Incidence of Periimplantitis following Autogenous Bone Transplantation
Khaldoun Darwich DMD
Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Head: Prof. Dr. Dr. R. Schmelzle)
Abstract:
Purpose: The implementation of dental implants is finding increasing acceptance for the oral rehabilitation in the field of dentistry as well in craniofacial surgery for the fixation of intraoral and extraoral prostheses. The advantages of this procedure are well known and documented in the medical literature, being the only method which facilitates a force transduction into the bone, mitigating the bone atrophy due to loss of function [Br?nemark et al. 1982]. This also holds true for implants inserted in transplanted bone, proving to be osteoprotective. One problem encountered is that endosteal implants are susceptible for bacterial colonisation with subsequent periimplantary inflammation, which could negatively influence the prognosis or life expectancy of an implant. Knowledge of the aetiology, progress and expression of the periimplantitis and the effects on the transplanted bone is vital to promote an adequate therapy which would prolong the life expectancy of the implants.
Materials and Methods: The retrospective investigation involved 52 patients (25 male, 27 female) who were treated at the department of Maxillofacial Surgery of the University Medical Center Hamburg-Eppendorf between the years 1994 and 2003. A total of 214 implants were included in the investigation.
Results: 122 implants (57%), showed no signs of inflammation, 42 (20%) suffered from periimplantary mucositis and by 50 (23%) fully manifested Periimplantitis was evident.
Discussion: Decisive for the development of periimplantary inflammation is an insufficient oral hygiene allowing plaque accumulation on the implants surface. In conjunction with other local or general factors like overloading or systemic diseases like diabetes mellitus or smoking the course can be accelerated. Following bone transplantation and implantation, further factors influence the prognosis of the implants like the general condition of the patient (e.g. age, compliance), therapies experienced (radiotherapy, chemotherapy) and the nature of the bone transplant (free bone transplant, revascularised transplant).
Nonetheless, periimplantitis is not an inevitable event and if certain rules are followed along the entire course of treatment (correct planning, hygiene instructions, stringent recall system) the life expectancy of the implants as well as the bone transplant can be considered as very good, easily exceeding 10 years and more [Adell et al. 1981].
Key words: dental implants, periimplantitis, jaw reconstruction
Introduction:
Large defects of the jaws following ablative surgery or trauma may often result in a cosmetically and socially unacceptable appearance of the patient making jaw reconstruction mandatory [Renk 1990]. With the improvement of the surgical procedures, especially the microsurgery and the advent of dental implants [Br?nemark et al. 1982], numerous alternatives exist for bone reconstruction and oral rehabilitations. Especially the treatment of patients following segmental jaw resection with microsurgically revascularised bone transplants and insertion of dental implants with subsequent prosthetical therapy allows restitution in form and function [Adell et al. 1990]. Dental implants play an integral role in this concept, allowing fixation of the prosthetics as well as being osteoprotective for the transplanted bone by leading to close to physiological loading of the bone [Boyne 1971].
Contrary to teeth which develop simultaneously with the periodontal tissue, building a functional unit, endosteal implants are artificial inorganic root substitutes [Listgarten et al. 1991]. Implants are inserted in a predrilled well of the bone with the expectation of developing a functional ancylosis allowing loading. The periimplantary soft tissue adapts to the foreign body whereby it must be emphasised that the relationship between the soft tissue and the implant cannot be compared to that seen in teeth and the periodontal gingiva. The anatomy of the tissues have some similarities but differ in composition of the connective tissue, the arrangement of the collagen fibres and the distribution of the vascular structures in the vicinity of the junctional epithelium [Lindhe 1999]. The supraalveolar soft tissue surrounding teeth is characterised by an acellular cement on the root's surface. Emanating from the cement are dentogingival and dentoalveolary fibres laterally, coronally and apically. This differs greatly from the situation seen surrounding implants. No cement exists on the implant, resulting in the collagen fibres of the mucosa inserting in periosteum of the alveolar crest and lie parallel to the implant surface or they are organised in bundles more or less parallel to the bone`s surface. Analysis of the connective tissues showed that the periimplantary mucosa contains markedly more collagen (85% vs. 60%) and less fibroblasts (1-3% vs. 5-15%) when compared to gingival surrounding teeth. Therefore the supraalveolar region of the periimplantary mucosa resembles in its composition scar tissue, being rich in collagen with few cells.
The blood supply of the gingiva originates from two different sources. The large subperiosteal vessels which feed the capillaries of the papillas below the oral epithelium and the plexus lateral of the junctional epithelium. The second source is the vascular plexus of the periodontal ligament. These pass coronal through the alveolar bone and terminate in the supraalveolary gingiva. The blood supply of the supracrestal periodontal tissue also emanates from two sources. In implants, the periodontal ligaments do not exist and subsequently the vascular plexus is also missing. Berglundh et al. observed in 1994 that the vascular system of the periimplantary mucosa originates only from the supraperiosteal blood vessels on the outside of the alveolar crest. These vessels supply the plexus below the oral epithelium and the junctional epithelium. The vascular systems below the gingival epithelium and the periimplantary mucosa therefore have the same source [Berglundh et al. 1994].
Berglundh et al. further demonstrated that close to the implants surface no plexus exists comparable with the one emanating from the periodontal ligament. Hence, the supraalveolary connective tissue apical of the junctional epithelium on the periimplantary mucosa is practically void of vascular system [Lindhe 1999].
In patients with bone transplantation, this is further compounded by certain accompanying factors:
- The body acceptance of the bone transplant and the development of its vascular supply influence the bone healing and the osseointegration of the implants.
- Following radiotherapy of the head and neck region certain detrimental effects must be considered. The general radio induced fibrosis, the radioxerostomia and the risk of developing an infected osteoradionecrosis threaten the prosthetic rehabilitation, whereby the summation of all these factors lead to an alteration of the oral environment conducive for the development of inflammation [Gr?tz et al. 1999]. Additionally the resection of the submandibulary gland as part of the cervical lymphadenoectomia leads to a decrease of the immune function of the saliva changing the entire composition of the oral flora or at least the activity of certain bacteria which are responsible for the development of the periimplantary inflammation.
With this in mind, the aim of this investigation was to evaluate the patency of the implants inserted in transplanted bone and to what extend the above factors influence the prognosis of the implant therapy.
Materials and Methods:
The retrospective investigation involved 52 patients (25 male, 27 female) who were treated at the department of Maxillofacial Surgery of the University Medical Center Hamburg-Eppendorf between the years 1994 and 2003. A total of 214 implants were included in the investigation. At the time of implant placement the patients' ages ranged from 28 to 81 years (average 55 years) of age. All patients underwent jaw reconstruction with bone transplants with subsequent introduction of implants.
The disorders which led to segmental or marginal jaw resection were: malignant tumors (21 patients), benignant tumors (4 patients), infection (osteomyelitis) (2 patients), trauma (2 patients), congenital malformations (clefts) (1 patient) and severe atrophy (22 Patients).
The methods of bone transplantation were either: microsurgically reanastomosed iliac crest (7 patients) or fibula (13 patients), free iliac crest (20 patients) of fibula (12 patients).
The implants which were implemented were: IMZ® Twinplus (cylinder) (82 implants), ITI Straumann® (screw) (77 implants), Semados® (screw) (41 implants), Branemark® (screw) (4 implants), Frialit® 2 (screw) (5 implants), Ankylos® (screw) (4 implants), Pitt-easy® bio oss (screw) (3 implants).
In conjunction to the assessment of the medical history (diabetes, smoking habits, cardiovascular diseases, thyroid function), periodontal clinical parameters were gathered. These comprised: The Plaque index (PI) according to Mombelli et al., the Bleeding index (BI) according to Mombelli et al., the probing depths, radiological assessment and bacterial isolation and identification using a gene-based testing kit (IAI Padotest 4.5).
Results:
In the presentation of the results the incidence of inflammation is correlated to different factors (gender, smoking, systemic disease etc). In the interpretation of these results it must be kept in mind, that more than one factor influenced the condition of many patients, for example, one patient suffered from diabetes mellitus and was a cigarette smoker also.
122 implants (57%), showed no signs of inflammation, 42 (20%) suffered from periimplantary mucositis and by 50 (23%) fully manifested Periimplantitis was evident
(fig. 1).
Gender specific relationship
In the male probands a total of 105 implants were investigated of which 66 (62.85%) showed no signs of inflammation, 26 (24.76%) suffered from a mucositis and 13 (12.38%) from periimplantitis. In the female probands a total of 111 implants were examined of which 60 (54.05%) showed no signs of inflammation, 14 (12.61%) signs of a mucositis and 37 (33.33%) from periimplantitis.
Primary disease
In the patient group who suffered from malignant tumors a total of 91 implants were examined of which 47 (51.64%) showed no signs of inflammation. 21 (23.07%) implants showed signs of a mucositis and 23 implants (25.27%) suffered from periimplantitis (fig 2).
In the patient group who suffered from atrophy of the jaws a total of 87 implants were investigated of which 50 (57.47%) showed no signs of inflammation, 15 (17.24%) suffered from a mucositis and 22 (25.28%) from periimplantitis.
In the group of benignant tumors a total of 14 implants were examined of which 12 (85.71%) showed no signs of inflammation and 2 (14.28%) signs of periimplantitis.
In the remaining small groups the following results were obtained. Following osteomyelitis a total of 8 implants were examined of which 2 (25%) showed no signs of inflammation and 2 (25%) signs of mucositis and 4 (50%) signs of periimplantitis.
In the patients suffering from congenital malformation a total of 8 implants were examined of which none showed signs of inflammation and in the group suffering from trauma a total of 6 implants were examined of which 3 (50%) showed no signs of inflammation and 3 (50%) signs of mucositis (fig. 2).
Type of reconstruction
In the patient group who were reconstructed using non revascularised bone from the iliac crest a total of 81 implants were examined of which 55 (67.9%) showed no signs of inflammation, with 12 (14.81%) suffering from mucositis and 14 (17.28%) from periimplantitis.
In the patient group who were reconstructed using non revascularised fibula graft a total of 50 implants were examined of which 16 (32%) showed no signs of inflammation, 13 (26%) suffering from mucositis and 21 (42%) from periimplantitis.
In the microsurgically reanastomosed grafts (revascularised), of the iliac crest 13 of 21 (61.9%) showed no signs of inflammation, with 5 (23.80%) suffering from mucositis and 3 (14.28%) from periimplantitis. and in the fibula flaps 40 of 62 implants (64.51%) showed no signs of inflammation, 10 (16.12%) suffering from mucositis and 12 (19.35%) from periimplantitis (fig. 3).
Implants positioning (maxilla or mandible)
Of the 63 implants which were localised in the upper jaw, 45 (71.42%) showed no signs of inflammation, 11 (17.46%) suffering from mucositis and 7 (11.11%) from periimplantitis.
From the 149 implants located in the lower jaw, 77 (51.67%) showed no signs of inflammation, 29 (19.46%) suffering from mucositis and 43 (28.85%) from periimplantitis.
Implant type and inflammation
43 of 82 (52.43%) IMZ implants showed no signs of inflammation, 19 (23.17%) suffered from mucositis and 20 (24.39%) from periimplantitis.
45 of 77(58.44%) ITI Straumann implants showed no signs of inflammation, 15 (19.48%) suffered from mucositis and 17 (22.07%) from periimplantitis.
26 of 41 (63.41%) Semados implants showed no signs on inflammation, 6 (14.63%) suffered from mucositis and 9 (21.95%) from periimplantitis.
All 4 Ankylos implants showed no signs of inflammation
2 of 4 (50%) of the Branemark implants showed no signs of inflammation, 2 suffered from mucositis.
3 of 5 (60%) of the Frialit implants showed no signs of inflammation, 2 suffered from mucositis.
All 3 Pitt easy implants showed no signs of inflammation.
Periimplantary status and duration of incorporation of implants
The examination duration was categorised in two groups: less than 4 years old and more than 4 years old.
In the group 4 years or younger a total of 81 implants were examined of which 52 (64.19%) showed no signs of inflammation, 15 (18.51%) suffering from mucositis and 14 (17.28%) from periimplantitis.
The group of 4 years and older a total of 138 implants were investigated of which 77 (55.79%) showed no signs of inflammation, 25 (18.11%) suffering from mucositis and 36 (26.08%) from periimplantitis (fig.4).
Concomitant disease
In the patients who had no accompanying general ailment, of the 135 implants examined 83 (61.48%) showed no signs of inflammation, 25 (18.52%) suffered from mucositis and 27 (20%) from periimplantitis.
In patients suffering from diabetes mellitus a total of 29 implants were examined of which 13 (44.83%) showed no signs of inflammation, 6 (20.69%) suffered from mucositis and 10 (34.48%) from periimplantitis.
In patients suffering from cardiovascular disease a total of 63 implants were examined of which 32 (50.79%) showed no signs of inflammation, 15 (23.81%) suffered from mucositis and 16 (25.39%) from periimplantitis (fig. 5).
Cigarette smoking and inflammation
A total of 23 patients admitted of being smokers, smoking on the average 19 cigarettes a day (pack a day smokers).
A total of 103 implants were examined of which 50 (48.54%) showed no signs of inflammation. In non-smokers 74 of 111 (66.66%) implants showed no signs of inflammation.
In smokers 25 (24.27%) implants suffered from mucositis, in comparison, in non-smokers 12 (10.81%).
In smokers 28 (27.18%) implants suffered from periimplantitis, in non-smokers 25 (22.52%).
Results of the Pado-test
The so called Pado-test utilises so called marker bacteria, which are characteristic for periodontal inflammation (fig. 6).
The first marker was Actinobacillus actinomycetemcomitans (Aa). In clinical healthy implants the average number of bacteria was 548, in implants with mucositis 2718 and in implants with periimplantitis 9647
The second marker was Bacteroides forsythus (Bf). In clinical healthy implants the average number of bacteria was 30424, in implants with mucositis 40514 and in implants with periimplantitis 162936.
The third marker was Porphyromonas gingivalis (Pg). In clinical healthy implants the average number of bacteria was 33245, in implants with mucositis 59487 and in implants with periimplantitis 130887.
The fourth marker was Treponema denticola (Td). In clinical healthy implants the average number of bacteria was 32318, in implants with mucositis 35332 and in implants with periimplantitis 129544.
Discussion:
Although a multitude of long term results concerning implants exist, very few have dealt with the incidence of periimplantitis. The incidence ranges from 0.8% [Buser et al. 1997] to 14% [Rutar et al. 2001]. The comparatively high value of 23% of this study is likely the result of the patient collective which was chosen for this evaluation. The low rates of incidence described by the swiss and scandinavian authors is likely the result of the successful recall program which is well established in these studies. Once minor signs of inflammation become apparent, immediately steps are taken to alleviate this problem.
It is well known that a poor oral hygiene is conducive for the development of periimplantitis and that the microbiological colonisation plays a decisive role (plaque theory) [Brandes et al. 1988]. Furthermore local as well as systemic factors can accelerate and promote this process. Biomechanical overloading as well as diabetes mellitus or cigarette smoking have also been identified as causative agents [Genco et al. 1990]. In our investigation we were able to verify using the Pado test, that the microflora typical for periodontal inflammation is increasingly present in the periimplantary pockets reflecting the similar aetiology as seen in periodontal disease.
With regards to patients who underwent reconstructive surgery involving bone transplantation, the aetiology and perpetuation of the inflammation seems to be affected by other factors as well. Close scrutiny of our patient collective revealed the following: Age- the majority of our patients were 45 years or older. Older patients' manual ability', i.e. handling of the tooth brush diminishes as they get older and thus have greater plaque accumulation on oral surfaces. Moreover, older patients are more likely to suffer from general ailments which often occur in the elderly like diabetes or diseases of the cardiovascular complex [Baltissen 1983]. Additionally, the rate of destruction, reflected in bone degeneration seems increased reflected in the increased levels of certain antibodies like IgA, IgM and C3 as well as other immune modulators (lactoferrin, lysocym, lactoperoxidase). The general wound healing seems compromised [Holm-Pedersen et al. 1971], the chemotaxis of the neutrohile granulocytes is reduced [Gale et al. 1983] and the plaques composition varies to that of young individuals [Holm-Pedersen et al. 1980].
Squamous cell carcinoma: The therapy of patients who suffered from this malignant entity promotes the development of periimplantary inflammation. These are: 1. Radiotherapy 2. Chemotherapy 3. Anatomic variations due to surgery 4. Recipient transplanted bone.
The radiotherapy leads to an early onset and late onset of tissue reactions [Ganstr?m et al. 1994]. The early tissue reactions influence especially the rapidly reproducing cells as seen in the oral mucosa. As a result the mucositis is a commonly seen sequelae of the radiotherapy. The late reactions are the typical radiotherapy induced fibrosis and demineralisation of osseous structures in conjunction with a decreased ability to ward off infection [Tjellstr?m et al. 1992]. It seems that the osteoblasts are extremely vulnerable to radiation and the histological examination of radiated bone reveals empty lacunae as a sign of their destruction [Granstr?m et al. 1993]. A well known side effect of the radiotherapy is also the xerostomia. The salivary production decreases markedly with the onset of the radiotherapy and the salivas viscosity changes becoming more viscous. This effect is not transient as the salivary glands are permanently damaged. Also the effect on the radiated bone is not of temporary nature, but rather the bone remains more prone to infection due to the decreased perfusion. These factors are conducive to the development of periimplantary inflammation.
The chemotherapeutic drugs also influence cells with a high turnover. Being a main pillar of the therapeutic schema of certain malignant transformations, this therapy alternative has led to an improved outcome of non-operable tumors in the head and neck region [Platz et al. 1985]. The cytotoxic effect is also observed in tissues with a high turnover, making the oral mucosa susceptible to the detrimental effects of this treatment. In some cases ulcers of the oral mucosa can be seen [Carl et al. 1991]. Contrary to the radiotherapy, this effect is not permanent and the oral mucosa can regain its vitality, recuperating with time.
Due to the extensive resections and subsequent reconstructions, the jaw or bone covering mucosal lining varies from the healthy one. Often no attached gingiva is present and the thickness of the mucosa exceeds that of healthy gums, predisposing the development of periodontal pockets or non-hygienic niches.
Also the type of bone transplantation seems to play a role for the prognosis of the implants. The vitality of the recipient bone is dependant on the nature of the transplantation i.e. if a revascularised flap or a free flap was used. The revascularised flap retains the perfusion of the bone at all times whereas in free flaps a decline or involution of the cells occurs and adsorbtion rates of up to 40% can be observed [Howald et al. 2002]. Additionally, not in all cases can the natural contours of the jaw bone be perfectly mimicked, resulting in anatomic variations with the above mentioned disadvantages.
Diabetes mellitus seems to play a decisive role in the likelihood of the implants to suffer from periimplantitis. The prevalence of this endocrine disorder is approximately 1% of the population. This disease is characterised by an absolute (type 1) or relative (type 2 or insulin resistance of the target organs) insulin deficiency. In the oral cavity this is associated with an increased likelihood and increased susceptibility of gingivitis and periodontitis by equal plaque accumulation as seen in healthy patients [Ringelberg et al. 1977, Cianciola et al. 1982]. This altered reaction can be associated to the impaired function of the polymorphic nuclear leucocytes as well as the micro- and macroangiopathia typical for diabetes [Keene 1975, Willershausen-Z?nnchen et al. 1988]. For sure the deleterious effects of this endocrine disorder influence various factors, terminating in an increased susceptibility to periodontitis and subsequently periimplantitis. As a result, especially in the care of patients suffering from diabetes type 1 (absolute insulin deficiency), special attention needs to be paid to the oral hygiene and the follow-ups with the general practitioner to ensure that normal glucose levels are maintained by these patients as a direct relationship between the glucose level and the susceptibility to infection seems to exist [Genco et al.1990]. Moreover, the secretion of saliva with a high glucose content fosters the development of plaque in the oral cavity [Tenovuo 1990].
In cigarette smokers an increased prevalence of periimplantary affections can be observed. Tobacco reduces the phagocytic response to periodontal pathogenic agents, reduces the perfusion of the tissue and delays wound healing [Kenney et al. 1977]. In periodontitis this is associated to an increased periodontal attachment loss [Preber et al. 1980]. Controlled transversal and longitudinal studies have verified that tobacco smoking leads to an increased bone loss, marked pocket development, attachment loss and calculus development by equal plaque levels as compared to non smoking individuals [Haber 1994]. Tobacco smoking seems to influence the unspecific and specific immune response and impairs the function of the neutrophile granulocytes [Milstam 1981, Bridges et al. 1990]. It is postulated that a reduction of certain cell metabolites, like ascorbic acid or secretory Ig A and IgG and a reduced number of T-helper cells promote periodontitis, i.e. periimplantitis [AAP (American academy of Periodontology) 1996]
In summarising, it must be assumed that the success of enossal implants in patients with segmental jaw reconstruction is dependant on various local as well as systemic factors. Nonetheless, the likelihood of developing a fulminate, irreversible periimplantitis can be kept low if certain behavioural patterns are abided by.
The systemic medical criteria, like the nature of the bone transplantation, the smoking habits, the patience compliance and the primary diagnosis are all factors which have significant bearing on the suitability of the patients for implantation as well as the long term success of the implants. A stringent recall scheme is eminently important for early detection and immediate treatment of periimplantary inflammation. This should include evaluation of the dental hygiene, the mucosal-, osseous and functional status, determined by indices like the plaque index, the bleeding index, pocket depth, radiological assessment and intermittently allotted microbiological testing. If this algorithm is followed, prosthetic rehabilitation with the help of dental implants in patients undergoing jaw reconstruction with bone transplantation is feasible and associated in a marked increase in the quality of life for the patients. If neglected the early success is deemed to terminate in a long term failure.
References:
Br?nemark PI, Albrektsson T. Titanium implants permanently penetrating human skin. Scand J Plast Reconstr Surg 1982;16:17-21.
Adell R, Lekholm U, Rockler B, Branemark PI. A 15-year study of osseointegrated implants in the treatment of the edentulous jaw. Int J Oral Surg 1981;10: 387-416.
Renk B. Probleme der epithetischen Versorgung von Gesichtsdefekten. ZM 1990; 80:590-594.
Adell R, Lekholm U, Grondahl K. Reconstruction of severly resorbed edentulous maxillae using osseointegrafixtures in immediate autogenous bone grafts. Int J Oral Maxillofac Imp 1990; 3:233-246.
Boyne PJ. Transplantation, implantation and grafts. Dent Clin North Am 1971;15:433-453.
Listagrten MA, Lang MP, Schr?der HI, Schr?der A. Periodontal tissue and their counterparts around endosseous implants. Clin Oral Impl Res 1991;2:1.
Lindhe J . Klinische Parodontologie und Implantologie. Berlin: Quintessenz, 1999:835-839.
Berglundh T, Lindhe J, Jonsson K, Ericsson I. The topography of the vascular systems in the periodontal and peri-implant tissues dog. J Clin Periodontol 1994; 21:189-193.
Gr?tz KA, Wahlmann UW, Krummenauer F, Wegener J, Al-Nawas B, Kuffner HD, Wagner W. Prognose und Prognosefaktoren enossaler Implantate im bestrahlten Kiefer. Mund Kiefer GesichtsChir 1999;3 (Suppl.):117-124.
Buser D, Mericske-Stern R, Bernard JP, Behneke N, Hirt HP, Belser U, Lang NP. Long-term evaluation of non-submerged ITI implants. Part1: 8-year life table analysis of a prospective multi-center study with 2359 implants. Clin Oral Imp Res 1997; 8:161-172.
Rutar A, Lang NP, Buser D,Bürgin W, Mombelli A. Retrospective assessment of clinical and microbiological factors affecting periimplant tissue conditions. Clin Oral Imp Res 2001;12:189-195.
Brandes R, Beamer B, Holt SC, Kornman K, Lang NP. Clinical-microscopic observation of ligature induced periimplantitis around osseo-integrated implants. J Dent Res 1988; 67:287.
Genco RJ, Wilson ME, De Nardin E. Periodontal complications and neutrophil abnormalities. In: Genco RJ, Goldman HM, Cohen DW (ed.): Contemporary Periodontics. C. Mosby, St. Louis 1990:203.
Baltissen R. Psychische und somatische Reaktionen auf affective visuelle Reize bei jungen und alten Personen. Diss. (Math.-Nat.-Fakult?t) Universit?t Düsseldorf 1983.
Holm-Pedersen P, L?e H .Wound healing in the gingiva of young and old individuals. Scand J Dent Res 1971;79:40.
Gale KM, Powell RN, Seymour GJ. The polymorphonuclear leukocyte chemotactic response to Bacteroides melaninogenicus. II. Effect of age and periodontal disease status. J Periodont Res 1983;18:126.
Holm-Pedersen P, Folke LEA, Gawronski T. Composition and metabolic activity of dental plaque from healthy young and elderly individuals. J Dent Res 1980;59:771.
Granstr?m G, Bergstr?m K, Tjellstr?m A, Br?nemark PI. A detailed analysis of implant losses in irradiated tissue/Ten years follow-up of implants lost in irradiated tissue. Int J Oral Maxillofac Impl 1994; 9:653-662.
Tjellstr?m A, Jansson K, Br?nemark PI. Craniofacial Defects in: (eds.) Worthington P, Br?nemark PI: Advanced Osseointegration Surgery. Chicago: Quintessence, 1992: 293-312.
Granstr?m G, Tjellstr?m A, Albrektsson T. Post-implantation irradiation on titanium implants for head and neck cancer treatment. Int J Oral Maxillofac Imp 1993;8:495-500.
Platz H, Hudec M. Aspekte der Biostatistik bei adjuvanten Chemotherapie-Studien. Dtsch. Zeitschrift Mund-Kiefer-Gesichtschirurgie 1985;9:292.
Carl W, Emrich LS. Management of oral mucositis during local radiation and systemic chemotherapy: a study of 98 patients. J Prosth Dent 1991;66:361-369.
Howaldt HP, Schmelzeisen R. Einführung in die Mund-, Kiefer-, Gesichtschirurgie München, Jena: Urban und Fischer, 2002:150.
Ringelberg ML, Dixon DO, Francis AO, Plummer RW. Comparison of gingival health and gingival crevicular fluid flow in children with and without diabetes. J Dent Res 1977; 56:108-111.
Ciancola LJ, Park BH, Bruck E. Prevalence of periodontal disease in insulin-dependent diabetes mellitus (juvenile diabetes). J Am Dent Assoc 1982;104:653-660.
Keene JJJR. Arteriosclerotic changes within diabetic oral vasculature. J Dent Res 1975;54: 77-82.
Willershausen-Z?nnchen B, Hamm G. Untersuchungen über den Einfluss des Diabetes mellitus (Typ 1) auf das Parodont. Dtsch Zahn?rztl Z 1988; 43:600.
Tenovuo J. Patients with locally and generally reduced host defence. J Clin Periodontol 1990;17:525.
Kenney E, Kraal JH, Saxe SR, Jones J. The Effect of cigarette smoke on human oral polymorphonuclear leukocytes. J Periodont Res 1977;12:227-234.
Preber H, Bergstrom J. Effect of cigarette smoking on periodontal healing following surgical therapy. J Clin Periodontol 1990;17(5):324-328.
Haber J. Smoking is a major risk factor for periodontitis. Curr Opin Periodontol 1994;2:12.
Milstam T. Uber die Auswirkungen des Zigaretten- und Tabakrauches auf die orale Hygiene, Plaqueentwicklung, Gingiva und Mundschleimhaut. Quintessenz 1981;31:301.
Bridges RB, Chow CK, Rehm SR. Micronutrient status and immune function in smokers. Ann NY Acad Sci 1990;587:218.
AAP: The research, science and therapy committee of the American academy of Periodontology. Position Paper: Tobacco use and the periodontal patient. J Periodontol 1996; 67:51. |
