Enhancement of peri-implant bone formation via parathyroid hormone administration in a rat model at risk for medication-related osteonecrosis of the jaw

Purpose@#Dental implant-associated medication-related osteonecrosis of the jaw has been frequently reported in patients administered bisphosphonates (BPs) to prevent osteoporosis. The aim of this study was to investigate the effect of intermittent administration of parathyroid hormone (PTH) on peri-implant bone in the maxillae of ovariectomized rats systemically administered BPs. @*Methods@#Thirty 8-week-old female Sprague-Dawley rats were randomly divided into 3 groups. The OVX-ZP group included ovariectomized rats administered 60 μg/kg of zoledronate once a week for 6 weeks and 30 μg/kg PTH after implant installation. The OVX-Z group included ovariectomized rats administered 60 μg/kg of zoledronate once a week for 6 weeks and saline after implant installation, and the control group included rats that underwent a sham operation and were then administered saline. Rats were sacrificed 4 weeks after implant placement for histomorphometric and micro-computed tomography (CT) analyses. @*Results@#The average bone area percentage was greater in the OVX-ZP group than in the OVX-Z group (53.4%±4.0% vs. 28.9%±9.5%, P=0.01). The bone-to-implant contact ratio was 50.8%±1.4% in the OVX-ZP group and 16.9%±2.4% in the OVX-Z group (P=0.012). The average bone volume ratio as shown on micro-CT was 31.3%±19.8% in the OVX-ZP group and 19.4%±9.3% in the OVX-Z group (P=0.045). The OVX-ZP and OVX-Z groups displayed similar trabecular thickness (0.06±0.004 mm vs. 0.06±0.002 mm) (P>0.05) and trabecular separation (0.21±0.02 mm vs. 0.29±0.13 mm) (P>0.05). However, the number of trabeculae in the OVX-ZP group was significantly higher than that in the OVX-Z group (4.3±1.33/mm3 vs. 2.2±0.19/mm3) (P=0.024). @*Conclusions@#The present findings indicate that intermittently-administered PTH can promote peri-implant bone formation and suggest that PTH administration may aid in effective treatment for medication-related osteonecrosis of the jaw after dental implantation.

Effect of Intermittent Parathyroid Hormone Administration on the Microstructure of Jaw Bone in the Ovariectomized Rats

PURPOSE: Parathyroid hormone (PTH) therapy has drawn attention, as an alternative to anti-resorptive drugs since PTH accelerates bone density by anabolic action. The purpose of this study was to identify the effect of intermittent PTH administration on jaw bones of rat undergone bilateral ovariectomy. MATERIALS AND METHODS: Nine female Sprague-Dawley rats were divided into three groups. PTH group was ovariectomized (OVX) to induce osteoporosis and PTH 30 microg/kg was administered 1 week after the surgery. In OVX group, ovariectomy was performed and only vehicle was administered by subcutaneous injection 3 times per week. Control group was subjected to sham surgery. The animals were sacrificed 8 weeks after the surgery and specimens were obtained from ilium and upper and lower jaw bones. Histological investigation was carried out by using an optical microscope and micro-computed tomography was taken to examine structural property changes in each bone sample. RESULT: In the ilium, the bone volume ratio (bone volume/total volume, BV/TV) of PTH, OVX and control groups was 53.75%+/-7.57%, 50.61%+/-12.89%, 76.20%+/-5.92% (P=0.061) and bone mineral density (BMD) was 1.12+/-0.09, 0.88+/-0.48, 1.38+/-0.07 g/cm3 (P=0.061). In the mandible, BV/TV of PTH, OVX and control groups was 64.60%+/-12.17%, 58.26%+/-9.63%, 67.54%+/-14.74% (P=0.670) and BMD was 1.21+/-0.17, 1.19+/-0.13, 1.27+/-0.18 g/cm3 (P=0.587). In the maxilla, BV/TV of PTH, OVX and control groups was 61.19%+/-8.92%, 52.50%+/-11.22%, 64.60%+/-12.17% (P=0.430) and BMD was 1.20+/-0.11, 1.11+/-0.16, 1.21+/-0.17 g/cm3 (P=0.561). No statistically significant difference was found in any variables in all groups. Histological observation revealed that the ilium in OVX group demonstrated sparsely formed trabecular bones compared with other groups. However, upper and lower trabecular bones did not present significant differences. CONCLUSION: Intermittent administration of PTH appears to affect the microstructure of rat jaw bones, but statistical significance was not found. However, the measurements in this study partly implicated the possible anabolic effect of PTH in vivo.

Biological markers around immediately placed titanium implant in the extraction socket of diabetic and insulin-treated rat maxilla

OBJECTIVES: Dental implants installation in patients with diabetes remains controversial as altered bone healing around implants has been reported. And little is known about the biological factors involved in bone healing around implants. The present study aimed to investigate the biological markers around immediately placed implants in rats with controlled and uncontrolled diabetes. MATERIALS AND METHODS: Twenty rats (40 sites) were divided into the control, insulin-treated and diabetic groups. The rats received streptozotocin (60 mg/kg) to induce diabetes; animals in the insulin-treated group also received three units of subcutaneous slow-release insulin. Two threaded titanium alloy implant (1.2x3 mm) were placed in the extraction socket of the both maxillary first molars and allowed for healing. Bone blocks including implant were harvested at 3 days, 1, 2 and 4 weeks. The levels of bone morphogenetic protein (BMP)-4, transforming growth factor (TGF)-beta1, osteocalcin (OC) and osteonectin (ON) were measured in the peri-implant osseous samples by RT-PCR. RESULTS: The BMP-4 level increased immediately in all groups by day 3, then decreased abruptly in the control and the insulin-treated groups. However, by week 4, all groups showed mostly the same amount of BMP-4 expression. The level of TGF-beta1 also instantly increased by day 3 in the insulin-treated group. This level elevated again reaching the same values as the control group by week 4, but was not as high as the diabetic group. In addition, the expression of OC and ON in the control and insulin-treated groups was higher than that of the diabetic group at 2 weeks and 4 weeks, indicating active bone formation in these groups. CONCLUSION: The immediate placement of titanium implants in the maxilla of diabetic rat led to an unwanted bone healing response. Conclusively, the results of this study suggest that immediate implant insertion in patients with poorly controlled diabetes might be contraindicated.

Soft tissue changes of upper lip and nose following posterosuperior rotation of the maxilla by Le Fort I osteotomy

INTRODUCTION: This study evaluate the soft tissue changes to the upper lip and nose after Le Fort I maxillary posterosuperior rotational movement. MATERIALS AND METHODS: Twenty Skeletal class III patients, who had undergone bimaxillary surgery with a maxillary Le Fort I osteotomy and bilateral sagittal split ramus osteotomy, were included in the study. The surgical plan for maxilla was posterosuperior rotational movement, with the rotation center in the anterior nasal spine (ANS) of maxilla. Soft and hard tissue changes were measured by evaluating the lateral cephalograms obtained prior to surgery and at least 6 months after surgery. For cephalometric analysis, four hard tissue landmarks ANS, posterior nasal spine [PNS], A point, U1 tip), and five soft tissue landmarks (pronasale [Pn], subnasale [Sn], A' Point, upper lip [UL], stomion superius [StmS]) were marked. A paired t test, Pearson's correlation analysis and linear regression analysis were used to evaluate the soft and hard tissue changes and assess the correlation. A P value <0.05 was considered significant. RESULTS: The U1 tip moved 2.52+/-1.54 mm posteriorly in the horizontal plane (P<0.05). Among the soft tissue landmarks, Pn moved 0.97+/-1.1 mm downward (P<0.05), UL moved 1.98+/-1.58 mm posteriorly (P<0.05) and 1.18+/-1.85 mm inferiorly (P<0.05), and StmS moved 1.68+/-1.48 mm posteriorly (P<0.05) and 1.06+/-1.29 mm inferiorly (P<0.05). The ratios of horizontal soft tissue movement to the hard tissue were 1:0.47 for the A point and A' point, and 1:0.74 for the U1 tip and UL. Vertically, the movement ratio between the A point and A' point was 1:0.38, between U1 tip and UL was 1:0.83, and between U1 tip and StmS was 1:0.79. CONCLUSION: Posterosuperior rotational movement of the maxilla in Le Fort I osteotomy results in posterior and inferior movement of UL. In addition, nasolabial angle was increased. Nasal tip and base of the nose showed a tendency to move downward and showed significant horizontal movement. The soft tissue changes in the upper lip and nasal area are believed to be induced by posterior movement at the UL area.

Bone response around immediately placed titanium implant in the extraction socket of diabetic and insulin-treated rat maxilla

INTRODUCTION: Dental implants are used routinely with high success rates in generally healthy individuals. By contrast, their use in patients with diabetes mellitus is controversial because altered bone healing around implants has been reported. This study examined the bone healing response around titanium implants placed immediately in rats with controlled and uncontrolled diabetes. MATERIALS AND METHODS: Twenty rats were divided into the control, insulin-treated and diabetic groups. The rats received streptozotocin (60 mg/kg) to induce diabetes; animals in the insulin-treated group also received three units of subcutaneous slow-release insulin. A titanium implant (1.2x3 mm) was placed in the extraction socket of the maxillary first molar and bone block was harvested at 1, 2 and 4 weeks. RESULTS: Bone formation around the implants was consistently (from 1 to 4 week post-implantation) slower for the diabetic group than the control and insulin-treated group. Bone morphogenesis in the diabetic rats was characterized by fragmented bone tissues and extensive soft tissue intervention. CONCLUSION: The immediate placement of titanium implants in the maxilla of diabetic rats led to an unwanted bone healing response. These results suggest that immediate implant insertion in patients with poorly controlled diabetes might be contraindicated.

Radiographic Bone Density Around Immediately Placed Titanium Implant on the Extraction Socket of Diabetic and Insulin-Treated Rat Maxilla

Template therapy for mouth opening limitation by temporomandibular joint disorders

INTRODUCTION: Limited mouth opening is a representative clinical symptom of temporomandibular disorders (TMD) with anterior disc displacement without reduction (ADDWOR). Various treatment methods have been proposed for patients with ADDWOR. This study examined the clinical effectiveness of template therapy for patients with mouth opening difficulty due to the ADDWOR. MATERIALS AND METHODS: A total of 14 patients (female 12, male 2, average age: 29.1+/-14.4), who had been treated in the template clinic, Sooncheonhyang University Bucheon Hospital, from January of 2006 to December of 2008, were enrolled in this study. The subjects were selected according to the following criteria: more than 2 weeks after the onset of locking, mouth opening range < 35 mm, and confirmed ADDWOR without a synovial pathology by magnetic resonance imaging (MRI). All patients were treated with the template appliance, instructed to wear it while sleeping and exercise for at least 10 hours per day. The maximum mouth opening (MMO) range and pain recognition scores before and after template therapy were recorded and compared. A paired t-test and Wilcoxon's signed rank test were used for statistical analysis. RESULTS: After the periodical follow up, significant improvement in the opening range was observed in the template treatment group. The average MMO range before treatment was 30.2+/-3.5 mm and the average MMO after treatment and follow up was 47.1+/-4.7 mm. The mean amount of mouth opening increment was 16.9+/-5.4 mm (P<0.01) and the pain recognition scores before and after treatment was also improved.(P=0.001) CONCLUSION: The template appliance proved to be efficient for the treatment of TMD with a closed lock and painful joint due to ADDWOR.

Metastasis of adenoid cystic carcinoma of the minor salivary grand to the scalp : A case report

Stress distribution pattern of the different diameter and length of short implants according to the bone quality: 3-D Finite Elements Analysis

Cone-beam computed tomography measurement of the position of the inferior alveolar nerve canal in mandibular prognathism

BACKGROUND AND OBJECTIVES: To determine the anatomic position of the inferior alveolar nerve (IAN) canal in patients with mandibular prognathism using the cone-beam CT (CBCT). MATERIALS AND METHODS: Fifty rami from 25 patients were evaluated. The images were taken by i-CAT and reconstructed 3-dimensionally using the Simplant 11 program. The linear distances between the IAN canal to the buccal cortex (a, a* and a**), from the IAN canal to the alveolar crest (b and b*) and the anterior margin (b**) and finally the buccal cortical thickness (c, c* and c**) were measured at three reference planes (VP, OP and HP). RESULTS: On the left side, the average distance of a, b and c were 7.12, 15.96 and 3.60 mm on the VP plane, respectively. On the OP, the distance of a*, b* and c* was 6.11, 8.83 and 2.63 mm. For the HP, the distance of a**, b** and c** was 4.84, 10.11 and 2.30 mm. On the right side, the distance of a, b and c, on the VP, was 7.10, 16.13 and 3.42 mm, respectively. On the OP, the distance of a*, b* and c* was 4.77, 8.75 and 2.68 mm. On the HP, the distance of a*, b* and c** was 4.55, 9.84 and 2.38 mm. Regarding the difference between genders, the distance in male's was longer than female's on the VP (p=0.019), and was thicker in males than females on the HP (p=0.002). CONCLUSION: The CBCT data provided accurate information about the location and course of the IAN.

Cone-beam computed tomography measurement of the position of the inferior alveolar nerve canal in mandibular prognathism

BACKGROUND AND OBJECTIVES: To determine the anatomic position of the inferior alveolar nerve (IAN) canal in patients with mandibular prognathism using the cone-beam CT (CBCT). MATERIALS AND METHODS: Fifty rami from 25 patients were evaluated. The images were taken by i-CAT and reconstructed 3-dimensionally using the Simplant 11 program. The linear distances between the IAN canal to the buccal cortex (a, a* and a**), from the IAN canal to the alveolar crest (b and b*) and the anterior margin (b**) and finally the buccal cortical thickness (c, c* and c**) were measured at three reference planes (VP, OP and HP). RESULTS: On the left side, the average distance of a, b and c were 7.12, 15.96 and 3.60 mm on the VP plane, respectively. On the OP, the distance of a*, b* and c* was 6.11, 8.83 and 2.63 mm. For the HP, the distance of a**, b** and c** was 4.84, 10.11 and 2.30 mm. On the right side, the distance of a, b and c, on the VP, was 7.10, 16.13 and 3.42 mm, respectively. On the OP, the distance of a*, b* and c* was 4.77, 8.75 and 2.68 mm. On the HP, the distance of a*, b* and c** was 4.55, 9.84 and 2.38 mm. Regarding the difference between genders, the distance in male's was longer than female's on the VP (p=0.019), and was thicker in males than females on the HP (p=0.002). CONCLUSION: The CBCT data provided accurate information about the location and course of the IAN.

Inferior alveolar nerve injury following removal of mandibular third molar and panoramic radiological risk sign

The hypermethylation of E-cadherin gene in oral squamous cell carcinoma

Loss of E-cadherin (E-cad) expression has been found in multiple cancers and is postulated to facilitate tumor cell dissociation and metastais. Promotor methylation may provides an alternative pathway for loss of gene function. This study evaluated the role of hypermethylation in the down-regulation of E-cad in oral squamous cell carcinoma (OSCC). We examined the E-cad expression by immunohistochemical staining and detected methylation status by methylation-specific polymerase chain reaction (MSP) in 20 OSCC tissues. Overally, 12 (60 %) cases of hypermethylation of E-cad were detected and we found there were no correlation between methylation and age, histologic grade, lympn node metastasis, tumor size and clinical stage. However, Eleven (73.3 %) of 15 samples which was negative for E-cad staining showed hypermethylation of E-cad promotor region. On the other hand, only one (20 %) of 5 E-cad positive sample was observed with methylated status. The underexpression of E-cad was found to be related to promotor hypermethylation (p=0.035). In conclusion, we suggest that hypermethylation play a role in inactivation of E-cad gene and may be a appreciable biomarker for diagnosis and treatment of OSCC.

The hypermethylation of E-cadherin gene in oral squamous cell carcinoma

Loss of E-cadherin (E-cad) expression has been found in multiple cancers and is postulated to facilitate tumor cell dissociation and metastais. Promotor methylation may provides an alternative pathway for loss of gene function. This study evaluated the role of hypermethylation in the down-regulation of E-cad in oral squamous cell carcinoma (OSCC). We examined the E-cad expression by immunohistochemical staining and detected methylation status by methylation-specific polymerase chain reaction (MSP) in 20 OSCC tissues. Overally, 12 (60 %) cases of hypermethylation of E-cad were detected and we found there were no correlation between methylation and age, histologic grade, lympn node metastasis, tumor size and clinical stage. However, Eleven (73.3 %) of 15 samples which was negative for E-cad staining showed hypermethylation of E-cad promotor region. On the other hand, only one (20 %) of 5 E-cad positive sample was observed with methylated status. The underexpression of E-cad was found to be related to promotor hypermethylation (p=0.035). In conclusion, we suggest that hypermethylation play a role in inactivation of E-cad gene and may be a appreciable biomarker for diagnosis and treatment of OSCC.

Osteogenesis by BMP-2 in adult stem cell derived from buccal fat pad

Bone morphogenetic proteins (BMPs) in combination with stem cells gain more significance for their use in bone tissue engineering. The mesenchymal stem cell can be differentiated into osteoblast by the treatment of BMP. The aim of this study is to characterize the osteogenic differentiation process of adult stem cells derived from buccal fat pad according to BMP-2 within culture media and decide the appropriate concentration of BMP-2 to facilitate osteogenesis. The authors procured the stem cell from buccal fat pad and analyzed for presence of stem cell by flow cytomety against CD-34, CD-105 and STRO-1. The buccal fat derived stem cells (BFDC) were treated by application of the different concentration with BMP-2 of 0, 10, 50, 100 and 200ng/ml, respectively. And their ability to differentiate into osteogenic pathway were checked by alkaline phosphatase(ALP) staining, Alizarin red staining and RT-PCR for osteocalcin(OC) gene expression at 7, 14 and 21day of culture. Flow cytometric analysis and biochemical assays demonstrated that BFDC might be a distinguished stem cells, and mineralization was accompanied in proportion to BMP-2 concentration. However, with 100ng/ml concentration of BMP-2, the BFDC demonstrated most efficent staining pattern of ALP and Alizarin red. The feasibilty of the osteogenic differentiation in the group of both 50ng/ml and 200ng/ml of BMP-2 showed similar activity and relatively weaker than that of 100ng/ml. These results suggest that the BMP-2 stimulate osteogenesis by BFDC effectively and that bone induction might be controlled through negative regulatory feedback in higher concentration.

Expression of BMP4, BMP6 following sinus elevation with DBBP in rabbit

0.05). 2. The expression of BMP6 increased at postoperative 1 and 3 days in both DBBP group and AGS group. In AGS group, it decreased at postoperative 5 days, increased again at postoperative 7 days, and decreased at postoperative 9 days. In DBBP group, it increased until postoperative 7 days and decreased at postoperative 9 days. Although the expression of BMP6 was higher in AGS group compared with DBBP group, it was not statistically significant (p>0.05). 3. There was no statistically significant difference in BMP expression in both groups during same period of time. It's probably because DBBP and AGS both functioned as a space retainer so that the BMP expression in blood clot seemed to be similar. 4. Thus, DBBP would not offer many benefits for early bone regeneration compared with AGS. The expression of BMP in early bone formation seems to be more influenced by physical carrier rather than the graft type.

Basaloid squamous cell carcinoma in the maxillary sinus

Basaloid squamous cell carcinoma (BSCC) is uncommon and distinct variant of squamous cell carcinoma that arises mostly in the upper aerodigestive tract and aggressive, high grade tumor with an increased tendency to be deeply invasive, multifocal, and metastatic even at the initial presentation. The typical microscopic features of carcinoma with a basaloid pattern in intimate association with a squamous component helps in diagnosis of this tumour. Since Wain's report in 1986, BSCC of oral cavity, the palate, floor of the mouth, nasopharynx, oropharynx and mastoid region have been reported. However, BSCC in the nasal cavity or in the paranasal sinuses is rare and there are few reports in the Korean literature. We had experienced a case of basaloid squamous cell carcinoma that occurred in the left maxillary sinus of 72-year-old woman and reported with review of the clinical and pathologic features from the literature.

Expression of e-cadherin and beta-catenin in relation to clinicopathologic features in oral squamous cell carcinoma

Differentiation of adult stem cell derived from buccal fat pad into osteoblast

For the repairing of bone defect, autogenous or allogenic bone grafting remains the standard. However, these methods have numerous disadvantages including limited amount, donor site morbidity and spread of diseases. Tissue engineering technique by culturing stem cells may allow for a smart solution for this problem. Adipose tissue contains mesenchymal stem cells that can be differentiate into bone, cartilage, fat or muscle by exposing them to specific growth conditions. In this study, the authors procured the stem cell from buccal fat pad and differentiate them into osteoblast and are to examine the bone induction capacity. Buccal fat-derived cells (BFDC) were obtained from human buccal fat pad and cultured. BFDC were analyzed for presence of stem cell by immunofluorescent staining against CD-34, CD-105 and STRO-1. After BFDC were differentiated in osteogenic medium for three passages, their ability to differentiate into osteogenic pathway were checked by alkaline phosphatase (ALP) staining, Alizarin red staining and RT-PCR for osteocalcin (OC) gene expression. Immunofluorescent and biochemical assays demonstrated that BFDC might be a distinguished stem cells and mineralization was accompanied by increased activity or expression of ALP and OC. And calcium phosphate deposition was also detected in their extracelluar matrix. The current study supports the presence of stem cells within the buccal fat pad and the potential implications for human bone tissue engineering for maxillofacial reconstruction.

A Case of Avascular Necrosis of Mandible Associated with the Use of Bisphosphonate in a Patient with Rheumatoid Arthritis and Osteoporosis / 대한류마티스학회지

Bisphosphonates decrease osteoclastic activity and reduce bone resorption, therefore they are used in the treatment of patients with hypercalcemia secondary to malignancy or metastatic bone cancer, Paget's disease and osteoporosis. Recently, cases of jaw bone necrosis have been reported to be associated with the use of bisphosphonates. In patients with rheumatoid arthritis, osteoporosis is frequently developed because of osteoclast activation and steroids which are used for treatment and bisphosphonates are frequently prescribed. A 76-year-old female patient with rheumatoid arthritis was treated with alendronate for the management of osteoporosis for 36 months, and she was presented with pain and swelling on left mandibular area and gingival pus discharge. The patient was treated with curettage of necrotic bone, and biopsy showed avascular necrosis of mandible.