Secondary Logo

Journal Logo

Basic and Clinical Research

Osseointegration of Dental Implants in Organ Transplant Patients Undergoing Chronic Immunosuppressive Therapy

Radzewski, Rafał MD, DDS*; Osmola, Krzysztof MD, DDS, PhD

Author Information
doi: 10.1097/ID.0000000000000916
  • Free

Abstract

Thanks to the advancement in transplantology, the number of patients with organ transplants in an overall population has been increasing. In 2015, there were more than 3200 transplantations in Europe, among which 61.46% concerned kidneys and 23.52% liver.1 A significant group of those patients requires dental rehabilitation; since in the course of preparations for the procedure, extraction of numerous teeth is often enforced by the need to sanitize oral cavity.2 This group encompasses very young people and mature patients.3 The issue of dental rehabilitation is very important for everyone, although among elderly patients other, sometimes more serious difficulties may be encountered. What is crucial is the fact that survival time of the patients after successful transplantation has been constantly on the increase. Many patients live more than 20 years after transplantation procedures; consequently, the question of life quality related to appropriate functioning of their stomatognathic system is absolutely crucial.

The use of titanium implants is considered the best method of replacing the missing teeth. However, the depressive impact of immunosuppressive medications used by patients after organ transplantations till the end of their lives is commonly known and well proven.4,5 For many years, it has been considered that immunosuppression is an absolute contraindication to undertake the treatment with the use of dental implants.6,7 What is more, all surgical procedures performed on these patients are associated with a higher risk of infection. This undoubtedly has got some bearing on the potential hazard of dental treatment failure and may influence the overall health condition of the patient.

Few studies conducted on animals provide inconclusive evidence as to the impact of immunosuppressive medications on the healing bone around dental implants.8–12 The case studies on human patients reveal that irrespective of unfavorable influence on bone structures, the implants do not have a negative impact on implant stabilization.13–16 So far, there have been 2 studies assessing the effect of immunosuppressive treatment on the dental implants in patients with organ transplants (heart and liver).17,18 Neither of them indicates any negative impact on dental implants.

Aim

The aim of our research is the assessment of functional and esthetic results of implantoprosthetic dental treatment in patients subject to immunosuppressive treatment after organ transplants. Moreover, the authors decided to examine whether in patients undergoing immunosuppression there occurs bone loss, what is its scale, and whether particular immunosuppressive medications differ as to their effect on osseointegration.

Materials and Methods

The study encompassed a group of 21 patients in the course of maintenance immunosuppression after transplantation procedures, in whom altogether 24 implants were inserted.

The following criteria for patient inclusion in the experimental group were adopted: >25 years of age, at least 1 year after organ transplant, at least one tooth missing with neighboring teeth present, and bone condition (with respect to volume and density) allowing to effect the implantation procedure without the need to perform guided bone regeneration (GBR). The exclusion from the experimental group took place when it was ascertained that the patient had active periodontal disease, substantial occlusion disorders, bone diseases, blood coagulation disorders, untreated dyslipidemia, or was a smoker. The control group comprised 15 people with 15 implants in place. The criteria for inclusion to the control group were lack of serious systemic diseases, more than 25 years of age, at least one tooth missing with neighboring teeth present, and bone condition (with respect to volume and density) allowing to effect the implantation procedure without the need to perform GBR. The criteria for exclusion from the control group are identical as in the experimental group. In addition, people taking immunosuppressive medications were excluded from the group, irrespective of the indications to use these drugs. In one of the participants of the control group, implant osseointegration was not obtained. The infection, which was the result of the patient's nonobservance of recommendations concerning the antibiotic therapy, leads to implant treatment failure. The patient was excluded from further participation in the experiment; in view of the fact that in his case, it was impossible to take measurements of the selected parameters.

The research protocol assumed replacing a single missing tooth with a titanium dental implant placed subcrestally (Naturactis; ETK, Sallanches, France). In 2 patients, more implants were inserted to compare the effect obtained in the maxilla and in the mandible, and one patient had the implants placed on 2 sides. The surgical procedure was every time preceded and followed by the administration of prophylactic antibiotic agents (orally, doxycycline 0.2 g—2 hours before the operations; 0.1 g, 2 times per day for 5 days, or clindamycin 0.6 g—2 hours before the operations; 0.3 g, 3 times per day for 5 days) and nonsteroidal anti-inflammatory drugs (ketoprofen 0.1 g, 3 times per day for 3 days).

After 4 months, a prosthetic reconstruction in the form of a single crown was performed. The time devoted to osseointegration was extended with respect to the standard span of 3 months, bearing in mind a potentially longer reconstruction process related to the use of immunosuppressive treatment. The research project was scheduled for 4 to 6 treatment months plus 3 years of observation. After 24 months, the preliminary assessment of treatment results was attempted (Fig. 1).

Fig. 1
Fig. 1:
Intraoral photographs of the patient from the experimental group taken to assess the healing of soft tissues. The view on the day of implant loading and 24 months later.Arrows indicate gum around crowns based on implants.

The researchers took into consideration the risk associated with the failure consisting in the lack of implant integration, the need to remove it, and lack of further possibilities of prosthetic reconstruction based on the implant.

Radiological assessment consisted in taking a series of radiovisiographic (RVG) pictures. The first one was taken on the day of the surgery, the next one after the integration period (4 months), and the subsequent ones every 6 months from the day of implant loading. The measured parameter was crestal bone level (CBL)—the distance from the reference point on the implant to the first visible contact between the bone and implant surface (mesial and distal sides—median). The scale of bone loss was assessed by 2 independent researchers to obtain more objective results (our analysis deploys average values of those measurements) (Fig. 2).

Fig. 2
Fig. 2:
Radiological assessment of the bone around implants: RVG images taken on the day of implant loading and 24 months later.

The mechanical assessment was performed in a 2-fold manner: by measuring the torque indispensable to locate the implant (with the use of torque wrench) and by an objective measurement of implant stability (with the use of specialized testing equipment—Osstell). Measurements were performed twice: the first one on the day of implantation and the second one after the integration period (4 months after the operation).

Statistical calculations were executed by means of STATISTICA (data analysis software system), version 12, from StatSoft, Inc. (2014), www.statsoft.com. Analyses were performed based on the assumption of significance level of P = 0.05. Owing to the lack of normal distribution, nonparametrical tests were applied.

Results

After 2 years of observation, the results of 35 patients, with altogether 39 implants, were analyzed. The average patient age in the experimental group equaled 39 years (min 31–max 68), and in the control group—43 years (min 22–max 58). Within the control group, 73.3% were women and 26.6% men, whereas in the experimental group, there were 45.8% women and 54.2% men, respectively. The average time elapsing from the transplantation procedure was 5 years (min 2–max 20) (Fig. 3).

Fig. 3
Fig. 3:
Analysis of the experimental group: Number of patients with specific transplanted organs.

Most patients were administered the same immunosuppressive medication, ie, tacrolimus, and the others took cyclosporin, sirolimus, or mycophenolate mofetil, respectively. Twelve patients were taking 2 immunosuppressive medications: mycophenolic mofetil or sirolimus. The therapeutic protocol in the case of 14 patients also included deployment of steroid medications Encorton or Metypred (Fig. 4).

Fig. 4
Fig. 4:
Analysis of the experimental group: Distribution of patients according to the basic immunosuppressive medication.

The basic measured parameter of CBL median in the experimental group and in the control group amounted to 0.325 mm (min 0–max 0.95) and 0.5 mm (min 0.15–max 1.8), respectively. The comparison of CBL medians revealed lack of significant differences between the experimental group and the control group (P = 0.089; U Mann-Whitney test with continuity correction).

The next analysis concerned the correlation between the torque and bone loss in the 2 groups. Both in the experimental group (P = 0.93) and in the control group (P = 0.9), no correlation was found (Spearman's rank correlation coefficient).

Afterward, the correlation between the scale of bone loss and basic immunosuppressive medication taken by the patient, as well as the administration of either 1 or 2 medications or a steroid, was examined (Table 1). The results presented indicate lack of statistically significant difference in the loss of bone around the implant between the patients taking 1 of those 4 medications (P = 0.212). The results indicate lack of statistically significant difference in CBL between patients taking steroids and those not taking medications from that group (P = 0.086) (Tables 2 and 3).

Table 1
Table 1:
Correlation Between CBL and the Basic Immunosuppressive Medication
Table 2
Table 2:
Correlation Between CBL and 2 Immunosuppressive Medications
Table 3
Table 3:
Correlation Between CBL and Steroids

In the course of statistical analysis, a significant difference in CBL was revealed between patients taking 1 or 2 medications (P = 0.042) (Fig. 5).

Fig. 5
Fig. 5:
Statistical analysis in the experimental group: a significant difference was observed in CBL between patients taking 1 or 2 immunosuppressive medications (P = 0.042). Results shown in a graphic form.

Implant stability measurement was performed with the use of implant stability quotient (ISQ). In all cases, the obtained values were higher than 55 ISQ, which denotes good or very good implant stability both directly after implantation—ISQ1, and 4 months later—ISQ2 (after the osseointegration period) (Table 4).

Table 4
Table 4:
Assessment of Implant Stability on the Day of the Procedure—ISQ1 and After the Osseointegration Period—ISQ2

Correlation between ISQ1/ISQ2 and CBL was assessed. Neither the analysis of the experimental group or control group nor the analysis of all participants without group divisions showed any significant correlations (all P values > 0.05). There are no statistically significant differences in ISQ values (P = 0.075).

In addition, the authors decided to specify the impact of immunotherapy on the secondary stabilization of implants after 4 months since implantation (ISQ2). The U Mann-Whitney test with continuity correction indicated no statistically significant differences (P = 0.075) in ISQ values between patients taking steroids (median 74; min 64–max 78) and those not taking steroids (median value 69.5; min 59–max 74.5). A similar result in the form of lack of statistically significant differences (P = 0.7) was brought by the comparison between the effect which taking 1 or 2 immunosuppressive medications has on ISQ2 (P = 0.7; U Mann-Whitney test with continuity correction) (Table 5).

Table 5
Table 5:
Impact of Immunosuppressive Therapy on Secondary Stability of Implants 4 Months After Implantation (ISQ2)

Discussion

The issue of dental rehabilitation of patients with organ transplants has not been a subject of too many studies so far.19 It is generally known that the best way to replace the missing teeth is to use dental implant treatment. While making a decision to choose this method, one must obviously bear in mind the contraindications that might have an impact on the occurrence of complications or even lead to treatment failure.20 Due to immunocompromised situation of the patient oral infections may put at risk not only the longevity of the implants but also the integrity of the transplanted organ. For many years, the list of these contraindications was extensive: metabolic diseases, osteoporosis, bone diseases, radiotherapy, or immunosuppression.21–25 Thanks to the advancement in therapeutic methods and the invention of new medications, we may effectively control the condition of patients. Enhancing the patients' quality of life through the use of implants repeatedly exceeds the risk related to dental implant treatment.26 The study of Montebugnoli et al27 along with the study of Paredes et al17 are the first 2 prospective studies in the world with the long observation period that were related to the issue.

Hitherto, a few descriptions of single cases with the short follow-up period have been published,13 2 publications by Gu et al from 2011,14 Gu and Yu,15 and a study describing 10 organ transplant patients (OTPs) and 10 patients from the control group.18,27 The outcomes of all the aforementioned studies have confirmed that there is no impact of immunosuppressive therapy after organ transplantation on the success of dental implant treatment. Substantial limitations of those studies were the considerably low numbers of patients included in the study or a very short observation time. There is also one very interesting case report by Dalla Torre D et al. from 2016.28 Researches prior to implant treatment performed bone augmentation in an organ (liver) transplant patient. After 2 years stable peri-implant conditions and totally integrated bone grafts were presented. Authors claim that not only dental treatment but also bone grafting might be possible in solid organ transplant patients.

The results of our prospective study indicate clearly that there is no difference in the effects of dental implant treatment between patients in the course of immunosuppressive therapy after organ transplantation and the control group of healthy people. None of the patients from either group had any related ailments, and successful osseointegration concerned 100% implants. The basic parameter subject to measurements, CBL median in the experimental group and in the control group, equaled 0.325 mm (min 0–max 0.95) and 0.5 mm (min 0.15–max 1.8), respectively. The results of the research mentioned earlier14,15,27 are not substantially different from the outcomes quoted by other authors who assessed bone loss around implants placed in healthy people.29,30,31 Gu et al14 measured the CBL median whose value equaled 1.30 ± 1.3 mm after 36 months in the organ transplant group (OTG), and Montebugnoli et al27 noted lower CBL value in both the experimental and control groups (0.28 ± 0.2 vs 0.42 ± 0.32 mm, respectively), but their observation period was only 3 months. Fransson et al32 obtained the CBL median result at the level of 1.68 ± 1.3 mm after the follow-up period which lasted 60 months. The study of Paredes et al16 reported that the CBL median equaled (1.53 ± 0.6 mm) in the OTG and (1.64 ± 1.3 mm) in the control group. The observation period lasted at least 8 years. The results obtained in our study are a little different. Diversity of the outcomes (lower bone loss in this study) is most likely caused by another implantation technique (all implants placed subcrestally), a shorter follow-up period (minimum 24 months), and different immunosuppression regimes. Similar results were obtained by investigators Gultekin et al.33 In their experimental group, where they applied comparable implants and surgical techniques, bone loss equaled 0.35 ± 0.13 mm after 15 months since implantation. Also, Annibali et al34 arrived at the result of the CBL median (MD) at the level of −0.55 mm, [−0.86; −0.24], and in their experiment, they used implants of analogous construction as ours. In the study projects mentioned earlier,13–18 the largest group of patients subject to immunosuppressive treatment regime took cyclosporin as the basic medication. It is a well-known fact that it is a medicine of the strongest negative impact on the process of bone healing around the implants.35 Most patients included in our study have been administered tacrolimus. This confirms the hypothesis that more contemporary medications exert considerably lower influence on osseointegration and are less toxic to bone36 and solid organs of the patient.37 What is more, over the years the scale of “permissible bone loss” has been substantially reduced. What used to be considered as an ordinary process,30,31 nowadays is treated as a failure and happens more and more rarely.38 Further follow-up of the patients should allow to confirm that the selected surgical technique and most of all appropriate immunosuppressive therapy shall induce the reduction of CBL. The authors extended the originally planned follow-up period up to 5 years, with the ensuing checkups taking place after 3, 4, and 5 years accordingly. Based on the findings arrived at so far, one can claim that an increase in the bone loss surrounding implants is neither caused by immunosuppression in the form of single medication (be it tacrolimus, cyclosporin, sirolimus, or mycophenolic mofetil), nor caused by any additional application of steroids (Encorton and Metypred). Only in the case of combination therapy with 2 immunosuppressive medications (nonsteroids), a statistically noteworthy difference was observed (P = 0.042). However, even in this context, the bone loss was minor and insignificant for implant stability (Table 6).

Table 6
Table 6:
Comparison of Results (Basic Measured Parameter—Bone Loss CBL) Obtained in Various Experiments

The question which was of special interest to the investigators working in the present project, was the impact of taking glucocorticosteroids (GS) on the healing bone surrounding the implant inserted in patients with organ transplants. The effect of these medications on bone structures is commonly known and well documented,4,5,39,40 especially in the case of immunosuppressive therapy with the use of these substances applied after transplantations. GS influence not only bone metabolism but also to a large extent disturb the processes of soft-tissue regeneration. In this study, however, no negative impact of GS has been observed. No statistically significant disparities in the CBL were found between patients taking GS and patients not taking GS within immunosuppressive therapy. What is more, no difference was observed between either of these groups and the patients from the control group. OTPs take high dosages of GS for many years. Based on the findings of our investigation, one may assume that the administration of these medications does not significantly influence the process of implant osseointegration. The research done by other authors also provides confirmation of this fact.41 This observation is especially valuable in view of very common application of GS in numerous diseases, which gives a chance to safely implement implantoprosthetic treatment in these patients as well.

Measurements of bone loss allow to reliably assess any alterations taking place over a long period of time. They are, however, fraught by certain errors. These first of all results from the fact that the obtained results are subjective (even despite the application of the read-out method by 2 independent researchers and calculating the median). Thus, the authors decided to perform additional objective measurements, aiming at a comparison of the quality of the bone site and osseointegration process. The first method assumed the need to measure the torque necessary to insert the implant. This helped to evaluate the primary stability of the implant, while indirectly facilitating the characteristics of the bone site quality. The obtained results indicate no statistically significant differences in the torque value between the OTG and control group. This means that bone conditions were very good in all the patients included in the study, even despite the use of immunosuppressive treatment in the OTG. It gives another confirmation of the assumption that there is no significant influence of this therapy on bone condition within the jaw and the mandible. The other method is the objective measurement of implant stabilization ISQ, which has a well-proven prognostic value.42 The researchers performed the measurement twice: on the day of implantation and after 4 months, which were adopted as a period indispensable for correct osseointegration. The obtained results indicate lack of significant impact of the applied immunosuppressive therapy on the secondary stabilization of implants. It does not matter whether a patient takes 1 immunosuppressive medication or 2, or whether he/she is treated with steroids. In all the cases, the results are higher than 55 ISQ. Almost identical results were obtained by researchers43 in 2017, measuring bone loss and implant stabilization, what is more, based on measurements acquired only in a group of healthy patients.

One of the keys to successful treatment is the minimization of the risk of complications in that specific group of patients who take immunosuppressive medications. It is crucial to perform regular checkups and comply with appropriate hygienic requirements.44 The basic issue is, however, a suitable antibiotic therapeutic regime, which has been applied to all the patients encompassed by our study. Despite the fact that it is not conclusively specified whether postoperative infections and implant failures can be reduced by the application of antibiotics and there are no adopted standards related to that issue,45 the authors, similar to Ziebolz et al,3 recommend the use of these medications because of the increased infection risk in patients in the course of immunosuppression. Analogous conclusions that implant treatment is feasible in immunocompromised patients when proper precautions are taken were drawn by Vissink et al., 2018.46

Conclusion

Immunosuppressive medications administered to the participants of our study—patients after organ transplants (kidney, pancreas, and liver)—do not have any impact on the osseointegration of dental implants. Implant stability and bone loss are not any different from those in healthy people. Steroids applied to OTPs have no influence on the effect of dental implant treatment, either at the bone level or soft tissues. Patients with organ transplants can safely and effectively undergo dental implant treatment. The condition is to adhere to appropriate procedures and postoperative checkups. The results arrived at in this study should become a significant contribution to further research of the group of patients submitted to immunosuppressive treatment, also for reasons other than transplantation.47 The subsequent acquisition and confirmation of comparable results among those people as well shall give opportunity to improve life quality of a vast group of patients.

Disclosure

The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.

Approval

Ethics approval was obtained on October 13, 2013, from the Ethics Committee of the Poznan University of Medical Sciences (reference number 1234/2013).

References

1. Matesanz R. International Figures on Organ, Tissue & Hematopoietic Stem Cell Donation & Transplantation Activities. Vol 20: Published jointly with the European Directorate for the Quality of Medicines & HealthCare of the Council of Europe (EDQM); 2015:4–14.
2. Guggenheimer J, Eghtesad B, Stock DJ. Medical management update: Dental management of the (solid) organ transplant patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontology. 2003;95:383–389.
3. Ziebolz D, Hraský V, Goralczyk A, et al. Dental care and oral health in solid organ transplant recipients: A single center cross-sectional study and survey of German transplant centers. Transpl Int. 2011;24:1179–1188.
4. Kulak CA, Borba VZ, Kulak Júnior J Jr, et al. Transplantation osteoporosis. Arq Bras Endocrinol Metabol. 2006;50:783–792.
5. Stein E, Ebeling P, Shane E. Post-transplantation osteoporosis. Endocrinol Metab Clin North Am. 2007;36:937–963.
6. Hwang D, Wang HL. Medical contraindications to implant therapy: Part I: Absolute contraindications. Implant Dent. 2006;15:353–360.
7. Mombelli A, Cionca N. Systemic diseases affecting osseointegration therapy. Clin Oral Implants Res. 2006;17:97–103 (Suppl. 2 )
8. Duarte P, Filho G, Sallum E, et al. The effect of an immunosuppressive therapy and its withdrawal on bone healing around titanium implants. A histometric study in rabbits. J Periodontol. 2001;72:1391–1397.
9. Poliana MD, Getúlio Rocha N, Enilson Antônio S, et al. Short-term immunosuppressive therapy does not affect the density of the pre-existing bone around titanium implants placed in rabbits. Pesqui Odontol Bras. 2003;17:362–366.
10. Sakakura C, Margonar R, Holzhausen M, et al. Influence of cyclosporin A therapy on bone healing around titanium implants: A histometric and biomechanic study in rabbits. J Periodontol. 2003;74:976–981.
11. Sakakura C, Marcantonio E, Wenzel A, et al. Influence of cyclosporin A on quality of bone around integrated dental implants: A radiographic study in rabbits. Clin Oral Implants Res. 2005;18:34–39.
12. Sakakura C, Margonar R, Sartori R, et al. The influence of cyclosporin A on mechanical retention of dental implants previously integrated to the bone: A study in rabbits. J Periodontol. 2006;77:2059–2062.
13. Heckmann SM, Heckmann JG, Linke JJ, et al. Implant therapy following liver transplantation: Clinical and microbiological results after 10 years. J Periodontol. 2004;75:909–913.
14. Gu L, Wang Q, Yu Y. Eleven dental implants placed in a liver transplantation patient: A case report and 5-year clinical evaluation. Chin Med J (Engl). 2011;124:472–475.
15. Gu L, Yu Y. Liver: Clinical outcome of dental implants placed in liver transplant recipients after 3 years: A case series. Transplant Proc. 2011;43:432678–432682.
16. Nakagawa A, Shitara N, Ayukawa Y, et al. Implant treatment followed by living donor lung transplant: A follow-up case report. J Prosthodont Res. 2014;58:127–131.
17. Paredes V, López-Pintor RM, Torres J, et al. Implant treatment in pharmacologically immunosuppressed liver transplant patients: A prospective-controlled study. Clin Oral Implants Res. 2018;29:28–35.
18. Montebugnoli L, Venturi M, Cervellati F, et al. Peri-implant response and microflora in organ transplant patients 1 year after prosthetic loading: A prospective controlled study. Clin Implant Dent Relat Res. 2014;17:972–982.
19. Radzewski R, Osmola K. The use of dental implants in organ transplant patients undergoing immunosuppressive therapy: An overview of publications. Implant Dent. 2016;25:541–546.
20. Bornstein MM, Cionca N, Mombelli A. Systemic conditions and treatments as risks for implant therapy. Int J Oral Maxillofac Implants. 2009;24(suppl):12–27.
21. Alsaadi G, Quirynen M, Komárek A, et al. Impact of local and systemic factors on the incidence of late oral implant loss. Clin Oral Implants Res. 2008;19:670–676.
22. Alsaadi G, Quirynen M, Michiles K, et al. Impact of local and systemic factors on the incidence of failures up to abutment connection with modified surface oral implants. J Clin Periodontol. 2008;35:51–57.
23. Hernández G, Lopez-Pintor RM, Arriba L, et al. Implant treatment in patients with oral lichen planus: A prospective-controlled study. Clin Oral Implants Res. 2012;23:726–732.
24. Javed F, Romanos GE. Impact of diabetes mellitus and glycemic control on the osseointegration of dental implants: A systematic literature review. J Periodontol. 2009;80:1719–1730.
25. Oczakir C, Balmer S, Mericske-Stern R. Implant-prosthodontic treatment for special care patients: A case series study. Int J Prosthodont. 2005;18:383–389.
26. Diz P, Scully C, Sanz M. Dental implants in the medically compromised patient. J Dent. 2013;41:195–206.
27. Montebugnoli L, Venturi M, Cervellati F. Bone response to submerged implants in organ transplant patients: A prospective controlled study. Int J Oral Maxillofac Implants. 2012;27:1494–1500.
28. Dalla Torre D. Burtscher Ridge augumentation in an organ transplant patient. Int. J. Oral Maxillofac. Surg. 2016;45:658–661.
29. Lindquist LW, Carlsson GE, Jemt T. A prospective 15-year follow-up study of mandibular fixed prostheses supported by osseointegrated implants. Clinical results and marginal bone loss. Clin Oral Implants Res. 1996;7:329–336.
30. Pikner SS, Gröndahl K, Jemt T, et al. Marginal bone loss at implants: A retrospective, long-term follow-up of turned Brånemark system implants. Clin Implant Dent Relat Res. 2009;11:11–23.
31. Laurell L, Lundgren D. Marginal bone level changes at dental implants after 5 years in function: A meta-analysis. Clin Implant Dent Relat Res. 2011;13:19–28.
32. Fransson C, Lekholm U, Jemt T, et al. Prevalence of subjects with progressive bone loss at implants. Clin Oral Implants Res. 2005;16:440–446.
33. Gultekin BA, Gultekin P, Leblebicioglu B, et al. Clinical evaluation of marginal bone loss and stability in two types of submerged dental implants. Int J Oral Maxillofac Implants. 2013;28:815–823.
34. Annibali S, Bignozzi I, Cristalli MP, et al. Peri-implant marginal bone level: A systematic review and meta-analysis of studies comparing platform switching versus conventionally restored implants. J Clin Periodontol. 2012;39:1097–1113.
35. de Molon RS, Sakakura CE, Faeda RS, et al. Effect of the long-term administration of cyclosporine A on bone healing around osseointegrated titanium implants: A histomorphometric study in the rabbit tibia. Microsc Res Tech. 2017;80:1000–1008.
36. Rubert M, Montero M, Guede D, et al. Sirolimus and tacrolimus rather than cyclosporine A cause bone loss in healthy adult male rats. Bone Reports. 2015;22:74–81.
37. Haywood S, Abecassis M, Levitsky J, et al. The renal benefit of mycophenolate mofetil after liver transplantation. Clin Transplant. 2011;25(1):E88–E95.
38. Qian J, Wennerberg A, Albrektsson T. Reasons for marginal bone loss around oral implants. Clin Implant Dent Relat Res. 2012;14:792–807.
39. van Staa TP. The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int. 2006;79:129–137.
40. Petsinis V, Kamperos G, Alexandridi F, et al. The impact of glucocorticosteroids administered for systemic diseases on the osseointegration and survival of dental implants placed without bone grafting - A retrospective study in 31 patients. J Cranio-Maxilo-Facial Sur., 2017;45(8):1197–1200.
41. Radzewski R, Osmola K. Treatment of edentulous patients on immunosuppressive therapy using prosthetic overdenture supported by implants. Description of two clinical cases. Implant Stom. 2016;2:784–788.
42. Serge B, Joan PA, Tara A, et al. The predictive value of resonance frequency analysis measurements in the surgical placement and loading of endosseous implants. J Oral Maxillofac Surg. 2016;74:1145–1152.
43. Simmons DE, Maney P, Teitelbaum AG, et al. Comparative evaluation of the stability of two different dental implant designs and surgical protocols-a pilot study. Int J Implant Dent. 2017;3:16.
44. Somacarrera ML, Lucas M, Cuervas-Mons V, et al. Oral care planning and handling of immunosuppressed heart, liver, and kidney transplant patients. Spec Care Dent. 1996;16:242–246.
45. Klinge B, Flemming T, Cosyn J, et al. The patient undergoing implant therapy. Summary and consensus statements. The 4th EAO Consensus Conference 2015. Clin Oral Implants Res. 2015;26(suppl 11):64–67.
46. Vissnk A, Spijkervet FKL, Raghoebar GM. The medically compromised patient: Are dental implants a feasible option?. Oral Diseases. 2018;24:253–260.
47. Altin N, Ergun S, Katz J, et al. Implant-supported oral rehabilitation of a patient with pemphigus vulgaris: A clinical report. J Prosthodont. 2013;22:581–586.
Keywords:

crestal bone level; solid-organ transplantation; endosseous implant; immunosuppression

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.