are considered to be responsible for alterations in the and thereby can account for of end with for end on is considered to be associated with leading to wound healing in patients with bone regeneration is on a level in with poor has been shown to affect the balance of bone factors in the peri-implant during implant of in conjunction with a defense and a capacity of peri-implant bone may compromise the success of implant treatment in patients with The effect of on implant success and the maintenance of peri-implant tissues has therefore been to for more than have analyzed this A recent of controlled clinical demonstrated that the risk ratio for implant loss between patients with and without was without a significant between the to an association between the of and an increased loss of dental implants is in line with The level of as by to have no effect on implant patients with have demonstrated a compromised process of implant a recent reported only evidence for as a risk factor for While implant loss and peri-implant tissue health are not affected by the of as management of the disease may a in the maintenance of peri-implant tissue health. A number of reports and have shown that patients with and poor have an increased risk of and associated peri-implant bone This has been reported to obvious at years of with is within the range and oral is the of inflammation have been shown to be to of The use of in oral surgical procedures in patients with is from the available clinical studies the use of but the evidence for is The immune is an of tissue healing and This also for bone are not only for regeneration but also for subsequent bone both and immune are for the defense following surgery, as well as during the period of and long-term can be for integration of dental implants and for the maintenance of peri-implant tissue health. can result from a large number of conditions. the exception of innate immune immune are mostly acquired in The immune can be affected by and or of can also be by as well as by and Iatrogenic immunosuppression as a result of is the of immune in dental implant A major for of the immune is patients are with a of drugs that aim to the of and to the number of to of the a of monoclonal antibody of that and drugs with of is During the drug are high to immune which are for maintenance of should not be during the of immune The effect of immunosuppression on the success of implant treatment in patients has rarely been that the peri-implant bone in a clinical from a case on patients with liver reported success two prospective controlled studies no significant in implant between patients and and years of without significant between have also been reported for clinical peri-implant soft tissue and for the of peri-implant The available evidence but suggests that the clinical of implant treatment are and not affected by drugs used by of in which medication is used is the of diseases. The for daily clinical are diseases, Syndrome, and disease, as well as conditions of oral and such as oral and systemic with oral or conditions that may local such as or disease, may be of of the systemic immunosuppression in and in disease is by a of drugs, such as monoclonal and drugs are a of that include and which are also used for immunosuppression in are by and of clinical leading to a level of treatment during This should be in treatment for these patients have the negative of this with to bone such as and bone also be taken into is considered to be present at of These patients should be for antiresorptive medication to the There is available patients with dental implants. A evaluation of patients with an implant success of The success but between patients with only and with tissue The stability of marginal bone by the medication drugs drugs and The of tissue was associated with a significant in peri-implant bone loss and higher bleeding with patients with an increased of peri-implant tissues to The of authors a smaller cohort of patients with a analysis of a cohort of patients did not identify as a significant risk factor for implant an of and systemic may these patients more to marginal peri-implant a maintenance The available for patients with disease are Two cross-sectional analyses and evaluation of cohorts of were by the and implant loss and the of implant the study of the cross-sectional analyses a significant association between disease and implant the other cross-sectional study the of this is to as the number of patients in this cohort with disease was not with oral Syndrome, systemic and oral in conjunction with dental have been reported at an level for almost In and systemic were to case reports years is considered to be for implant and not only as a result of but more so of leading to increased and bleeding as well as a higher of As a result of the oral and patients with are to and can from implant The level of evidence for the effect of on the success of implant treatment is Two case and case reports into 17 patients with a of with implants years of Two recent cohort studies reported success of and soft tissues a higher but in the of patients with with The suggests that implants in patients with are not compromised by the underlying disease or The for peri-implant in these patients the around in patients with Syndrome, and during is a disease associated with general of tissues in with subsequent with and dental has been reported in conjunction with dental implants on an level in individual and for two as of two case with a of implants. implant was in the all the implants were but are associated with as a result of which can also a loss of and in of progressive following Patients with to Therefore, the provision of can of about the effect of on dental implant success is only available from case and case patients with of which were during a period of One factor may to loss of in severe cases, of the in the loss of individual and the of a the oral and are by and of such as and/or in conjunction with and or is considered to be for implant success of the to which may be for the maintenance of peri-implant tissue health. it should be in that treatment of and other which can both wound healing and long-term peri-implant tissue conditions. than with the much of the evidence for the impact of oral on implant therapy is from cohort studies with In to two small case on patients with two cross-sectional studies with and as well as prospective controlled have analyzed the effect of oral on the success of treatment with dental implants. of and were reported for patients with oral a period of in the individual studies. significant in radiographic marginal bone loss or peri-implant soft tissue parameters were between the patients with oral and within the of patients with oral with a increased of peri-implant In the evidence for the use of implants in patients with to be The number of case reports and case the number of cohort studies or controlled in for oral diseases. All of have been in recent years by a number of The body of available evidence suggests that implants in patients with disease have a high likelihood of success in the that is to it should be in that of the reported on are and long-term are with to maintenance This is in that have a increased risk of such as oral A recent review of peri-implant oral that of of peri-implant from oral An with and The of and by in progressive failure of with subsequent and of The of therapy has the of this disease and has also the of into a disease, new have to be with an aging population with to cardiovascular and include and loss of bone health of therapy in conjunction with a immune status may place implants in patients increased A large number of case reports have been in the last years on the use of implants in patients that were in a recent review with two and prospective controlled implant of implants the authors that implant treatment in patients not to be associated with a higher risk of implant loss. This is by a analysis of implants in patients with an period of to years that did not a increased implant loss with studies that implant loss as a result of and of A case on implants in patients to an increased to peri-implant and evidence suggests that implants can be in patients as in There may, however, be an increased risk of peri-implant that maintenance and The relevance of the as an of the immune status has been in a number of studies, but has been shown to not be of relevance for the treatment This is attributable to the that of within tissues rather than and a poor of the population. is of to used in the treatment of are at various drugs and and interfere with during the during and of such as recent for treatment on the of individual include antibody therapy factor or small for drugs are in tissues but can also affect other tissues in the body with high such as the bone and interfere with an increased demand for during tissue repair and wound for can thereby immune defense a effect in conjunction with an jeopardize the success of implant of peri-implant bone by has been shown for and for in a clinical a recent analyses and controlled clinical during the last few the underlying in all patients were and The used were and the individual studies were with to or about treatment was in > of the included studies. a was in a risk ratio of between patients with and without and no significant effect of treatment on the loss of implants evidence on the effect of on implant treatment is therefore taking into account from narrative case or case it to that patients have are not at a risk of implant loss than Some should be as no on therapy is available it is to study patients for treatment using and for therapy using or as both these of drugs have been reported to of the that may complicate implant by patients or have may include or or use may affect peri-implant health on various has a number of on peri-implant health and tissue maintenance as a result of of increased platelet and of the other a number of such as that are associated with an in which may interfere with peri-implant bone and of or with that to the of the capacity of in which may to healing capacity and tissue has been shown to be associated with a shift in the peri-implant a more an of to the deterioration of peri-implant health and implant may result from the that have been associated with a level of with peri-implant therapy and has been to evaluation as a risk factor for implant failure for almost have shown on that may be associated with increased marginal bone and higher implant recent and have as of the significant risk factors for implant treatment on has been shown to be associated with a risk of postoperative that is as high as in and a risk of that is as of peri-implant bone is also with a reported of and an increased of bone loss of in a of for implant failure in have been reported to be between and This risk ratio may to implants are placed into The level of has not shown a association with implant but it that is not to a higher risk of implant > is associated with a increased risk ratio of about the impact of on the of dental implant treatment are and to from as both daily may be associated with and vitamin as well as and compromising peri-implant tissue healing and maintenance. In a prospective study of patients with a of of > of was associated with a peri-implant marginal bone loss than with of The risk of of was reported to be increased with an of > evidence for the of is in patients with and is associated with to oral in and of and soft of tissue regeneration from these may a significant risk for both the process of and the long-term maintenance of peri-implant tissue health. To these at in implant placement during surgery has been therapy is the of implant placement in patients of therapy is much more and has to into account to oral tissues. The effect of on the success of dental implants has been analyzed in a number of recent narrative and The risk ratio for implants in patients with without therapy was as with a significant negative effect of therapy on implant in to have a than ratio which has been in subsequent The for bone in implants have shown a with an ratio of The use of to peri-implant bone regeneration and implant has not evidence for a clinical from for the of dental implants in A number of factors have been that may the effect of therapy on the success of implant the type of implant has been shown to be in that implants with a than implants with The effect of is factor that may implant the which the risk of implant loss Some reports have have that result in higher failure The between the of therapy and the of implants may also be An of to of has been for implant Although these have been on a recent review of clinical studies this that implants placed had a risk ratio of for implant loss to placed treatment with to implant in may be affected by the of following implant placement in during were with during patients had more recent protocols did not a negative effect of therapy on the of implants patients with treatment protocols factors could not be in as of the studies included were case studies that did not for a analysis of these as of these studies not clinical with implant and a negative effect of on the success of implant treatment to be considered with and local conditions may compromise the success of implant Cardiovascular not to be a direct risk factor for implant has not been shown to a risk factor for implant loss in and but to be for the maintenance of long-term peri-implant health and tissue maintenance. in systemic bone as a result of are not associated with increased implant however, patients are with antiresorptive drugs, should be of the risk of of the in patients with or may be associated with an increased risk of implant loss. In with an and in patients with a maintenance protocols to be Patients have during treatment are not at higher risk of implant however, treatment may the risk of of the of the and has been shown to be associated with a increased risk for implant loss. protocols and the use of implants with to the of dental implants in