Management of anticoagulated patients in dentoalveolar surgery: a clinical comparative study.

OBJECTIVES: This prospective, comparative, clinical study analyzed the postoperative bleeding risk of patients on anticoagulation therapy (AT) who were undergoing tooth extractions and osteotomies. MATERIALS AND METHODS: Patients with the following ATs were included (test groups): (1.) platelet aggregation inhibitors (PAIs), (2.) vitamin K inhibitors, (3.) low molecular weight heparin (LMWH), and (4.) direct oral anticoagulants (DOACs). Patients in the control group were not on any AT (non-AT group). Patients were subdivided into the following treatment groups: (1.) single tooth extraction, (2.) serial extraction (≥ 2 adjacent teeth), and (3.) tooth osteotomy. Pre-, intra-, and postoperative data concerning the treatment, extent of the surgery, and bleeding were recorded and statistically evaluated. RESULTS: There were 15 postoperative bleeding events in 838 patients (1.7%): four (0.7%) in the non-AT group (n = 603 patients) and 11 (4.7%) in the AT group (n = 235 patients). The surgical procedure had no statistically significant effect on postoperative bleeding frequencies. Patients taking vitamin K inhibitors had a significantly higher risk of postoperative bleeding compared with patients without AT (p < 0.00001). Four patients were hospitalized due to the severity of the bleeding (vitamin K inhibitor group). Postoperative bleeding events were all controlled with local hemostatic measures. CONCLUSIONS: The postoperative bleeding risk after tooth extractions and osteotomies in patients continuing AT is low, and bleeding can be controlled with local hemostatic measures. CLINICAL RELEVANCE: AT should be continued in patients undergoing tooth removal procedures under the provision that local hemostatic measures are applied.

Management of anticoagulated patients in implant therapy: a clinical comparative study.

OBJECTIVES: This prospective clinical comparative study aimed to analyze the postoperative bleeding risk of patients continuing their anticoagulation therapy (AT) and undergoing implant surgery and bone grafting procedures. MATERIALS AND METHODS: The treatments ranged from the insertion of single or multiple dental implants over implant exposures to sinus floor augmentation and vertical and/or lateral bone grafting with autologous bone grafts. The patients of the test groups (AT groups) were treated with platelet aggregation inhibitors (PAIs), Vitamin-K inhibitors, Vitamin-K inhibitor withdrawal bridged with heparin (LMWH), or new/direct oral anticoagulants (NOACs/DOACs). Patients of the control group were non-anticoagulated (non-AT group). Surgical procedures were performed in the same manner in all groups. Pre, intra, and postoperative data concerning the treatment, extent of the surgery and bleedings was recorded and statistically evaluated. RESULTS: There were seven postoperative bleedings in 564 patients (1.2%), four in the AT groups (3.4%), and three in the non-AT group (0.6%). No thromboembolic complication occurred in the whole observation period. The invasiveness of the surgical procedure had no statistically significant effect on bleeding frequencies. Patients taking Vitamin-K inhibitors had a significantly higher risk of a postoperative bleeding compared to patients without any AT (P = 0.038). Two patients were hospitalized due to the severity of the bleeding as a precautionary measure (one in the non-AT and one in the PAI group). All bleedings were easily controllable with local hemostatic measures. There was no postoperative bleeding recorded for patients taking DOACs. CONCLUSIONS: Anticoagulation therapy should be continued in patients undergoing implant surgery and bone grafting procedures avoiding thromboembolic complications. Surgeons should always apply the most minimally invasive approach to reduce postoperative risks and be able to apply local hemostatic measures in terms of a bleeding complication.

[Speech Ability and Psychological Outcome After Treatment of Oral Cancer]. / Sprechqualität und psychische Beeinträchtigung nach der Therapie von Mundhöhlentumoren.

BACKGROUND: In recent years interactions between surgical treatment of oral carcinoma and incidence of anxiety or depression have become a subject of discussions. This prospective study is a comparison between the extent of loss of speech intelligibility and presence of depressive symptoms or anxiety as a result of oral carcinoma. MATERIAL AND METHODS: One year after surgical therapy for oral carcinoma, 90 patients of an average age of 60±12 years were examined. Their speech intelligibility degree was measured using standardized automatic speech recognition (word recognition rate, WR). Symptoms of anxiety and depression were detected by use of HAD-Scales (HADS). Next to the relationship between WR and HADS other influential variables related to WR and HADS were statistically evaluated. RESULTS: The WR average was 53.2±17.2. Female WR was better than male. The difference between tumor classifications T1 and T4 compared to the WR reached statistical significance. Significant differences were detected between WR and "tumor localization", "graft donor site", "graft morphology", "tongue motility", and "tracheostoma" groups. There was a relationship between tongue motility and graft morphology, graft donor site and tumor localization. HAD-Scores in the mean were elevated: HADS-Total=43.3%, HADS-A=43.3% und HADS-D= 51.1%. WR correlates with HADS-D-Subscale, but not with HADS-A-Subscale. CONCLUSION: Communication disorders as a result of neoplasmic orofacial surgery may be related to extent of the treatment and to affective impairments. This should receive attention in the concept of rehabilitation.

Macrophage polarisation changes within the time between diagnostic biopsy and tumour resection in oral squamous cell carcinomas--an immunohistochemical study.

BACKGROUND: The prognosis of solid malignancies has been shown to depend on immunological parameters, such as macrophage polarisation (M1/M2). Recently, it was reported that preoperative oral surgery leads to a worsening of oral squamous cell carcinomas (OSCC) prognosis. Diagnostic incision biopsies are oral surgery procedures that might lead to healing-associated M2 macrophage polarisation with a potential negative influence on tumour biology. No studies have compared macrophage polarisation in OSCC biopsies and tumour specimens. METHODS: Preoperative diagnostic incision biopsies (n=25) and tumour resection specimens (n=34) of T1/T2 OSCC were processed for immunohistochemistry to detect CD68-, CD11c-, CD163- and MRC1-positive cells. Samples were digitised using whole-slide imaging, and the expression of macrophage markers was quantitatively analysed. RESULTS: Carcinoma tissues obtained during OSCC tumour resections showed a significantly (P<0.05) increased CD163 cell count (M2 macrophages) compared with tissues obtained during preoperative incision biopsies. Additionally, the CD163/CD68 ratio (an indicator of M2 polarisation) was significantly (P<0.05) higher in tumour resection specimens than in biopsies. CONCLUSIONS: This study revealed for the first time an increase in M2 polarisation in samples obtained during OSCC tumour resection surgery compared with preoperative incision biopsies. The biopsy-induced tissue trauma might explain the observed shift in macrophage polarisation towards the tumour-promoting M2 type and could lead to accelerated tumour progression.

i.lect, a pre-graduate education model of implantology.

OBJECTIVE: In 2008, a consensus meeting of the Association for Dental Education in Europe stated that dental implant treatment represents a popular treatment alternative and, therefore, it should be an integral part of dental student pre-graduate education. In 2009, the Friedrich-Alexander University, Erlangen-Nuremberg implemented a voluntary, structured, education program for pre-graduate dental students, called 'i.lect'. The present study evaluated the effectiveness of the i.lect program. METHODS: Concurrent to the dental curriculum, the i.lect program provides 200 hours in 3 years of theoretical and practical education on all aspects of modern dental implantology. We recruited dental students in the i.lect program and additionally students from 15 other universities that voluntarily participated in a single, 3-day implantology camp (R = 58). To demonstrate their knowledge on dental implant issues, both student groups completed a written examination that covered 'Basic information and materials of implantology', 'Implant planning' and 'Soft tissue management'. RESULTS: The students in the i.lect program achieved higher scores than students from the implantology camp on questions concerning 'basic implantology' and 'implant planning'. CONCLUSION: The results indicated that the structured i.lect undergraduate curriculum enhanced individual knowledge in the specific field of implantology. This program could have pilot character for use in other universities.

Prediction of recurrence using exfoliative cytology and melanoma-associated antigen-A mRNA analysis following wide excision of oral squamous cell carcinoma: short report.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer. The local recurrence of OSSC might result from the existence of occult cancer cells around tumour margins. Exfoliative cytology has lately gained great importance as a method for obtaining RNA samples from suspicious oral mucosal lesions in order to carry out molecular diagnosis. In addition, melanoma associated-A antigens (MAGE-A) are expressed in various tumours and their detection is a highly accurate sign that cancer cells are present. OBJECTIVE: The prediction of a recurrence using MAGE-A mRNA expression analysis to follow-up OSCC cases using a newly established molecular diagnostic technique applied to cytological materials. METHODS: RNA was extracted from three recurrent OSCC cases and from 20 healthy volunteers as a control group using a cytobrush. The expression of MAGE-A3, A4, A6, A10 and A12 was investigated in these specimens using quantitative real-time (RT-PCR). RESULTS: There was no expression of MAGE-A in the specimens of normal oral mucosa. However, the expression analysis of five different MAGE-A genes indicated a high potential for malignant change in biopsy-proven recurrent OSCC cases. Except for MAGE-A10, the rest of the genes were expressed in different ratios by the three recurrent cases, which had been determined on histopathology to be OSCC or carcinoma in situ. CONCLUSION: It is suggested that analysis of MAGE-A expression may be used as a risk prediction method in the diagnosis of recurrence after wide excision of OSCC to enhance the accuracy of exfoliative cytology, which has limitations due to false negative and false positive results.

Survival benefit for patients treated in a certified head and neck tumor center.

OBJECTIVE: Increasing effort has been put in the implementation and certification of head and neck tumor centers in order to establish standardized, quality assured health care for head and neck tumor patients. This study evaluated survival rates after treatment in a certified head and neck tumor center (CHNTC) vs. a non-certified head and neck tumor center (non-CHNTC) in Middle Franconia, Germany. PATIENTS AND METHODS: Age, sex, possible obituary, and typical relevant prognostic variables were analyzed. Diagnosis was recorded according to ICD10. Clinical and pathological TNM staging, tumor grading, localization, R-stage, and morphology were assessed (ICD-0). Patients diagnosed with oral cancer (N=1047) were divided into groups based on where they received their primary treatment; CHNTCs or non-CHNTCs. RESULTS: Patients treated at CHNTCs had significantly higher survival rates vs. those treated at non-CHNTC (p=0.023) in univariate analysis. In a Cox regression model, survival rates for patients with pN0 and pN+ stage were similar at both types of centers. Men with pN0 had significantly lower survival rates (HR=0.497, p<0.001). Age had a statistically significant influence on survival rates independently from pN stage (HR=1.031 per year, p<0.001 in both groups). CONCLUSIONS: Patients treated at CHNTC had better survival rates than those treated at non-CHNTC.

[Enophthalmos correction in complex orbital floor reconstruction : computer-assisted, intraoperative, non-contact, optical 3D support]. / Enophthalmuskorrektur bei komplexer Orbitarekonstruktion : Computerassistierte, intraoperative, berührungsfreie, optische 3D-Unterstützung.

In the case of displacement of the globe such as enophthalmos induced by trauma, the patient is affected on both counts: function and aesthetics. To prevent double vision or conspicuous asymmetry, exact correction of the globe position is required. The aim of this case report is to demonstrate an intraoperative computer-assisted, non-contact, optical 3D procedure for identification of the globe position to aid in placing the eyeball in the position required in complex reconstruction of the orbital floor. A 33-year-old man presented with a sunken eye on the right side in the horizontal and vertical plane 6 months after having undergone surgery elsewhere for a zygomatico-orbital fracture, also including the orbital floor. The patient was affected by double vision and a noticeable defective globe position. In planning the correction of the globe position, a three-dimensional image of the face with opened eyes was made with the optical sensor. Automatic comparison of symmetry revealed enophthalmos of 4 mm on relative en- and exophthalmometry. The decision was made to lift the orbital floor with a split calvarial bone graft. During surgery the position of the globe was also controlled by the three-dimensional optical technique. At the end of surgery there was exophthalmos of 1 mm. Six weeks after surgery the patient was not affected by any double vision. After 3 and 24 months enophthalmos was 1 mm. This case demonstrates how the non-ionizing, non-contact, optical 3D technique can help in planning, intraoperative transformation, and clinical monitoring to identify the correct position of the corneal vertex in complex orbital floor reconstruction.

[Computer-assisted orbital floor reconstruction. Use of a CAD/CAM implant with intraoperative contact-free 3D endo- and exophthalmometry]. / Computerassistierte Enophthalmuskorrektur. Nutzung eines CAD/CAM-Implantats unter intraoperativer, berührungsfreier 3D-en- und exophthalmometrischer Kontrolle.

Pronounced enophthalmos can restrict patients both functionally and aesthetically. Typical symptoms are double vision on both eyes and obvious asymmetry, both of which were present in the 67-year-old male patient presented in this paper. The resulting data of computed tomography was used to fabricate a patient specific ceramic implant for reconstruction of the left orbital floor with an enophthalmos of 4mm. During the surgery the implant fitted anatomically correct, but exophthalmos occurred. The implant needed to be regraded and recontoured in the dorsal fraction, so that overcorrection could be reduced. With the assistance of optical 3D en- and exophthalmometry during surgery, the position of the cornea vertex was reproducible measured. At the end of surgery, exophthalmos was 1.5 mm. After 12 months, enophthalmos of only 1mm exists. This case displays the combination of a patient specific fabricated implant for reconstruction of the orbital floor with optical 3D-en-and exophthalmometry to correct enophthalmos with a high degree of accuracy. Therefore these two techniques in combination should be used when complex corrections of enophthalmos are needed.

The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone defects.

Successful bone-implant osseointegration in large peri-implant bone defects is often difficult, even through autologous bone grafting. Recently, cell-mediated regional gene therapy was introduced to deliver potent morphogens or growth factors in regenerative medicine. We applied liposomal vectors carrying bone morphogenetic protein (BMP)-2 cDNA directly into freshly created peri-implant bone defects on pig calvariae, with or without autologous bone graft. The BMP-2 gene was efficiently introduced into immigrating cells and trabecular cells lining the marginal bone surrounding the bony defect. After 1 week, abundant BMP-2 protein was detected throughout the peri-implant bone defect by immunohistochemistry. At 4 weeks, BMP-producing cells were still present in the defect and peri-implant area, which significantly enhanced new bone formation, compared with the control groups. Interestingly within a week of BMP-2 gene delivery with bone grafts, most osteoblastic cells lining the grafted bone chips also produced BMP-2. Particulated bone was immediately reorganized into newly formed trabecular bone. Grafted bone without BMP-2 gene delivery was still scattered and new bone matrix formation was not detected until 4 weeks after bone grafting. In conclusion, direct application of the BMP-2 gene using a liposomal vector enhanced bone regeneration in a bony defect and gene delivery combined with bone graft could induce a rapid osseointegration of the bone-implant interface at earlier stage.

The interleukin-8 (-251A/T) polymorphism is associated with increased risk for oral squamous cell carcinoma.

AIMS: In light of recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of interleukin-8 gene (IL-8) to increased risk of oral cancer. METHODS: The IL-8 (-251 A/T) polymorphism, which influences IL-8 gene expression, was evaluated by restriction fragment length polymorphism analysis in DNA samples of 158 German and Greek patients with oral squamous cell carcinoma and 156 healthy controls of equivalent sex, ethnicity and age. RESULTS: Significant increase of mutant (A-251) allele, which results in higher IL-8 gene expression, was observed in all patients in comparison to normal controls (P<0.001). The A/T heterozygotes had a two-fold greater risk (odds ratio 1.76, CI 1.11-2.79) for developing oral cancer compared to normal TT homozygotes. Furthermore, significantly increased values of mutant allele frequencies compared to controls were observed in all patients as well as in subgroups of patients with or without positive history of cancer (P<0.05 and P<0.001, respectively) and with or without positive history of thrombophilia (P<0.05 and P<0.001, respectively). CONCLUSIONS: In light to known observations of elevated plasma levels of IL-8 in several types of cancer including oral squamous cell carcinoma, the findings of this study suggest that the mutant allele of the (-251 A/T) polymorphism may be a major contributing genetic factor to risk for oral cancer.

[Solitary fibrous tumor in the tongue: case report and review of the literature]. / Solitärer fibröser Tumor der Zunge: Fallbericht und Literaturübersicht.

Solitary fibrous tumors (SFT) are rare, mostly fibroblastic tumors usually situated in the pleura. Extrapleural manifestations have been described. However, the oral cavity is an uncommon localisation of this tumor. We report the very unusual case of an SFT affecting the tongue that could be removed completely because of its clear delineation. Intraoperative incisional biopsies were used to exclude malignancy. For definitive classification of the tumor, additional histopathologic examinations had to be carried out. Because SFT exhibit malignant behavior only in exceptional cases and their recurrence after complete removal has never been encountered, surgery can focus on the preservation of undisturbed function of the tongue.

State of the art of fusion of computed tomography data and optical 3D images.

When three-dimensional imaging is necessary in dentistry, oral surgery or maxillofacial surgery, conventional computed tomography or cone beam computed tomography is chosen regularly. However, there are two obvious drawbacks. Metallic restorations lead to pronounced streak artefacts in conventional computed tomography. Moreover, the resolution of both conventional computed tomography and cone beam computed tomography is limited to 0.3 mm. This resolution is not sufficient for the fabrication of dental restorations. In order to improve the quality of the two different computed tomography techniques and to eliminate streak artefacts, fusion with optical 3D images can be considered. The resolution of optical 3D images can reach the range of some microms depending on the calibration of the sensor. Metal artefacts do not occur. The fusion of computed tomography images without artefacts and optical 3D images leads to a mean deviation of corresponding points for the two imaging techniques of 0.1262 +/- 0.0301 mm. When computed tomography images with metal artefacts are used, the deviation increases up to 0.2671 +/- 0.0580 mm. The accuracy of image fusion is significantly reduced by metal artefacts (p < 0.0005). When image fusion of computed tomography and optical 3D images is used in clinical studies, the mean deviation of corresponding points for the two imaging techniques for mandible and maxilla is 0.66 +/- 0.49 mm and 0.56 +/- 0.48 mm, respectively. The available data on image fusion show that the quality of computed tomography data without streak artefacts can be significantly improved by registration with optical 3D images. The precision of the fused images exceeds the resolution of the original computed tomography. When streak artefacts are present, image fusion makes it possible to increase the quality of the data to the level of the original resolution of computed tomography without artefacts.

Gingival esthetics and oral health-related quality of life in patients with cleft lip and palate.

While the oral health-related quality of life (OHRQoL) is known to be reduced in patients with cleft lip and palate (CLP), its inter-dependency with the soft tissue characteristics of the CLP area remains unclear. This study aimed to evaluate the soft tissue characteristics in the treated cleft area in order to investigate whether gingival esthetics correlate with OHRQoL. Thirty-six patients with unilateral or bilateral CLP (46 cleft areas) were investigated after secondary/tertiary alveolar bone grafting and orthodontic/prosthetic implant treatment using an adapted score to rate gingival esthetics (clinical esthetic score, CES). The patient's OHRQoL was determined using the German short version of the Oral Health Impact Profile questionnaire (OHIP-G14). The results showed a significantly better rating in patients with their own teeth in situ (12.05±1.10) than in patients with implants (6.95±4.78) or prosthetics (4.00±3.58). The best OHRQoL values were achieved by patients with their own teeth integrated into the cleft area (1.32±2.31), followed by patients with implants (2.33±2.33) and prosthetics (3.75±5.87). A significant (P=0.017) correlation was found between OHIP-G14 and CES scores, suggesting an increased OHRQoL in cases with higher oral esthetics in the cleft area. The therapeutic strategy contributes to both gingival esthetics and OHRQoL. The patient's subjective perception of OHRQoL can be attributed to objective gingival esthetic ratings.

Methylenetetrahydrofolate reductase polymorphism and minor increase of risk for oral cancer.

PURPOSE: We investigated whether the mutant methylenetetrahydrofolate reductase (MTHFR) increases risk for oral cancer. The common germ-line mutation C677T in the MTHFR gene significantly diminishes specific activity of the enzyme, which is responsible for the circulating form of folate. Folate deficiency is associated with increased risk for thrombosis, as well as for several types of cancer, through disruption of DNA methylation, DNA synthesis and deficient DNA repair. METHODS: We searched for the C677T mutation by restriction fragment analysis of PCR products in DNA samples of 110 patients with oral squamous cell carcinoma and 120 healthy controls of comparable ethnicity, age and sex. RESULTS: The number of heterozygotes was significantly different in the two groups (P<0.005), as well as in subgroups of patients with or without a positive family history for cancer, compared to normal controls (P<0.01 and P<0.005, respectively). Furthermore, the subgroup of patients with a positive family history for thrombophilia had a significant increase both in the frequencies of mutant alleles (P<0.01) and heterozygotes (P<0.001) in comparison to normal controls. CONCLUSIONS: The obtained results suggest that the MTHFR mutation is a minor contributing factor in oncogenesis in the oral region, in conjunction with low dietary uptake of folate.

Association of platelet glycoprotein Ia polymorphism with minor increase of risk for oral cancer.

AIMS: In light to association of increased platelet glycoprotein Ia (GPIa) expression with tumor invasion and metastasis in several types of cancer, we investigated the possible contribution of a common polymorphism (C807/T807), affecting the GPIa gene expression, in the development of oral cancer. METHODS: DNA samples of 110 patients with oral cancer and 114 healthy controls were examined by allele-specific polymerase chain reaction followed by electrophoretic analysis. RESULTS: The mutant T807 allele homozygotes were significantly increased in the group of patients compared to the control group (P < 0.001). Furthermore, significantly increased frequency of mutant alleles compared to controls was observed in the subgroup of patients with a positive history for cancer (P < 0.01). CONCLUSIONS: The obtained results indicate that the C807/T807 polymorphism is indeed a genetic predisposing factor which contributes to increased risk for oral cancer.

Plasminogen activator inhibitor-1 polymorphism is associated with increased risk for oral cancer.

In light of the recently observed contribution of thrombosis-related factors to carcinogenesis, we investigated the possible association of plasminogen activator inhibitor-1 (PAI-1) with increased risk for oral cancer. In DNA samples of 104 patients with oral squamous cell carcinoma and 106 healthy controls of comparable ethnicity, age and sex, we studied the 4G/5G polymorphism in the PAI-1 gene, which affects its expression. The mutant 4G allele and carrier frequencies were significantly increased in patients compared to controls (65.9% versus 49.5%; 88.5% versus 69.8% respectively, P<0.01). That increase was even higher in patients with a positive family history for thrombophilia or without one for cancer (P<0.001). Interestingly, significant difference from controls was observed only in patients with cancer stages I and II. These findings suggest that the 4G allele, by resulting in higher PAI-1 expression, is a major contributing factor in early stages of oral oncogenesis. Possibly, increased PAI-1 promotes initial development of oral cancer through regulation of cell detachment and delays further tumor progression by inhibiting vascularization.

Strong association of interleukin-6 -174 G>C promoter polymorphism with increased risk of oral cancer.

In view of the recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of interleukin-6 (IL-6) with an increased risk of oral cancer. In DNA samples of 162 patients with oral squamous cell carcinoma and 156 healthy controls of comparable ethnicity, age and sex, we studied the -174 G>C polymorphism in the IL-6 gene, which affects its transcription. C allele frequencies were significantly increased in patients compared to controls, 42.6% versus 23.1% (p<0.001). The CC homozygotes had a 7-fold greater risk of developing oral cancer (odds ratio 7.39, 95% CI 2.61-20.92), while the GC heterozygotes had a 4-fold greater risk (odds ratio 3.74, 95% CI 2.29-6.11). A significant increase in C alleles was observed in patients regardless of their smoking or alcohol consumption habits, early or advanced stage of cancer, and presence or absence of a family history for cancer or thrombophilia (p<0.001; Fisher's exact test). These findings suggest that the -174 G>C polymorphism, by affecting IL-6 gene expression, is strongly associated with oral oncogenesis.

Feasibility of an endoscopic approach to the submandibular neck region--experimental and clinical results.

We have investigated the feasibility of an exclusively endoscopic approach to the submandibular region in four pigs, four cadavers and two women. We inflated the subplatysmal space with carbon dioxide at low pressure. The submandibular gland and the jugulodigastric region were easy to identify once the correct anatomical space had been dissected and inflated. Four endoscopic resections of the submandibular gland were done successfully.

Search for a reliable model for bisphosphonate-related osteonecrosis of the jaw: establishment of a model in pigs and description of its histomorphometric characteristics.

The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains unknown, and the development of a reliable experimental model would help to improve our understanding of it. We used 12 domestic pigs of which 6 made up the experimental group and were treated with zoledronate 4mg intravenously weekly for 5 weeks, while the control group (n=6) were given no drugs. On day 60 the right second maxillary and mandibular third molars were extracted. Thirty days later 3 animals in each group were killed; the rest were killed 90 days later. Histopathological specimens from the extraction sites were analysed for bone density, collagen architecture, density of osteons, and the amount of non-mineralised bone. Bone density, amount of non-mineralised bone, and density of osteons differed significantly between the 2 groups (p<0.001 in each case), but the chromatic pattern dictated by the collagen architecture did not. Our results correspond to the observations that have been made in patients with BRONJ, which means that the histomorphometric conditions seen in patients can be reproduced in this experimental setting.