Kpvsobm! Pg! Tupnbupmphz

CBMLBO! KPVSOBM! PG! TUPNBUPMPHZ

Pggjdjbm! qvcmjdbujpo! pg! uif! CBMLBO! TUPNBUPMPHJDBM! TPDJFUZ

! !Wpmvnf!24! !!!!!!!!!!!!!!!!Op!2! !!!!!!!!!!!!Nbsdi!!311:!

JTTO!2218!.!2252

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Editor-in-Chief Ljubomir TODOROVIĆ, DDS, MSc, PhD Faculty of Dentistry University of Belgrade Dr Subotića 8 11000 Belgrade Serbia

Editorial board ALBANIA ROMANIA Ruzhdie QAFMOLLA - Editor Address: Andrei ILIESCU - Editor Address: Emil KUVARATI Dental University Clinic Victor NAMIGEAN Faculty of Dentistry Besnik GAVAZI Tirana, Albania Cinel MALITA Calea Plevnei 19, sect. 1 70754 Bucuresti, Romania BOSNIA AND HERZEGOVINA Maida GANIBEGOVIĆ - Editor Address: Naida HADŽIABDIĆ Faculty of Dentistry SERBIA Mihael STANOJEVIĆ Bolnička 4a Vojislav LEKOVIĆ - Editor Address: 71000 Sarajevo, BIH Slavoljub ŽIVKOVIĆ Faculty of Dentistry BULGARIA Zoran STAJČIĆ Dr Subotića 8 Nikolai POPOV - Editor Address: 11000 Beograd, Serbia Nikola ATANASSOV Faculty of Dentistry Nikolai SHARKOV G. Sofiiski str. 1 TURKEY 1431 Sofia, Bulgaria Ender KAZAZOGLU - Editor Address: FYROM Pinar KURSOGLU Yeditepe University Julijana GJORGOVA - Editor Address: Arzu CIVELEK Faculty of Dentistry Ana STAVREVSKA Faculty of Dentistry Bagdat Cad. No 238 Ljuben GUGUČEVSKI Vodnjanska 17, Skopje Göztepe 81006 Republika Makedonija Istanbul, Turkey GREECE CYPRUS Anastasios MARKOPOULOS - Editor Address: George PANTELAS - Editor Address: Haralambos PETRIDIS Aristotle University Huseyn BIÇAK Gen. Hospital Nicosia Grigoris VENETIS Dental School Aikaterine KOSTEA No 10 Pallados St. Thessaloniki, Greece Nicosia, Cyprus

International Editorial (Advisory) Board Christoph HÄMMERLE - Switzerland George SANDOR - Canada Barrie Kenney - USA Ario SANTINI - Great Britain Predrag Charles LEKIC - Canada Riita SUURONEN - Finland

Kyösti OIKARINEN - Finland Michael WEINLAENDER - Austria

F J

T ! BALKAN STOMATOLOGICAL SOCIETY ! M B JD H MP UP TUPNB Council: Members: R. Qafmolla A. Adžić President: Prof. M. Vulović P. Kongo B. Rašović M. Ganibegović A. Vucur Past President: Prof. A. Iliescu S. Kostadinović A. Creanga President Elect: Prof. P. Koidis N. Sharkov D. Stamenković Vice President: Prof. H. Bostanci V. Mihovska M. Barjaktarević M. Carčev E. Kazazoglu Secretary General: Prof. L. Zouloumis A. Minovska M. Akkaya Treasurer: Dr. E. Hassapis A. Pissiotis G. Pantelas Editor-in-Chief: Prof. Lj.Todorović S. Dalambiras S. Solyali

The whole issue is available on-line at he web address of the BaSS (www.e-bass.org) CBMLBO! KPVSOBM! PG! TUPNBUPMPHZ

Pggjdjbm! qvcmjdbujpo! pg! uif! CBMLBO! TUPNBUPMPHJDBM! TPDJFUZ

! !Wpmvnf!24! !!!!!!!!!!!!!!!!Op!2! !!!!!!!!!!!!Nbsdi!!311:

JTTO!2218!.!2252

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

VOLUME 13 NUMBER 1 March 2009 PAGES 1-64

Contents

RP P. Papadopoulos Biphosphonates: A Concern for Dental Practice - 4 A. Kolokotronis A Review of the Literature 133 RP V. Boka Tooth Eruption: Topical and Systemic Factors that 11 A.K. Markopoulos Influence the Process A.K. Poulopoulos

RP M. Carević Combating Early Childhood Caries 15 M. Vulović M. Šindolić

OP Ç.E. Çubukçu Retention of Glass Ionomer Cement and 21 Resin-Based Fissure Sealant and Their Effect on Caries Outcome During Chemotherapy: A Pilot Study

OP P. Beltes Shear Bond Strength of 2 Root Canal Sealers to 26 M. Pashali Human Dentin N. Economides C. Gogos

OP K. Kodonas Intra-Tubular Reactions in Restored Human Teeth: 29 A SEM Study

OP H. Gedik Cleaning Efficiency of Alkaline Peroxide Type Denture Cleansers on 35 Y.K. Özkan Silicone-Based Soft Lining Materials Colonized With Candida Albicans

OP T. Koksal Effect of Shade and Thickness of Porcelain Veneers on 41 A. Civelek Depth of Cure of Light-Cured Resin-Based Luting Cement E. Kazazoglu M. Soyman

OP F.N. Pekiner Burning Mouth Syndrome in a Sample of Turkish Population 46 B. Gümrü S. Özbayrak Balk J Stom, Vol 13, 2009 3

CR G. Özcan A Useful Approach to a Combined Implant Application: 52 H. Develioglu Report of a Case after a 13-Year Assessment B. Kurtis D. Nalbant

CR K. Lyroudia Intraosseous Odontoma in the Maxilla and 56 G. Stephanopoulos Its Impact on Underlying Teeth. A Case Report

CR D. Mangoudi Rhino-Orbito-Cerebral Mucormycosis: 60 E. Bourlidou A Case Report and Review of the Literature G. Venetis V. Antoniadis

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Biphosphonates: A Concern for Dental Practice - A Review of the Literature

Petros Papadopoulos1, SUMMARY 2 Objectives: To review current knowledge of biphosphonates with respect Alexandros Kolokotronis to oral cavity pathology and dental procedures. The scope is the chemistry, 1Private Practice properties, chemical uses and recommendations that refer to biphosphonates 2Department of Oral Medicine and Maxillofacial and are of oral and maxillofacial interest. Pathology, Dental School, Aristotle University Thessaloniki, Greece Sources: “PUBmed” and e-articles searched electronically with key words biphosphonates, oral cavity, oral pathology and manifestations. Conclusions: Biphosphonates are analogues of pyrophosphate, com- prising of 2 phosphate groups linked by a phospho-ether bond. This particular structure is responsible for their resistance to hydrolysis and their great variation in biological and therapeutic background. There are nitrogen and non-nitrogen containing biphosphonates of 4 generation types: I, II, III and IV. Etidronate is the main representative of the first type and zoledronic acid, pamidronate and ibandronate are some of the newer ones. Biphosphonates act almost exclusively on bone in proximity to the osteoclasts. They aren’t metabolized and persist within the bone for long periods of time. The mechanisms that characterize their action are closely related to bone resorption and a decrease in bone turnover. Their action is explained on the basis of calcification, delay of the dissolution of calcium phosphate crystals, inhibition of formation and aggregation of calcium phosphate crystals. They are focused on the treatment of Paget’s disease, hypercalcemia, bone metastases and present an anti-osteolytic effect, counteract bone loss in chronic periodontitis or play an anti-neoplastic role. Osteonecrosis, avascular necrosis of the jaws, renal toxicity, fever, bone pain, hypocalcemia, mild gastrointestinal complains and jaw fracture after extraction can follow biphosphonate therapy. All these underline the need of certain preventive measures and recommendations. REVIEW PAPER (RP) Keywords: Bisphosphonates; Osteoclasts; Osteonecrosis; Prevention; Treatment Balk J Stom, 2009; 13:4-10

Introduction bone diseases that are able to put the success of dental procedures and not only. Biphosphonates have been known to chemists since the These facts designate the need of special refers to middle of the 19th century, when the first synthesis in 1865 the characteristics, properties of the medicine and their occurred in Germany1. Our knowledge of the biological correlation with bone diseases and dental practice. This is characteristics of biphosphonates dates back 30 years2. the goal of this review. They are a group of medication that have become increasingly and more widely used especially in the management of certain bone diseases, some of which are very common in our ageing population. However, Chemistry and Classification daily clinical practice and research reveal the existence of several side-effects of biphosphonates, as well as Biphosphonates are synthetic compounds, analogues an association between them and the implication or of pyrophosphate, an endogenous regulator of bone Balk J Stom, Vol 13, 2009 Dental Concern of the Use of Biphosphonates 5 mineralization. They are comprised of 2 phosphonate cells, cells of mononuclear phagocyte and immune system, groups linked by phospho-ether bonds (P-C-P structure). such as macrophages or tumour cells. This structure makes them resistant to hydrolysis in acid It is very important to mention that the 2 families conditions or by pyrophosphatases. The P-C-P structure of biphosphonates have different pathways of action. allows a great number of possible variations either Nitrogen containing ones act through the mevalonate by changing the 2 lateral chains on the carbon, or by pathway, but non-nitrogen containing biphosphonates, esterifying the phosphate groups; therefore, the biological such as etidronate, tiludronate and clodronate, are therapeutic and toxicological characteristics of different incorporated into phosphate chain of adenosine 3-5 generations of biphosphonate vary dramatically . triphosphate (ATP) containing compounds, so that they Currently there are 2 main types of biphosphonates: become non-hydrolysable. The new P-C-P containing ATP nitrogen-containing and non-nitrogen containing. According analogues inhibit cell function and lead to cell death by to evolution, literature classifies them in 4 generation types: apoptosis. I, II, III and IV. Etidronate is the main representative of the The cellular uptake of biphosphonates is mostly first, and zolendronic acid, pamidronate and ibandronate taking place in the cytosol, and the concentration are some of the newer ones. expressed in terms of cellular water can be several folds higher than in the medium. They have a very low bioavailability from a few % to Mechanism of Action 1% - mostly for the newer ones. This is explained by their low lipophilicity, which hampers trans-cellular transport Biphosphonates act almost exclusively on bone when and their negative change which hampers para-cellular administered because of specific affinity to it where they transport. The absorption in the intestine mainly follows a deposit in newly formed bone and in proximity to the para-cellular route11. osteoclasts. The administration of ethylene-diaminotetraacetic The half life of biphosphonates is quite short, ranging acid, a strong Ca chelator, favours the absorption of from 30 min to 2 hours. They are not metabolized and biphosphonates and increased doses of them will lead persist within bone for long periods of time6,7. They to an increase in their own absorption12. Once in the decrease both osteoclast activity and osteoclast numbers. blood, biphosphonates disappear very rapidly, mostly to The first is exemplified by internalization by osteoclasts bone13. This is due to the fact that they are characterized causing disruption of osteoclast mediated bone resorption, by a rapid and strong binding to hydroxyapatite crystals. the second by inhibiting osteoclast recruitment and Skeletal uptake might be determined above all by the apoptosis of them, thus reducing their number. The result is vascularization of the bone. bone resorption and a decrease in bone turnover. However, The various biphosphonates display some differences once incorporated into bone tissue biphosphonates persist in their affinity for the hydroxyapatite surface14. They for up to 10 years depending on the skeletal turnover time. were found to deposit under the osteoclasts besides those The mechanisms of action of these medicines are locations within the bone where new bone is formed15. The described on the basis of several processes. The most distribution of the amount deposited in bone formation important of these is calcification throughout which and resorption sites depends upon the amount of medicine biphosphonates inhibit the formation and aggregation of administered. Small quantities deposit mostly under the calcium phosphate crystals, block the transformation of osteoclasts while bigger ones go to both forming and amorphous calcium phosphate into hydroxyapatite, and resorption sites. Soft tissues on the other hand are exposed delay the aggregation of apatite crystals8-10. They delay to these compounds for only short periods, explaining the dissolution of calcium phosphate crystals and inhibit their bone specific effects and their low toxicity. However, the formation and aggregation of calcium oxalate crystals. Biphosphonates’ action is also taking place by bone some biphosphonates, especially pamidronate, can at resorption, which is performed by inhibition of mineral times deposit in other organs, such as stomach, liver and 16-18 dissolution, on tissue level by reduction in bone turnover, spleen . on cellular level by inhibition of osteoclast recruitment Once the biphosphonates are buried in the skeleton, and osteoclastic adhesion to mineralized matrix, and they will be released only when the bone is destroyed in by shortening of life span of osteoclasts and inhibition the course of the turnover. The skeletal half-life of various of their activity as well. On the molecular level, various biphosphonates is sometimes more than 10 years. They biphosphonates, especially clodranate, inhibit lysosomal aren’t metabolized in vivo due to the stability of their enzymes and prostaglandin synthesis; prostaglandins are P-C-P bond to heat and most chemical reagents, as well as involved in bone resorption. They can also have several their resistance to hydrolysis by the enzymes found in the effects through other cells, such as osteoblast lineage body. Biphosphonates are excreted renally19. 6 P. Papadopoulos, A. Kolokotronis Balk J Stom, Vol 13, 2009

Clinical Uses with important adverse effects including renal toxicity, fever, bone pain, hypocalcemia and mild gastrointestinal Biphosphonates appear to play a multifactorial role in complains26-30. In particular, the biphosphonate associated many kinds of clinical cases. One of the early clinical uses of osteonecrosis of the jaws is a subject that draws the biphosphonates was as bone scan imaging agent3. They are intense interest of the dental community. Osteonecrosis also used in the treatment of Paget’s disease, hypercalcemia is characterized by the death of bone that results as a (the result of excessive bone resorption and release of Ca natural consequence of a wide variety of systemic and into circulation) related to malignancy, in the management local factors compromising the blood flow of bone, such of bone metastases by reducing skeletal tumour burden in as haemoglobinopathies, anticardiolipin antibodies, patients with multiple myeloma and prostate cancer20. They defects of thrombotic and fibrinolytic systems, fat emboli, play an extinguished role - reduce the incidence of new alcoholism, systemic lupus erythematosus (SLE) 31-34, fractures in the management of osteoporosis characterized corticosteroid administration and recently, as proven, by abnormal rarefaction of bone, especially the third biphosphonate therapy. Bone exposure caused by generation biphosphonates (riserdronate) in postmenopausal osteonecrosis has particular sites of establishment on the women21. They have an anti-osteolytic effect by inhibition jaws: the posterior mandible in the molar area along the of osteoclastic action22. They can be applied to counteract mylohyoid ridge is the most common one, followed by the bone loss in chronic periodontitis23. Besides all these, they posterior maxilla. play an anti-neoplastic role by interacting with osteoclasts, The complication of exposed bone jaws associated osteoblasts, tumour cells, cytokine and growth factor with biphosphonate therapy (osteonecrosis/osteopetrosis) production, leading to the interruption of bone destruction; is explained by 2 theories. The leading theory suggests by immunomodulating properties on γδ T cells (activate that it is caused by cessation of bone remodelling and them), they have pre-apoptotic and anti-angiogenic bone turnover by the basic osteoclast inhibiting effect potentials - their use as radiation sensitizers. of the drugs when given to reduce loss of bone density in osteoporosis, or to prevent cancer spread in bone. Since the jaws have a greater blood supply than other bones, and a faster turnover rate related both to their Properties daily activity and the presence of teeth (which mandates daily bone remodelling around the periodontal ligament), The first is inhibition of calcification when given biphosphonates are highly concentrated in the jaws. at high doses and bone resorption24,25. Biphosphonates Coupled with chronic invasive dental diseases and impair the mineralization of normal calcified tissues, treatments and the thin mucosa over bone, this anatomic such as bone and cartilage and dentine, enamel and concentration of biphosphonates causes this condition to cementum2. In the latter case, their administration can be manifested exclusively in the jaws. Thus the exposed lead to a reduction of the extraction force. In addition bone in the jaws is the direct result of the action of the to it, they decrease bone loss or actually increase bone drugs on the daily remodelling and replenishment of bone. mineral density. At the cellular level, biphosphonates Osteoblasts and osteocytes live for only about 150 days. increase proliferation of osteoblasts and cartilage cells, If upon their death the mineral matrix is not resorbed biosynthesis of collagen and osteocalcin by bone cells, and by osteoclasts which release the cytokines of bone proteoglycans by cartilage cells. The effect on collagen morphogenetic protein and insulin-like growth factors may be due to impaired intracellular collagenolysis. It is to induce new osteoblasts from the stem cell population, very interesting to mention that bone that has been treated the osteon becomes acellular and necrotic. The small with biphosphonates is still able to show an anabolic capillaries within the bone become involuted and the bone response to intermittent parathyroid hormone although avascular. A spontaneous breakdown of the overlying the effect is blunted2. They also exhibit anti-angiogenic mucosa, injury or invasive surgery in the jaws, usually properties by depriving tumour cells of adequate cause this necrotic bone to expose. It then fails to heal. nutrient and blood supply. Biphosphonates alter the bone According to the competing theory (based only on microenvironment making it less favourable for tumour experimental evidence) biphosphonates, pamidronate and cell proliferation20. zoledronate, inhibit endothelial cell proliferation in the jaws thus leading to loss of blood vessels and avascular necrosis35,36. We must underline that osteonecrosis is actually a chemically induced form of osteopetrosis, Side-Effects an inherited autosomal dominant trait characterized by the loss of osteoclast development with 7 subtypes. In Biphosphonate therapy is presented by many osteopetrosis, as in biphosphonate induced exposed bone, scientists and case reports observations to be related angiogenesis in the soft tissues is normal. Balk J Stom, Vol 13, 2009 Dental Concern of the Use of Biphosphonates 7

Moreover, the comparison between osteonecrosis and drug of choice19. In case of penicillin allergy, combination osteoradionecrosis is useful for the differential diagnosis of of guinolones and metronidazole would be appropriate. the first. Unlike osteoradionecrosis (ORN), biphosphonate Before initiating biphosphonate therapy and for non associated osteonecrosis (BAO) doesn’t appear to be invasive dental care, biphosphonate therapy need not amenable to hyperbaric oxygen therapy. In ORN, radiation to be delayed. In case of invasive procedures, such as induced tissue damage is characterized by hypoxia, extractions, commencement of biphosphonate therapy hypocellularity and hypovascularity which are reversible should be delayed for a month to allow sufficient time or preventable to some degree with revascularization for home recovery and healing. Once the regimen of of bone. By contrast, in BAO the alteration in bone biphosphonate therapy has begun, surveillance schedule metabolism is such that revascularization alone is of once every 4 months is recommended40. insufficient to alter the course of the lesions because While receiving biphosphonate therapy, tooth biphosphonates are not metabolized appreciably and have extractions should be avoided as well as selective surgery the potential to remain in the bone indefinitely37,38. It has within the jaws, replaced by alternatives including root been reported that BAO is refractory to hyperbaric oxygen canal treatment and amputation of the crown. Patients therapy and advised against using hyperbaric oxygen in with dentures should have well maintained soft liners the treatment of these patients. to minimise trauma of the oral mucosa, or leave their A distinguished feature between the 2 situations dentures out. Pain control is important Fluoride and is coming out from the observation that the maxilla is possibly 0.12% chlorhexidine may be considered to commonly involved in BAO, whereas this is sighted rarely 26 in cases of ORN. It is critical to mention that BAO has decrease the possibility of tooth extraction . Placing 41 substantial clinical implications because many patients fail implants should be strictly avoided . to heal after dental surgical procedures, e.g. extraction. Osteonecrosis is often related to a site of previous dental treatment but can also occur in regions without it. Jaw pain is present, as well as an infection secondary to Treatment of Patients with bone exposure26. Extractions make the conditions worse Osteonecrosis/ Established Avascular with a non-healing socket sequestration, pain, offensive Necrosis of the Jaws smell, soft tissue infections and deformity3. The class of biphosphonates that is mostly related with osteonecrosis is Attempts to accomplish debridement, cover the the nitrogen-containing (zolendronate, pamidronate). exposed bone with flaps, or bone contouring procedures Besides osteonecrosis and exposed bone lesions, are being considered only in cases refractory to non- biphosphonate therapy is being associated with avascular surgical management, and in the face of continuing necrosis although our current knowledge of the related symptoms19. This model of therapy is suitable for process is limited, showing that these drugs are a direct avascular necrosis of the jaws being shown by table 1. factor in a multifactorial aetiology leading to avascular necrosis in the jaws. They are suggested to produce Bone grafting either as a free graft or by ischemic changes in the maxilla and mandible3. microvascular transfer involves affected bone. There is a Finally dental implant failure attributable to oral risk that there could be 2 problem areas, the donor graft biphosphonate therapy has been reported in patients with site as well as the recipient jaw site. Major resection 5 osteoporosis39. surgery should be avoided . In osteonecrosis, treatment should be directed towards eliminating or controlling pain, preventing progression of the exposed bone .The necrotic exposed Preventive Measures and bone itself is not painful and will remain structurally Recommendation sound to support normal jaw function. Once secondarily infected, it will become painful and may lead to cellulitis 42, 43 The whole description of the implications of the and fistula formation . Pathologic fractures do not biphosphonate therapy reflects the critical value of several usually occur unless debridement surgeries have reduced preventive measures and recommendations in order to the structural integrity of the mandible. avoid them. Generally, impacted teeth that are completely Therefore, aside from rounding off sharp bony covered by bone or soft tissue should be left undisturbed, projections that produce soft tissue inflammation, and a but those with an oral communication are recommended long term course of penicillin V-K 500 mg, 4 times a day, to be removed and given a month healing period. and 0.12% chlorhexidine44 is prescribed. Occasionally, Prophylactic antibiotic coverage for invasive dental severe cellulitis will warrant hospital care using IV procedures is necessary and thus penicillin remains the antibiotics (ampicillin). 8 P. Papadopoulos, A. Kolokotronis Balk J Stom, Vol 13, 2009

Table 1: Therapeutic management of the established avascular necrosis of the jaws

Ensure correct diagnosis

Cease biphosphonate if possible minimum 3 months before surgical intervention (it is possible that this time span is too short)

Antibiotics if secondary infection (penicillin, cephalosporin, clindamycin) Antiseptic mouth wash (e.g. Chlorhexidine gluconate) Cover with periodontal pack.

Localised surgical debridement without primary reconstruction

Minimal mucoperiosteal flap reflection to preserve the blood supply to underlying bone should be used

Resolution Non-Resolution

Alternatives to biphosphonate Surgical resection without primary therapy reconstruction

Conclusions pathologies, biphosphonates and dosage regiments. The most important question, however, is whether this is a Summarising the main points concerning cumulative problem. biphosphonates, on the basis of dental interest, we should Moreover, biphosphonate therapy has become a mention that they are used in the treatment of Paget’s standard of care for patients with malignant bone disease. disease, multiple myeloma and in chronic periodontitis by Preclinical and preliminary clinical data suggest that counteracting bone loss. However, it is critical to notice biphosphonates may prevent cancer-treatment induced that biphosphonate therapy needs to be stopped 6 months bone loss in patients with breast or prostate cancer before the attempt of any surgical or invasive method in receiving oestrogen/androgen therapies. In addition to it, the mouth, including tooth extraction, thus minimising the biphosphonates have demonstrated anti-tumour activity in danger of osteonecrosis. preclinical models and clinical evidence supports the fact There are many unknown facts regarding the process that biphosphonates may slow the progression of bone of biphosphonate related osteonecrosis of the jaws. The lesions or prevent bone metastases45. Therefore, trials to incidence is currently low, 0.1-1% of all patients on determine the anti-tumour effects of these drugs in patients biphosphonates, and may differ among different bone with early stage breast and prostate cancer, non-small Balk J Stom, Vol 13, 2009 Dental Concern of the Use of Biphosphonates 9 cell lung cancer and renal cell carcinoma will provide 16. Larsson A, Rohlin M. In vivo distribution of C-labelled important insight into the optimal timing and modality ethylene-1- hydroxy-1, 1-diphosphonate in normal and treated of biphosphonate therapy in those patient populations. young rats. An autoradiographic and ultrastructural study. The clinical applications of these medicines are likely Toxicology and Applied Pharmacology, 1980; 52:391-399. to expand further in oncology as these trials mature. 17. Wingen F, Schmahl D. Distribution of 3- amino-1- hydroxypropane-1, 1-diphosphonic acid in rats and This whole concept reveals a part of the new horizons in 45 effects on rat osteosarcoma. Arzneimittelforschung, 1985; biphosphonate therapy research . 35:1565-1571. 18. Monkkonen J, Koponen HM, Ylitalo P. Comparison of the distribution of three bisphosphonates in mice. Pharmacol Toxicol, 1990; 66:294-298. References 19. The Endocrine Society. Editorial Long-Term Safety of Biphosphonates. The Journal of Clinical Endocrinology & 1. Menschutkin M. Ueber die Einwirkung des Chloracetyls auf Metabolism, 2005; 90:1897-1899. phosphorige Saüre. Annals of Chemical Pharmaracology, 20. Melo DM, Obeid G. Osteonecrosis of the Maxilla in a 1865; 133:317-320. Patient with a History of Biphosphonate Therapy. J Can 2. Von Baeyer H, Hofmann KA. Acetodiphosphorige Saure. Dent Assoc, 2005; 71:111-1113. Berichte der Deutschen Chemischen Gesellschaft, 1897; 21. Woodward J, Coleman R, Holen I. Preclinical evidence for 30:973-1978. the effects of biphosphonates and cytotoxic drugs on tumour 3. Cheng A, Marrokokki A, Carter G, Stein B. The dental cell invasion. Anticancer Drugs, 2005; 16:11-19. implications of biphosphonates and bone disease. Australian 22. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Dental Journal - Medications Supplement, 2005; 50:4. Roodman GD, Mundy GR, Boyce BF. Bisphosphonates 4. Sparidans RW, Twiss IM, Talbot S. Biphosphonates in bone promote apoptosis in murine osteoclasts in vitro and in vivo. diseases. Pharmacology World Science, 1998; 20:206-213. Journal of Bone and Mineral Research, 1995; 10:1478-1487. 5. Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, 23. Figara G, Beninati F, Rubino I, Vannucchi A, Longo G, Monkkonen J, Frith JC. Cellular and molecular mechanisms Tonelli P, Pini Prato G. Osteonecrosis of the jaws in of action of biphosphonates. Journal of Cancer, 2000; periodontal patients with a history of biphosphonates 88:2961-2978. treatment. J Clin Periodont, 2005; 141:4793-4796. 6. Martin TJ, Grin V. Biphosphonates-mechanisms of action. 24. King WR, Francis MD, Michael WR. Effect of disodium Australian Prescriber, 2000; 23:130-132. ethane-1-hydroxy-1,1-biphosphonate on bone formation. 7. Carter GD, Goss AN. Letter to the editor. Biphosphonates Clinical Orthopaedics and Related Research, 1971; and avascular necrosis of the jaws. Aus Dent J, 2003; 78:251-270. 48:268. 25. Flora L, Hassing GS, Parfitt AM, Villanueva AR. 8. Francis MD, Russel RGG, Fleisch H. Biphosphonates Comparative skeletal effects of two biphosphonates in inhibit formation of calcium phosphate crystals in vitro and dogs. Metabolic Bone Disease & Related Research, 1980; pathological calcification in vivo. Journal of Science, 1969; 2:389-407. 165:1264-1266. 26. Bukowski JF, Dascher CC, Das H. Alternative biphosphonate 9. Hansen NM, Felix R, Bisaz S, Fleisch H. Aggregation of targets and mechanisms of action. Biochemical and hydroxyapatite crystals. Biochimica et Biophysica Acta, Biophysical Research Communications, 2005; 328:746-750. 1976; 451:549-559. 27. Pavlakis N, Schmidt R, Stockler M. Bisphosphonates 10. Francis MD. The inhibition of calcium hydroxyapatite for breast cancer. The Cochrane Database of Systematic crystal growth by polyphosphonates and polyphosphates. Reviews, 2005; CD003474 Calcified Tissue Research, 1969; 3:151-162. 28. Smetana S, Michlin A, Rosenman E, Biro A, Boaz M, Katzir 11. Boulenc X, Marti E, Joyeux H, Roques C, Berger Y, Fabre G. Z. Pamidronate-induced nephrotoxic tubular necrosis:a case Importance of the paracellular pathway for the transport of a report. Clinical Nephrology, 2004; 61:63-67. new biphosphonate using the human CACO-2 monolayers 29. Dicuonzo G, Vincenzi B, Santini D, Avvisati G, Rocci L, model. Biochemical Pharmacology, 1993; 46:1591-1600. Battistoni F, et al. Fever after zoledronic acid administration 12. Boulenc X, Roques C, Joyeux, Berger Y, Fabre G. is due to increase in TNF-alpha and IL-6. Journal of Biphosphonates increase tight junction permeability in the Interferon and Cytokine Research, 2003; 23:649-654. human intestinal epithelial (Caco-2) model. Int J Pharmacol, 30. Teramoto S, Matsuse T, Ouchi Y. Increased cytokines and 1995; 123:13-24. pamidronate-induced bone pain in adults with cystic fibrosis. 13. Fleisch H. Bisphosphonates: Mechanisms of action. Lancet, 1999; 353:750. Endocrine Reviews, 2006; 19:80-100. 31. Merigo E, Manfredi M, Meleti M, Corradi D, Vescovi P. 14. Bisaz S, Jung A, Fleisch H. Uptake by bone of Jaw bone necrosis without previous dental extractions pyrophosphate, biphosphonates and their technetium associated with the use of biphosphonates (pamidronate and derivatives. J Clin Sci Mol Med, 1978; 54:265-272. zoledronate): a four-case report. J Oral Pathol Med, 2005; 15. Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson 34:613-617. DD, et al. Biphosphonate action. Alendronate localization 32. Bouquot JE, McMahon RE. Neuropathic pain in in rat bone and effects on osteoclast ultrastructure. J Clin maxillofacial osteonecrosis. J Oral Maxillofac Surg, 2000; Invest, 1991; 88:2095-2105. 58:1003-1020. 10 P. Papadopoulos, A. Kolokotronis Balk J Stom, Vol 13, 2009

33. Assouline-Dayan Y,Chang C, Greenspan A, Shoenfeld 39. Ruggiero LS, Mehrotra B, Rosenberg JT, Engroff SL. Y, Gershwin ME. Pathogenesis and natural history of Osteonecrosis of the Jaws Associated with the Use of osteonecrosis. Seminars in Arthritis and Rheumatism, 2002; Biphosphonates: A Review of 63 Cases. J Oral Maxillofac 32:94-124. Surg, 2004; 62:527-534. 34. Gruppo R, Glueck CJ, McMahon RE, Bouquot J, 40. Schwartz HC. Osteonecrosis and biphosphonates: correlation Rabinovich BA, Becker A, et al. The pathophysiology of versus causation. J Oral Maxillofac Surg, 2004; 62:763-764. alveolar osteonecrosis of the jaw: anticardiolipin antibodies 41. Carter GD, Goss AN, Doecke C. Bisphosphonates and thrombophilia and hypofibrinolysis. J Lab Clin Med, 1996; avascular necrosis of the jaw: a possible association. Medical Journal of Australia, 2005; 182:413-415. 127:481-488. 42. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) 35. Zigic TM, Marcous C, Hungerford DS, Dansereau JV, induced avascular necrosis of the jaws: a growing epidemic. Stevens MB. Corticosteroid therapy associated with ischemic J Oral Maxillofac Surg, 2003; 61:1115-1117. necrosis of bone in systemic lupus erythematosis. Am J Med, 43. Migliorati CA. Biphosphonates and oral cavity avascular 1985; 79:596. bone necrosis. J Clin Oncol, 2003; 21:4253-4254. 36. Marx ER, Sawatari Y, Fortin M, Broumand V. 44. Dimitrakopoulos I, Magopoulos C, Karakasis D. Biphosphonate-induced exposed bone (Osteonecrosis/ Biphosphonates-induced avascular osteonecrosis of the Osteopetrosis) of the jaws: Risk factors, recognition, jaws: a clinical report of 11 cases. J Oral Maxillofac Surg, prevention and treatment. J Oral Maxillofac Surg, 2005; 2006; 35:588-593. 63:1567-1575. 45. Lipton A. Towards New Horizons. The Future of 37. Melo DM, Obeid G. Osteonecrosis of the jaws in patients Biphosphonate Therapy. The Oncologist, 2004; 9:38-47. with a history of receiving biphosphonate therapy. Strategies for prevention and early recognition. J Am Dent Assoc, 2005; 136:1675-1681. Correspondence and request for offprints to: 38. Russel RG, Rogers MJ, Frith JC, Luckman SP, Coxon FP, Petros Papadopoulos Benford HL, et al. The pharmacology of biphosphonates and 542 48, Thessaloniki new insights into their mechanisms of action. J Bone Miner Greece Res, 1999; 14:53-65. E-mail: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Tooth Eruption: Topical and Systemic Factors that Influence the Process

SUMMARY Vasiliki Boka, Anastasios K. Markopoulos, Several topical and systemic factors have been reported to influence Athanassios K. Poulopoulos the eruption of teeth. Some of the local lesions include eruption cysts, erup- Aristotle University, School of Dentistry tion sequestra, fibrous developmental malformations and dentigerous cysts. Department of Oral Medicine & The systemic factors include Down’s syndrome, cleidocranial dysostosis, Maxillofacial Pathology Thessaloniki, Greece hypothyroidism, hypopituitarism and achondroplastic dwarfism. All these lesions and factors generally influence the eruption of the primary, as well as the permanent dentition. The purpose of this review article is to present up-to-date aspects of these conditions. Keywords: Eruption cysts; Dentigerous Cysts; Down’s Syndrome; Cleidocranial REVIEW PAPER (RP) Dysostosis; Hypothyroidism; Hypopituitarism; Dwarfism, achondroplastic Balk J Stom, 2009; 13:11-14

Introduction erupting tooth. They are considered soft tissue analogues of the dentigerous cysts. Lately, eruption cysts are Numerous studies have been performed to understand described as a possible adverse effect of cyclosporine-A the process of tooth eruption better. The most common (CyA) administration during tooth eruption4. general symptoms during tooth eruption include anxiety There is a gender predilection; the male to female (15%), diarrhea (13%), a combination of the two (8%), ratio is 2:15,6. They usually appear in the region of fever1 and increased salivation2. Apart from general the molars7. Eruption cysts clinically appear as soft symptoms that end up to normal eruption of the teeth, translucent swelling in the gingival mucosa. Their colour several local and systemic factors have been reported varies between deep blue and azure7. to influence the eruption of teeth. The exact nature of Surface trauma may result in a considerable amount of the factors responsible for tooth eruption is not fully blood in the cystic fluid. Such lesions are sometimes referred understood. It is believed that these factors influence the as eruption haematomas. Their basic clinical characteristics matrix formation and the calcification process. are swelling, fluctuation and deep blue colour6. Pain may The most important local conditions that influence appear only if the cyst is traumatized7. Histologically, they tooth eruption are: eruption cysts, eruption sequestra, are characterized by non-keratinized, squamous epithelium fibrous developmental malformations and dentigerous lining in the cystic wall7. Differential diagnosis includes cysts. Systemic factors include Down’s syndrome, haematoma, amalgam tattoo, cysts and haemangioma8,9. cleidocranial dysostosis, hypothyroidism, hypopituitarism The treatment of the eruption cysts is surgical and and achondroplastic dwarfism. includes the excision of tissues over the crowns of the The purpose of this review article is to present the responsible teeth. In most cases, even this treatment is current aspects of these conditions. not necessary, because the cysts rupture and never appear again3.

Eruption Cysts Eruption Sequestrum Eruption cysts occur within the mucosa overlying a tooth that is about to erupt3. They develop as a result of The eruption sequestrum usually appears during the separation of the dental follicle from around a crown of an eruption of the first permanent molars. Intraorally, the 12 V. Boka et al. Balk J Stom, Vol 13, 2009 lesions presents as a small hard tissue fragment, white in Inflammatory Dentigerous Cysts colour, and with bone-like hardness on the occlusal surface of the mandibular second molar that was erupting10. Inflammatory dentigerous cysts are the most common Histopathologically, the fragments consist of necrotized type of developmental odontogenic cysts and mostly they cortical bone11. Studies involving X-ray micro-analyzer are found in the mixed dentition24. They are usually single revealed that the percentages of calcium and phosphorous and they are located in the posterior mandible25. They (by weight) were 78.41% and 21.59%, respectively, with are associated with the roots of non-vital deciduous teeth a calcium to phosphorous ratio of 3.63, which was higher and the crown of their unerupted permanent successors26. than that seen in normal osseous tissue11. Generally, the The cysts are not painful except in the case of secondary sequestra have little clinical significance as they can appear infection, or unless their size has created a pathological and disappear. However, they may retain plaque in close fracture24. association with the newly erupting tooth12. The retained There are 2 leading theories about the formation 24 eruption sequestrum may lead to pericoronitis or pit and of dentigerous cysts . The first begins with fluid fissure caries13. In dental practice the presence of multiple accumulation between the reduced enamel epithelium developmental dental anomalies expressing simultaneous and the crown of the tooth. The other theory begins with defects in different stages of tooth development should a breakdown of the stellate reticulum, which forms a fluid between the inner and outer enamel epithelium. raise suspicion of possible manifestation of an underlying Radiographically, the tooth may be displaced: it is systemic abnormality, such as Ehlers-Danlos syndrome14. not surprising to see teeth displaced to the condylar neck, Treatment is not always necessary. Surgical removal the nasal floor or high in the maxillary sinus approaching is usually chosen only if it is usually traumatized or the orbit24. Histologically, they are composed of a thin annoys the patient2. connective tissue wall lining the lumen. The epithelium is usually parakeratinized or orthokeratinized. Rete peg formation is usually absent and an inflammatory cell infiltration of the connective tissue is common. In about Fibrous Developmental 50% of cases, dentigerous cysts can cause resorption of Malformation the adjacent unerupted teeth. Treatment of choice is the extraction of the infected In most cases, fibrous developmental malformation deciduous tooth and continuous drainage of the cyst27. manifests as enlargement of the gingiva, often correlated Simultaneous with the eruption of the permanent with the eruption of deciduous or permanent teeth15. tooth, ossification of the bony defect can take place28. Gingival fibromatosis may be familial or idiopathic. The reparatory process is completed in 1-2 years26. The familial variations may occur as isolated finding Marsupialization is less ideal; it runs the risk of allowing an 24,29 or in association with hereditary syndromes, such as ameloblastoma in situ . This treatment is indicated only Zimmermann-Laband syndrome, Rutherford syndrome or in 2 situations: (1) if it will allow a tooth to spontaneously multiple hamartomas. erupt or to be orthodontically guided into a functional Tagaki et al16 described 6 categories of fibrous position in the arch; or (2) if the surgeon identifies a developmental malformation; (1) isolated familial gingival realistic risk of damaging developing teeth or neurovascular bundles during the enucleation24. fibromatosis; (2) isolated idiopathic gingival fibromatosis; (3) gingival fibromatosis associated with hypertrichosis; (4) gingival fibromatosis associated with hypertrichosis and mental retardation, or epilepsy, or both; (5) gingival Down’s Syndrome fibromatosis associated with mental retardation, or epilepsy, or both; (6) gingival fibromatosis associated with Down’s syndrome (trisomy 21) is one of the hereditary syndromes. congenital pathologic conditions in which delayed eruption In most cases the enlargement begins before the age of the teeth is frequently observed. Various studies in of 20. The gingiva is firm, normal in colour and covered children with Down’s syndrome have shown that delayed 17-21 by a smooth surface . Histopathologically, fibrous tooth eruption is common, but sporadic30,31. The eruption developmental malformations consist of poorly cellular, usually follows an abnormal sequence and some of the richly collagenous fibrous connective tissue underneath deciduous teeth may be retained until the age of 15 years. a normal or acanthotic epithelium. Mild peri-vascular The eruption abnormalities are associated with retardation chronic inflammation and small foci of dystrophic in the growth of maxilla and mandible. A reduction of the calcification may be observed22. anterior skull base and protrusion of lower incisors is often Treatment is required only if the lesion annoys the observed, which is related to a tendency to anterior cross- patient. Surgical removal is the treatment of choice23. bite and, to a lesser extent, to diminished overbite32. Balk J Stom, Vol 13, 2009 Factors that Influence Tooth Eruption 13

Cleidocranial Dysplasia often results in hypopituitarism. The dental findings of the syndrome include delayed eruption of the teeth. Cleidocranial dysplasia is a hereditary disorder Hutchinson-Gilford disease or progery is caused by characterized by abnormal clavicles, delayed fusion of anterior pituitary lobe malfunction. Delayed eruption of the bones in the skull, extra teeth and short stature. Other the teeth is also included in the clinical findings of this bones, such as the ribs, pelvis and bones of the hands and disease. feet may also be affected. Most patients with cleidocranial dysplasia do not have significant physical or mental disability33. The development of the dentition is delayed and may Achondroplastic Dwarfism reach the age of 15 years. Oral radiographs usually show Achondroplastic dwarfism is the most common many unerupted and supernumerary permanent teeth. type of dwarfism and is clinically manifested with a Even after extraction of the deciduous or supernumerary characteristic appearance. There are short muscular tooth, eruption of the permanent dentition may be delayed extremities, brachycephalus, and bowed legs. The oral without the proper orthodontic intervention34. manifestations include retruded maxilla, disparity in the size of the jaws resulting in malocclusion, and delayed eruption of the teeth38. Hypothyroidism

Undetected and untreated congenital hypothyroidism References is a rare condition that leads to mental deficiency and dwarfism. This pathologic entity is known as cretinism. 1. Peretz B, Ram D, Hermida L, Otero MM. Systemic The head of these patients is disproportionately large. manifestations during eruption of primary teeth in infants. J They are obese and their extremities are abnormally Dent Child, 2003; 70:170-173. short. The dentition of the child with cretinism is delayed 2. Mc Donald RE, Avery DR. Dentistry for the child and th in all stages, including the primary and the permanent adolescent. 7 ed. St Louis: Mosby, 2000; pp 162-163, dentition. Due to the small size of the jaws teeth are 186-187. 3. Kramer IR, Pindborg JJ, Shear M. The World Health usually crowded. The tongue is large and often causes Organization histological typing of odontogenic tumours. anterior open bite and malocclusion. Delayed eruption of Introducing the second edition. Eur J Cancer Oral the permanent dentition may also be observed in juvenile Oncology, 1993; 29:169-171. hypothyroidism (acquired hypothyroidism), which usually 4. Kuczek A, Beikler T, Herbst H, Flemming TF. Eruption cyst occurs between 6 and 12 years of age. Because juvenile formation associated with cyclosporin A: a case report. J hypothyroidisms appears after the period of rapid growth, Clin Periodontol, 2003; 30:462-466. its orofacial manifestations are more mild compared to 5. Boj JR, Poirier C, Espasa E, Hernandez M, Jacobson B. 35 Eruption cyst treated with a laser powered hydrokinetic congenital hypothyroidism . system. J Clin Pediatr Dent, 2006; 30:199-202. 6. Bodner L, Goldstein J, Sarnat H. Eruption cysts: a clinical report of 24 new cases. J Clin Pediatr Dent, 2004; 28:183-186. Hypopituitarism 7. Aguilo L, Cibrian R, Bagan IV, et al. Eruption cysts: retrospective clinical study of 36 cases. ASDC J Dent Child, Hypopituarism in children leads to nanism. 1998; 65:102-106. Characteristic orofacial features are the maldevelopment 8. Chiang ML, Huang WH. Odontogenic keratocyst clinically mimicking an eruption cyst: report of a case. J Oral Pathol of the face, the defective development of jaws and the Med, 2004; 33:373-375. delayed eruption of teeth. Cases of long delays of the 9. Nunn JH. Eruption problems: a cautionary tale. J Dent absorption of primary teeth roots have been reported, Child, 1993; 60:207–209. which results in the delay of permanent teeth eruption36. 10. Priddy RW, Price C. The so-called eruption sequestrum. This delay usually lasts 1-3 months for the teeth that erupt Oral Surg Oral Med Oral Pathol, 1984; 58:321-326. during the first decade, and 3 to 10 years for the teeth that 11. Maki K, Ansai T, Nishida I, et al. Eruption sequestrum: x-ray erupt during the second decade of life. Another frequent microanalysis and microscopic findings. J Clin Pediatr Dent, 2005; 29:245-247. finding is the absence of germs of the third mandibular 12. Ho KH. Eruption sequestrum. Ann Acad Med Singapore, 37 molars . 1986; 15:454-455. Frohlich’s syndrome, or lipogenetic dystrophy, is 13. Schuler JL, Camm JH,Houston GH. Bilateral eruption usually caused by neoplasms of the pituitary region and sequestra: report of case. ASDC J Dent Child, 1992; 59:70-72. 14 V. Boka et al. Balk J Stom, Vol 13, 2009

14. Yassin OM, Rihani FB. Multiple developmental dental 29. Kavadia-Tsatala S, Tsalikis L, Kaklamanos EG, Sidiropoulou anomalies and hypermobility type Ehlers-Danlos syndrome. S, Antoniades K. Orthodontic and periodontal considerations J Clin Pediatr Dent, 2006; 30:337-341. in managing teeth exhibiting significant delay in eruption. 15. Kavvadia K, Pepelassi E, Alexandridis C, et al. Gingival World J Orthod, 2004; 5:224-229. fibromatosis and significant tooth eruption delay in an 30. Jara L, Ondarza A, Blanco R, Valenzuela C. The sequence 11-year-old male: a 30-month follow-up. Int J Pediatr Dent, of eruption of the permanent dentition in a Chilean sample 2005; 15:294-302. with Down’s syndrome. Arch Oral Biol, 1993; 38:85-89. 16. Takagi M, Yamamoto H, Mega H, et al. Heterogeneity in the 31. Ondarza A, Jara L, Munoz P, Blanco R. Sequence of gingival fibromatoses. Cancer, 1991; 68:2202-2209. eruption of deciduous dentition in a Chilean sample with 17. Bakaeen G, Scully C. Hereditary gingival fibromatosis in a family with Zimermann- Laband syndrome. J Oral Pathol Down’s syndrome. Arch Oral Biol, 1997; 42:401-406. Med, 1991; 20:457-459. 32. Quintanilla JS, Biedma BM, Rodriguez MQ, et al. 18. Coletta RD, Graner E. Hereditary gingival fibromatosis: a Cephalometrics in children with Down’s syndrome. Pediatr systematic review. J Periodontol, 2006; 77:753-764. Radiol, 2002; 32:635-643. 19. Lata J, Singh R. Idiopathic gingival fibromatosis. A case 33. Gorlin RJ, Cohen MM, Levin LS. Cleidocranial dysplasia. report. Indian J Dent Res, 2003; 14:234-237. In: Syndromes of the Head and Neck. 3rd ed. New York: 20. Jorgensson RJ, Cocker ME. Variations in inheritance and Oxford Press, 1990; pp 249-253. expression of gingival fibromatosis. J Periodontol, 1974; 34. Trimble LD, West RA, McNeil RW. Cleidocranial dysplasia: 45:472-476. Comprehensive treatment of the dentofacial abnormalities. J 21. Denloye O, Bankole OO, Aderinokun GA. Teething myths Am Dent Assoc, 1982; 105:661-666. among community health officers. Odontostomatol Trop, 35. Scully C, Cawson RA. Medical problems in Dentistry. 4th ed. 2005; 28:19-22. Oxford: Wright, 1998; pp 277-280. 22. Gunhan O, Gardner DG, Bostanci H, et al. Familial gingival 36. Kosowicz J, Rzymski K. Abnormalities of tooth development fibromatosis with unusual histologic findings. J Periodontol, in pituitary dwarfism. Oral Surg Oral Med Oral Pathol, 1995; 66:1008-1011. 23. Odessey EA, Cohn AB, Casper F, Schechter LS. Hereditary 1977; 44:853-863. gingival fibromatosis: aggressive 2-stage surgical resection in 37. Sarnat H, Kaplan I, Pertzelan A, et al. Comparison of dental lieu of traditional therapy. Ann Plast Surg, 2006; 57:557-560. findings in patients with isolated growth hormone deficiency 24. Delbem AC, Cunha RF, Afonso RL, Bianco KG, Idem AP. treated with human growth hormone (hGH) and in untreated Dentigerous cysts in primary dentition: report of 2 cases. patients with Laron-type dwarfism. Oral Surg Oral Med Pediatr Dent, 2006; 28:269-272. Oral Pathol, 1988; 66:581-586. 25. Kozelj V, Sotosek B. Inflammatory dentigerous cysts of 38. Collins WO, Choi SS. Otolaryngologic manifestations of children treated by tooth extraction and decompression- achondroplasia. Arch Otolaryngol Head Neck Surg, 2007; report of four cases. Br Dent J, 1999; 187:11. 133:237-244. 26. Slater LJ. Dentigerous cyst versus paradental cyst versus eruption pocket cyst. J Oral Maxillofac Surg, 2003; 61:149. 27. Naclerio H, Simoes WA, Zindel D, Chilvarquer I, Aparecida TA. Dentigerous cyst associated with an upper permanent Correspondence and request for offprints to: central incisor: case report and literature review. J Clin Dr. A. Markopoulos Pediatr Dent, 2002; 26:187-192. Dept. of Oral Medicine and Maxillofacial Pathology 28. Ertas U, Yavuz MS. Interesting eruption of 4 teeth School of Dentistry, Aristotle University associated with a large dentigerous cyst in mandible by only 54006 Thessaloniki, Greece marsupiulization. J Oral Maxillofac Surg, 2003; 61:728-730. E-mail: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Integrated Approach in Combating Early Childhood Caries

SUMMARY M. Carević, M. Vulović , M. Šindolić Early childhood caries (ECC), as the most common oral disease occur- University of Belgrade, Faculty of Dentistry ring in infants and pre-school children, is steel very frequent in most Balkan Clinic of Paedodontics and Preventive Dentistry countries. The reason for this is existing old fashion attempt to control it by Belgrade, Serbia early diagnosing, preventing its further development by secondary prevention, treatment with expensive curative measures without significant success, what leads to conclusion that ECC is a hopeless dental problem. Identification and elimination of caries risk factors before dental treatment is essential for successful caries management. Caries control measures must be establish as a first step towards caries suppression, which will cause long-term chan ges in the surrounding oral environment, with the aim of altering it from being cariogenic to non-cariogenic. Failing to do so, all restorative works done in cariogenic oral environment will stay for a very short period. In clinical management of caries, the dentist’s role consists in seeking the cause, correcting bad habits or deficiency states they may be contributing factors, restoring the teeth, and finally, making use of all available preventive and control measures. Therefore, a successful management of the ECC problem demands integrated approach of preventive and restorative measures, such as carefully completed dental and medical history, the use of currently accepted diagnostic aids, application of sound principles of restorative dentistry, a comprehensive preventive programme, and regular recall appointments for maintenance work and reemphasis of the preventive procedures. REVIEW PAPER (RP) Keywords: Early Childhood Caries; Prevention; Rehabilitation Balk J Stom, 2009; 13:15-20

Introduction of any primary tooth; (2) Severe ECC is stratified by age and described for each year to age of 6. Criteria for Early childhood caries (ECC) is a special form of definition of severe ECC are: (a) for children up to 3 years rampant tooth decay that affects primary dentition in old - present lesion on any smooth surface; (b) for children infants, toddlers and pre-school children. This type of from 3 to 6 years old - caries lesions and cavities on upper caries has an early onset (evident in children ≤ 1-year- frontal teeth, extracted or filled teeth, dmfs = 4 for age 3, old) and is initially located on the smooth surfaces of dmfs = 5 for age 4, dmfs = 6 for age 5, respectively. At primary teeth, followed by a very fast progression. First the workshop that was organized by National Institute signs of ECC are in the form of white-spot lesions on of Dental and Craniofacial Research (NIDCR) in 1999, anterior primary teeth, leading quickly to complete tooth following 4 different ECC patterns were suggested: (1) destruction, pulp involvement, infections, thus impairing caries lesion on any surface of maxillary incisors (Fig. 2a); overall child’s health (Fig. 1)15,16. (2) caries lesion on occlusal surface of the first molars; (3) In direct relation to age and primary teeth eruption caries lesions in pits and fissures of the second molars, chronology, different patterns of ECC were observed. 2 on maxillary lingual and mandibular vestibular surfaces, main categories of caries are recognized in children from respectively (Fig. 2b); (4) caries lesions on smooth birth to age 6: (1) ECC is caries on at least one surface surfaces of other primary teeth 1,2. 16 M. Carević et al. Balk J Stom, Vol 13, 2009

ECC can cause serious problems concerning oral and general health (Fig. 3), such as infections, abscesses, pain, fear, sleeplessness, chewing and eating difficulty, malnutrition, gastrointestinal disorders and other, which can lead to failure to thrive, delay in proper development, malocclusion, poor aesthetics and speech articulation, ab caries in the permanent dentition, thus affecting child’s Figure 1. (a) First signs of ECC; (b) Complete teeth destruction by ECC quality of life12-14,34. Despite the recent improvements in the oral health of children, ECC remains to be the most common oral disease in toddlers and pre-school children, presenting a serious challenge to child’s wellbeing. Estimated prevalence in developed countries ranges from 18-25% of children 2-6 year olds, while in some ethnic groups prevalence is as high as 40-45%. (California Department of Health ab Services, 1995). However, in developing countries and in disadvantaged groups within developed countries, Figure 2. (a). Caries lesions on maxillary incisors; (b) Caries lesions on the prevalence could be as high as 70%1,10. The reason molar surfaces for this is the existing approach to control the disease by early diagnosing (absence of widely accepted standards), preventing its progression by secondary prevention, Earlier attempts to identify causes of ECC were treatment with expensive curative measures which may based on limited number of variables, predominantly on lead to the conclusion that ECC is a never ending dental nutritional and biological factors. Such research approach problem12,25,26,34. resulted with prediction models high in sensitivity, but For many centuries dental decay has been the low in specificity. It became obvious that it is mandatory number one problem in dentistry because dentists have to take into account interaction of nutritional, biological, been treating just the consequences of the disease. The cultural, social and environmental factors for better tendency has been ever since to treat these patients understanding caries risk and caries development in as one’s that have mechanical dental problems. They infants and toddlers7,17-19. therefore had a false belief that restored teeth are equal to ECC is also known as baby bottle tooth decay, good dental health12,27. nursing bottle caries, milk bottle syndrome, melanodontia, Dental caries today is considered to be the result of a molted teeth and etc. Since ECC is considered as a disturbance in the ecologic balance of the oral cavity. This multifactor infectious disease with behavioural, systemic balance is resembled by aggressive (demineralization) and social component, the term early childhood caries was factors and defensive (re-mineralizing) factors. If and adopted lately to emphasize the complexity of etiological when factors that promote demineralization prevail, the balance will shift in favour of enamel demineralization factors associated with this disease12,20,34. and the formation of caries lesion12,15,29. Etiological factors contributing to the occurrence Therefore successful management of ECC must of ECC are found to bee parental lack of information be accomplished by integrated (joint) approach and regarding the disease, forwarding poor habits to the implementation of the following procedures: child, inappropriate feeding practices, poor oral hygiene, 1. Conditioning (re-modification) of oral environment inadequate fluoride intake, maternal caries status, (primary prevention); socioeconomic status and genetics7,4,18,21-24. 2. Caries treatment (secondary prevention); 3. Rehabilitation (tertiary prevention); 4. Maintenance of achieved oral health.

Conditioning of Oral Environment (Primary Prevention)

ab Caries control measures must be establish as a first step towards caries reduction, which will cause long- Figure 3. ECC can cause serious problems term changes in the oral environment, with the aim Balk J Stom, Vol 13, 2009 Early Childhood Caries 17 of transforming it from cariogenic to non-cariogenic. also give us information about motivation and behavioural Failing to achieve this, the restorative work done in habits of the child and family to follow recommendations cariogenic oral environment will have a short-term effect. for oral health care. Collectively, identification and elimination of all (risk) Caries prevalence can be estimated by noticing: factors prior to dental treatment is essential for successful number of teeth missing, number of fillings, and number caries management. of cavities, incipient lesions or deep tissue lesions. Aggravating factors can be checked by noticing: Identification of factors that caused the disease crowded teeth, deep fissures, overhangs, enamel or Taking into consideration that etiological factors dentin disturbances (hypocalcification - local, systemic of oral diseases are relatively well known today, or hereditary disturbance), and acquired tooth defects identification of factors that can cause the disease must be (abrasion, erosions). made and actions has to be taken in order to neutralize risk Assessing presence of factors ultimately involved in that can cause problems in future. the caries process Caries risk for dental caries can be diagnosed and - Oral hygiene effective measures offered to prevent or reduce the - Saliva factors prevalence. At this point, we are able of identifying patient’s level of risk for cavities and utilize specific C. Caries “Chair Side Tests” for Some Selected Factors treatment options to prevent caries from occurring and Available “chair side tests” for identification of caries progressing. To accomplish this task information that we risk factors are: plaque accumulation rate test, salivary need can be obtained by: flow rate test, salivary buffer capacity test, Mutans a. Case history; streptococci level test, and Lactobacilli level test. b. Clinical investigation; Plaque accumulation rate test (Fig. 4) is based on the c. “Caries risk tests”. amount of plaque which deposits within 24 hours after professional tooth cleaning. For estimation of plaque A. Case History accumulation rate, the simplified “OHI debris index” By interviewing the patient, we are trying to find out according to Green and Vermillion can be used. factors that may influence the disease. Such factors usually belong to one or more of the following groups: - General information about diseases (beside general information about the present oral disease, attention must be focused on existence of general diseases as well. Several diseases may directly or indirectly influence oral diseases, ether through affecting saliva properties, dietary ab patterns or by use of various medicines); - Oral hygiene (good or bad); Figure 4. Plaque accumulation - Use of fluorides (yes or no); Salivary flow rate test is a natural first step in - Dietary habits (it is well known that in making up obtaining a general information of saliva factors. It can the “risk profile” of the patient, diet and dietary habits be disturbed by: medication, radiation therapy, salivary are of great importance. Information about the diet of the stone or other local factors, anorexia nervosa, diabetes patient can bi obtained by the “interview method”, the mellitus etc. “three-day record” and by presence of bad feeding/eating Salivary buffer capacity test is giving us a general habits); idea about the quality or ability of saliva to control pH - Drug use (frequent use of sweet medication against of the oral environment in physiological borders. It can be certain diseases in early childhood could contribute ECC measured by “Dentobuff” kit (Fig. 5). formation); - Socio-economic background (the common finding is that families from a lower socio-economic background may experience lack of understanding regarding oral hygiene, increased consumption of high cariogenic diet, vertical transmission of cariogenic bacteria to their children and difficulties in getting proper dental health services).

B. Clinical Findings ab The aim of clinical findings is to get a proper information about severity of the caries problem. It can Figure 5. Salivary buffer capacity test -“Dentobuff” 18 M. Carević et al. Balk J Stom, Vol 13, 2009

High count of Mutans streptococci in saliva indicates Professional tooth-cleaning means removal of all high risk for caries formation. This levels can be recorded supragingival and clinically visible hard and soft coatings by Mutans streptococci level test by dentally educated professional personnel. High frequency of sucrose consumption and dietary Topical application of high and low concentrated carbohydrates intake causes higher salivary concentrations fluorides is effective for remineralization of early lesion of Lactobacilli colonies which are most responsible for (Fig. 7). The presence of fluorides in oral cavity strongly dental caries formation. the amount of salivary lactobacilli prejudices the remineralization/demineralization equation can be measured by Lactobacilli level test using towards remineralization. Beside the crystals containing “Dentocult LB” kit (Fig. 6). fluoride are more resistant to acid dissolution, it is a highly effective antimicrobial that is specific to acid-producing organisms. Fluoride toothpaste should be used daily at home and fluoride varnish or foam can be applied by the dentist periodically.

Figure 6. Lactobacilli level test - “Dentocult LB” ab

Risk factors control (elimination of factors that Figure 7. Fluoride topical application caused the disease) Risk factors control, or elimination of factors that Fissure sealing should be applied as a primary caused the disease, can be accomplish by applying preventive measure to non-carious and the patients judged professionally instructed home-preventive measures and to be at some risk to caries formation12,28,32,33. chair-side prevention programme in order to suppress caries promotion factors and modify oral environment from being high to low risk for ECC occurrence. Caries Treatment A. Professional basis of home-applied preventive (Secondary Prevention) measures Home-applied preventive measures comprise: Following the clinical findings, on the basis of child’s dietary guidance, oral hygiene counselling and fluoride medical history and the treatment needs, a thorough application on regular basis. treatment plan must be designed. The most important The basic connections between caries and nutrition objective is to get the disease under control as soon as are well known. The most important basics of practical possible. recommendation on dietary guidance are as follow: A clinical protocol for treating ECC includes correction of bad feeding/eating habits; avoidance of proper diagnosis and effective disease control. The main sugar-containing food; the use of sucrose alternatives; and objectives for the placement of dental restorations (Fig. 8) decreasing the frequency of snacks between meals. are: reconstruction of the lost tooth surfaces, prevention of First objective of proper oral hygiene counselling is further complications, regaining basic functions (feeding, to prevent plaque formation, or to remove it completely speech, phonetic articulation), maintaining space and, as early as possible, which can be seen as a basic caries finally, aesthetic and communication rehabilitation. home-preventive measure. Caries removal and temporization are designed to Use of fluoride-containing preparations in caries eliminate the presence of bacteria as quickly as possible. prevention is of great importance for improvement of oral Once the caries lesion is completely removed, restorations health. It can be accomplished by: fluoride-containing dentifrices, fluoride tablets; and home fluorides mouth rinses.

B. Chair side prevention programme Beside home-applied preventive measures to maintain achieved oral health, “chair side preventive programme” is ab recommended as well to keep oral environment at low risk for caries disease for longer time period. Figure 8. Caries treatment Balk J Stom, Vol 13, 2009 Early Childhood Caries 19 of lost tooth surfaces are recommended with the use providing emotional support and enhancing child’s sense of fluoride-release restorative materials (glass ionomer of self-worth (in itself important for health). restorations). Endodontic therapy is performed only if the Similarly to eating problem, speech is also affected. tooth is restorable. Any tooth that cannot be restored has Ability to speak “normally” is one of the primary ways in to be extracted. which one makes contact with others in the surroundings. The basic idea of radical EEC treatment (tooth If ability to speak is affected, clearly, this could have a extractions) is to: (1) eliminate sources of infections; (2) detrimental effect upon basic social interaction. Such prevent further infection progression (bacteraemia); and children may increasingly begin to dread occasions when 12,29,34 (3) improve child health and the quality of life . they have to socialize and interact (communicate) with their friends and playmates. This could, in the worst- case scenario, result in withdrawal, social isolation and a Rehabilitation (Tertiary Prevention) negative spiral in which the individual loses confidence in himself and draw further away from the social world. Beside having basic functional problems in terms Therefore, the rationale solution for the rehabilitation of chewing and eating, which can cause disturbances of lost oral structures (Fig. 9) in this early life period in growth and development, the consequences of early must provide: proper food consumption, aesthetic and tooth loss have shown that social isolation can have a communication rehabilitation, and maintaining space. detrimental effect upon a young person general health as This can be accomplished with removable space retainers well. Obviously, social support plays an important role in which can serve as small partial prosthetic appliance that enhancing general health-related behaviours, as well as can satisfied all the mentioned demands as well29,30,34.

a b c Figure 9. Oral rehabilitation

Maintenance of contributing factors and restoring the function by using Achieved Oral Health all available preventive and control measures. Therefore successful management of early childhood caries demands integrated approach of preventive and restorative Maintenance of the achieved oral health is to be kept measures. These measures include carefully completed further on by regular recalls or check-up visits, performing dental and medical history, use of currently accepted caries control-preventing programmes, which will diagnostic aids, application of comprehensive preventive consider: (1) evaluation of the effect of casual treatment programs, use of sound principles of restorative dentistry, and rehabilitation; (2) caries risk factors control with as well as regular recall appointments in order to maintain comprehensive preventive programs; and (3) prediction health and reemphasize preventive measures. and suppression regarding further development or continuation of the disease. Frequency of regular recalls or check-up visits should be organised on individual basis, regarding patients potential risk susceptibility and the References already achieved level of oral health rehabilitation30,31. 5. Milnes AR. Description and epidemiology of nursing caries. J Public Health Dent, 1996; 56:38–50. 6. Wyne AH. Early childhood caries: nomenclature and case definition. Community Dent Oral Epidemiol, 1999; Conclusion 27:313-315. 7. Featherstone JD. The continuum of dental caries - evidence Combating ECC consists of addressing the cause, for a dynamic disease process. J Dent Res, 2004; 83(Spec correcting bad habits or deficiency that may act as No C):C39-C42. 20 M. Carević et al. Balk J Stom, Vol 13, 2009

8. Seow WK. Biological mechanisms of early childhood caries. 25. Bown JP, Junner C, Leiw V. A study of Streptococcus Community Dent Oral Epidemiol, 1998; 26(Suppl):8-27. mutans levels in both infants with bottle caries and their 9. Lai PY, Seow WK, Tudehope DI, Rogers Y. Enamel mothers. Aust Dent J, 1985; 30:96-98. hypoplasia and dental caries in very-low birthweight 26. Dilley GJ, Dilley DH, Machen JB. Prolonged nursing habit: children: A case-controlled, longitudinal study. Pediatr Dent, a profile of parents and their families. J Dent Child, 1980; 1997; 19:42-49. 47:102-108. 10. Li Y, Navia JM, Bian JY. Caries experience in deciduous 27. Katz S, Muhler JC. Prenatal and postnatal fluoride and dentition of rural Chinese children 3-5 years old in relation dental caries experience in deciduous teeth. J Am Dent to the presence or absence of enamel hypoplasia. Caries Assoc, 1968; 76:305-311. Res, 1996; 30:8-15. 28. Zita A, McDonald RE, Andrews AL. Dietary habits and the 11. Milgrom P, Riedy CA, Weinstein P, Tanner AC, Manibusan dental caries experience in 200 children. J Dent Res, 1959; L, Bruss J. Dental caries and its relationship to bacterial 38:860-865. infection, hypoplasia, diet, and oral hygiene in 6- to 29. Stookey GK. Caries prevention. J Dent Educ, 1998; 36-month-old children. Community Dent Oral Epidemiol, 62:803-811. 2000; 28:295-306. 30. Wright JT, et al. Effect of conventional dental restorative 12. Seow WK, Amaratunge A, Bennett R, Bronsch D, Lai treatment on bacteria and saliva. Community Dent Oral PY. Dental health of aboriginal pre-school children in Brisbane, Australia. Community Dent Oral Epidemiol, Epidemiol, 1992; 20:138-143. 1996; 24:187-190. 31. Waldman HB. The future of dentistry: we need to tell the 13. Williams SA, Kwan SY, Parsons S. Parental smoking whole story. J Am Coll Dent, 1990; 57(3):46-54. practices and caries experience in pre-school children. 32. Brathall D, Tynelius-Brathall G. Diagnostics as basis casual Caries Res, 2000; 34:117-122. treatment: Tools and tests for evaluation of caries and 14. Vulović M, Carević M. Evaluacija Programa preventivne periodontal diseases. In: Professional prevention in dentistry. stomatološke zaštite 1996 - 2000. Stom Glas S, 2003; Advances in dentistry 1. Williams & Wilkins, 1994; 2:31-68. 50(Suppl) 33. Elderton RJ. Principles of decision-making to achieve oral 15. Mikkelsen L. Effect of sucrose intake on numbers of bacteria health. In: Professional prevention in dentistry. Advances in in plaque expressing extracellular carbohydrate metabolizing dentistry 1. Williams & Wilkins, 1994; 1:3-27. enzymes. Caries Res, 1996; 30:65-70. 34. Anderson MH. Oral health maintenance by preventive 16. Vulović M, et al. Preventive Dentistry. Beograd: Draslar, therapy. In: Professional prevention in dentistry. Advances 2005; pp 379-407. (in Serb) in dentistry 1. Williams & Wilkins, 1994; 4:111-125. 17. Acs G, Lodolini G, Kaminsky S, CisnerosGJ. Effect of 35. Levin RP. Marketing and preventive dentistry. In: nursing caries on body weight in a pediatric population. Professional prevention in dentistry. Advances in dentistry Pediatr Dent, 1992; 14:302-305. 1. Williams & Wilkins, 1994; 6:143-156. 18. Slavkin HC, Baum BJ. Relationship of dental and oral 36. Einwag J. Oral health maintenance by plaque control. In: pathology to systemic illness. JAMA, 2000; 284:1215-1227. Professional prevention in dentistry. Advances in dentistry 19. Bown WH. Dental caries: is it an extinct disease? J Am Dent 1. Williams & Wilkins, 1994; 3:71-108. Assoc, 1991; 122(10):49-52. 37. Ernst CP, Willershusen-Zonnchen B. Professional 20. Rapa LW. Nursing caries: a comprehensive review. Pediatr toothcleaning. In: Professional prevention in dentistry. Dent, 1988; 10:268-282. Advances in dentistry 1. Williams & Wilkins, 1994; 21. Weddell JA, Klein AI. Socioeconomic correlation of oral 5:129-139. disease in six- to thirty six-month children. Pediatr Dent, 38. Beloica D, et al. Paediatric Dentistry. Belgrade: Elit-Medica, 1981; 3:306-311. 22. Berkowitz RJ, Jones P. Mouth-to-mouth transmission of the 2003; pp 131-167. (in Serb) bacterium Streptococcus mutans between mother and child. Arch Oral Biol, 1985; 30:377-379. 23. Bibby BG. Effect of sugar content of foodstuffs on their Correspondence and request for offprints to: caries-producing potentials. J Am Dent Assoc, 1955; Prof. M. Carević 51:293-306. Faculty of Dentistry 24. Jenkins GN. Recent changes in dental caries. Br Med J, Clinic of Paedodontics and Preventive Dentistry 1985; 291:1297-1298. 11000 Belgrade, Serbia

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Retention of Glass Ionomer Cement and Resin-Based Fissure Sealant and Their Effect on Caries Outcome During Chemotherapy: A Pilot Study

SUMMARY Çiğdem Elbek Çubukçu The retention and caries preventive efficacy of light-cured resin-based Uludağ University, Faculty of Medicine fluoride fissure sealant (RBS) in comparison with glass ionomer cement Pediatric Dental Care Unit (GIC) were studied during chemotherapy. The survival rates of GIC and Bursa, Turkey RBS were: 44.8% and 51.7% at 3 months, 26.2% and 43.9% at 12 months, respectively. The percentage of fully retained sealants at month 3 was 25.9% in GIC group and 12% in RBS group. At 12 months, the difference between the percentages was insignificant in both groups. The percentage of carious lesions seen in GIC sealant and RBS group was 6.9% at month 3. At month 12, 7.3% carious molar was found in RBS group, whereas the same estimation was 19% in GIC group. Regarding caries development on molars at 12 months, in which sealants were fully disappeared at month 3, the percentage was 29.3% for RBS and 33.3% for GIC groups. Caries preventive efficacy and survival rate of GIC were not found superior compared to RBS at the end of 12 months. ORIGINAL PAPER (OP) Keywords: Chemotherapy; Pit-Fissure Sealant; Caries Prevention; Children Balk J Stom, 2009; 13:21-25

Introduction composite resin and/or a glass ionomer9,10, and different combinations of these preventive measures. Only effective Various reports have indicated the relationship clinical regimen available for preventing occlusal caries is between dental caries and chemotherapy1-4. These studies the use of pit-and-fissure sealants11,12. suggested that children with malignant diseases had more Pit-and-fissure sealing has been described as a carious teeth compared to healthy subjects. Depending procedure of introducing a material into the occlusal pits on the reduced buffer and antibacterial action of saliva and fissures of caries-susceptible teeth, therefore forming encountered during chemotherapy, cariogenic flora a micro-mechanically bonded protective layer that blocks increases, and this results in an increased susceptibility to nutrients of caries-producing bacteria13. To the best of our dental caries. This fact indicates the need for preventive knowledge, neither retention nor caries preventive efficacy strategies to promote dental health and to avoid the of sealing materials has been investigated in children who development of caries prior to chemotherapy. A number of caries preventive measures have been were on chemotherapy. In the present study, the retention developed for children with malignant diseases, as well and caries preventive efficacy of glass ionomer cement as the healthy ones2,3,5. These include cleaning tooth (GIC) in comparison with light-cured fluoride resin-based surfaces with a toothbrush and a fluoridated toothpaste6,7, sealant (RBS) were studied intra-individually in a period application of a fluoride varnish8, application of a of 1 year in children who were on chemotherapy for solid chlorhexidine varnish, sealing pits and fissures with a tumours. 22 Ç.E. Çubukçu Balk J Stom, Vol 13, 2009

Materials and Methods appearance, indicative of appropriate etching. The RBS material was applied by using the tip of a small excavator Sample Selection and cured by applying visible light for 30 seconds using Eligible subjects among the children diagnosed with a dental-curing unit (LA 500, Model Blue-light, Apoza solid tumours between 2002 and 2005 in the Department Enterprise Co, Taiwan). of Pediatric Oncology, Faculty of Medicine of Uludağ The occlusal surfaces of molars where GIC material University were included in this prospective clinical was applied, was cleaned with a brush mounted on a low study. Criteria for eligibility were as follows: The patient speed engine, washed and dried, and isolated with cotton should suffer from solid tumour, be hospitalized for wool rolls and high volume suction. The occlusal surfaces chemotherapy, and had no carious teeth; patients should of each tooth were conditioned with polyacrylic acid for have no stain and/or soft debris, and supragingival calculus 10-15 seconds, and dried for a further 10 seconds. The 15 covering not more than one third of their exposed tooth GIC was applied according to the ART manual . Subjects surface14, and should follow the same oral care guideline were instructed not to eat for at least 1 hour. during the therapy. In order to follow oral care guideline, Post-Operative Assessment teeth and tongue were cleaned 4 times a day (after meals and before bed time) with a soft-bristled brush to remove After completion of treatment, 2 calibrated dentists, plaque and debris. Once brushing was completed, 10 ml who were not operators, carried out the evaluation at of 8.4% sterile sodium bicarbonate (Drogsan®, Turkey) 3 months, during intensive chemotherapy, and at 12 was administered as a rinse to remove loose debris and to months when the therapy was completed using the criteria 15 irrigate healthy tissue. described by Frencken et al (Table 1) . The follow-up All the first permanent molars should fully be erupted examination was performed using a No.4 plain mirror and and sound, with absence of mobility due to periodontal a No.6 right-angle probe. It was decided that if caries was disease, and with no evidence of hypoplasia or history of detected clinically in any of the teeth included in the study, previous sealant application. the patient would be appointed for restorative care and the specific tooth/teeth would be excluded from the study. The Pre-Operative Assessment inter-examiner reliability was assessed by examination The study was approved by the Ethics Review of an independent sample of sealants of children who attended for reviews (5 molars during each of the 3 and Committee of the faculty. Informed written consents were 12 month follow-up periods), by the 2 examiners. Each obtained from each family using separate forms written examiner was unaware of the other examiner’s findings. in simple clear native language. A systematic and precise This ensured a constant check on the reliability of the dental examination was performed and the teeth were examiners. examined for caries with a No.4 plain mirror and a No.6 right-angle probe. Table 1. Evaluation criteria of the GIC and RBS Assignment of the Teeth to the Study Groups The material was randomized with respect to teeth, Scores Evaluation criteria mandibular and maxillary, and left and right side. The 0 Present, good seal study consisted of 33 children with a total of 132 molars. Partly present, visible pits and/or fissures are free of 1 66 maxillary and mandibular first permanent molars were active caries; no sealant needed ® Partly present, visible pits and/or fissures show signs sealed with a RBS (Alpha-Seal , Dental Technologies, 2 Inc.) and a GIC (Fuji IX®, GC Europe). of active caries; treatment needed Not present, pits and/or fissures show no signs of 3 Sealant Procedure active caries; no treatment needed Not present, pits and/or fissures show signs of active The sealant procedure was performed on every 4 caries; treatment needed child by a resident dentist in Pediatric Dental Care Unit. 5 Unable to diagnose Following the initial dental examination, the sealant materials were applied on molars of each child in 1 session Survival: Scores 0 and 1 Failure: Scores 3 and 4 before chemotherapy has been initiated. The occlusal Retention: Scores 0, 1, and 2 surfaces of the teeth where RBS material was applied No retention: Scores 3 and 4 were cleaned with a brush mounted on a low speed engine, washed and dried, and isolated with cotton wool rolls and high volume suction. The teeth were etched for 30 seconds Statistical Analysis using 37% orthophosphoric acid, washed for 10 seconds, The data were entered into a database, checked for and dried for a further 10 seconds. The occlusal surface errors and analyzed using SPSS software (Release 11.0 was checked for the characteristic chalky white matt version). All the data in this study were categorical and Balk J Stom, Vol 13, 2009 Control of Caries During Chemotherapy 23 therefore non-parametric statistics was used. Analysis of Table 2. Description of the sample the data was carried out using Chi-square test, which is used to assess quantitatively whether or not the observed Patient characteristics n frequencies differ significantly from those expected on Males 18 the basis of the null hypothesis. For purposes of analysis Females 15 of sealant procedure, we considered the tooth and not the Age (years) patient to be the unit sample. Retention was considered Mean 9.2 yr present for the combined scores 0, 1, and 2. Scores 3 and Range 7-14 yr 4 represented no retention. Survival of the sealants placed Type of cancer was identified with the combined scores of 0 and 1. Caries Medulloblastoma 15 Osteosarcoma scores 0, 1, and 3 were combined in the analyses as sound. 4 Lymphoma 14 Caries was considered present for the combined scores 2 and 4. A probability value less than 0.05 were considered The Number of Molars Evaluated at 3 and significant16. 12 Months Follow-Ups At the beginning of the study, a total of 132 sealants were placed on occlusal surfaces of molar teeth. After Results 3 months, 116 molars were available in 29 children. 4 children did not attend their follow-up. At evaluation on In this study, 33 children who were on chemotherapy month 12, there were 21 children available, with a total of for solid tumours (mean age 9.2±1.8 years - 7-14 yr; male/ 83 molars. Table 3 presents the number and percentage of female ratio: 18/15) were included (Tab. 2). teeth lost at follow-ups at 3 and 12 months.

Table 3. The number and percentage of sealed teeth lost to follow-up after 3 and 12 month

Sealant material No. placed No. evaluated % lost to follow-up At 3-months At 12-months At 3-months At 12-months GIC (Fuji IX®) 66 58 42 12% 36.3% RBS (Alpha-Seal®) 66 58 41 12% 37.9%

Table 4. The cumulative survival percentage of sealants according to the evaluation periods

No. transfers Time span (months) No. failures No. survival Survival rate (%/SD) (teeth without caries) GIC (Fuji IX®) 0-3 32 26 54 44.8/1.2 3-12 31 11 34 26.2/3.3 RBS (Alpha-Seal®) 0-3 28 30 54 51.7/1.3 3-12 23 18 38 43.9/1.6 SD: standard deviation Survival: Scores 0 and 1 Failure: Scores 3 and 4

Retention Rates at 3 and 12 Months Follow-Ups was 15 (25.9%), whereas 7 RBS (12%) were fully retained (p<0.05). At evaluation on month 12, fully retention was Almost 1 out of the 2 RBSs (51.7%) and GIC detected on 3 RBSs out of 41 (7.3%). However, the result sealants (44.8%) had found disappeared at evaluation on was found significantly different (p<0.05) in the 7 GIC month 3 (p>0.05). However, the evaluation made at month sealants out of 42 teeth (16.6%). 12 indicated a survival rate of 43.9% for RBS material, whereas the same estimation was determined to be 26.2 in Caries Rates at 3 and 12 Months Follow-Ups GIC group, and the difference was significant (Tab. 4). The The percentages of caries development in GIC number of fully retained (score 0) GIC sealants at month 3 sealant and RBS groups were: 6.9% (n=4 for each group) 24 Ç.E. Çubukçu Balk J Stom, Vol 13, 2009 at 3 months and 19% (n=8) and 7.3% (n=3) at 12 months, fissure sealant, thus demonstrated worse results than in respectively. The results obtained on month 12 in GIC this study after 1 years of clinical evaluation (16.6%). The group were significantly different (p<0.01) from those difference between survival rates of these 2 materials was obtained on month 3. Additionally, the results obtained on statistically insignificant at the month 3. However, our month 12 in GIC and RBS groups were also significantly findings obtained at month 12 clearly indicated that the different (p<0.01) from each other. The percentages of survival rate of the resin based sealant was significantly children with carious molars in GIC sealant and RBS higher than that of the glass ionomer material. groups were: 13.8% (n=4) at 3 months and 28.6% (n=6) at To the best of our knowledge, clinical trials related 12 months, respectively. Out of 4 subjects, 1 patient was to effectiveness of glass ionomer materials have usually excluded from the study at month 3 since the patient had discouraged their use as fissure sealants22,23. But, all developed caries on 4 molar teeth. of them were held on healthy subjects17. However, the present study investigated the efficacy of this material on Evaluation for Caries Development on Molars patients receiving chemotherapy. on Month 12, in which Sealants were Fully Although, recently published clinical trials have Disappeared (Score 3) at Month 3 consistently found poorer retention of glass-ionomers than resin-based materials18-21,24,25, there appears no difference The percentages of carious molars in GIC sealant and in their caries preventive effect over a long period19-21,25,26. RBS groups were 7% (n=3) and 2.4% (n=1), respectively. Williams et al26 found no difference in the effect on caries 2 In the RBS group, no caries development was detected or 4 years after the sealant application. However, Forss and in 29.3% of molars (n=12), whereas in the GIC sealant Halme21 found an increased risk of caries in glass-ionomer- group, it was as high as 33.3%. The difference between sealed teeth compared with resin-sealed-teeth after a 7-year the percentages was insignificant (p>0.05). follow-up. This later finding is consistent with clinical results of GIC we have reported previously. However, evaluation of caries development on molars where sealants fully disappeared (Score 3) at month 3 were in accordance Discussion with the results conducted by Williams et al26. Chemotherapy regimen of the subjects varied The results of this study provided data on retention according to the diagnosis, which comprised BFM-95 and caries preventive efficacy of GIC and RBS applied to (Berlin-Frankfurt-Munsten-95), ABVD (Adriamycine- children with solid tumours during chemotherapy. In the Bleomycine-Vinblastine-DTIC), carboplastine, vincristine, literature, other investigations on this subject were held only CCNU and/or VP-16 agents. However, the subjects with 17 in healthy children from different socioeconomic status . medulloblastoma (n=15) were provided post radiotherapy The present investigation has preliminary results. chemotherapy. Before chemotherapy was initiated, the Therefore, the power calculation was not performed. children had cranial radiotherapy 180 cGy per day within However, it was still possible to randomize the sealants 5 days (total 5400 cGy irradiation). Then these subjects over the first molars by the jaw of the mouth. Another with this disease (45% of the study population) had important aspect that needs discussion is that the carboblastine, vincristine, CCNU and/or VP-16 agents. cumulated lost to follow-up observed in the present study Intensive chemotherapy combined with and without was high (37.1%). This can be explained by the fact that therapeutic radiation to the head can result in both short- and children and their parents became too debilitated to stick to long-term debilitating oral side-effects, such as mucositis, regular dental follow-ups during intensive chemotherapy. loss of salivary function, and taste loss. These side-effects, Fissure sealant application is one of the preventive particularly oral mucositis and loss of salivary function, measures recommended before the onset of chemotherapy may cause lowered pH in oral environment and resultant to ameliorate its impact on dental tissues. 2 materials are demineralization of enamel, dentinal hypersensitivity, and commonly used as a sealant material: composite resin and dental caries27. Therefore, it is logic to assume that the glass ionomer. It is generally accepted that composite resin complete retention rates of sealants in children undergoing as a sealant retains longer than glass ionomer18-20. cancer therapy would be lower compared to healthy Many researchers demonstrated low retention rates children, even they are in high-risk group for dental caries. for glass ionomer when it is used as a fissure sealant in All subjects had the same oral care regimen during periods of 6 months and 7 years20,21. A total retention rate this highly oral-toxic therapy. It is known that the intensive of polyacid-modified resin composite was found 20% oral care may not completely eliminate the deteriorative after 1-year follow-up18. In our study, RBS indicated a effect of chemotherapy on dental tissues28. Additionally, lower complete retention rate (7.3%) from those obtained the subjects and parents may not stick to regular dental in the trial conducted by Aranda et al18. Some authors19,21 care during the therapy. This could be the possible reason observed a 10% total retention rate after 3- and 7-year of the low survival rates of these 2 materials during follow-ups of a conventional glass ionomer used as chemotherapy (at 3 months). Balk J Stom, Vol 13, 2009 Control of Caries During Chemotherapy 25

Despite the higher rate of complete retention of GIC 14. Oral hygiene index. WHO Oral Health Country/Area Profile sealants at the end of 3 months; their caries preventive Programme, Department of Noncommunicable Diseases effect and survival rate was found unsatisfactory compared Surveillance/Oral Health. Available in: whocollab.od.mah. to RBS at the end of 12 months. Therefore, application of se/expl/ohigv60.html 15. Frencken JE, Makoni F, Sithole WD. Atraumatic restorative RBS was recommended as a caries preventive measure treatment and glass-ionomer sealants in a school oral health in children with malignancy before chemotherapy was programme in Zimbabwe: evaluation after 1 year. Caries initiated. It is obvious that further long-term comparative Res, 1996; 30:428-433. clinical studies, in which additional measures are 16. Armitage P, Berry G. Inferences from proportions. In: established to maintain oral health, such as regular Statistical methods in Medical Research. Oxford, UK: applications of fluoride and artificial saliva, are needed Blackwell Scientific Co, 1994; pp 118-132. to discuss the longevity of GIC sealant and RBS in the 17. Ahovuo-Saloranta A, Hiiri A, Nordblad A, Worthington H, presence of chemotherapy. Makela M. Pit and fissure sealants for preventing dental decay in the permanent teeth of children and adolescents. Acknowledgements: We express our gratitude to Vedat Cochrane Database Syst Rev 3: CD001830. Comment in: Gültekin, Doctor of Oral Surgery in the Centre of Oral Evid Based Dent, 5:93-94, 2004. Health Care of Ministry of Health, and Alper Sönmez, 18. Aranda M, Garcia-Godoy F. Clinical evaluation of the retention and wear of a light-cured pit and fissure glass Doctor of Orthodontics in Bursa, for their invaluable help ionomer sealant. J Clin Pediatr Dent, 1995; 19:273-287. with the evaluation period of the study. 19. Karlzen-Reuterving G, van Dijken JW. A three-year follow- up of glass ionomer cement and resin fissure sealants. ASDC J Dent Child, 1995; 62: 108-110. 20. Simonsen RJ. Glass ionomer as fissure sealant: A critical References review. J Public Health Dent, 1996; 56:146-149. 21. Forss H, Halme E. Retention of a glass ionomer cement and a 1. Duggal MS, Curzon MEJ, Bailey CC, et al. Dental resin-based fissure sealant and effect on caries outcome after parameters in the long term survivors of childhood cancer 7 years. Community Dent Oral Epidemiol, 1998; 26:21-25. compared with siblings. Oral Oncol, 1997; 33:348-353. 22. Komatsu H, Shimokobe H, Kawakami S, Yoshimura 2. Joyston-Bechal S. Prevention of dental diseases following M. Caries preventive effect of glass ionomer sealant radiotherapy and chemotherapy. Int Dent J, 1992; 42:47-53. reapplication: Study presents 3-year results. J Am Dent 3. Sonis S, Kunz A. Impact of improved dental services on Assoc, 1994; 125:43-49. the frequency of oral complications of cancer therapy for 23. Waggoner WF, Siegal M. Pit and fissure sealant application: patients with non head and neck malignancies. Oral Surg updating the technique. J Am Dent Assoc, 1996; 127:351-361. Oral Med Oral Pathol, 1988; 65:19-22. 24. Poulsen S, Beiruti N, Sadat N. A comparison of retention and 4. Pajari U, Ollila P, Lanning M. Incidence of dental caries in the effect on caries of fissure sealing with a glass-ionomer children with acute lymphoblastic leukaemia is related to the and a resin-based sealant. Community Dent Oral Epidemiol, therapy used. ASDC J Dent Child, 1995; 62:349-352. 2001; 29:298-301. 5. Fayle SA, Duggal MS, Williams SA. Oral problems and the 25. Mejare I, Mjör IA. Glass ionomer and resin-based fissure dentists’ role in the management of paediatric oncology sealants: a clinical study. Scand J Dent Res, 1990; 98:345-350. patients. Dental Update, 1992; 5:152-159. 26. Williams B, Laxton L, Holt RD, Winter GB. Fissure sealants: 6. Carvalho JC, Thylstrup A, Ekstrand KR. Results after 3 a 4-year clinical trial comparing experimental glass years of non-operative occlusal caries treatment of erupting polyalkenoate cement with a bis glycidil methacrylate resin first permanent molars. Community Dent Oral Epidemiol, used as fissure sealants. Br Dent J, 1996; 180:104-108. 1992; 20:187-192. 27. Jansma J, Vissink A, Spijkervet FLK, Roodenburg JLN, 7. Arrow P. Oral hygiene in the control of occlusal caries. Panders AK, Vermey A, et al. Protocol for the prevention Community Dent Oral Epidemiol, 1998; 26:323-330. and treatment of oral sequelae resulting from head and neck 8. Zimmer S, Robke FJ, Roulet J-F. Caries prevention radiation therapy. Cancer, 1992; 70:2171-2179. with fluoride varnish in a socially deprived community. 28. Borowski E, Benhamon E, Pico JL, Laplanche A, Community Dent Oral Epidemiol, 1999; 27:103-108. Margainaud JP, Hayat M. Prevention of oral mucositis in 9. Arrow P, Riordan PJ. Retention and caries-preventive effects patients treated with high-dose chemotherapy and bone of a GIC and a resin-based fissure sealant. Community Dent marrow transplantation. A randomized controlled trial Oral Epidemiol, 1995; 23:282-285. comparing two protocols of dental care. Oral Oncol Eur J 10. Morphis TL, Toumba KJ. Retention of two fluoride pit-and- Cancer, 1994; 30:93-97. fissure sealants in comparison to a conventional sealant. Int J Paed Dent, 1998; 8:203-208. 11. Weintraub JA. The effectiveness of pit and fissure sealants. J Public Health Dent, 1989; 49:317-330. Correspondence and request for offprints to: 12. Simonsen RJ. Retention and effectiveness of dental sealant Çiğdem Elbek Çubukçu after 15 years. J Am Dent Assoc, 1991; 122:34-42. Pediatric Dental Care 13. Simonsen RJ. Chapter 2: Pit and fissure sealants. In: Clinical Uludağ University, Faculty of Medicine Applications of the Acid Etch Technique. 1st ed. Chicago, Bursa, Turkey Ill: Quintessence Publishing Co, 1978; pp 19-42. E-mail: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Shear Bond Strength of 2 Root Canal Sealers to Human Dentin

SUMMARY P. Beltes, M. Pashali, N. Economides, The purpose of the present study was to compare the shear bond strength C. Gogos to human dentin of 2 root canal sealers: Sultan U/P (zinc-oxide euge nol) Aristotle University of Thessaloniki and 2seal (epoxy resin). The dentin specimens were divided randomly into Faculty of Dentistry 2 groups (A, B) of 12 specimens each, and etched with 3 ml of EDTA 17% Thessaloniki, Greece before rinsing with NaOCl 2.5% and distilled water. The 2 sealers were mixed according to the manufacturer instructions and placed on dentin surfaces. Bond strength was tested using a universal test machine at a cross-head speed of 0.5 mm/min. Data were analyzed with Student t-test. The results indicated that 2seal presented statistically significant higher values of bond strength than Sultan U/P. ORIGINAL PAPER (OP) Keywords: Shear Bond Strength; Root Canal Sealers Balk J Stom, 2009; 13:26-28

Introduction Materials and Methods

The main goal of endodontic treatment is the The dentin substrate was obtained from 12 single- 3-dimensional obturation of the root canal system rooted human teeth. The teeth were stored in the distilled with biocompatible materials, such as gutta-percha in water at -20°C. Before use, they were debrided with combination with a sealer. One of the basic properties ultrasonic scalers and washed several times in water. A of a root canal sealer is to have good sealing ability and low-speed diamond disk saw (Isomet, Buehler, USA) to adhere firmly to dentinal walls. The inadequate bond was used to cut off the apical and cervical parts of the strength of a sealer can lead to an increased possibility roots. The remaining sections were split longitudinally of subsequent microleakage and failure of endodontic in a bucco-lingual direction using the diamond disk. The treatment. portions of the root surface where the canal had been located were ground flat against #600 grit SiC paper. Zinc oxide-eugenol (ZOE) sealers have been used Teflon tape with a circular hole 3 mm in diameter was then widely in clinical praxis and they are based on Grossman’s centred on the dentin surface to standardize the exposed formula. However, problems regarding their setting time7, area. The dentin samples were mounted on a single plane microleakage2 and adhesion to dentin6 have been reported. shear test assembly, as described by Watanabe et al10. Epoxy resin-based root canal sealers are characterized The dentin specimens were divided randomly into 2 by the reactive epoxy ring and are polymerized by the groups (A, B) of 12 specimens each and etched with 3 ml breaking of this ring. These sealers have good adhesion to of EDTA 17% (Pulpdent) before rinsing with NaOCl 2.5% 1,3,4,9,12 dentin and this property is improved by the removal and distilled water. Finally, the dentin surfaces were dried 12 of smear layer . 2-seal is a relatively new epoxy resin- with paper points. based sealer, and in the literature there is no information The 2 sealers (2seal - group A; Sultan - group B) about the adhesion of this material to dentin. were mixed according to the manufacturer instructions and The purpose of the present study was to compare the placed on dentin surfaces. The entire assemblies (plates, shear bond strength of Sultan U/P (zinc oxide-eugenol dentin specimens, and bonded materials) were transferred sealer, Sultan Chemists, USA) and 2seal (epoxy resin- to an incubator (37°C, 100% relative humidity) for 1 based sealer) to human root dentin. month. Balk J Stom, Vol 13, 2009 Root Canal Sealers and Human Dentin 27

Bond strength was tested using a test machine study, fixes the shear loading device in-line with the bond (Accuforce III; Ametec) by subjecting samples to a shear interface zone and applies the stress through this zone load at a cross-head speed of 0.5 mm/min. The force in a specific plane, thereby minimizing the offsetting required to break the bond between the cements and dentin problem11. was recorded in kg using a personal computer connected In this study the dentin substrate was pre-treated with to the testing machine. Shear bond strength was calculated NaOCl and EDTA. This combination removes the smear in mega-Pascals (MPa) using the formula BSMPa=MVKg/ layer from the dentin surface and permits the penetration BA * 9.80665 (where BSMPa= bond strength in MPa, of sealers into the dentinal tubules, allowing the creation MVKg = measured value in kg, BA= bonding area = π*r2 of mechanical interlocking which may increase the bond = 3.14 * 1.52 = 7.065 mm2 and 9.80665 is the equivalent strength values8. in MPa of kg/mm2). The best results in the present study were observed Data were analyzed with Student t-test. The selected in the 2seal group. There was a statistically significant level of significance was 0.01. difference in bond strength between 2seal and Sultan. The epoxy resin-based sealers in many studies have shown that they have both good sealing ability and high bond strength to dentin. Lee et al6 compared the adhesion Results of 4 root canal sealers both to dentin and gutta-percha. The sealers evaluated were a ZOE root canal sealer (Kerr), The results are presented in figure 1. The mean shear an epoxy resin-based root canal sealer (AH-26), a calcium bond strength in group A (2seal) was 5.43 MPa ± 1.53 and hydroxide sealer (Sealapex) and a glass-ionomer sealer in group B (Sultan) was 1.97 MPa ± 0.75. (Ketac-Endo). AH-26 sealer gave better results than the Statistical analysis showed that there a was a other materials, with statistically significant differences. In statistically significant difference between the 2 groups another study, the Topseal, an epoxy resin sealer, showed (p<0.01). higher adhesion than Endion and CRCS, although the best results were obtained with Fibrefill (a methacrylate resin- 8 based sealer)4.

7 The results obtained with epoxy resin-based sealers may be associated with their ability to react with any 6 exposed amino groups in collagen to form covalent bonds 5.43 ± 1.97 2seal 5 between the resin and collagen when the epoxide ring Sultan opens6, although other mechanisms may also contribute to 4 MPa the observed bond strength. 3 The results of the present study showed that, the

2 adhesion between Sultan and dentin was very weak. This 3 1.53 ± 0.75 finding is in agreement with the results of Gettleman et al 1 who found that AH-26 bonded to dentin better than Sultan.

0 One potential problem with the ZOE sealers is their long 7 Figure 1. Means (MPa) and SDs of the experimental groups setting time , which may contribute to their low adhesion to dentin. It should be stated that the adhesive properties of sealers can not be correlated directly with microleakage; Discussion however, the weak bonding of ZOE sealers to dentin may explain their lower sealing ability than epoxy resin Many different methods have been used for sealers2,5. measuring the adhesion of endodontic sealers. These methods include tensile strength test, shear testing and push-out test. However, none of them seems to be generally accepted. References The shear test is a common method for the bond strength evaluation. The main problem with this test is the 1. De Gee AJ, Wu MK, Wesselink PR. Sealing properties of difficulty in the placement of the shear-loading device in Ketac-Endo glass ionomer cement and AH26 root canal close alignment with the bond interface. The load is offset sealers. Int Endod J, 1994; 27:239-244. at some distance from the bonded interface, resulting 2. Economides N, Liolios E, Kolokuris I. Beltes P. Long- term evaluation of the influence of smear layer removal in unpredictable torque loading of the specimen. The on the sealing ability of different sealers. J Endod, 1999; single plane shear test assembly, as used in the present 25:123-125. 28 P. Beltes et al. Balk J Stom, Vol 13, 2009

3. Gettleman BH, Messer HH, El Deeb ME. Adhesion of 10. Watanabe LG, Marshall GW Jr, Marshall SJ. Dentin sealer cements to dentin with and without the smear layer. J shear strength: effects of tubule orientation and intratooth Endod, 1991; 17:15-20. location. Dent Mater, 1996; 12:109-115. 4. Gogos C, Economides N, Stavrianos C, Kolokouris I, 11. Watanabe LG, Marshall G Jr, Marshall SJ. Variables Kokorikos I. Adhesion of a new methacrylate resin-based sealer to human dentin. J Endod, 2004; 30:238-240. influence on shear bond strength testing to dentin. In: 5. Khayat A, Jahanbin A. The influence of smear layer on Tagami J, Prati C (eds). Advanced adhesive dentistry. coronal leakage of Roth 801 and AH26 root canal sealers. Granada International Symposium, 3-4 December 1999, Aust Endod J, 2005; 31:66-68. Como: Kuraray Co, 2000; pp 75-90. 6. Lee KW, Williams MC, Camps JJ, Pashley DH. Adhesion 12. Wennberg A, Orstavik D. Adhesion of root canal sealers to of endodontic sealers to dentin and gutta-percha. J Endod, bovine dentine and gutta-percha. Int Endod J, 1990; 23:13-19. 2002; 28:684-688. 7. Mazinis E, Eliades G, Lambrianides T. An FTIR study of the setting reaction of various endodontic sealers. J Endod, 2007; 33:616-620. Correspondence and request for offprints to: 8. Saleh IM, Ruyter IE, Haapasalo M, Orstavik D. The effects of dentine pretreatment on the adhesion of root-canal Dr. Christos Gogos sealers. Int Endod J, 2002; 35:859-866. Aristotle University 9. Tagger M, Tagger E, Tjan AH, Bakland LK. Measurement Faculty of Dentistry of adhesion of endodontic sealers to dentin. J Endod, 2002; Thessaloniki, Greece 28:351-354. E-mail: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Intra-Tubular Reactions in Restored Human Teeth: A SEM Study

SUMMARY K. Kodonas The aim of this study was to examine restored human teeth in order to Aristotle University, School of Dentistry evaluate tissue changes in primary dentin or in primary-secondary dentin Department of Endodontology continuum. 16 non-carious and restored human molars were used. All teeth Thessaloniki, Greece were processed for scanning electron microscopic (SEM) analysis. Analysis was focalised at 3 parts of the dentin matrix; at the dentin-restoration interface, at the middle part of the remaining dentinal thickness and at the dentin- pulp interface. The results showed that in most cases dentinal tubules were wide open, from the dentin-restoration interface to the dentin-pulp interface. No sign of dentinal sclerosis or tubular obturation was found. Consequently, dentinal tubules could provide a pathway for bacteria to penetrate the dentin pulp complex. Nevertheless, dentinal tubules under composite resin restorations seemed to have been sealed by the composite material, at the dentin-restoration interface. Parameters like the age of the patient, the reason of extraction or longevity of restoration did not, indirectly, affect by any way dentin continuum. In general, it can be concluded that unlike previously reported studies, dentinal sclerosis was absent in most of the teeth studied. Keywords: Dentin Pulp Complex; Pulp Inflammation; Tubule Obturation; ORIGINAL PAPER (OP) Restorative Material Balk J Stom, 2009; 13:29-34

Introduction dentinal tubules may occur as a result of aging, dental caries, or can develop in response to any kind of stimuli, The bulk of the structure of the tooth, both crown and including the affect of some properties of the restorative root, is made up of a mineralized tissue known as dentin1. materials used3,5-7. The most prominent features of dentin are the dentinal Biologic reactions in dentin pulp complex must be at tubules1,2. In the periphery, there are approximately 10.000 the centre of attention in restorative dentistry7-9. With all to 25.000 tubules per square millimeter with a diameter the steps involved in restorative procedure, it is apparent of 0.5μm. On the contrary, near the pulp there are about that the biologic effects on dental tissues are multifactorial 45.000-90.000 tubules per square millimeter, each having and the effect from 1 factor alone is impossible to separate a diameter of 2.5 to 3μm2,3. Thus, from a clinical point of from the combined effect of all factors8. view, it should be recognized that dentin beneath a deep Many investigators have studied the effect of dental cavity preparation is much more permeable than dentin materials on mineralized dental tissues. Some data are underlying a shallow cavity3. available on the effect of amalgam, resin composite, zinc During time, dentinal tubules progressively narrow oxide eugenol cement, and calcium hydroxide on dentin8. by the deposition of peritubular dentin in their walls1,4. Besides chemical toxicity, some of the properties of the Additionally, dentinal tubules could be blocked by the materials used that are capable of producing injury include precipitation of hydroxyapatite and whitlockite crystals acidity, absorption of water, production of heat during within their structure. These biologic procedures represent setting, or poor marginal adaptation10-12. The aim of this dentinal sclerosis3. Partial or complete obturation of study was to examine non-carious and restored human 30 K. Kodonas Balk J Stom, Vol 13, 2009 teeth in order to evaluate tissue changes in primary dentin Teeth were divided into 3 groups according to the or in primary-secondary dentin continuum. patient’s age. In group A patients were at least 40 years old, in group B between 20 and 40 years old, and in group C they were at most 20 years old (Tab. 1). For each the extracted tooth, details concerning the reason of extraction, Materials and Method the presence of symptoms, or longevity of restoration were recorded (Tab. 2). 16 volunteers of both sexes, ranging in age from 12 All teeth were processed for scanning electron to 72 years, enrolled the study. All had been scheduled to microscopic analysis in a JEOL JSM-840 A SEM. When undergo tooth extraction for various therapeutic reasons, needed, Energy Dispersive (EDS) analysis was performed including orthodontic therapy, prosthetic rehabilitation or for qualitative examination of the chemical composition of periodontal treatment. In all cases the extracted teeth were the material at the tooth-restoration interfaces. In all cases molars. Each tooth carried an amalgam or resin composite SEM analysis was focused at 3 parts of the dentin matrix; restoration, had no sign of clinically, or by x-ray, at the dentin-restoration interface, at the middle part of diagnosed secondary caries, and no sign of pulp necrosis, the remaining dentinal thickness and at the dentin-pulp as pulp vitality tests indicated. interface (Fig. 1). Teeth were previously denuded of any soft tissue and stored in 10% formalin. The apical third of the root was removed in order the specimen to consolidate fast. After teeth were vertically sectioned in 2 by a mechanical fracture, they were cleaned in water, immersed in 0.5% sodium hypochlorite solution and gradually dehydrated in alcohol.

Table 1. Teeth processed for SEM evaluation

Groups Number of teeth Restorative material A 7 5 amalgam, 2 composite B 6 5 amalgam, 1 composite C 3 1 amalgam, 2 composite

Table 2. Specimen details

Reason of Figure 1. Parts that analysis was focalized at (specimen A1). (a) dentin- Teeth Pain symptoms* Age extraction restoration interface, (b) middle part of the remaining dentinal thickness, (c) dentin-pulp interface. A1 periodontitis no 66 A2 prosthetic no 52 A3 periodontitis no 58 A4 prosthetic no 72 Results A5 prosthetic no 52 A6 prosthetic no 63 The results of the SEM analysis showed that A7 periodontitis no 53 dentinal tubules were wide open in most of the cases. No B1 periodontitis no 38 sign of dentinal sclerosis or tubular obturation was found B2 unknown no 34 (Tab. 3). Occlusion of dentinal tubules was absent, not B3 prosthetic no 37 only at the dentin-restoration interface, but also at the B4 periodontitis no 40 middle part of dentin and at the dentin-pulp interface. In some cases (specimen B3, A4, B4), it was quite obvious B5 prosthetic no 35 that their structural continuity formed a wide pathway B6 prosthetic no 33 towards the pulp chamber (Fig. 2). C1 orthodontic no 12 The protective cavity base or liner used under C2 orthodontic no 15 amalgam restoration could not be easily identified using C3 orthodontic no 13 EDS analysis. Nevertheless, no sign of dentinal sclerosis *Vitality tests took place when needed was found under the cavity base application sites. Balk J Stom, Vol 13, 2009 Intra-Tubular Reactions in Restored Teeth 31

Figure 2. Occlusion of dentinal tubules was absent not only at the dentin-restoration interface (a), but also at the middle part of dentin (b) and at the dentin-pulp interface (c) (specimen B2)

Table 3. Results of electron microscopic analysis In 5 cases (specimens A5, A7, B6, C2, C3), where the restorative material was composite resin, it was obvious EDS that tubules at the dentin restoration interface were Teeth Restorative material Open tubules analysis infiltrated by the resin monomer. Thus, tubules seemed to A1 amalgam + Ca , P , Zn have been sealed, but only at that specific part of dentin. A2 amalgam + Ca , P The rest dentinal matrix and the dentin-pulp interface showed tubules being open, with no sign of obturation or A3 amalgam + Ca(0H)2 infiltration by any kind of material (Figs. 3 and 4). A4 amalgam + Zn A5 resin composite - Ca , P A6 amalgam + Ca , P , Zn A7 resin composite - Ca , P B1 amalgam + Ca , P , Zn B2 amalgam + Ca , P , Zn B3 amalgam + Ca , P , Zn B4 amalgam + Zn , Sr, Sn B5 amalgam + Ca , P , Zn B6 resin composite - Ca , P C1 amalgam + Ca , P , Zn C2 resin composite - Ca , P C3 resin composite - Ca , P Figure 4. Detail of figure 3

Discussion

No material that has been developed to date is ideal for all situations, nor is any absolutely perfect for any one situation13. It has long been recognized that dentinal tubules are the main pathways from any prepared surface to the pulp8. Consequently, occlusion of dentinal tubules reduces dentin permeability and eliminates pulpal reactions to restorative procedures and materials1,3,8. As stated before, tissue changes in dentin continuum may occur as an accelerated formation of peri-tubular dentin or by the precipitation of dissolved mineral salts within the tubules3,8. Additionally, mechanical obturation of dentinal tubules may be achieved by the application of adhesive Figure 3. Dentin-restoration interface (specimen A5) filling materials8. 32 K. Kodonas Balk J Stom, Vol 13, 2009

These biological changes in dentin seem to be a collagen fibril network is exposed8. Resin monomers multifactorial as they depend on many factors, including are then infiltrated into the collagen network as the the type of the material used. Amalgam, still widely used primer and resin or a combined primer-resin is applied8. in restorative dentistry, is not considered injurious to the However, some concerns remain about pulpal reactions, pulp, but requires protection in deep cavities14,15. In spite hypersensitivity and longevity of restoration of this of its limitations, it is very popular because of its strength, material17,18. Specifically, it has been well documented 16 longevity, low cost and relatively ease of handling . One that using composite resin as a filling material, without of the most significant disadvantages of amalgam that a protective base or liner, in deep cavities could impair leads to marginal leakage is lack of adhesion to tooth irreversible pulp damage, due to the diffusion of structure. Amalgam may also discolour dentin because un-polymerized and toxic components of the material to of penetration of mercury8. Nevertheless, that is unlikely the pulp through the remaining dentin17,18. to initiate any biologic reaction in dentin and is of no Apart from toxic or allergenic agents in restorative importance compared with the amount of mercury released materials, bacteria and their products are also capable in the oral cavity8. 19,20 Resin based materials are included among direct of eliciting an inflammatory reaction . The invasion adhesive restorative materials. To achieve optimal bonding of dentinal tubules by oral bacteria has been clearly 21,22 to dentin, the adhesive must penetrate the de-mineralized demonstrated by many in vivo and in vitro studies . dentin, enter the dentinal tubules and their branches and Thus, bacteria present within dentinal tubules may be then be polymerized8. Beside the variety of the different responsible for pulp infection. In this study, dentinal tubules bonding systems that are commercially available, they could provide a pathway for bacteria to penetrate the dentin all have a unique bonding protocol. In detail, phosphoric pulp complex23. In detail, the tubule width, as estimated by acid etching removes the smear layer and de-mineralizes SEM, was more than 0.5μm, which is the average diameter dentin. After conditioning of dentin with acid solution, of many bacteria species23 (Figs. 5 and 6).

Figure 5. Detail of 3 dentinal tubules with no sign of obturation Figure 6. Application site of Ca(OH)2 , with no sign of tubular occlusion (specimen B4) (specimen A3)

Unlike previously published data, in this report it most important factor seemed to be the type of the filling is well shown that obturation of dentinal tubules did not material used in each case. occur apart from 5 cases, when resin composite was used Information about the base cements and liners as a filling material5. In these cases obturation took place used in the tested teeth is limited. Generally, it has been only at the dentin-restoration interface (Figs. 3 and 4). documented that zinc oxide-eugenol cements inhibit These data are completely justified considering the nature bacterial growth and promote slight, but statistically of resin based composite adhesion to dentin. Doubtless, significant, increase in hardness on cavity walls8,10. the results found in 5 teeth restored with resin composite Calcium hydroxide is a substance that promotes limited indicate a surface seal but not institute anything more. sclerosis when applied to dentin24. Sclerosis is caused In this report, parameters like the age of the patient, by the precipitation of a crystalline material produced by the reason of the extraction or longevity of restoration did calcium ions within dentinal tubules24-26. Additionally, not, indirectly, affect by any way dentin continuum. The it has important but time limited antibacterial effect, Balk J Stom, Vol 13, 2009 Intra-Tubular Reactions in Restored Teeth 33 attributed to its high PH25-27. On the other hand, glass- 8. Mjor I, Ferrari M. Pulp dentin biology in restorative ionomer cements have advantages including chemical dentistry. Part 6. Reactions to restorative materials, tooth bonding to mineralized tissues and release of fluorides to restoration interfaces and adhesive techniques. Quintessence the dentin-material interface28. Int, 2002; 33:35-62. In this study, EDS analysis showed that most of the 9. Mjor I. Pulp dentin biology in restorative dentistry. Part intermediate materials used were eugenol based. At all 2: Initial reactions to preparation of teeth for restorative cases, no sign of tubular obturation was found under the procedures. Quintessence Int, 2001; 32:537-553. cavity base application sites. Additionally, no precipitation 10. Smith A, Murray P, Cox C. Bacterial microleakage and pulp of crystalline material occurred when calcium hydroxide inflammation associated with various restorative materials. was used (Fig. 6). However, it should be well understood Dent Mater, 2002; 18:470-478. that there are other factors determining biological changes 11. Ngo N, Mount G, Peters M. A study of a glass ionomer at the dentin-base interface, such as the application cement and its interface with enamel and dentin using a low procedure followed in each case. temperature, high-resolution scanning electron microscopic Unexceptionably, the procedure followed by each technique. Quintessence Int, 1997; 28:63-69. dentist affects the interplay between injury, defence and 12. Demarco P, Tarquino S, Jaeger M, Matson K. Pulp response repair, events of dentin pulp complex15,29. In all cases and cytotoxicity evaluation of 2 dentin bonding agents. where amalgam was used, parameters like possible lack Quintessence Int, 2001; 32:211-218. of condensation or the low degree of perfection of easily 13. Hilton T. Cavity sealers, liners, and bases: current purchasable materials used, contribute to our findings. philosophies and indications for use. Oper Dent, 1996; Nevertheless, it should be well recognised that in order 21:134-146. to achieve a surface seal under a restoration, not only 14. Wisithphrom K, Murray PE, About I, Windsor LJ. materials used should be standardized by international Interactions between cavity preparation and restoration associations, but new materials that provide optimal events and their effects on pulp vitality. Int J Periodontics Restorative Dent, 2006; 26:596-605. bonding with dentin should be preferable. 15. Tyler D, Thurmeier J. Amalgam Bonding. Visualization and clinical implications of adhesive displacement during Acknowledgments: The author wishes to express amalgam condensation. Oper Dent, 2001; 26:81-86. sincere appreciation to Professor Dimitrios Tziafas for his 16. Marchiori S, Baratiery L, Andrada M, Monteiro S, Ritter instruction and guidance in this study. A. The use of liners under amalgam restorations: An in vitro study on marginal leakage. Quintessence Int, 1998; 29:637-641. 17. Seki Y, Shimada Y, Foxton RM, Tagami J. Pulpal response References to a newly developed MMA based resin cement for bonding tooth-colored indirect restorations. Am J Dent, 2006; 1. Olgart L, Bergenholtz G. The dentin pulp complex: 19:297-302. responses to adverse influences. In: Bergenholtz G, Horsted 18. Huang FM, Chang YC. Cytotoxicity of resin-based P, Reit C (ed). Textbook of Edodontology. Oxford: Blackwell restorative materials on human pulp cell cultures. Oral Publishing, 2003; pp 21-42. Surg Oral Med Oral Pathol Oral Radiol Endod, 2002; 2. Mjor I, Sveen O, Heyeraas K. Pulp dentin biology in 94:361-365. restorative dentistry. Part 1: Normal structure and physiology. 19. Pashley DH, Pashley EL, Carvalho RM, Tay FR. The effects Quintessence Int, 2001; 32:427-446. of dentin permeability on restorative dentistry. Dent Clin 3. Trowbridge H, Kim S, Suda H. Structure and functions North Am, 2002; 46:211-245. of the dentin pulp complex. In: Cohen S, Burns S (ed). 20. Cox CF, Hafez AA. Biocomposition and reaction of pulp Pathways of the Pulp. 8th ed. Philadelphia: CV Mosby, tissues to restorative treatments. Dent Clin North Am, 2001; 2002; pp 411-455. 45:31-48. 4. Morse D. Age-related changes of the dental pulp complex 21. Love R, McMillan MD, Park Y, Jenkinson HF. Coinvasion and their relationship to systemic aging. Oral Surg Oral Med of dentinal tubules by Porphyromonas gingivalis and Oral Pathol, 1991; 72:721-745. Streptococcus gordonii depends upon binding specificity 5. Klinge R. The ultra structure of copper amalgam-covered of streptococcal antigen I/II adhesion. Infect Immun, 2000; dentin from human deciduous teeth. Acta Odontol Scand, 68:1359-1365. 1993; 51:223-228. 22. Love R. The effect of tissue molecules on bacterial invasion 6. Orchardson R, Gillam D. Managing dentin hypersensitivity. of dentine. Oral Microbiol Immunol, 2002; 17:32-37. J Am Dent Assoc, 2006; 137:990-998. 23. Love R, Jenkinson H. Invasion of dentinal tubules by oral 7. Hahn C, Liewehr F. Relationships between caries bacteria, bacteria. Crit Rev Oral Biol, 2002; 13:171-183. host responses, and clinical signs and symptoms of pulpitis. 24. Tronstad L. Reaction of the exposed pulp to Dycal treatment. J Endod, 2007; 33:213-219. Oral Surg Oral Med Oral Pathol, 1974; 38:945-953. 34 K. Kodonas Balk J Stom, Vol 13, 2009

25. Olsson H, Petersson K, Rohlin M. Formation of a hard tissue 29. Singer L. Evidence-based dental plans: dentistry’s future is barrier after pulp cappings in humans. A systematic review. now. J Am Coll Dent, 1999; 66:21-26. Int Endod J, 2006; 39:429-442. 26. Ranly D, Garcia F. Current and potential pulp therapies for primary and young permanent teeth. J Dent, 2000; Correspondence and request for offprints to: 28:153-161. 27. Smith A. Pulpal responses to caries and dental repair. Caries K.Kodonas Res, 2002; 36:223-232. Kaukasou 26 54632, Sykies Thessaloniki 28. Smith D. Development of glass-ionomer cement systems. Greece Biomaterials, 1998; 19:467-478. E-mail: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Cleaning Efficiency of Alkaline Peroxide Type Denture Cleansers on Silicone-Based Soft Lining Materials Colonized With Candida Albicans

SUMMARY Hale Gedik1, Yasemin Kulak Özkan2 Background. Silicone-based soft lining materials have been found to 1Haydarpaşa Hospital, Istanbul, Turkey be more susceptible to Candidal adhesion. Denture hygiene is essential to 2University of Marmara maintain the serviceability of the denture, and denture cleaners have been Department of Prosthetic Dentistry suggested for denture disinfection. Istanbul, Turkey Purpose. The purposes of this study were to investigate the Candida albicans adhesion, and determine the effectiveness of peroxide-type denture cleaners in the disinfection of silicone-based soft lining materials. Material and Methods. 2 different silicone-based soft lining materials have been used in this study (Molloplast-B and Luci-Sof). For each soft lining materials, 7 specimens have been prepared (10mm×10mm×3mm in diameter). Sterile specimens have been contaminated with Candida albicans and immersed in 4 different denture cleaners (Efferdent, Polident, Steradent, Correga tabs). The reduction in viable, adherent cells have been calculated by comparison with appropriate control specimens that have been treated in same way as test specimens, but without a disinfection regime. Results. Both soft liners showed Candidal adherence, but Luci-Sof soft liner exhibited higher Candidal adherence than Molloplast-B soft liner. Alkaline peroxide-type denture cleaners have been found effective in the disinfection of silicone-based soft liners contaminated with C. albicans. Conclusion. Alkaline peroxide-type denture cleansers can be used in order to maintain effective denture hygiene. Clinical Implications. Heat cured silicone based soft liners materials could be safely disinfected with alkaline peroxide type denture cleansers. ORIGINAL PAPER (OP) Keywords: Denture Cleansers; Soft Lining Materials; Candida Albicans Bakj J Stom, 2009; 13:35-40

Introduction plaque is a major factor of denture stomatitis6-17. Denture plaque is important factor in the pathogenesis of denture Resilient denture lining materials are widely used in stomatitis18-20. Therefore, denture cleansing should include prosthetic dentistry because they can assist the clinician removal of Candida organisms that have been reported to in restoring health to the inflamed and distorted denture be closely related to the disease 6,21. supporting tissues1-5. However, these materials have some Chemical cleansing with immersion denture physical and microbial disadvantages. One of the most cleansers is suggested as the first choice for plaque serious problems has been colonisation and infection of the control with these soft-lining materials, since brushing is material surface by Candida albicans and related Candida likely to damage the liners, and ultrasonic treatment per species, resulting in the denture induced stomatitis. Also, se is not effective22-24. Also, geriatric or handicapped effective denture plague control is indispensable for denture wearers can use chemical cleansers more clinical use of these materials, because bacterial and yeast advantageously24-26. 36 H. Gedik, Y.K. Özkan Balk J Stom, Vol 13, 2009

A variety of experimental approaches have been washed in phosphate-buffered saline solution (PBS), 0.15 tested in attempt to examine the efficacy of denture mol/L, pH 7.234,35. This procedure was repeated 2 times. cleansers. Some authors have investigated the minimal inhibitory or minimal bactericidal concentration of these Adherence Assay agents27, while others have examined the fungicidal The principle of the experiment was to contaminate effects28,30, Candida lytic effects28-30, or the agents’ ability sterile specimens of Molloplast-B and Luci-Sof soft to remove attached Candida cells from acrylic resins 25-27. lining materials with Candida albicans and to determine Many types of cleansers have been commercialised; any reduction in count of viable adherent cells after test sparse data are available on the efficacy of denture disinfection regimes. The reduction in viable, adherent cleansing agents. These agents may be classified as cells were calculated by comparison with appropriate alkaline peroxides, neutral peroxide with enzymes, crude control specimens that were treated in the same way drugs, acid detergents, and mouthrinses for dentures31. as test specimens, but without a disinfection regime36. The purposes of this study were to examine: (1) the At the commencement of the experiment, specimens ability of Candida albicans to adhere to 2 permanent soft were autoclaved at a temperature of 121ºC for 15 liners; and (2) the effectiveness of alkaline peroxide-type minutes. Sterile specimens were deposited in 20 ml yeast denture cleansers in the disinfection of long-term soft suspensions inserting the sterile universal bottles. They lining materials contaminated with Candida albicans. were incubated for 1 hour at room temperature to provide the adherence of Candida albicans34,35,37,38. All specimens were washed with PBS for 1 minute. Material and Methods Table 2. Type and manufacturers of denture cleansers Material Type Manufacturer Preparation of Specimens Warner-Lambert, Efferdent (A) Alkaline-peroxide 2 heat-cured soft lining materials (Molloplast-B, NJ Regneri GmbH and Co; and Luci-Sof, Dentsply,) were Polident double used in this study (Tab. 1). Square of specimens for Alkaline-peroxide Block Drug, NJ each soft liners were prepared (10mm×10mm×3mm) action (B) Steradent triple Reckitt & Colman and polymerized according to recommendation of Alkaline-peroxide the manufacturer. They were prepared in a stainless- action (C) Ltd, NJ steel mould with highly polished surfaces to produce Stafford-Miller Correga (D) Alkaline-peroxide reproducible results. All specimens were saturated with Ltd, UK sterile water for 24 hours at room temperature32-34. Specimens for each soft liner were randomly divided into Procedure 5 subgroups; 4 of test and 1 of control (n: 7). Control groups were stored in 40 ml sterile distilled water for 2 hours before fixation period. Disinfection Table 1. Type and manufacturer of soft denture materials regimes were carried out for each test group34. 4 denture cleaners (Efferdent - A, Polident duble action - B, Material Type Manufacturer Steradent triple action - C , and Correga - D) were used Molloplast-B Heat-cured silicone Regneri GmbH and Co. for the disinfection regime. Denture cleaner solutions were (Group I) rubber prepared according to manufacturers’ instructions. The test Luci-Sof Heat-cured silicone Dentsply, IntL, Pa. specimens were immersed in 40 ml of disinfection solutions (Group II) rubber in sterile universal bottles at 37ºC for 2 hours39-41 . All specimens were washed twice with PBS Preparation of Candida Albicans (Phosphate Buffer Solutions) with gentle rocking to A reference C. albicans (ATCC 2091, Istanbul remove non-adherent cells after discarding disinfection University, School of Medicine, Kükens) was used to solutions and sterile water. Excess of PBS solution was investigate the efficacy of disinfection. Candida strains drained from specimens. After they were dried, adherent were incubated in Sabouraud’s broth supplemented with cells were fixed in methanol, stained with crystal violet sucrose 500 mmol/L overnight at 37°C. This medium and examined by light microscopy. Adherent cells in 30 was used because previous studies have shown increased fields of view (0.25 mm2 per field) were enumerated by Candidal adherence to acrylic resin after culture in light microscopy and the results were expressed as yeast Sabouraud’s broth supplemented with sucrose34. Candidal cells/mm2 of material remaining after each cleanser in growth was harvested after 24 hours by centrifugation comparison with the control group34,39. Scheffe F-test was (3000 g 15 minutes, 10ºC). The Candidal cells were used to analyze the data. Balk J Stom, Vol 13, 2009 Cleaning Efficiency of Alkaline Peroxide Cleaners 37

Results disinfection, adhesion of Candida albicans to the Luci- Sof soft liner was found statistically higher than to the Both soft liners showed Candidal adherence. At Molloplast-B in control groups (p<0.0001). There were disinfection period, inhibition was observed for Candida statistical differences between the soft liners and denture albicans for both tested soft lining materials. Table cleansers (Tab. 4). After disinfection, Cleaner B showed 3 shows the mean and standard deviation values of the highest cleaning efficiency for the 2 tested lining Candida albicans adherence to the silicone-based soft materials. However, Cleaner D and A was found the least lining materials before and after the disinfection. Before effective for Group 1 and 2, respectively (Tab. 5).

Table 3. Mean and SD of the tested materials

Denture cleanser Control A B C D Totals 7 7 7 7 7 35 Group 1 33(26) 130 (35) 30 (26) 21(7) 32(19) 49

7 7 7 7 7 35 Group 2 486 (123) 286 (169) 141 (76) 183 (152) 196 (97) 258 14 14 14 14 14 70 Totals 308 81 114 108 158 154

Table 4. Two-way ANOVA results

Source df Sum of square Mean square F-test P value Mollo-Luci (A) 1 764836 764836 9 0.0001 Denture cleansers (B) 4 457966 114492 13 0.0001 AB 4 129717 32429 4 0.0079 Error 60 510067 8501

Table 5. Scheffe-F tests results; comparison denture cleanser to colonize easily and penetrate denture materials34,42, and soft lining materials particularly tissue conditioners, and mechanical cleaning per se is insufficient to remove harboured Candida and Denture cleansers Molloplast-B Lucisoft denture harmful to soft liners43,44, chemical cleansing is suggested denture liners liners. to be indispensable to denture plaque control43,45. Co. vs B S S Therefore, many denture cleansers have been marketed for Co. vs D S S removal or reduction of denture plaque. Co. vs C S S For the past years, resilient denture-lining materials Co. vs A S S have been widely used in prosthodontic treatment. However, severe deterioration of these materials have been B vs D NS NS reported to be caused by some denture cleansers36,43,45 in a B vs C NS NS relatively short period, depending upon the combination B vs A NS S of the soft liners and cleansers. The deteriorated surface D vs C NS NS of soft liners should facilitate further plaque accumulation. D vs A NS NS Therefore, denture cleansers used for plaque control with tissue-conditioned dentures should consider both microbial C vs A NS S and physical requirements41. Scheffe-F test: Significant at 95 %, NS: Non-significant Plaque control for soft-lining materials has not been stressed by either clinicians or researchers, and there are scant data available on either the material or microbiologic aspects of denture cleansers. This may be a result of the Discussion lack of recognition of the importance of plaque control for soft liners, since the prevention of Candida invasion Bacterial and yeast plaque on dentures is thought and denture plaque formation may be achieved not only to be an important factor in the pathogenesis of denture by plaque but also by replacement of the lining materials stomatitis18,20. Since these fungi have been reported every few days. However, plaque control is particularly 38 H. Gedik, Y.K. Özkan Balk J Stom, Vol 13, 2009 essential in the clinical use of soft liners and aetiology of denture cleansers tested was less effective with a soaking denture stomatitis18,20. Accordingly, the purposes of this period of 30 minutes, as compared with 2-hour incubation study were to examine the ability of Candida albicans to periods, in accordance with the conclusions of other adhere to 2 permanent soft liners, and the effectiveness of investigators43,46. Thus, a 2-hour incubation period was alkaline peroxide-type denture cleansers in the disinfection used to asses the efficacy of the cleansers28,29. of long-term soft lining materials contaminated with In this study, surface roughness and concentration, Candida albicans. viability, and culture conditions of the assay were The adherence of a microorganism to a surface is classically considered to be a 2-stage process. The kept constant except surface free energy and chemical initial interactions between the 2 surfaces are non- properties of the materials tested. Conflicting reports have specific and reversible, although the secondary phase been published regarding the role of the materials’ surface is caused by specific intermolecular interactions. free energy on the degree of microorganism adhesion. It Many approaches have been used to explain the initial has been reported that the higher the surface free energy adherence of microorganisms to surfaces, including the of the substrata, the higher the amount of adhesion of thermodynamic approach to adhesion, which describes microorganisms47,48. This unclear situation highlights the the adhesion of microorganisms to surfaces in terms of importance of the surface properties of the lining materials free energies of the surfaces and the microorganisms. and surface tensions of the suspending denture cleansing In addition, the hydrophobicity of the microorganisms medium, both not measured. Therefore, there is need for has been theorized as a reason for high adherence and further investigations. also for electrostatic interactions between surfaces. The The results of the experiment clearly indicated that second phase of the adhesion process involves specific adhesin-receptor interactions. The microorganism carries all peroxide-type denture cleansers were effective in the adhesins that bind stereo-chemically to complementary 2-hour test period. In this study, peroxide-type denture receptors on the surface. This stage is necessary for the cleansers were used for disinfection regimes, because tight binding of the microorganisms to the surface, which these cleansers are commonly used by denture wearers permits colonization. In addition to tightly binding the and more often found in the markets. microorganisms to the surface, the irreversible interactions are also responsible for the site-specific colonization of the oral microorganisms, which provides a selective advantage for microorganisms that possess relevant adhesins. Conclusion Adhesins have been postulated to be associated with the microorganisms surface appendages that, by virtue of their The ability of Candida albicans to adhere to 2 small radius, are unable to overcome the energetic barrier permanent soft liners and the effectiveness of alkaline of the primary force37. peroxide-type denture cleansers in the disinfection of Other factors associated with the adherence of yeast long-term soft lining materials contaminated with Candida to surfaces include surface roughness, presence of salivary proteins, presence of other adherent microorganisms, albicans were examined. The following conclusions may strain variability, concentration, viability of yeast cells, be made: and culture conditions37 . Both Luci-Sof and Molloplast-B soft liners showed In this study, a simple in vitro model was used to Candidal adherence; compare the adherence of C. albicans with 2 soft lining Luci-Sof soft liner exhibited higher Candidal materials. We aimed to provide a reproducible variables adherence than Molloplast-B soft liner; that could be examined in future studies. In light of this, 2-hour immersion period was found effective to the material surfaces were reproduced in a stainless-steel reduce Candidal colonization clinically; mould; the variability of surface roughness was therefore Alkaline peroxide-type denture cleansers can be used not examined. The concentration, viability, and culture in order to maintain effective denture hygiene; conditions of the assay were kept constant. Adhesion was There is a need for further investigations to explain initially carried out on surfaces with no saliva coating to if there is any relation between Candidal adherence and produce a reproducible assay before the introduction of variables. Only one dye - crystal violet - used within the surface free energy of the materials and microorganisms. study is commonly used in microbiology. Because crystal violet stains all cells present, with no ghost cells evident34. Acknowledgements: The study is based on a thesis Even though this study did not evaluate the fungicidal submitted to the Dental faculty, University of Marmara, in effects of denture cleansers, there are many studies that partial fulfilment of the requirements for the MS degree. examine the fungicidal effects of denture cleansers. This investigation was supported in part by Research Nikawa et al28,29 reported that fungicidal effects of some Grant from the TUBITAK. Balk J Stom, Vol 13, 2009 Cleaning Efficiency of Alkaline Peroxide Cleaners 39

References 22. Lambert JP, Kolstad R. Effect of a benzoic acid-detergent germicide on denture-borne Candida albicans. J Prosthet 1. Mack PJ. Denture soft linings: material available. Aus Dent Dent, 1986; 55:699-700. J, 1989; 34:517-521. 23. Palenic CJ, Miller CH. In vitro testing of three denture- 2. Mack PJ. Denture soft lining materials: clinical indications. cleaning system. J Prosthet Dent, 1984; 51:751-754. Aus Dent J, 1989; 34:54-58. 24. Dills S, Olshan AM, Goldner S, Brogdon AC. Comparison of the antimicrobial capability of an abrasive paste and 3. Maginnis MJ, Gaubert GT. Soft liners. In: Morrow R, Rudd chemical-soak denture cleaners. J Prosthet Dent, 1988; K, Rhoads J (eds). Dental Laboratory procedures: Complete 60:467-470. dentures. St Louis: Mosby, 1986; pp 441-459. 25. Keng SB, Lim M. Denture plaque distribution and the 4. Van Noort R. Dental materials: 1992 literature review. J effectiveness of a perborate-containing denture cleanser. Dent, 1994; 22:5-28. Quintesence Int, 1996; 27:341-345. 5. Brown D. Resilient soft liners and tissue conditioners. Br 26. Ödman PA. The effectiveness of an enzyme-containing Dent J, 1988; 164:357-359. denture cleanser. Quintessence Int, 1992; 23:187-190. 6. Budtz-Jorgensen E, Bertram U. Denture Stomatitis. I. The 27. Nakamoto K, Tamamoto M, Hamada T. A review of in vitro etiology in relation to trauma and infection. Acta Odont and in vivo methods to evaluate the efficacy of denture Scand, 1970; 28:71-92. cleansers. Int J Prosthodont, 1999; 12:153-159. 7. Bascom PW. Resilient denture base materials. J Prosthet 28. Nikawa H, Yamamoto T, Hamada T, Rahardjo MB, Murata Dent, 1966; 16:646-649. H. Commercial denture cleansers-cleansing efficacy against 8. Graham BS, Jones DW. In vivo fungal presence and growth Candida albicans biofilm and compatibility with soft on two resilient denture liners. J Prosthet Dent, 1991; denture-lining materials. Int J Prosthodont, 1995; 8:434-444. 65:528-532. 29. Nikawa H, Yamamoto T, Hamada T, Sadamori S, Agrawal 9. Wrigth PS, Young KA, Riggs PD, Parker S, Kalachandra S. S. Cleansing efficacy of commercial denture cleansers: Evaluating the effect of soft lining materials on the growth Ability to reduce Candida albicans biofilm activity. Int J of yeast. J Prosthet Dent, 1998; 79:404-409. Prosthodont, 1995; 8:527-534. 10. Masella RP, Dlaln CT, Laney WR. The prevention of the 30. Nakamoto K, Tamamoto M, Hamada T. Evaluation of growth of Candida on Silastic 390 soft liner for dentures. J denture cleansers with and without Candida albicans. J Prosthet Dent, 1975; 33:250-257. Prosthet Dent, 1991; 66:792-795. 11. Waters MGJ, Williams DW, Jagger RG. Adherence of 31. Chan ECS, Iugovaz I, Siboo R, Bilyk M Barolet R, Amsel R, Candida albicans to experimental denture soft lining Wooley C, Klitorinos A. Comparison of two popular methods materials. J Prosthet Dent, 1997; 77:306-312. for removal and killing of bacteria from dentures. Journal, 12. Radford DR, Sweet SP, Challacombe SJ, Walter JD. 1991; 57:937-939. Adherence of Candida albicans to denture-base materials 32. Dixon DL, Breeding LC, Faler TA. Microwave disinfection with different surface finishes. J Dent, 1998; 26:577-583. of denture base materials colonized with Candida albicans. 13. Wrigth PS, Clark P, Hardie M. The prevalence and J Prosthet Dent, 1999; 81:207-214. significance of yeasts in persons wearing complete dentures 33. Waters MG, Jagger RG, Winter RW. Water absorption of with soft-lining materials. J Dent Res, 1985; 64:122-125. (RTV) silicone denture soft lining material. J Dent, 1996; 14. Nikawa H, Hamada T, Makihira S, Kumagai H Murata 24:105-108. H. Interactions between thermal cycled resilient denture 34. Waters MG, Jagger RG, Winter RW. Adherence of Candida lining materials, salivary and serum pellicles and Candida albicans to experimental denture soft lining materials. J albicans in vitro: Part II. Effect on fungal colonization. J Prosthet Dent, 1997; 77:306-312. Oral Rehabil, 2000; 27:124-130. 35. Samaranayake LP, McCourtie J, Macfarlane TW. An 15. Fenlon MR, Sherriff M, Walter JD. Factors associated in-vitro study of the adherence of Candida albicans to with the presence of denture related stomatitis in complete acrylic surfaces. Arch Oral Biol, 1980; 25:603-609. denture wearers: a preliminary investigation. Eur J 36. Baysan A, Whiley R, Wrigth PS. Use of microwave energy Prosthodont Rest Dent, 1998; 6:145-147. to disinfect a long-term soft lining material contaminated 16. Rodrigez LO, Minah GE, DriscollCF. Candida albicans with Candida albicans or Staphylococcus aureus. J Prosthet colonization of surface-sealed interim soft liners. J Dent, 1998; 79:454-458. Prosthodont, 2000; 9:184-188. 37. Samaranayake LP, McCourtie J, Macfarlane TW. Factors 17. Nikawa H, Iwanaga H, Kameda M, Hamada T. In vitro affecting the in-vitro adherence of Candida albicans to evaluation of Candida albicans adherence to soft-lining acrylic surfaces. Arch Oral Biol, 1980; 25:611-615. materials. J Prosthet Dent, 1992; 68:804-808. 38. Verran J, Motteram KL. The effect of adherent oral 18. Budtz-Jorgensen E. The significance of Candida albicans in streptococci on the subsequent adherence of Candida denture stomatitis. Scan J Dent Res, 1974; 82:151-190. albicans to acrylic in vitro. J Dent, 1987;15:73-76. 19. Arendorf TM, Walker DM. Denture stomatitis; a review. J 39. Nakamoto K, Tamamoto M, Hamada T. Evaluation of Oral Rehabil, 1987; 14:217-227. denture cleansers with and without enzymes against Candida 20. Budtz-Jorgensen E, Stenderup A, Grabowski M. An albicans. J Prosthet Dent, 1991; 66:792-795. epidemiologic study of yeasts in elderly denture wearers. 40. Nikawa H, Yamamoto T, Hamada T, Sadamori S, Agrawal S. Community Dent Oral Epidemiol, 1975; 3:115-119. Cleansing efficacy of commercial denture cleansers: Ability 21. Davenport JC. The oral distribution of Candida in denture to reduce Candida albicans biofilm activity. Int Prosthodont, stomatitis. Br Dent J, 1970; 129:151-156. 1995; 8:527-534. 40 H. Gedik, Y.K. Özkan Balk J Stom, Vol 13, 2009

41. Nikawa H, Yamamoto T, Hamada T, Rahardjo MB, Murata 47. Van Dijk J, Herkstrorer F, Busscher H, Weerkamp A, Jansen H. Commercial denture cleansers-Cleansing efficacy against H, Arends J. Surface-free energy and bacterial adhesion. Candida albicans biofilm and compatibility with soft An in vivo study in beagle dogs. J Clin Periodontol, 1987; denture lining materials. Int Prosthodont, 1995; 8:434-444. 14:300-304. 42. Allison RT, Douglas WH. Micro-colonization of the denture- 48. Dexter SC, Sullivan JD, Williams J, Watson SW. Influence fitting surface by Candida albicans. J Dent, 1973; 1:198. of substrata wettability on the attachment of marine bacteria 43. Harrison A, Basker RM, Smith IS. The compatibility of to various surfaces. Appl Microbiol, 1975; 30:298-308. temporary soft materials with immersion denture cleansers. Int J Prosthodont, 1989; 2:254-258. 44. Connor JNE, Schoenfeld CM, Taylor RL. An evaluation of an Correspondence and request for offprints to: enzyme denture cleanser. J Prosthet Dent, 1977; 37:147-157. Prof. Yasemin Ozkan 45. Davenport JC, Wilson HJ, Basker RM. The compatibility of University of Marmara, Faculty of Dentistry tissue conditioners with denture cleansers and chlorhexidine. Güzelbahçe Büyükçiftlik Sok. No.6 J Dent, 1978; 6:239-246. 34365 Nişantaşı, Istanbul 46. Palenik CJ, Miller CH. In vitro testing of three denture- Turkey cleaning systems. J Prosthet Dent, 1984; 51:751-754. E-mails: [email protected], [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Effect of Shade and Thickness of Porcelain Veneers on Depth of Cure of Light-Cured Resin-Based Luting Cement

SUMMARY Temel Koksal1, Arzu Civelek2, Objective: The purpose of this in vitro study was to evaluate the effect Ender Kazazoglu1, Mubin Soyman2 of shade and thickness of porcelain veneers on depth of cure of 2 light-cured Faculty of Dentistry, Yeditepe University resin-based luting cements with 2 different shades. Istanbul, Turkey Material and Methods: Veneer samples (Empress 2 -Ivoclar) were pre- 1Department of Prosthodontics 2 pared in 1mm and 1.8 mm thickness and 10mm diameter (shade 1M2, 2M2). Department of Operative Dentistry The test materials (RelyX and Variolink II Base; A1 and A3 shade) of this study were cured through the porcelain samples. Measurements of depth of cure were performed according to ISO 4049. Statistical analysis was performed with Tukey HSD test. Results: The highest depth of cure results were obtained with Vario- link II Base (A1) covered with Empress 2 (1M2 shade - 1mm thickness) as 3.051mm. 0.937mm was the lowest data which was obtained with RelyX (A3) covered with Empress 2 (2M2 shade - 1.8mm thickness) (p<0.05). Conclusions: Darker shade of the resin-based luting material is a significant factor on decreasing depth of cure, especially for RelyX. Thickness of porcelain veneers had a greater influence on the depth of cure than the shade of porcelain. ORIGINAL PAPER (OP) Keywords: Porcelain Thickness; Resin Cement; Cure, depth Balk J Stom, 2009; 13:41-45

Introduction materials because of their simplicity to manipulate and more timesaving properties. Besides, dual-cured and self- Porcelain veneers are an increasing demand of the cured luting materials have some disadvantages because of patients to achieve aesthetic indirect anterior restorations the catalysts they incorporate. These are the potential for and improve the smile design. These restorations enable to discoloration of the luting resin and for interference with some self-etching adhesives, which causes lower bond change the colour, form and/or position of anterior teeth, strength4,5. Therefore, using solely light-curing composite which are important elements of anterior aesthetics. resin would have certain clinical advantages. The porcelain veneer technique includes the bonding The success of the porcelains can be affected procedure of a porcelain laminate to teeth using an by the exposed dental hard tissue (enamel or dentin), adhesive system and a luting material. These adhesive bond strength of the luting material and the occlusal 1 2 systems comprise dual cured , self-cured and light-cured relationship. Luting materials’ performance depends on 3 resin based cements . Light activated luting resins are the physical and mechanical properties of the material, used for anterior porcelain veneers, while thick posterior which includes especially bond strength, viscosity, elastic ceramic restorations require the use of dual activated, modulus and depth of cure. Adequate polymerization is a self-cured resin cements or resin modified glass ionomer crucial factor in obtaining optimal physical properties and cements2. Light-cured resin luting materials may be a satisfying clinical performance of composite resin luting preferred to dual-cured and self-cured resin luting materials. Inadequate polymerization causes inferior 42 T. Koksal et al. Balk J Stom, Vol 13, 2009 physical properties and changes in strength, stiffness, Empress 2 porcelain sample (Vitapan 1M2 or 2M2 shade) water sorption and colour stability1,6. on the mould. The depth of polymerization is very important The specimens were removed from the mould and the in direct composite application and in cementation of inadequately cured soft luting material was removed from veneers7. The curing capacity (depth of cure) of light- the bottom of the mould with a plastic spatula. The height cured luting cements depends on the translucency8 and of the cylinder of the cured material was measured with a the thickness9 of the porcelain material. Light source digital micrometer (Mitutoyo, UK Ltd) to an accuracy of also plays an important role on the depth of cure. ±0.1mm (Mount & others, 2002; Fan & others, 2002; Cobb Type of light1,6,10, light intensity1,11,12, mode1,13 and & others, 2000). The obtained values were divided by 2 and exposure period10 are the effecting factors. Additionally, recorded as the depth of cure, according to ISO 4049:2000. formulation, photo-sensitizer and shade of the resin-based The data were analyzed by ANOVA (SPSS 15.0 cement can be influencing factors on the polymerization package programme) and for multiple comparisons Tukey of the luting material through the porcelain veneer. HSD was used. Different methods can be used to evaluate the efficiency of light-cured materials. Measuring micro- hardness or depth of cure tests are the most common methods for this purpose1. Micro-hardness tests are used as Results an indirect measurement of degree of cure rate8,9, whereas micrometer evaluation is a direct determination method of Mean depth of cure values and standard deviations are depth of cure, which is used in the present study. given in table 1, figure 1 and figure 2. The highest curing The purpose of this in vitro study was to evaluate depth results were obtained with Variolink II Base (shade the effect of shade and thickness of porcelain veneers on A1) under the porcelain laminate with the shade of 1M2 depth of cure of 2 light-cured resin-based luting cements and thickness of 1mm. The mean value for this group was with 2 different shades. 3.05 ± 0.04 mm. 0.93 ± 0.01 mm was the lowest data which was obtained with Rely X (shade A3) under the porcelain laminate with the shade of 2M2 and 1.8 mm thickness. Rely X (shade A3) gave the lowest values under all porcelain Material and Method laminate specimen groups when compared with the other luting cements. Under the porcelain specimens with the In this study, veneer samples (IPS-Empress 2, Ivoclar shade of 2M2 and thickness of 1.8mm, the depth of cure Vivadent, Liechtenstein) were prepared in 1mm and 1.8mm values of all resin cement groups were lowest. thicknesses, 1M2 and 2M2 shades and 10mm diameter. The Rely X Veneer (3M ESPE, Canada) and Variolink II Table 1. Mean and standard deviation of the depth of cure values Base (Ivoclar Vivadent, Liechtenstein) composite resin- based cements were used for determination of depth of Shade and thickness of Shade of the Mean (±) S.D. cure in 2 different shades (A1 and A3). Rely X Veneer is porcelain specimens luting cement (mm) used for only light-curing purposes, whereas Variolink II Rely X, A1 2.72 0.10 can be used as light-cured or dual-cured luting material. Rely X, A3 1.01 0.04 In this study Variolink II base (light-cured) was used to 1M2, 1mm compare with Rely X Veneer. Measurements of depth of Variolink, A1 3.05 0.04 cure were performed according to ISO 4049:2000. Variolink, A3 2.43 0.04 The experimental procedure was as follows: A Rely X, A1 2.42 0.03 stainless steel mould was used for the preparation of a Rely X, A3 0.94 0.02 cylindrical luting composite resin (8mm long x 4mm in 1M2, 1,8mm diameter). A black bottom was chosen for preparing the Variolink, A1 2.67 0.06 samples. The mould was placed onto a strip of transparent Variolink, A3 2.40 0.02 film on a glass microscope slide on the black bottom. The Rely X, A1 2.79 0.09 mould was filled with the test material (Rely X Veneer and Rely X, A3 1.02 0.03 Variolink II Base; A1 or A2 shade), prepared according 2M2, 1mm to the manufacturer’s instructions and care was taken to Variolink, A1 2.75 0.14 avoid air bubbles. The mould was overfilled slightly and Variolink, A3 2.35 0.05 a second strip of the transparent film was placed on the Rely X, A1 2.37 0.03 top, followed by the second microscope slide. The mould Rely X, A3 0.93 0.01 and strips of film were pressed between the glass slides to 2M2, 1,8mm Variolink, A1 2.50 0.03 displace excess material. Polymerization (Kavo Polylux II, 750-mW/cm2) was performed for 40 seconds after placing Variolink, A3 2.32 0.04 Balk J Stom, Vol 13, 2009 Depth of Cure of Light-Cured Resin-Based Luting Cement 43

Figure 1: Mean depth of cure values of each luting cement under Figure 2: Mean depth of cure values of different luting cements under different porcelain specimens same porcelain specimen group

Table 2. Comparison of the mean depth of cure values under Table 3. Comparison of the mean depth of cure values under same porcelain specimens different porcelain specimens

1M2, 1M2, 2M2, 2M2, Rely Rely Variolink Variolink Luting material Porcelain specimens 1mm 1.8mm 1mm 1.8mm X A1 X A3 A1 A3 Rely X A1 a e h k 1M2, 1mm a d f i Rely X A3 b f i l 1M2, 1.8mm b e g i k Variolink A1 c g h m 2M2, 1mm a d g k l Variolink A3 d e j k 2M2, 1.8mm b c e h l

Same letters in the same column indicate non-significant Same letters in the same column indicate non-significant differences differences (p>0.05, Tukey HSD test) (p>0.05, Tukey HSD test)

Table 4. Tests of between-subject effects

Type III Source df Mean Square F Sig. Sum of Squares Type of porcelain ,890 3 ,297 77,063 .000 Resin cement 39,023 3 13,008 3379,036 .000

Type of porcelain & Resin cement ,648 9 ,072 18,713 .000

Comparisons of the mean depth of cure values under Discussion the same and different porcelain specimens are given in tables 2 and 3. Under the porcelain specimen group with The thickness, opacity and shade of composite the shade of 1M2 and thickness of 1mm, the depth of resin materials were reported to reduce the available 14,15 cure values of all resin cement groups were significantly light energy to polymerize light cured resin systems . Therefore in this study the effect of shade and thickness different from each other (p<0.05). of porcelain veneers on depth of cure of 2 light-cured According to the analysis of variance (ANOVA), the resin-based luting cements with 2 different shades was effects of both luting cements and porcelain specimens evaluated. To evaluate the effect of the curing capacity either separately or together on depth of cure were found of the luting cement, depth of cure test method was used. to be significant - p<0.001 (Tab. 4). As stated by Fan et al16 the ISO scraping test used to 44 T. Koksal et al. Balk J Stom, Vol 13, 2009 determine depth of cure requires minimal instrumentation The present study showed that data obtained from and can be performed easily. For this reason this method is Variolink A1, A3 and RelyX A1 resemble each other and also advisable for practitioners to establish the appropriate that they can be used safely in clinical application. curing times for the various resin based composites used in the dental office and periodically verify the adequacy of the curing light and composite performance. It is reported that light curing systems must emit Conclusions radiation between 400 and 500nm9, while the radiation intensity must be at least 280 mW/cm2 to polymerize Within the limitations of this in vitro study, the a 1mm thickness of composite resin17. For composite following conclusions can be drawn: resins, generally, a light intensity of more than 400 mW/ 1. The shade of a luting resin material is an important cm2 is recommended1. Therefore in the present study, a influencing factor on depth of cure. When the shade halogen light cure device (Kavo Polylux II) of 750-mW/ gets darker, the depth of cure significantly decreases; 2 cm was used. 2. The porcelain thickness affects the depth of cure The depth of satisfactory polymerization is very significantly (except Variolink A3). However, the unpredictable in areas where the composite thickness is porcelain shade exerts no effect on the depth of cure; greater than 2mm18. This concept is important in direct 3. When the resin cement Variolink gets darker (A3), composite application. But a very thin layer of luting the porcelain thickness (1mm and 1.8mm) has no resin is sufficient to cement porcelain veneers. Therefore influence on the depth of cure; however, the shade the thickness and opacity of porcelain becomes more does have an effect. important in effecting the polymerization of luting resin cement. O’Keefe et al19 and Strang et al20 determined that thickness of a porcelain veneer affects the intensity of the light source to a greater extent than shade and opacity. The References results of this study supported these findings. Chan and Boyer21 reported similar findings and 1. Jung H, Friedl KH, Hiller KA, Haller A, Schmalz B. Curing efficiency of different polymerization methods through established a formula to predict the required exposure time ceramic restorations. Clin Oral Invest, 2001; 5:156-161. of composite resins under porcelain of varying shades 2. van Dijken JW. Resin-modified glass ionomer cement and and thicknesses. In the present study, similar to the study self-cured resin composite luted ceramic inlays. A 5-year performed by Jung et al1, 40 seconds of exposure time was clinical evaluation. Dent Mater, 2003; 19:670-674. assumed to be enough for a satisfactory polymerization 3. Horn HR. Porcelain Laminate Veneers bonded to etched because of the light intensity of the light-curing device enamel. Dent Clin North Am, 1983; 27:671-684. used. 4. Cheong C, King NM, Pashley DH, Ferrari M, Toledano The results obtained in this study showed that the M, Tay FR. Incompatibility of self-etch adhesives with chemical/dual-cured composites: two-step vs. one-step composition (different brands) and shade of the luting systems. Oper Dent, 2003; 28:747-755. material affected the depth of cure. Besides these affecting 5. Tay FR, Pashley DH, Yiu CK, Sanares AM, Wei SH. Factors factors, porcelain thickness and porcelain shade is also an contributing to the incompatibility between simplified-step influencing variable on depth of cure. adhesives and chemically-cured or dual-cured composites. The obtained results showed that darker shade of Part I. Single-step self-etching adhesive. J Adhes Dent, the resin-based luting material is a significant factor 2003; 5:27-40. on decreasing depth of cure. Especially, Rely X (Shade 6. Usumez A, Ozturk AN, Usumez S, Ozturk B. The efficiency A3) decreased the depth of cure dramatically (nearly 2.5 of different light sources to polymerize resin cement beneath porcelain laminate veneers. J Oral Rehabil, 2004; 31:160– times). According to our results, when a dark shade of 165. resin cement is needed, Variolink is a better alternative 7. Rasetto FH, Driscoll CF, von Frauenhofer JA. Effect of compared to Rely X. When shade of the resin cement light source and time on the polymerization of resin cement is a lighter one (A1), the depth of cure values showed through ceramic veneers. J Prosthodont, 2001; 10:133-139. differences between Variolink and Rely X. But it seems 8. Koch A, Kroeger M, Hartung M, Manetsberger I, Hiller KA, not to be of clinical importance. Schmalz G, Friedl KH. Influence of ceramic translucency on The second finding was that the thickness of curing efficacy of different light-curing units. J Adhes Dent, porcelain veneers influenced the depth of cure, except 2007; 9:449-462. 9. Jung H, Friedl KH, Hiller KA, Furch H, Bernhart S, Schmalz Variolink A3. But also these differences could not be G. Polymerization efficiency of different photocuring units interpreted as clinically important. through ceramic discs. Oper Dent, 2006; 31(1):68-77. The shade of porcelain affected the depth of cure of 10. Barghi N, McAlister EH. LED and halogen lights: effect of Variolink luting material significantly, but this difference ceramic thickness and shade on curing luting resin. Compen is clinically non-significant. Contin Educ Dent, 2003; 24:497-500. Balk J Stom, Vol 13, 2009 Depth of Cure of Light-Cured Resin-Based Luting Cement 45

11. Gagliani M, Fadini L, Ritzmann JM. Depth of cure efficacy 18. Rueggeberg FA, Caughman WF, Curtis JW. Effect of light of high-power curing devices vs. traditional halogen lams. J intensity and exposure duration on cure of resin composite. Adhes Dent, 2002; 4:41- 47. Oper Dent, 1994; 19:26-32. 12. Mills RV, Jandt KD, Ashworth SH. Dental composite 19. O’Keefe KL, Pease PL, Herrin HK. Variables affecting the depth of cure with halogen and blue light emitting diode spectral transmittance of light through porcelain veneer technology. Br Dent J, 1999; 186:388-390. samples. J Prosthet Dent, 1991; 66:434-438. 13. Hammesfahr PD, O’Connor MT, Xiuling W. Light-curing 20. Strang R, McCrosson J, Muirhead GM, Richardson SA. The technology: past, present, and future. Compen Contin Educ setting of visible light-cured resins beneath etched porcelain Dent, 2002; 23(Suppl 1):18-24. veneers. Br Dent J, 1987; 163:149-151. 14. Moseley H, Strang R, Stephen KW. An assessment of visible- 21. Chan KC, Boyer DB. Curing light-activated composite light polymerizing sources. J Oral Rehabil, 1986; 13:215- cement through porcelain. J Dent Res, 1989; 68:476-480. 224. 15. Kanca J 3rd. The effect of thickness and shade on the polymerization of light-activated posterior composite resins. Quintessence Int, 1986; 17:809-811. Correspondence and request for offprints to: 16. Fan PL, Schumacher RM, Azzolin K, Geary R, Eichmiller FC. Curing-light intensity and depth of cure of resin-based Temel Koksal Yeditepe Universitesi composites tested according to international standards. J Am Dis Hekimligi Fakultesi Dent Assoc, 2002; 133:429-434. Bagdat Caddesi No: 238 17. Rueggeberg FA, Jordan DM. Effect of light tip distance on Goztepe 34728, Istanbul polymerization on resin composite. Int J Prosthodont, 1993; Turkey 6:364-370. E-mail: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Burning Mouth Syndrome in a Sample of Turkish Population

SUMMARY F.N. Pekiner, B. Gümrü, S. Özbayrak Objectives: The purpose of this study was to investigate and compare Marmara University, Faculty of Dentistry age, gender, menopause, duration of symptoms, laboratory results, location Department of Oral Diagnosis and Radiology of burning symptoms, type of denture and the psychological aspects accor- Istanbul, Turkey ding to the type of burning mouth syndrome (BMS) in a sample of Turkish population. Methods: 63 patients complaining of burning, pain and xerostomia over the last 6 months or longer were examined clinically and radiographically; laboratory evaluation was performed as well. Non-stimulated whole salivary flow rate was determined. Psychological disturbances were evaluated by the Speilberger State-Trait Anxiety Inventory for anxiety and Zung Self-Rating Depression Scale for depression. Results: Of the total of 63 cases, 50 (79.4%) were females and 13 (20.6%) were males. 34 of these subjects were Type 1 and 29 were Type 2 BMS. There was no statistically significant difference for age, gender, menopause, location of burning symptoms and type of denture between Type 1 and Type 2 groups (p>0.05). Non-stimulated whole salivary flow rate and all data were within normal ranges for both groups. For anxiety and depression, there were no statistically significant differences between Type 1 and Type 2 BMS patients (p>0.05), but anxiety scores (SAI and TAI) of both groups were found to be significantly higher than normal ranges. How ever, Zung Depression Scores for both groups were within normal ranges. All patients had cancer-phobia, and the mean VAS scores were 3.32±0.91 and 3.55±0.95 for Type 1 and Type 2 BMS patients, respectively. Conclusion: The psychological element has been an important aspect of the pathological picture for BMS, and anxiety is the most important factor in both types of BMS. ORIGINAL PAPER (OP) Keywords: Anxiety; Depression; Psychological Disturbance; Visual Analogue Scale Balk J Stom, 2009; 13:46-51

Introduction often accompanied by other phenomena, such as dryness, paraesthesia and changes in the sensations of taste The term Burning Mouth Syndrome (BMS) is in (predominantly bitter or metallic) and smell. This condition widespread use, although in the past, terms such as is known as BMS7-10,18,19,25-27,36,40,42. The aetiology and glossodynia, glossalgia, stomatodynia, stomatopyrosis pathogenesis are unknown2,3,5,6,16,21,23,26-28,32,34,38-41, but and oral dysaesthesia have been used to describe patients recently, the psychological element has been an important complaining of intra-oral burning symptoms. When aspect of the pathological picture4,12,15,17,18,32,37,42. The the burning symptoms persist for over 6 months, and prevalence of BMS is unknown25, but international objective clinical findings of local and systemic disorders estimates of the prevalence vary from 0.7% to 15%27,35,40, have not been demonstrated, in contrast to the clinically and a higher prevalence is found among middle-aged normal appearance of the oral mucosa, patients with women8,18,20,36, mean age ranging between 55-60 years8,18,36. burning symptoms pronounce excessive complaints, The site of burning is variable, but most often affects the Balk J Stom, Vol 13, 2009 Burning Mouth Syndrome 47 tongue, followed by the palate, upper alveolus, lips and persists throughout the day; in Type 3 BMS, patients have the lower denture bearing area. More than 1 site is usually symptoms-free days. affected and there is nearly always a bilateral involvement. The patients were requested to sign a written Other sites in the oral mucosa and the throat may be informed consent statement. The study was carried involved8,9,20,30,33,35,37,38. out according to the recommendations of the Helsinki The pattern of daily symptoms seems fairly stable declaration. for the individual patient. The symptoms of BMS tend to At their first examination, the patients were given a fall into three broad categories: Type 1, Type 2 and Type chart containing a 10 cm horizontal visual analogue scale 3. There are similarities between these subtypes. In Type (VAS) to record the degree of their discomfort due to the 1 BMS, patients suffer no symptoms on waking, but pain. The left end of the scale indicated “no discomfort” the burning begins and increases in severity as the day and the right end “unendurable discomfort”7,20. Patients goes on; in Type 2 BMS, patients suffer from burning were asked about possible “symptoms of the climacteric” 20 on waking and it persists throughout the day; in Type 3 and “cancer-phobia” . BMS, patients have symptom-free days and also complain Saliva collections were always performed between 9 of involvement at unusual sites, such as the floor of the and 11 am. Subjects were instructed not to eat, consume mouth or the throat21. fluids, brush teeth and smoke for 1 hour prior to the The purpose of this study was to investigate investigation. Non-stimulated whole saliva was collected and compare the age, gender, menopause, duration from all of the patients. The patients were asked to bend of symptoms, laboratory results, location of burning their heads forward and after an initial swallow, to allow symptoms at the oral mucosa, type of dentures and the saliva to flow into the mouth. Subjects expectorated the psychological aspects in relation to the type of BMS in a saliva into a test tube once per min for 5 min, and the flow sample of Turkish population rate was recorded in ml/min. UWSFR of <0.1 ml/min was considered very low, 0.1-0.2 ml/min low, and >0.2 ml/min normal24. In this study, we investigated 63 patients using the Material and Methods Speilberger State-Trait Anxiety Inventory for anxiety (SAI-TAI)18 and Zung Self-Rating Depression Scale for depression (ZDS)44. The border line of the SAI-TAI A total of 63 patients with burning or pain symptoms for adults is 33.97 and 42.65, respectively. The answers were examined in the Department of Oral Diagnosis and given to each question in ZDS were graded from 1 to 4. Radiology, Faculty of Dentistry, Marmara University in According to this, the following grading system was used Istanbul, Turkey. The diagnosis of BMS was based on to determine the severity of depression: less than 50 - established diagnostic criteria7,12,20,21,24,27,31: (1) Patients within normal range, no psychopathology; 50-59 - mild were initially interviewed for complaints of dysgesia, depression; 60-69 - moderate depression; 70 and above - xerostomia, burning, and/or painful sensations in the oral severe depression. cavity; (2) All patients underwent a thorough clinical Statistical analysis of the study was performed by examination of the head and neck region to the oral cavity using GraphPad Prisma V.3 programme. Descriptive and dental status. If dentures were worn then their design statistical methods (mean, standard deviation) were used and condition were assessed; (3) All patients underwent for the evaluation of the data. Independent t-test was used radiographic examination including panoramic radiographs for the comparison of 2 groups and the quantitative data and additional radiographs as necessary to exclude organic was compared by chi-squared test. The value of p<0.05 findings; (4) Laboratory evaluation included fasting blood was considered significant. glucose, haemoglobin, haematocrit, levels of vitamin B12, serum iron, total iron binding capacity, folic acid; (5) Non-stimulated whole salivary flow rate (UWSFR) was determined in all patients; 6. Patients suffering from Results systemic or local conditions, such as diabetes mellitus, lichen planus, neuralgia, chronic pain conditions in other Of the total of 63 cases of BMS identified, 50 regions and geographic tongue were excluded from the (79.4%) were females and 13 (20.6%) were males. No study; (7) Patients were interviewed if the complaints statistically significant difference was found in relation could be relieved by eating or drinking; (8) History of to age between female and male patients (Tab. 1). Type 1 regularity of BMS over the last 6 months or longer; (9) BMS was detected in 34 and Type 2 BMS in 29 of these Type of the BMS was recorded - in Type 1 BMS, patients subjects; no Type 3 BMS patients were detected in this suffer no symptoms on waking, but the burning begins study (Tab. 2). and increases in severity as the day goes on; in Type The comparison of Type 1 and Type 2 BMS patients 2 BMS, patients suffer from burning on waking and it was performed using independent t-test. The mean ages 48 F.N. Pekiner et al. Balk J Stom, Vol 13, 2009 of Type 1 and Type 2 BMS patients were 49.41±13.45 Table 2. Comparison of type 1 BMS and type 2 BMS patients and 52.45±9.69, the mean duration of symptoms reported according to age, duration of symptoms and non-stimulated salivary flow rate (UWSFR) by these patients were 2.54±3.21 and 3.24±2.38 years, and the mean UWSFR of 2 groups were 0.45±0.06 Type 1 (n:34) Type 2 (n:29) tp and 0.33±0.04 ml/min, respectively. There were no mean±SD mean±SD statistically significant differences in age, duration of Age 49.41 ± 13.45 52.45 ± 9.69 -1.01 >0.05 Duration of symptoms and UWSFR between Type 1 and Type 2 stimulation 2.54 ± 3.21 3.24 ± 2.83 -0.91 >0.05 BMS patients (Tab. 2). In addition, UWSFR were within (yr) normal ranges for both groups. UWSFR 0.45 ± 0.06 0.33 ± 0.04 -0.21 >0.05 (ml/min)

Table1. Comparison of male and female patients with BMS A chi-square test was applied to determine whether according to age there was a difference in relation to gender, menopause, location of burning symptoms and types of denture Male (n:13) Female (n:50) Patients tpbetween Type 1 and Type 2 BMS patients. No statistically mean±SD mean±SD significant relationships were observed in relation to all Age 52.08 ± 7.53 50.48 ± 12.81 0.42 >0.05 these parameters (Tab. 3).

Table 3 Evaluation of type 1 BMS and type 2 BMS patients according to gender, menapouse, type of denture and sites

Type 1 Type 2 (n: 34) (n: 29) Male 8 (23.5%) 5 (17.2%) χ²:0.37 Gender Female 26 (76.5%) 24 (82.8%) p>0.05 Post-menopause 9 (26.5%) 6 (20.7%) χ²:2.33 Menopause Menopause 9 (26.5%) 13 (44.8%) p>0.05 Non-menopause 8 (23.6%) 5 (17.3%) No denture 5 (14.7%) 1 (3.4%) Full removable denture 6 (17.6%) 5 (17.2%) χ²:6.80 Type of denture Partial removable denture 4 (11.8%) 7 (24.1%) p>0.05 Fixed denture 13 (38.2%) 6 (20.7%) Partial removable + fixed denture 6 (17.6%) 10 (34.5%) Buccal mucosa + lips 12 (46.2%) 4 (19%) χ²:3.80 Sites Buccal mucosa + tongue 9 (34.6%) 11(52.4%) p>0.05 Buccal mucosa + palate + lips 5 (19.2%) 6 (28.6%)

Table 4. The laboratory tests of all BMS patients

Type 1 (n: 34) Type 2 (n: 29) tp Mean ± SD Mean ± SD Fasting blood glucose 91.65 ± 13.34 91.08 ± 15.63 0.16 >0.05 Hb 13.72 ± 1.90 13.38 ± 1.68 0.76 >0.05 Hct 40.24 ± 3.65 39.31 ± 4.53 0.91 >0.05 Fe+2 99.29 ± 32.75 87.28 ± 35.75 1.39 >0.05 Fe+2 binding 356.76 ± 71.62 335.59 ± 87.14 1.06 >0.05 Vit. B12 332.76 ± 149.51 397.55 ± 181.69 -1.55 >0.05 Folic acid 8.47 ± 3.30 8.72 ± 4.47 -0.26 >0.05 Normal values: Fasting blood sugar:70-120mg % Hb:14-17gr % male, 12-14gr% female Hct: 40-54ml % male, 37-47ml % female Fe+2: 40-150 UG/DL Fe+2 binding: 200-460 UG/DL Vit B12: 150-825 PG/ML Folic acid: 3-17 ng/ml Balk J Stom, Vol 13, 2009 Burning Mouth Syndrome 49

Table 4 presents the laboratory results of Type 1 complaints, and the time constitute important factors in and Type 2 BMS patients. There were no statistically differential diagnosis10,19,26,30,40. significant differences in relation to the laboratory This study showed that there seemed to be no results between the investigated groups (p>0.05), and all correlations between denture usage, hormonal effects, laboratory results were within normal ranges. nutritional disturbances, vitamin deficiency, anaemia, Table 5 summarizes psychological component salivary flow rate and the type of the BMS. All data was for Type 1 and Type 2 BMS patients. For anxiety within normal ranges. Clinically and radiographically, and depression, there were no statistically significant the soft and hard tissues were observed to be within differences between the groups (p>0.05), but anxiety normal limits. Therefore according to our study it can be scores (SAI and TAI) for both groups were found to be mentioned that dental or medical reasons did not cause significantly higher than the normal ranges. However, BMS. mean Zung Depression scores for 2 groups were The presence of a psychological component in the determined as 45.85±8.45 and 43.52±8.68, respectively, symptoms of the BMS patients has been suggested, such e.g. within normal ranges. In addition, all patients in as elevation in anxiety, depression, somatic reactions to this study had cancer-phobia, and the mean VAS scores stress, neuroticism, and psychiatric disorders1,4,7,11,12,15,17,18 were 3.32±0.91 and 3.55±0.95 for Type 1 and Type 2 ,29,37,42 BMS patients, respectively. There were no significant . Psychometric studies have discovered more severe differences in relation to VAS scores (p>0.05). psychiatric symptoms in BMS patients than in normal populations and other chronic patients, but less severe symptoms than in other psychiatric populations10,25,29,30,37. Table 5. Comparison of type 1 BMS and type 2 BMS patients Zilli et al43 reported depression in 75% of cases and according to Visual Analogue Scale (VAS), The State and Trait anxiety in 41% of cases. Similarly, Rojo et al29 reported Anxiety Inventory (SAI-TAI) and Zung-self Rating Depression that depression was the prevalent psychiatric diagnosis Scale (ZDS) among patients with BMS (31%), anxiety was much less Type 1 (n:34) Type 2 (n:29) common and affected only 8 patients (10.8%). Contrary, tp mean ± SD Mean ± SD anxiety was found to be a more important psychological VAS 3.32±0.91 3.55±0.95 -0.97 >0.05 factor in BMS than depression by Lamey and Lamb22 and 27 SAI 41.12±8.43 39.34±10.73 0.73 >0.05 Pekiner et al . In the present study, psychological component of TAI 48.44±10.14 43.76±11.09 1.75 >0.05 BMS patients was measured by the Speilberger State- ZDS 45.85±8.45 43.52±8.68 1.08 >0.05 Trait Anxiety Inventory for anxiety and Zung Self-Rating Depression Scale for depression. No psychopathologic phenomenon was detected in Type 1 and Type 2 BMS Discussion patients and Zung Depression scores were within normal ranges; however, Speilberger State Anxiety Inventory In the present study, Type 1 and Type 2 BMS patients and Speilberger Trait Anxiety Inventory score were participating the study were mostly women (76.5% and significantly higher, which is in accordance to other 29,43 82.8%, respectively), and the mean ages of patients were studies . 49.41±13.45 and 52.45±9.69, respectively, which is similar This condition may lead to cancer-phobia, and it to the data published in the previous studies8,18,20,25,27,35,36. is important that the dentist working with BMS patients The pain is mainly located in the anterior two thirds cooperates with the patients’ physician, psychologist or a 14,26 of the tongue (71-78%), followed by the dorsum and multidisciplinary pain clinic . the right and left sides of the tongue, the anterior part of In conclusion; many organic causes have been the hard palate and lips. Other sites in the oral mucosa proposed as possible aetiological factors for burning and the throat may also be involved. More than one site symptoms, including local irritation by environmental is usually affected and there is nearly always bilateral factors, but the psychological element has been an involvement13,21,33,35,37,38. In the present study, we noted important aspect of the pathological picture for BMS, that more than one site was usually affected. The burning and anxiety is the most important factor in all types of the sensation was mostly in the buccal mucosa and lips for condition. Detailed and correct history of the patients with Type 1 and in the buccal mucosa and tongue for Type 2 psychosomatically originated BMS is an obligation for the BMS patients. definite diagnosis and skills of the clinician is required In previous studies, BMS was considered as a for that process. In addition, reference of such patients to diagnosis in which a dental or medical cause has been experienced clinics or dentists is important in achieving excluded. The clinically normal appearance of the oral the life quality standards and the proper treatments of all mucosa, which contrasts with the patient’s pronounced types of BMS patients. 50 F.N. Pekiner et al. Balk J Stom, Vol 13, 2009

References 21. Lamey PJ, Lamb AB. Prospective study of aetiological factors in burning mouth syndrome. Br Med J, 1988; 1. Al Quran FA. Pyschological profile in burning mouth 296:1243-1246. syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol 22. Lamey PJ, Lamb AB. The usefulness of the HAD scale in Endod, 2004; 97:339-344. assessing anxiety and depression in patients with burning 2. Bergdahl M, Bergdahl J. Burning mouth syndrome: mouth syndrome. Oral Surg Oral Med Oral Pathol, 1989; Prevalence and associated factors. J Oral Pathol Med, 1999; 67:390-392. 28:350-354. 23. Lamey PJ, Murray BM, Eddie SA, Freeman RE. The 3. Botha PJ, van der Bijl, van Eyk AD. A literature review and secretion of parotid saliva as stimulated by 10% citric acid pilot study to characterize the treatment of burning mouth is not related to precipitating factors in burning mouth syndrome. SADJ, 2001; 56:353-358. syndrome. J Oral Pathol Med, 2001; 30:121-124. 4. Browning S, Hislop S, Scully C, Shirlaw P. The 24. Narhi TO, Meurman JH, Ainamo A, Nevalainen JM, association between burning mouth syndrome and Schmidt-Kaunisaho KG, et al. Association between salivary psychosocial disorders. Oral Surg Oral Med Oral Pathol, 1987; 64:171-174. flow rate and the use of systemic medication among 76-, 5. Carlson CR, Miller CS, Reid KI. Psychosocial profiles of 81-, and 86-year-old inhabitants in Helsinki; Finland. J Dent patients with burning mouth syndrome. J Orofac Pain, 2000; Res, 1992; 71:1875-1880. 14:59-64. 25. Palacios-Sanchez MF, Jordana-Comin X, Gracia-Sivoli CE. 6. Danhauer SC, Miller CS, Rhodus NL, Carlson CR. Impact Burning mouth syndrome: A retrospective study of 140 cases of criteria-based diagnosis of burning mouth syndrome on in a sample of Catalan population. Med Oral Patol Oral Cir treatment outcome. J Orofac Pain, 2002; 16:305-311. Bucal, 2005; 10:388-393. 7. Eli I, Kleinhauz M, Baht R, Littner M. Antecedents of 26. Pedersen AML, Smidt D, Nauntofte B, Christiani CJ, Jerlang burning mouth syndrome (glossodynia) - Recent life events BB. Burning mouth syndrome: Etiopathogenic mechanisms, vs. psychopathologic aspects. J Dent Res, 1994; 73:567-572. symptomatology, diagnosis and therapeutic approaches. 8. Gorsky M, Silverman S, Chinn H. Clinical characteristics Oral Biosci Med, 2004; 1:3-19. and management outcome in the burning mouth syndrome. 27. Pekiner FN, Özbayrak S, Çanakçı E. Burning mouth An open study of 130 patients. Oral Surg Oral Med Oral Pathol, 1991; 72:192-195. syndrome in patients wearing prosthesis: Evaluation of type 9. Grushka M, Ching V, Epstein J. Burning mouth syndrome. I and type II. The Pain Clinic, 2005; 17:269-273. Adv Otorhinolaryngol, 2006; 63:278-287. 28. Pinto A, Stoopler ET, DeRossi SS, Sollecito TP, Popovic R. 10. Gruskha M, Epstein JB, Gorsky M. Burning Mouth Burning mouth syndrome: guide for the general practitioner. Syndrome. Am Farm Physician, 2002; 65:615-620. Gen Dent, 2003; 51:458-461. 11. Gruskha M, Sessle BJ, Hawley TP. Psychophysical 29. Rojo L, Silvestre FJ, Bagan JV, De Vincente T. Psychiatric assessment of tactile, pain and thermal sensory functions in morbidity in burning mouth syndrome. Oral Surg Oral Med burning mouth syndrome. Pain, 1987; 28:169-184. Oral Pathol, 1993; 75:308-311. 12. Gruskha M, Sessle BJ, Miller R. Pain and personality 30. Santoro V, Caputo G, Peluso F. Clinical and therapeutic profiles in burning mouth syndrome. Pain, 1987; 28:155- experience in twenty eight patients with burning mouth 167. syndrome. Minerva Stomatol, 2005; 54:489-496. 13. Gruskha M. Clinical features of burning mouth syndrome. 31. Sardella A, Lodi G, Demarosi F, Uglietti D, Carrassi Oral Surg Oral Med Oral Pathol, 1987; 63:30-36. A. Causative or precipitating aspects of burning mouth 14. Hakeberg M, Hallberg LR-M, Berggren U. Burning mouth syndrome: experience from the perspective of female syndrome: A case-control study. J Oral Pathol Med, 2006; patients. Eur J Oral Sci, 2003; 111:305-311. 35:466-471. 15. Hampf G, Vikkula J, Ylipaavalniemi P, Aalberg V. Psychiatric 32. Scala A, Checchi L, Montevecchi M, Marini I, disorders in orofacial dysaesthesia. Int J Maxillofac Surg, Giamberardino MA. Update on burning mouth syndrome: 1987; 16:402-407. overview and patient management. Crit Rev Oral Biol Med, 16. Hugoson A, Thorstensson B. Vitamin B status and response 2003; 14:275-291. to replacement therapy in patients with burning mouth 33. Svensson P, Bjerring P, Arendt-Nielsen L, Kaaber S. Sensory syndrome. Acta Odontol Scand, 1991; 49:367-375. and pain thresholds to orofacial argon laser stimulation in 17. Jerlang B. Burning mouth syndrome (BMS) and the concept patients with chronic burning mouth syndrome. Clin J Pain, of alexithymia - A preliminary study. J Oral Pathol Med, 1993; 9:207-215. 1997; 26:249-253. 34. Svensson P, Kaaber S. General health factors and denture 18. Lamb AB, Lamey PJ, Reeve PE. Burning mouth syndrome: function in patients with burning mouth syndrome and psychological aspects. Br Dent J, 1988; 165:256-260. matched control subjects. J Oral Rehabil, 1995; 22:887-895. 19. Lamey PJ, Hammond A, Allam BF, McIntosh WB. Vitamin status of patients with burning mouth syndrome 35. Tammiala-Salonen T, Hiidenkari T, Parvinen T. Burning and the response to replacement therapy. Br Dent J, 1986; mouth syndrome in Finnish adult population. Community 160:81-84. Dent Oral Epidemiol, 1993; 21:67-71. 20. Lamey PJ, Lamb AB. Lip component of burning mouth 36. Tourne LPM. Burning mouth syndrome. Critical review and syndrome. Oral Surg Oral Med Oral Pathol, 1994; proposed clinical management. Oral Surg Oral Med Oral 78:590-593. Pathol, 1992; 74:158-167. Balk J Stom, Vol 13, 2009 Burning Mouth Syndrome 51

37. van der Ploeg HM, van der Waal N, Eijkman MAJ, van 43. Zilli C, Brooke RI, Lau CL, Merskey H. Screening for der Waal I. Psychological aspects of patients with burning psychiatric illness in patients with oral dysaesthesia by mouth syndrome. Oral Surg Oral Med Oral Pathol, 1987; means of the General Health Questionnaire - twenty-eight 63:664-668. item version (GHQ-28) and Irritability, Depression and 38. van der Waal I. The burning mouth syndrome. Copenhagen: Anxiety Scale (IDA). Oral Surg Oral Med Oral Pathol, Munksgaard, 1990; pp 5-90. 1989; 67:384-389. 39. Vucicevic-Boras V, Topic B, Cekic-Arambasin A, Zadro R, 44. Zung WWK. A self-rating depression scale. Arch Gen Stavljenic-Rukavina A. Lack of association between burning Psychiatry, 1965; 65:12. mouth syndrome and hematinic deficiencies. Eur J Med Res, 2001; 6:409-412. 40. Zakrzewska JM, Glenny AM, Forssell H. Interventions Correspondence and request for offprints to: for the treatment of burning mouth syndrome. Cochrane Database Syst Reu, 2005; (1):CD002779. Dr. Filiz Pekiner Marmara Üniversitesi, Dişhekimliği Fakültesi 41. Zakrzewska JM. The burning mouth syndrome remains on Oral Diagnoz ve Radyoloji Anabilim Dalı enigma. Pain, 1995; 62:253-257. Büyükçiftlik Sok. No: 6 34365 Nişantaşı 42. Zegarelli DJ. Burning mouth: An analysis of 57 patients. Istanbul, Turkey Oral Surg, 1984; 58:34-38. E-mail: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

A Useful Approach to a Combined Implant Application: Report of a Case after a 13-Year Assessment

SUMMARY Gönen Özcan1, Hakan Develioglu2, Bülent Kurtis1, Dilek Nalbant3 Dental implants are commonly used in dentistry. A fixed prosthesis is 1Gazi University, Faculty of Dentistry a generally the preferred method of replacing the missing teeth which are Department of Periodontology, Ankara, Turkey lost for various reasons. In this case, we aimed to evaluate the success of a 2Cumhuriyet University, Faculty of Dentistry Department of Periodontology, Sivas, Turkey different dental implant application supported with a full mouth-fixed bridge 3Gazi University, Faculty of Dentistry in a patient after 13 years of implantation. It seems that a combined implant Department of Prosthodontics, Ankara, Turkey application could be useful . CASE REPORT (CR) Keywords: Dental Implant; Full Mouth Bridge Balk J Stom, 2009; 13:52-55

Introduction 26 and 27 caries was detected as well. In the mandible, except the present teeth 44, 43, 42, 32 and 33, there were The long-term predictability of osseointegrated the edentulous ridges bilaterally (Fig. 1). implants for tooth replacement have been reported by several longitudinal studies, resulting in a wide use of dental implants1,2. Factors that allegedly influence the survival rates of dental implants include the quantity and quality of bone in the selected site3, the lack of keratinized tissue around the implant4, the patients’ periodontal status5, the type of micro-flora in the sulci/pockets of the remaining natural teeth and implants6, the patients’ plaque control7, professional maintenance8, smoking9, parafunctional habits10, and the characteristics of dental implants11. A wide variety of implant designs are available to satisfy the varying needs of patients12. The fixed prostheses are generally preferred as a way of replacing missing teeth. A 65-year-old woman patient applied for her dental cure and rehabilitation with a prosthodontic. The present case report aims: (1) to present a way of treatment of the patient with different dental implants and a full mouth-fixed Figure 1. Intraoral view of the first examination at baseline prosthesis; and (2) to evaluate their long-term results.

Before planning an implant placement, teeth were filled and a periodontal therapy was retrieved Report of a Case for elimination the pockets. Additionally, plaque was reduced via audio-visual educations advised for the Clinical Examination patient. And in general, no systemic disease except a mild Plaque and bleeding on probing was seen slightly. hypertension and menopause was reported. Using any of Moreover, the tooth 33 needed a filling and in the teeth the medicaments for this reason was also not emphasized. Balk J Stom, Vol 13, 2009 Combined Implant Application 53

Radiographic Examination for the patient. Oral hygiene instructions were repeated The panoramic X-ray taken at first visit (March (Fig. 4). 1993) showed that the maxillary teeth 18, 16, and 28, and After 13 years, in 2006, the patient was evaluated mandibular teeth 31, 34, 35, 36, 37, 38, 41, 45, 46, 47, 48 again, radiographically and clinically. A successful bone were missing. A fixed prosthesis was seen on the upper implant interrelationship was noted (Figs. 5 and 6). jaw right site between tooth 15 and 17. In addition, in some areas there was an alveolar bone loss area that was visible on the radiograph (Fig. 2).

Figure 3. Intraoral view of the placed implant after the operation

Figure 2. Panoramic view of the jaws at baseline

Surgical Examination In addition to the clinical examination and radiographs, a model was obtained for better analyzing of the implant placement ridges. As first, a linear incision was performed on the gingiva for exposing the alveolar ridge. Flaps were removed carefully so that the alveolar ridges were visible. Then, holes were created with a special bur under saline irrigation on the right site of the alveolar ridge of the mandible, and holes were created with a special bur on the left site of the alveolar ridge for the blade and other root-form implants. The blade implant Figure 4. Intraoral view of the full mouth bridge on the implants after (Nobel Biocare AB, Goteborg,Sweden) was placed firmly treatment and a drill was used with saline irrigation at ultralow speed to complete the root-form implant (ITI, Straumann, Switzerland) placements (Fig. 3). Care was taken not to do perforations in the mandibular alveolar ridge. The flaps were readapted and sutured with a 3-0 black silk. The patient was instructed to take postoperative Siprosan® (Drogsan, Ankara, Turkey) 4 times daily for 1 week. After 1 week, sutures were removed and recorded, and the healing appeared to be within normal limits, with no complications seen.

Post-op Examination After a 6-month healing period, we examined the related sites and have noted that all implants had successfully integrated, both clinically and radiographically. Full mouth-fixed prosthetic restoration covered the Figure 5. Intraoral view of the full mouth bridge on the implants after remained mandibular teeth and placed implants fabricated 13 years 54 G. Özcan et al. Balk J Stom, Vol 13, 2009

References

1. Apse P, Ellen RP, Overall CM, Zarb GA. Microbiota and crevicular fluid collagenase activity in the osseointegrated dental implant sulcus: a comparison of sites in edentulous and partially edentulous patients. J Periodontal Res, 1989; 24(2):96-105. 2. Buser D, Schenk RK, Steinemann S, Fiorellini JP, Fox CH, Stich H. Influence of surface characteristics on bone integration of titanium implants. A histomorphometric study in miniature pigs. J Biomed Mater Res, 1991; 25(7):889-902. 3. Block MS, Gardiner D, Kent JN, Misiek DJ, Finger IM, Guerra L. Hydroxyapatite-coated cylindrical implants in the posterior mandible: 10-year observations. Int J Oral Figure 6. Panoramic view of the case after completing all treatments Maxillofac Implants, 1996; 20:36-40. after 13 years 4. Artzi Z, Tal H, Moses O, Kozlovsky T. Mucosal considerations for osseointegrated implants. J Prosthet Dent, 1993; 70:427-432. 5. Bauman GR, Mills M, Rapley JW, Hallmon WW. Plaque- Discussion induced inflammation around implants. Int J Oral Maxillofac Implants, 1992; 7:330-337. Dental implant treatment did not become a reliable 6. Kohavi D, Greenberg R, Raviv E, Sela MN. Subgingival and way until 1952, when P I Branemark’s researches of supragingival microflora around healthy osseointegrated implants in partially edentulous patients. Int J Oral bone marrow in the rabbit fibula evolved the idea of Maxillofac Implants, 1994; 9:673-678. osseointegration. Osseointegration is known as a “direct 7. Meffert RM, Langer B, Fritz ME. Dental Implants: A review. structural and functional connection between ordered, living J Periodontol, 1992; 63:859-870. bone and the surface of a load-carrying implant”. It contains 8. Matarasso, Quaremba G, Coraggio F, Vaia E, Cafiero C, the incorporation of non-biological material within the Lang NP. Maintenance of implants: An in vitro study of human skeleton without initiating a rejection phenomenon titanium implant surface modifications subsequent to the and allows for permanent penetration of the soft tissues application of different prophylaxis procedures. Clin Oral without a chronic inflammatory reaction. Osseointegration Implant Res, 1996; 7:64-72. is a dynamic phenomenon that is possible due to the 9. De-Bruyn H, Collaert B. The effects of smoking on early characteristics of the implants composition13. In our case, a implant failure. Clin Oral Implant Res, 1994; 5:260-264. 10. Becker W, Becker B. Replacement of maxillary and good osseointegration was also observed. mandibular molars with single endoosseous implant In the literature there has not been found any case with restorations: A retrospective study. J Prosthet Dent, 1995; 14 implant combination . Our case can have a significant 74:51-55. role from this point of view. Postoperative panoramic films 11. Gher ME, Quintero G, Assad D, Monaco E, Richardson showed a successful implant bone correlation. Additionally, AC. Bone grafting and guided bone regeneration for there was no evidence of implant failure in this case, and immediate dental implants in humans. J Periodontol, 1994; implant failure is very important in implantology14,15. 65:881-891. Partially edentulous patients with single or multiple 12. Josefovici N. Use of an extraction site for implant missing teeth represent another viable treatment population, placement: case report. J Oral Implantol, 2001; 27:204-206. and introduce an additional challenge to achieve a long- 13. Branemark PI, Zarb GA, Albrektsson T. Tissue integrated 16 prostheses: osseointegration in clinical dentistry. Chicago: lasting, successful rehabilitation . In the present case, Quintessence, 1985. the bridge was found physiologically and aesthetically 14. Shen TC. The use of a combination of different dental acceptable17,18. For further evaluation, the patient has been implants in a patient. J Oral Implantol, 1987; 13(3): invited to the recall programme. 454-460. In conclusion, we are of the opinion that in particular 15. Susarla SM, CHuang SK, Dodson TB. Delayed versus cases an application using different dental implants immediate loading of implants: survival analysis and risk rehabilitated with a full prosthodontics could be useful and factors for dental implant failure. J Oral Maxillofac Surg, satisfactory for the patients. 2008; 66(2):251-255. Balk J Stom, Vol 13, 2009 Combined Implant Application 55

16. Montes CC, Pereira FA, Thome G, Alves ED, Acedo RV, 18. Pylant T, Triplett RG, Key MC, Brunsvold MA. A retrospective evaluation of endosseous titanium implants de Souza JR, Melo AC, Trevilatto PC. Failing factors in the partially edentulous patient. Int J Oral Maxillofac associated with osseointegrated dental implant loss. Implant Implants, 1992; 7(2):195-202. Dent, 2007; 16(4):404-412. Correspondence and request for offprints to: 17. Lekholm U, van Steenberghe D, Hermann I, et al. Dr. Hakan Develioglu Osseointegrated implants in the treatment of partially Cumhuriyet University, Faculty of Dentistry edentulous jaws: A prospective 5-year multicenter study. Int Department of Periodontology Sivas, 58140, Turkey Oral Maxillofac Implants, 1994; 9:627. Email: [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Intraosseous Odontoma in the Maxilla and Its Impact on Underlying Teeth. A Case Report

SUMMARY Kleoniki Lyroudia, G. Stephanopoulos Odontomas are the most common odontogenic tumours. They are Aristotle University, Dental School usual ly asymptomatic and often are discovered during routine radiography. Department of Endodontology Here, we report a case of an odontoma located at the anterior maxilla that Thessaloniki, Greece initially caused inflammatory reactions around the overlying teeth; later on, it was associated with a generalized inflammation of the area. Endodontic re-treatment of the 4 front maxillary incisors and 2 surgical procedures were performed aiming the patient to recover. CASE REPORT (CR) Keywords: Odontoma; Maxilla; Endodontic Re-treatment; Apicectomy Balk J Stom, 2009; 13:56-59

Introduction Case Report

Odontoma, one of the most common odontogenic A 40-year-old male reported to a general dentist in tumours, is a tumour-like malformation (hamartoma) in March 2004, complaining of pain to all front maxillary which enamel, dentin or cementum are present. 2 types are teeth (central and lateral incisors). The patient’s medical recognised using criteria of their histological appearance: history was not contributory. Clinically, there were no compound and complex odontomas7. Complex odontomas facial asymmetries or localised swellings and the intraoral are less common than the compound lesions in the ratio examination did not reveal any abnormalities. However, the 1:22,4. They differ in that in the complex odontoma radiological examination using panoramic and intradental calcified tissues are presented as an irregular mass, while periapical radiographs revealed a well defined radiopaque the compound type is composed of tooth-like structures mass situated in bone and underlying the upper central and that can be seen radiographically as opacities. The most lateral incisors, but with a greater density than bone and homogenous tissue can be dentin, while enamel and pre- equal to or greater than that of the teeth (Figs. 1 and 2). The enamel related structures can be totally abnormal in their pre-operative diagnosis was central compound odontoma shape, size and site8. Using clinical criteria, 3 types are and the diffused pain reported by the patient was attributed to its presence. Surgical intervention and extraction of the described: central (intraosseous) odontoma, peripheral odontoma was the treatment of choice. The teeth 21 and and erupted odontoma. Central odontomas occur 22 were already insufficiently treated endodontically, and predominantly in the anterior maxilla and less frequently an apicectomy of 21 and 22 was performed with amalgam in the mandibular molar region. More specifically, in a used for retrograde filling (Fig. 3). rather extended study, it was shown that 55.7% of all odontoma cases were located in the maxilla while 44.3% in the mandible. The anterior portion of the maxilla was the most common location of odontomas3,4. In another study, the proportions regarding odontomas’ localization were for the maxilla (70%) and for the anterior region of the jaw (83%), particularly for the anterior maxilla (62%)1. Odontomas are in general inherited or they are shown after a genetic interference during tooth development. As main causes for the development of an odontoma are mentioned Figure1. Panoramic radiograph. The odontoma is seen overlying teeth trauma, infection, or growth pressure5. 21 and 22 Balk J Stom, Vol 13, 2009 Intraosseous Odontoma 57

Figure 2. Intradental periapical radiograph of the case, before any Figure 3. Intradental periapical radiograph 9 months after the first surgical treatment surgical procedure

Figure 5. Intradental periapical radiograph after endodontic re-treatment of 4 upper incisors

6 months later, the patient returned complaining for the same diffused pain to the front teeth and a general lip swelling. His dentist decided to treat endodontically the tooth 11 (Fig. 3). 3 months later, he was referred to the Department of Endodontology, Dental School, since the clinical symptoms have not subsided. The teeth 11, 12, 21 and 22 responded with great sensitivity to percussion and palpation tests. The patient complained of a light swelling of the area and especially of the upper lip. Teeth 11, 12, 21 and 22 were decided to be re-treated endodontically on the Figure 4. Intradental periapical radiograph following the endodontic basis that all of them were under-filled, simultaneously re-treatment of the teeth 21 and 22 showing signs of localized periapical inflammation 58 K. Lyroudia, G. Stephanopoulos Balk J Stom, Vol 13, 2009

(Figs. 4 and 5). Although re-treatment of all the above Discussion mentioned teeth was sufficiently completed, the patient still complained for diffuse pain in the area and therefore a Odontomas are entities that can cause different second surgical clearance of the area was performed at the complications in the related teeth. Delayed eruption of the oral surgery department in order to eradicate any remnants neighbouring teeth, or occurrence of impacted permanent of the “calcified structure” as it was thought that this was teeth, especially in relation with maxillary central incisor possible reason for continuous pain (Fig. 5). A biopsy of (27%), are mentioned1. Pain, expansion of the cortical the upper lip was taken as well, as the patient complained bone and tooth displacement are referred as well. In the for a light diffused swelling. Antibiotics were prescribed present case, the impacted odontoma was the cause of and given to the patient for a period of 2 weeks. periapical inflammation of the underlying teeth. One of 6 months later the symptoms totally subsided (Fig. 6) the problems that had to be solved was the endodontic and permanent restorations were placed 1 year thereafter re-treatment of the teeth with clinical signs of infection, (Fig. 7). as we believed that microflora in the root canals of the involved underlying teeth, was one of the probable reasons for the patients’ problems, in combination with microleakage. On the other hand, it is well known that in several cases amalgam used as a filling material in periapical surgery can produce hypersensitivity of the neighbouring soft tissues, or even the treated teeth fail to heal as a result of corrosion of the apical amalgam6. Cases like that, may confuse diagnosis, since the signs are not totally clear and radiographically these cases could be held as various other lesions9. Therefore before any treatment plan is decided, there is a need to differentially diagnose cementoblastoma, osteoid osteoma, fibro-osseous lesions from odontomas. A cementoblastoma presents a well defined radiopaque mass attached to a tooth and root and surrounded by a radiolucent area10. Osteoid osteomas are characterized by a small ovoid or round radiolucent area surrounded by a rim of sclerotic bone; the central radiolucency exhibits some calcification Figure 6. Intradental periapical radiograph after the second apicectomy as it matures. Cemento-ossifying fibroma is presented that followed for the upper incisors and removal of the odontoma’s remnants as a well-defined radiolucency with increasing degree of calcification as it matures; it is not surrounded by a radiolucent rim and it is diffused with normal bone10. One of the major drawbacks regarding diagnosis in this case was the lack of histological data for confirmation of the preoperative diagnosis. In the present case, no eruption was mentioned or seen, although we assume that the case started during an eruption process that was followed by inflammation, which was extended and gave signs of periapical inflammation to the underlying teeth. Furthermore it can’t be assessed as well, to what extend the undertreatment of the involved teeth was the cause for the patient’s chief complaints or it was actually the remnants of the odontoma that caused the inflammation signs and discomfort of the patient, as both followed on the same time.

References

1. Chang JY, Wang JT, Wang YP, Liu BY, Sun A, Chiang CP. Figure 7. Periapical tissues radiographically show signs of healing 6 Odontoma: a clinicopathologic study of 81 cases. J Formos months later Med Assoc, 2003; 102:876-882. Balk J Stom, Vol 13, 2009 Intraosseous Odontoma 59

2. Cohen DM, Bhattacharyya I. Ameloblastic fibroma, 8. Veis A, Tziafas D, Lambrianidis T. Delayed eruption of ameloblastic fibroodontoma and odontoma. Oral Maxillofac a central maxillary incisor: Clinical and microscopic Surg Clin North Am, 2004; 16(3):375-384. evaluation. J Endod, 2000; 26(8):477-479. 3. Crincoli V, Scivetti M, Di Bisceglie MB, Lucchese A, 9. Worth HM (ed). Odontomas and cysts of the jaws. In: Favia G. Odontoma: a retrospective study and confocal Principles and practice of oral radiographic interpretation. laser scanning microscope analysis of 52 cases. Minerva Chicago: Year Book Medical, 1963; pp 420-424. Stomatol, 2007; 56(11-12):611-620. 10. Wood NK, Goaz PW, Lehnert J. Mixed radiolucent- 4. Cuesta A, Albiol G, Aytes B, Escoda G. Review of 61 cases radiopaque lesions associated with teeth. In: Wood NK, Goaz of odontoma. Presentation of an erupted complex odontoma. PW (eds). Differential diagnosis of oral and maxillofacial Med Oral, 2003; 8(5):366-373. lesions. Singapore: Harcourt Brace and Company Asia Pte 5. Hitchin AD. The aetiology of the calcified composite Ltd, 1998; pp 289-314. odontomas. Br Dent J, 1971; 130:475-482. 6. Hohenfeldt PR, Aurelio JA, Gerstein H. Electrochemical corrosion in the failure of apical amalgam. Report of two Correspondence and request for offprints to: cases. Oral Surg Oral Med Oral Pathol, 1985; 60(6):658-660. Kleoniki Lyroudia 7. Kitano M, Tsuda-Yamada S, Semba I, Mimura T, Nozoe E, 23, Papafi Str. Setoyama M. Pigmented ameloblastic fibro-odontoma with 54638 Thessaloniki melanophages. Oral Surg Oral Med Oral Pathol, 1994; Greece 77(3):271-275. [email protected]

F J

T ! ! BALKAN JOURNAL OF STOMATOLOGY M ISSN 1107 - 1141 B JD H MP UP TUPNB

Rhino-Orbito-Cerebral Mucormycosis: A Case Report and Review of the Literature

SUMMARY Doxa Mangoudi, Eleni Bourlidou, Rhino-orbito-cerebral mucormycosis is a rare, opportunistic and often Gregory Venetis, Vasilis Antoniadis fatal fungal infection usually occurring in immuno-compromised or diabetic Department of Oral and Maxillofacial Surgery patients. The treatment involves administration of Amphotericin B and surgi- University Clinic “G. Papanikolaou” General Hospital cal debridement. Due to its lethal nature, early recognition of the infection is Thessaloniki, Greece essential. This paper reports a case of rhino-orbito-cerebral mucormycosis, which developed in a 60-year-old female patient with latent diabetes mellitus after a tooth extraction. The patient, unfortunately, succumbed due to the delayed diagnosis. This case study is combined with a review of the literature. CASE REPORT (CR) Keywords: Mucormycosis; Diabetes Mellitus Balk J Stom, 2009; 13:60-64

Introduction Case Report

Rhino-orbital-cerebral mucormycosis (ROCM) is an A 60-year-old female patient was admitted to “G. acute, opportunistic, often fatal fungal infection occurring Papanikolaou” General hospital 2 days after a tooth mainly in diabetics, particularly those with ketoacidosis. extraction, with headache, malaise, left mid-facial pain, Other predisposing factors include leukemia, lymphoma, erythema, swelling and an abscess in the buccal vestibule disseminated neoplasms, extensive burn injuries and resistant to surgical drainage. The patient was well- prolonged corticosteroid or immuno-suppressive therapy. oriented and her vital signs were stable. Her past medical The disease provokes diffuse tissue necrosis. history was not significant, but laboratory examination The fungi invade the walls of blood vessels, causing immediately after the admission revealed uncontrolled thrombosis and ischemia. Progression of the disease diabetes. White blood cells were 18000 per mm3, the is rapid and intracranial dissemination may become blood glucose level 380 mg/dl, while the urine analysis fatal. The disease presents symptoms of sinusitis, nasal showed 3+ for glucose and ketones. ulceration and palatal necrosis, while orbital invasion Within 14 hours the patient’s clinical picture may lead to opthalmoplegia, proptosis, vision loss, and deteriorated significantly. Physical examination showed chemosis. Further progression of the disease may result in left periorbital cellulitis, chemosis, a dilated left pupil non- cerebral involvement with poor prognosis. reactive to light, proptosis with limited movement, and The principles of management comprise a high index decreased vision acuity of the left eye (Fig. 1). Examination of suspicion, early diagnosis and combined treatment with of the nasal cavity showed nothing significant, but the Amphotericin B and aggressive surgical debridement. following day a necrotic lesion on the left side of the Hyperbaric oxygen therapy has also been reported5,37,50. hard palate was revealed during oral examination. The The following report presents a case of ROCM, patient rapidly developed necrotic lesions in the nose, which developed in a patient with latent diabetes who upper lip and left infraorbital area, while chemosis and unfortunately succumbed. A review of the literature is also erythema progressively extended to the right side (Fig. 2). presented. CT scan disclosed occupation of the left maxillary sinus, Balk J Stom, Vol 13, 2009 Rhino-Orbito-Cerebral Mucormycosis 61 a perforated hard palate, and oedema of the left orbit, polymorphonuclear cells in the cerebrospinal fluid. however, without any significant intracranial findings. The patient was finally intubated and admitted to the intensive care unit, where empiric treatment was given with intravenous metronidazole (500mg, 3 times daily), vancomycin (1gr, twice daily) and ceftriaxone (1gr, twice daily).

Figure 3. Photomicrographs showing non-septate right-angled branching hyphae of mucormycosis in the ground of necrotic tissue (HE, 40x10)

Figure 1. Presentation of the patient 14 hours after the admission and the drainage of the abscess

Figure 2. Progressing chemosis and erythema of the left eye, expanding to the right eye. Necrotic lesions in the nose, upper lip and infraorbital area

The patient became progressively disoriented, pre- Figure 4. Final picture of the patient in the intensive care unit. Note the senting neck rigidity. Lumbar puncture was performed extensive necrotic lesions in the left orbit, cheek, nose and the lips and revealing cerebral involvement with a large count of the chemosis and erythema covering almost all the face 62 D. Mangoud et al. Balk J Stom, Vol 13, 2009

A biopsy of the vestibule was performed. The altered sensorium, hemiparesis and meningeal signs40. histopathological findings revealed non-septate fungal Patients with keto-acidosis whose clinical picture does hyphae consistent with mucormycosis (Fig. 3); the not improve after appropriate treatment, may suggest triple antibiotic scheme was stopped and Amphotericin mucormycosis28. Cavernous sinus thrombosis results from B (0.25 mg/kg daily) was administered. However, the spread of infection from the orbit and presents with early patient did not respond to the treatment. During the vision loss. Internal carotid artery thrombosis is a rare following 2 days the left eye became more proptotic complication leading to cerebral ischemia and infarction. and the facial necrosis rapidly spread, extending to the Diagnosis can be made by direct microscopy, right side (Fig. 4). The neurological picture gradually histopathological examination or by culturing on Sabroud’s deteriorated and the patient manifested renal failure and agar. Cultures are often negative, but this should not affect sepsis before unfortunately succumbing. treatment and prognosis47,50. The fungi can be easily detected as aseptate hyphae with right-angled branching on Haematoxylin and Eosin stained sections; with periodic acid-Schiff reaction; or by Grocott-Gomonii methenamine Discussion silver nitrate stained section1,8,29,40,44,37. The predominant histological findings are ischemia and haemorrhaging ROCM is an acute opportunistic fatal fungal necrosis, moderate suppurative inflammation and vascular infection caused by the species Rhizopus, Rhizomucor and thrombosis8,29,44. Plain orbit or sinus radiography are non- Absidia17,42,47. These saprophytic fungi can be found in specific, while CT or MRI are useful imaging modalities soil, bread mould, rotten fruit and vegetables3,36,38,39,49,50, for evaluating the extension of the disease. and seem to infect humans with compromised systemic Initial cerebritis is presented with bifrontal lucencies health. The disease most commonly originates in the oral without mass. Abscess formation and bone destruction can and nasal mucosa where in healthy individuals the spores be easily detected1,8,24. In areas of anatomic complexity, normally parasitize, but are prevented from development where CT or MRI are not helpful, angiography or surgical by the mechanism of phagocytosis. In immuno- exploration should be performed1,15,23. Cerebrospinal fluid compromised patients this mechanism fails, resulting in findings are usually non specific and blood cultures are the development of the infection. rarely positive35. The fungi show a remarkable affinity for arteries and The treatment of ROCM includes correction of any grow along the internal elastic lamina causing thrombosis, underlying disorder, administration of Amphotericin B, and ischemia and infraction6,19,20,22. The infection spreads prompt surgical intervention1. In diabetics, management of from the oral and nasal cavity to the paranasal sinuses the keto-acidosis and dehydration improve overall survival and enters the orbit via the ethmoid and maxillary sinuses, rate, while the management of the immuno-suppressed or through the nasolacrimal duct2. Further progression patients is more difficult to achieve. Hyperbaric oxygen may lead to intra-cerebral extension from the orbit via therapy has been reported as an adjunctive modality5,48, the orbital apex, orbital vessels or via cribriform plate2. as it not only exerts a fungistatic effect but also boosts Diabetes, especially uncontrolled, predisposes to this neovascularization30,31,37. infection8,19,28,38,50. The iron and glucose rich acidic Amphotericin B is a fungostatic agent that is usually environment in diabetics creates suitable conditions for ineffective in eradicating the primary lesion, but it can fungal proliferation14,50. Other factors predisposing to control early micro-metastases41. Doses of 0.7-1 mg/kg/ mucormycosis include haematological malignancies, day are usually recommended26. In the past, Amphotericin extensive burn injuries, chemotherapy, transplantation, B was administered after a test dose and, depending on prolonged corticosteroid or immuno-suppressive the patient’s response, the dosage could be gradually therapy and, rarely, AIDS10,25,34,40,41,47. Also, patients increased. In cases of rapid progression, a sharp increase under deferoxamine therapy should be highly suspect is recommended if the degree of adverse reaction is for mucormycosis as deferoxamine provides iron to tolerated48. Medication side-effects are fever, headaches, Mucorales, facilitating their growth11-13,16,33,45. nausea, vomiting, hypokalemia, thrombophlebitis, ROCM presents with a characteristic clinical picture, azotemia and renal dysfunction. The last years Liposomal consisting of fever, malaise, sinusitis, chemosis, black Amphotericin B replaced conventional Amphotericin B, as nasal eschar, peri-orbital cellulites, and palatal necrosis. it is less nephrotoxic and may enhance delivery properties Paranasal sinuses were involved in all patients7 while sinus to infected areas21,40. The lethal dose (LD50) is 10-15 involvement was found in 69% and 79% according to other higher than that of conventional Amphotericin B27. The authors19,50. As the infection progresses to the orbit, the recommended dose can be raised to 5mg/kg/day. patient manifests ophthalmoplegia, proptosis, chemosis, Extensive surgical debridement enhances survival rate vision loss due to ischemic necrosis of the intraorbital and is necessary except in cases with terminal neoplasms1. cranial nerves, orbital cellulites or ocular invasion of the Orbital exenteration is required in patients with ocular mucorales4,9,43,48,50. Intracranial extension presents with involvement or signs of retinal artery thrombosis8. Balk J Stom, Vol 13, 2009 Rhino-Orbito-Cerebral Mucormycosis 63

Prognosis depends on the nature of the underlying 15. Courey WR, New PF, Price DL. Angiographic manifestations disease, early diagnosis and prompt management1. of craniofacial phycomycosis. Radiology, 1972; 103:329- Diabetics seem to have a better survival rate1,8. Indicators 334. of poor prognosis are hemiparesis or hemiplegia, bilateral 16. de Locht M, Boelaert JR, Schneider YJ. Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating infection, renal disease leukaemia, deferoxamine therapy, 8,48,50 spores of Rhizopus microsporus. Biochem Pharmacol, 1994; palatal and facial necrosis . Considering the fact 47:1843-1850. that even when appropriate treatment is instituted, only 17. Denning DW, Wilson GE. Fungal infections. In: James DG, about half of the ROCM cases survive, it can be easily Zumla A (eds). The granulomatous disorders. Cambridge: concluded that early diagnosis and immediate, aggressive Cambridge University Press, 1999; pp 235-256. treatment are of great importance. 18. Ferry AP. Cerebral mucormycosis (phycomycosis). Ocular findings and review of the literature. Surv Ophthalmol, 1961; 6:1-7. 19. Ferry AP, Abedi S. Diagnosis and management of rhino- References orbito-cerebral mucormycosis (phycomycosis): a report of 16 personally observed cases. Ophthalmology, 1983; 90:1096-1104. 1. Abedi E, Sismanis A, Choi K, Pastore P. Twenty-five years’ 20. Finn DG, Farmer JCJ. Chronic mucormycosis. experience treating Cerebro-Rhino-Orbital Mucormycosis. Laryngoscope, 1982; 92:761-766. Laryngoscope, 1984; 94:1060-1062. 21. Fisher EW, Toma A, Fisher PH, et al. Rhinocerebral 2. Abramson E, Wilson D, Arky RA. Rhinocerebral mucormycosis: use of liposomal amphotericin B. J Laryngol phycomycosis in association with diabetic ketoacidosis. Ann Otol, 1991; 105:575-577. Intern Med, 1967; 66:735-742. 22. Groote CA. Rhinocerebral phycomycosis. Arch Otolaryngol, 3. Baker RD. The phycomycoses. Ann N Y Acad Sci, 1970; 1970; 92:288-292. 174:592-605. 23. Kohn R, Hepler R. Management of limited rhino-orbital 4. Bendet E, Talmi YP, Kronenberg J. Rhino-orbito-cerebral mucormycosis without exenteration. Ophthalmology, 1985; mucormycosis. Otolaryngol Head Neck Surg, 1996; 14:830- 92:1440-1444. 832. 24. Lazo A, Wilner HI, et al. Craniofacial mucormycosis. 5. Bentur Y, Shupak A, Ramon Y, Abramovich A, Walfin Computed Tomographic and angiographic findings in two N. Hyperbaric oxygen therapy for cutaneous/soft tissue cases. Radiology, 1981; 139:623-626. zygomycosis complicating diabetes mellitus. Plast Reconstr 25. Lee F, Mossad SB, Adal KA. Pulmonary mucormycosis. The Surg, 1998; 102:822-824. last 30 years. Arch Intern Med, 1999; 159:1301-1309. 6. Berger CJ, Disque FC, Topazian RG. Rhinocerebral 26. Lehrer R, Howard DH, Sypherd PS, et al. Mucormycosis. mucormycosis: Diagnosis and treatment. Report of two Ann Intern Med, 1980; 93(Part I):93-108. cases. Oral Surg Oral Med Oral Path, 1975; 40:27-33. 27. Lister J. Amphotericin B lipid complex (Abelcet) in the 7. Bhansali A, Bhadad S, Sharma A, Suresh V, Gupta A, Singh treatment of the invasive mycosis: The North American P, Chekarbanti A, Dash RJ. Postgrad Med J, 2004; 80:670- experience. Eur J Haematol, 1996; l57(suppl):18-23. 674. 28. Manigila AJ, Mintz DH, Novak S. Cephalic mucormycosis: a 8. Blitzer A, Lawson W, Meyers BR, et al. Patient survival report of eight cases. Laryngoscope, 1982; 92:755-760. factors in paranasal sinus mucormycosis. Laryngoscope, 29. Marchewsky AM, Bottone EJ, et al. The changing spectrum 1980; 90:635-648. of disease, etiology and diagnosis of mucormycosis. Human 9. Bodenstein NP, Mc Intosh WA, Vlantis AC, et al. Clinical Path, 1980; 11:457-467. signs of orbital ischemia in rhino-orbito-cerebral 30. Marx RE, Ehler WJ, Tayapongsak P, Pierce LW. Relationship mucormycosis. Laryngoscope, 1993; 103:1357-1361. of oxygen dose to angiogenesis induction in irradiated tissue. 10. Boelaert JR. Mucormycosis (zygomycosis): is there news Am J Surg, 1990; 160:519-524. for the clinician? J Infect, 1994; 28:1-6. 31. Marx RE, Johnson RP, Klive SN. Prevention of 11. Boelaert JR, de Locht M, Schneider YJ. The effect of osteoradionecrosis. A randomized prospective clinical trial deferoxamine on different zygomyces. J Infect Dis, 1994; of hyperbaric oxygen versus penicillin. J Am Dental Assoc, 169:231-232. 1985; 111:49-54. 12. Boelaert JR, Van Austen J, de Locht M, et al. Deferoxamine 32. Marx RE, Stern D. Oral and Maxillofacial Pathology. augments growth and pathogenicity of Rhizopus while Hannover Park, IL: Quintessence Publishing, 2003; pp 104- hydropiridinone chelators have no effect. Kidney Int, 1994; 106. 45:667-671. 33. Mc Nabb AA, Mc Kelvie P. Iron overload is a risk factor for 13. Boelaert JR, Van Roost GF, Vergauwe PL, et al. The role zygomycosis. Arch Opthalmol, 1997; 115:919-921. of desferrioxamine in dialysis-associated mucormycosis: 34. Morrison VA, Mc Glove PB. Mucormycosis in the BMT Report of three cases and review of the literature. Clin population. Bone Marrow Transplant, 1993; 11:383-388. Nephrol, 1988; 29:261-266. 35. Mucormycosis. Ann Intern Med, 1980; 93:93-108. 14. Cohen SG, Greenberg MJ. Rhinomaxillary mucormycosis 36. Ochi JW, Harris JP, Feldman JI, et al. Rhinocerebral in a kidney transplant patient. Oral Surg Oral Med Pathol, mucormycosis: results of aggressive surgical debridement 1980; 50:33-38. and amphotericin B. Laryngoscope, 1988; 98:1339-1342. 64 D. Mangoud et al. Balk J Stom, Vol 13, 2009

37. O’Neill MB, Alessi SA, Geirge BE, Piro J. Disseminated 46. Stave GM, Heimberger T, Kerkering TM. Zygomycosis of rhinocerebral mucormycosis: A case report and review of the the basal ganglia in intravenous drug users. Am J Med, 1989; literature. J Oral Maxillofac Surg, 2006; 64:326-333. 86:115-117. 38. Pilsbury HC, Fischer ND. Rhinocerebral mucormycosis. 47. Sugar AM. Mucormycosis. Clin Infect Dis, 1992; 14(sup Arch Otolaryngol, 1977; 103:600-604. 1):126-129. 39. Rangel-Guerra RA, Martinez HR, Saenz C, et al. 48. Talmi YP, Goldschmied-Reouven A, Bakon M, Barshak I, Rhinocerebral and systemic mucormycosis: clinical Wolf M, Horovich Z, Berkovich M, Keller N, Kronenberg experience with 36 cases. J Neurol Sci, 1996; 143:19-30. J. Rhino-orbital and rhino-orbito-cerebral mucormycosis. 40. Ribeiro NFF, Cousin GCS, Wilson GE, Butterworth RTM Otolaryngol Head Neck Surg, 2002; 127:22-31. Woodwards. Lethal invasive mucormycosis: case report and 49. Yanagisawa E, Friedman S, Kundargi RS, et al. recommendations for treatment. Int J Oral Maxillofac Surg, Rhinocerebral phycomycosis. Laryngoscope, 1977; 87:1319- 2001; 30:156-159. 1335. 41. Rubin RH. Infection in the immunosupressed host. In: 50. Yohai RA, Bullock JD, Aziz AA, et al. Survival factors in Scientific American Medicine. Vol 2. Scientific American, rhino-orbital-cerebral phycomycosis. Surv Ophthalmol, Inc, 1982; pp 12-14. 1994; 39:3-22. 42. Salisbury PL, Caloss R, Cruz JM, Powell BC, Cole R, Kohut RI. Mucormycosis of the mandible after dental extraction in a patient with acute myelogenous leukemia. Oral Surg Oral Med Oral Path, 1977; 83:340-344. 43. Schwartz JN, Donnelly EH, Klinworth GK. Ocular and orbital phycomycosis. Surv Ophthalmol, 1977; 22:3-28. 44. Smith JL, Stevens DA. Survival in cerebro-rhino-orbital Correspondence and request for offprints to: zygomycosis and cavernous sinus thrombosis with combined Doxa Mangoudi therapy. South Med J, 1986; 79:340-344. P.O. Box 34 45. Spellberg B, Fu Y, Edwards JE Jr, Ibrahim AS. Combination 570-10, Elta Asvestochori therapy with amphotericin B lipid complex and caspofungin Thessaloniki acetate of disseminated zygomycosis in diabetic ketoacidotic Greece mice. Antimicrob Agents Chemother, 2005; 49(2):830-832. E-mail: [email protected]