A growing body of evidence support the cause–effect relationship between microbial plaque colonization and the pathogenesis of peri-implantitis 1–3. The major complications that may affect dental implant are: peri-implant mucositis, which is a reversible inflammatory reaction in the mucosa adjacent to an implant, and peri-implantitis, which is defined as a series of inflammatory reactions affecting the tissues around an osseointegrated implant in function, resulting in the loss of the supporting alveolar bone 4. However, a previous history of periodontitis, cigarette smoking, polymorphisms of the interleukin-1 gene cluster, or occlusal overload was also identified to be associated with an increased risk for peri-implant bone loss 5–8.
The clinical diagnostic aspects that may aid in assessing of peri-implant defect include mobility, bleeding on probing, modified gingival index, probing depth (PD) and loss of attachment, pus formation, and bone resorptions as evidenced by radiographs 9.
Diabetes mellitus is one of the world’s major chronic health problems, which is associated with increased rates of edentulism. As dental implants and techniques for controlling diabetes have evolved, they improve the quality of life in diabetic patients. Dental implant therapy has become increasingly common among patients with diabetes 10.
The hypothetical mechanisms have been proposed regarding the influence of diabetes on biological responses to implant placement. Such mechanisms include impairment in bone healing response, reduction in vascular supply due to microangiopathies, decrease in host defense, formation of advanced glycation end-products, reduction in collagen production, and increased collagenase activity 11. However, the rising success of dental implants, along with the realized benefits of implant therapy, has shifted current trends to accommodate patients with controlled diabetes as good candidates for treatment 10.
According to a cause-related concept, several treatment modalities have been recommended for the management of peri-implantitis. Although the clinical outcomes of nonsurgical therapy have been reported, there is no reliable evidence suggesting its effectiveness in treating deep peri-implant defects. Therefore, surgical intervention may provide better access and may allow further therapies to change the peri-implant tissue morphology, to establish the site during the healing phase, or to promote the regeneration of bone 12.
Regenerative treatment modalities have been extensively investigated using bone grafts for regeneration in intrabony defects around dental implants 13,14. Therefore, synthetic biomaterials are being developed 15. Of the synthetic biomaterials, amorphous calcium phosphate and micromacroporous biphasic calcium phosphate show promise as bone substitutes in bone regeneration 16,17.
Hydroxyapatites (HAs) represent a family of bone-grafting materials with a high degree of biocompatibility, which is largely attributable to its presence in natural calcified tissue. HA, Ca10(PO4)6(OH)2, is a calcium phosphate-based bioceramic material that makes up the majority of the inorganic components of human bones and teeth. The HA bone-grafting materials exhibited decreased osteoconductivity and poor degradation characteristics 18. The healing after treatments with these graft materials evidenced a long junctional epithelium with only a limited regenerative potential 19,20. In pursuit of improving these shortcomings, a novel fully synthetic nanocrystalline hydroxyapatite (NHA) has been introduced for augmentation procedures in osseous defects 21,22. NHA, containing about 65% water and nanoscopic apatite particles (35%) in aqueous dispersion, has been recommended for augmentation procedures in osseous defects 22,23. In particular, experimental animal studies have pointed to an undisturbed osseointegration and complete resorption of the material within 12 weeks 22,24. Owing to its specific physicochemical properties, NHA is intended to be used without the additional application of a barrier membrane.
Diabetic patients are more susceptible to develop peri-implant defects; however, NHAs have not been thoroughly investigated in the treatment of peri-implant bone defect.
The study was designed to provide answers to the following two questions: (i) does the use of different bone graft materials significantly improves clinical parameters and radiographic evidence in treatment of peri-implantitis in control diabetic patients? and (ii) Does NHA bone graft provides a significant improvement?
Patients and methods
This parallel design double-blind study was conducted on 15 completely edentulous patients having moderate peri-implantitis. The participants were selected from the outpatient clinic, referred from Oral and Maxillofacial Surgery Department to Oral Medicine and Periodontology Department, Faculty of Dental Medicine for Girls, Al-Azhar University, for treatment of peri-implantitis during a period from March 2012 to June 2013.
Each patient was informed of the objectives and nature of the study, including benefits and risks, and was required to sign informed consent before participation in the study. This study complied with the Helsinki Declaration of 1975, as revised in 2000, and was approved by the Committee on Ethics Involving Human Subjects.
Eligible patients fulfilled the following criteria
Patient population consisted of completely edentulous type II diabetic patients (nine women and six men) who were 41–60 years of age, exhibiting a total of n=20 peri-implant defects. Carefully selected patients with well-controlled diabetes [glycosylated hemoglobin levels (Hba1c)<8% and managed by insulin] suffering from mild peri-implantitis with at least one dental implant determined by both clinical (i.e. PD≥5 mm, bleeding on probing, and/or suppuration) and radiographic evidence (bone loss≥3 mm at mesial or distal site of the implants). The implants should have been in function for more than 1 year, free from any systemic disease, which was contraindicated dental surgery other than controlled diabetes, and not receiving any medication (except insulin). Exclusion criteria for this study were any systemic disease rather than diabetes, uncontrolled diabetes, hypersensitivity, smoking, a history of alcohol abuse, and participation in other clinical trials.
At initial visit, participants who met the inclusion/exclusion criteria were assigned numbers in ascending order by the study coordinator and written medical history was taken verbally. Vital signs were recorded, together with comprehensive intraoral examination, by a single investigator who also carried out oral hygiene instructions and were treated at one visit by nonsurgical instrumentation of the peri-implant bony defect followed by pocket irrigation with 0.2% chlorhexidine digluconate.
All patients had mandibular overdenture with ball and socket attachments, which were easily cleaned. Once all these stages were completed (1–3 months according to individual patient needs) and the standard of oral hygiene instruction was considered appropriate, clinical and radiographic parameters were recorded.
Clinical criteria were presence of at least one peri-implant intrabony defect with PD of greater than 5 mm and intrabony component of greater than 3 mm as detected on radiographs, no implant mobility, no evidence of occlusal overload, presence of adequate keratinized peri-implant mucosa, no signs of acute periodontal conditions, and a good level of OH (plaque index<1) 25.
The following clinical parameters were measured immediately before and at 6 and 9 months after treatment using graduated William’s probe. PD was measured from the mucosal margin to the bottom of the peri-implant defect. All measurements were made by six aspects of peri-implant – mesiovestibular, midvestibular, distovestibular, mesooral, midooral, and distooral – by a blinded and previously calibrated investigator.
Standardized digital periapical radiographs were used to measure bone density (BD). The exposure parameters were fixed for all patients and over the follow-up period.
Radiographic measurements were assessed as follows. BD was assessed using the DBS-Win 1.5 Software (OT100, Instrumenterium Imaging, G.E. Corporation, Finland), which is a part of the recently introduced Vista Scan System. The mean gray value in each region of interest was calculated (256 gray levels of colors resolution) by assigning the gray value 0 to black and 256 to white. To measure BD, linear density measurements were performed by drawing three lines parallel to the implant surface. The line extended from the apex of the alveolar crest to the level of the apex of the implant. Three lines were drawn 1-mm apart from each other. The gray level along each line was recorded in the beginning of the line, in the middle, and at the end. The average of three readings was calculated to obtain the mean average density (gray level) along each line (Fig. 1).
All patients were randomly assigned by the study coordinator, using a coin toss, to receive one of the two treatments. They were treated either with access flap surgery (AFS) and the application of HA or with AFS and the application of NHA. The randomization process led to comparable mean values of all investigated clinical parameters at baseline in both groups.
To facilitate good surgical access around the implants, the mandibular overdenture was removed. Only sites showing peri-implantitis were surgically treated. All surgical procedures were performed by the same surgeon who remained masked to treatment assignment.
Following local anesthesia (2% xylocaine/adrenaline), an intracrevicular incision was made; the positions of the incisions were dependent on the pocket depth as well as on the width and thickness of the peri-implant mucosa (Fig. 2). Full-thickness flaps raised buccally and lingually were elevated vestibularly and orally. Vertical-releasing incisions were performed when needed for a better access or to achieve a better closure of the surgical site. All granulation tissues were carefully removed using hand curettes. The implant surfaces were thoroughly debrided under chlorhexidine irrigation. Following cleaning, the exposed implant and bony surfaces were rinsed with sterile physiologic saline (Fig. 2). The bony defect in most instances was vertical in nature; the bone graft [either microhydroxyapatite (HA) (150–250 μm) or NHA (20–40 nm)] was condensed in the angular bone defect starting from the bottom and slightly over-filled around the implant by a blinded periodontist (Fig. 2). Thereafter, flaps were repositioned coronally and fixed with vertical or horizontal mattress sutures in such a way as to ensure a nonsubmerged healing, and the overdenture were refitted.
One day before the surgery, all patients received prophylactic systemic antibiotic therapy (Dalacins; Pfizer, Sollentuna, Sweden; tablet 300 mg, three/day for 1 week).
Following surgery, the patients were advised to rinse twice a day for 1 min with chlorhexidine 0.12% for a period of 2 weeks. The sutures were removed 10 days after the surgery.
The patients were recalled every month for the following 9 months for re-evaluation and maintenance care. At each recall, the overdenture was removed to have proper access for implant examination. Neither probing nor subgingival instrumentation was performed during the first 6 months after the surgery. The clinical parameters and radiographic evaluations were carried out at 6 and 9 months (Fig. 2).
Data were presented as mean and SD. Repeated measure analysis t-test and post-hoc tests were used. The significance level was set at P value less than or equal to 0.05. Statistical analysis was performed using statistical package for scientific Studies (SPSS) (version 16.0; SPSS Inc., Chicago, Illinois, USA) for Windows.
Examination of the surgical defect revealed that all implants in both groups exhibited horizontal bone loss of the supporting alveolar bone, without dehiscence or fenestration of the adjacent vestibular and oral alveolar bone; neither allergic reactions nor suppuration was observed in any patients postoperatively.
The results of the present investigation revealed that all patients in both treatments showed significant clinical and radiographic improvement over the study period. Moreover, beneficial clinical impacts of both modalities – flap surgery (AFS) and the application of HA or AFS and the application of NHA – were observed. In both groups, the mean plaque index values and bleeding on probing remained low throughout the study period.
At baseline, there was no significant difference between groups regarding probing pocket depth and BD. The mean PD in both groups at baseline and after 6 and 9 months is summarized in Table 1. In particular, at 9 months after therapy, the HA group showed a reduction in mean PD from 7.00±1.69 at baseline to 4.70±0.05, and the mean BD changed from 47.39±4.9 at baseline to 54.84±2.986. However, when comparing the 6-month parameters with 9-month parameters, the HA group showed a nonsignificant difference.
In the NHA group, at 9 months after therapy, the mean PD changed from 7.88±1.36 at baseline to 3.44±0.52, and the mean BD changed from 49.26±7.38 at baseline to 66.60±4.248. However, when comparing the 6-month parameters with 9-month parameters, the HA group showed a nonsignificant difference.
In both groups, the radiological observation at 9 months revealed a decreased translucency within the intrabony component of the respective peri-implant bone defect. Compared with the radiographs obtained at 6 months, there was difference in peri-implant translucency noted within the groups (Tables 2 and 3).
The use of osseointegrated dental implants to support a mandibular overdenture has become an accepted treatment modality because of the high implant success rates observed by clinicians and researchers. Diabetes mellitus is a systemic disease with a number of major complications that often adversely affect the quality and length of life, particularly as it relates to cardiovascular events and sudden death. Periodontal infection represents one of the diabetes-associated complications that may be involved in altering the vascular pathology in the diabetic patients 26.
The present study was conducted on diabetic patients because diabetes mellitus and edentulousness are both highly prevalent in the elderly. Diabetic patients are more liable to suffer from peri-implantitis, which is considered a major complication for implant survival; hence, treatment of bone destruction around dental implant is challenging. Evidence exists to indicate that the complications are related to the duration and degree of lack of glycemic control, which is affected by body weight and a patient’s compliance with the treatment regimen 27. However, normal healing occurs in patients with good metabolic control 28,29. Hence, the selected patients enrolled in this study were well-controlled diabetics.
The results of the present study have indicated that treatment of intrabony peri-implantitis defect with both HA and NHA resulted in clinically important reduction in PD and an increase in BD and decrease in radiotranslucency within the intrabony component of respective peri-implant defect at 9 months after the surgical treatment in both groups.
The clinical improvement noted in both groups seemed to be within the range of other regenerative treatment procedures reported in previous studies 30–32.
With respect to the re-osseointegration at failing implants following the application of NHA 22, the fate of the bone graft was assessed histologically; they reported complete resorption of the material at 12 weeks. Furthermore, at microradiography level the indicated mineralization rates in the two bone substitute groups were not significantly lower than those found in the control group 22. Similar results were also reported by Chris et al.24, as NHA was mostly osseointegrated after 8 weeks. Furthermore, it was observed that nonosseointegrated NHA remnants were actively being resorbed by osteoclasts 24. When interpreting these results, however, it must be kept in mind that the acute-type defects involved in these studies might not necessarily represent the real situation encountered in a chronic, plaque-infected peri-implantitis defect. Indeed, histological studies on nonhuman primates have shown that, in acute defect models, ∼50–70% spontaneous regeneration can be expected, which in turn may lead to difficulties in interpreting the results 33.
Another important factor that was demonstrated to influence re-osseointegration strongly after treatment of peri-implantitis defects is the surface characteristic of the implant 34. Accordingly, the variety of different implant types and surface topographies may complicate a generalization of the present results.
Within the limits of the present investigation, it can be concluded that both treatment modalities have shown a predictable result over the 9-month study period; however, the application of NHA may result in more clinical and radiographic improvement of healing outcomes.
Further studies, with a much higher number of patients and defects, would be needed to detect an eventual difference between the treatments.
Conflicts of interests
There are no conflicts of interests.
1. Mombelli A, Buser D, Lang NP.Colonization of osseointegrated titanium implants in edentulous patients. Early results.Oral Microbiol Immunol1988;3:113–120.
2. Alcoforado GA, Rams TE, Feik D, Slots J.Microbial aspects of failing osseointegrated dental implants in humans.J Parodontol1991;10:11–18.
3. Becker W, Becker BE, Newman MG, Nyman S.Clinical and microbiologic findings that may contribute to dental implant failure.Int J Oral Maxillofac Implants1990;5:31–38.
4. Albrektsson T, Isidor FLang NP, Karring T.Consensus report of session IV.Proceedings of the First European Workshop on Periodontology1994.London, UK:Quintessence;365–369.
5. Isidor F.Histological evaluation of peri-implant bone at implants subjected to occlusal overload or plaque accumulation.Clin Oral Implants Res1997;8:1–9.
6. Feloutzis A, Lang NP, Tonetti MS, Burgin W, Bragger U, Buser D, et al..IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a well-maintained population.Clin Oral Implants Res2003;14:10–17.
7. Gruica B, Wang HY, Lang NP, Buser D.Impact of IL-1 genotype and smoking status on the prognosis of osseointegrated implants.Clin Oral Implants Res2004;15:393–400.
8. Roos-Jansa ker AM, Lindahl C, Renvert H, Renvert S.Nine-to-fourteen-year follow-up of implant treatment. Part I: implant loss and associations to various factors.J Clin Periodontol2006;33:283–289.
9. Meffert RM.How to treat ailing and failing implants.Implant Dent1992;1:25–33.
10. Courtney MW Jr, Snider TN, Cottrell DA.Dental implant placement in type II diabetics: a review of the literature.J Mass Dent Soc2010;59:12–14.
11. Kotsovilis S, Karoussis IK, Fourmousis I.A comprehensive and critical review of dental implant placement in diabetic animals and patients.Clin Oral Implants Res2006;17:587–599.
12. Mombelli A, Moene R, Decaillet F.Surgical treatments of peri-implantitis.Eur J Oral Implantol2012;5SupplS61–S70.
13. Rosen PS, Reynolds MA, Bowers GM.The treatment of intrabony defects with bone grafts.J Periodontol2000;22:88–103.
14. Christian T, Safwan S, Michael T, Philipp S, Wilhelm NF, Emeka N.Bone regeneration in osseous defects – application of particulated human and bovine materials.Oral Surg Oral Med Oral Pathol Oral Radiol Endod2008;105:430–436.
15. Yukna RA.Synthetic bone grafts in periodontics.Periodontology1993;1:92–99.
16. Gauthier O, Goyenvalle E, Bouler JM, Guicheux J, Pilet P, Weiss P, Daculsi G.Macroporous biphasic calcium phosphate ceramics versus injectable bone substitute: a comparative study 3 and 8 weeks after implantation in rabbit bone.J Materials Sci Mater Med2001;12:385–390.
17. Lee IS, Zhao B, Lee GH, Choi SH, Chung SM.Industrial application of ion beam assisted deposition on medical implants.Surface and Coatings Technology2007;201:5132–5137.
18. Meffert RM, Thomas JR, Hamilton KM, Brownstein CN.Hydroxylapatite as an alloplastic graft in the treatment of human periodontal osseous defects.J Periodontol1985;56:63–73.
19. Froum SJ, Kushner L, Scopp IW, Stahl SS.Human clinical and histologic responses to durapatite implants in intraosseous lesions. Case reports.J Periodontol1982;53:719–725.
20. Moskow BS, Lubarr A.Histological assessment of human periodontal defect after durapatite ceramic implant. Report of a case.J Periodontol1983;54:455–462.
21. Bezrukov VM, Grigor’iants LA, Zuev VP, Pankratov AS.The surgical treatment of jaw cysts using hydroxyapatite with an ultrahigh degree of dispersity.Stomatologiia (Mosk)1998;77:31–35.
22. Thorwarth M, Schultze-Mosgau S, Kessler P, Wiltfang J, Schlegel KA.Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite.J Oral Maxillofac Surg2005;63:1626–1633.
23. Moghadam HG, Sandor GK, Holmes HH, Clokie CM.Histomorphometric evaluation of bone regeneration using allogeneic and alloplastic bone substitutes.J Oral Maxillofac Surg2004;62:202–213.
24. Chris AJJ, Verdonschot N, Schreurs BW, Buma P.The use of a bioresorbable nano-crystalline hydroxyapatite paste in acetabular bone impaction grafting.Biomaterials2006;27:1110–1118.
25. Löe H.The Gingival index, the plaque index and the retention index systems.J Periodontol1967;38Suppl610–616.
26. Southerland JH, Moss K, Taylor GW, Beck JD, Pankow J, Gangula PR, Offenbacher S.Periodontitis and diabetes associations with measures of atherosclerosis and CHD.Atherosclerosis2012;222:196–201.
27. Nathan DM.Long term complications of diabetes mellitus.N Engl J Med1993;328:1676–1685.
28. Hough S, Avioli LV, Bergfeld MA, Fallon MD, Slatopolsky E, Teitelbaum SL.Correction of abnormal bone and mineral metabolism in streptozotocin-induced diabetes mellitus in the rat by insulin therapy.Endocrinology1981;108:2228–2234.
29. Goodman WG, Hori MT.Diminished bone formation in experimental diabetes. Relationship to osteoid maturation and mineralization.Diabetes1984;33:825–831.
30. Haas R, Baron M, Dortbudak O, Watzek G.Lethal photosensitization, autogenous bone and e-PTFE membrane for the treatment of peri-implantitis: preliminary results.Int J Oral Maxillofac Implants2000;15:374–382.
31. Ragy N, Ezz ElAarab A, Gawish A.Clinical and radiographic evaluation of alloplastic bone graft in treatment of peri-implantitis.Egypt Den J2001;47:241–248.
32. Gawish A, Hassan S.A six-year clinical, microbiological and radiological study outcome following treatment of peri-implantitis.Egypt J Hospit Med2003;13:123–134.
33. Caton J, Mota L, Gandini L, Laskaris B.Non-human primate models for testing the efficacy and safety of periodontal regeneration procedures.J Periodontol1994;65:1143–1150.
© 2014 Egyptian Associations of Oral and Maxillofacial Surgery
34. Persson LG, Berglundh T, Lindhe J, Sennerby L.Re-osseointegration after treatment of peri-implantitis at different implant surfaces. An experimental study in the dog.Clin Oral Implants Res2001;12:595–603.