• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제42권5호
• /
• pp.271-277
• /
• 2016

Objectives: The objective of this study was to retrospectively investigate the association of diseases having an influence on inhibition of angiogenesis such as hypertension, diabetes mellitus type II, hypercholesterolemia, and rheumatoid arthritis (RA) with the development of osteonecrosis of the jaws. Materials and Methods: The 135 patients were allocated into 4 groups of bisphosphonate-related osteonecrosis of the jaw (BRONJ) group (1A); non-BRONJ group (1B); osteonecrosis of the jaw (ONJ) group (2A); and control group (2B), according to histologic results and use of bisphosphonate. This retrospective study was conducted with patients who were treated in one institute from 2012 to 2013. Fisher's exact test and logistic regression analysis were used to analyze the odds ratios of diseases having an influence on inhibition of angiogenesis for development of ONJ. Results: The effects of diabetes and hypertension were not statistically significant on development of ONJ. When not considering bisphosphonate use, RA exhibited a high odds ratio of 3.23 (P=0.094), while hyperlipidemia showed an odds ratio of 2.10 (P=0.144) for development of ONJ. More than one disease that had an influence on inhibition of angiogenesis showed a statistically significant odds ratio of 2.54 (P=0.012) for development of ONJ. Conclusion: Patients without diseases having an influence on inhibition of angiogenesis were at less risk for developing ONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제35권3호
• /
• pp.158-163
• /
• 2009

Objective : Recently, we are interested in bisphosphonate related osteonecrosis of the jaw (BRONJ). Most of patients with osteonecrosis have taken medicine bisphosphonate for a long time. But the mechanism of osteonecrosis in BRONJ was not clarified yet. The aim of this study is to evaluate the difference of bone healing effect after bone graft from ilium to maxillary sinus in rabbits between zoledronate-treated and zoledronate-not treated groups. Method : The subjects was divided into two groups. The experimental group was 9 rabbits, treated with intraperitoneal administration of zoledronate(0.06mg/kg) once per week for 3 weeks. In control group, same procedure was applied but administerd saline instead of zoledronate. After 4 weeks, surgical operation under local anesthesia (ketamine 3.0cc, xylazine 1.0cc) was done. At postoperative 1, 2, 4, 8 weeks later, each rabbits were sacrificed and removed the bone grafted area. Gross, radiologic and histopathologic exminations of bone grafted area were performed. Result : There were no conspicuous differences of radiological findings between experimental and control groups in any experimental weeks. In experimental group, new bone formation appeared earlier than control group at 1 week after operation, and maturation of bony tissue were more conspicuous at 2 and 4 weeks after operation, compared with control group. In 8 weeks after operation, similar microscopic findings were noted in both groups. Conclusion : In the bisphosphonate-treated rabbits, new bone formation in the bone grafted area appeared earlier and bony maturation was more concpicuous, even though there were no significant differences of gross and radiological findings. These findings suggest that bisphosphonate might be promotive effect in the healing process in early stage after administration.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제40권6호
• /
• pp.291-296
• /
• 2014

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphophonate therapy that has been reported in recent years. Osteoclastic inactivity by bisphosphonate is the known cause of BRONJ. Bone morphogenetic protein-2 (BMP-2) plays an important role in the development of bone. Recombinant human BMP-2 (rhBMP-2) is potentially useful as an activation factor for bone repair. We hypothesized that rhBMP-2 would enhance the osteoclast-osteoblast interaction related to bone remodeling. Materials and Methods: Human fetal osteoblast cells (hFOB 1.19) were treated with $100{\mu}M$ alendronate, and 100 ng/mL rhBMP-2 was added. Cells were incubated for a further 48 hours, and cell viability was measured using an MTT assay. Expression of the three cytokines from osteoblasts, receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF), were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Cell viability was decreased to $82.75%{\pm}1.00%$ by alendronate and then increased to $110.43%{\pm}1.35%$ after treatment with rhBMP-2 (P<0.05, respectively). OPG, RANKL, and M-CSF expression were all decreased by alendronate treatment. RANKL and M-CSF expression were increased, but OPG was not significantly affected by rhBMP-2. Conclusion: rhBMP2 does not affect OPG gene expression in hFOB, but it may increase RANKL and M-CSF gene expression.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제36권6호
• /
• pp.508-514
• /
• 2010

Bisphosphonates are used effectively for many medical conditions, such as multiple myeloma, Paget's disease, osteoporosis, etc. However, recently, osteonecrosis of the jaw was observed in patients receiving long-term bisphosphonate therapy, including oral administration. This osteonecrosis is refractory, and complete recovery is not guaranteed despite a standard treatment protocol being established by many associations related to oral and maxillofacial surgery. The treatment outcome of oral bisphosphonate-related osteonecrosis of jaw (BRONJ) is reported with a review of the relevant literature.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제35권1호
• /
• pp.39-40
• /
• 2009

Maxillary sinusitis is an infectious disease which can arise from odontogenic etiology and a maxillary osteomyelitis can spread into the sinus and consequently develop maxillary sinusitis. In this case report, a mid eighty's lady was diagnosed as BRONJ with maxillary sinusitis as a complication. The patient was managed successfully in collaboration with a endocrinologist. Through serial follow-up of serum CTX, we could decide the timing of surgical intervention.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제33권1호
• /
• pp.10-18
• /
• 2011

Purpose: The purpose of this study is to find out the effects of bisphosphonates (BPs) on the proliferation and the alkaline phosphatase (ALP) activity of human bone marrow derived mesenchymal stem cells (hMSCs), and thus state its correlation with bisphosphonate related osteonecrosis of the jaw (BRONJ). Methods: hMSCs was obtained by collecting and culturing cancellous bone fragments from a patient undergoing iliac bone graft. Alendronate (Aln) and Pamidronate (Pam), Ibandronate (Ibn) were added to the culture media in the concentration from $10^{-3}$ M to $10^{-11}$ M and cell toxicity, viability were measured. For ALP activity evaluation, Aln and Pam were added to the culture media in the concentration from $5{\times}10^{-7}$ M to $1{\times}10^{-8}$ M and were cultured for 1 week, 2 weeks and 3 weeks. ALP activity data were standardized using protein assay. Control groups were prepared for each examination. Results: Aln, Pam and Ibn all failed to increase the proliferation of hMSCs. With 1 week, 2 weeks of $5{\times}10^{-8}$M of Aln treatment, the ALP activity increased. Pam treatment increased the ALP activity with 2 weeks of $5{\times}10^{-8}$ M and$1{\times}10^{-8}$M. Also Ibn treatment increased the ALP activity with 2 weeks of $5{\times}10^{-8}$ M and $1{\times}10^{-8}$ M. Conclusion: It is considered that BPs are not capable of improving the proliferation of hMSCs. Also, after a transient increase in the ALP activity with the lower concentration of BPs, the activity decreased again. Therefore, in patients on long-term medication of BPs, the proliferation and osteoblast differentiation of hMSCs are restrained, and thus delayed wound healing and increase in BRONJ complications may occur.

• Parasites, Hosts and Diseases
• /
• 제55권4호
• /
• pp.433-437
• /
• 2017

Pentastomiasis, a zoonotic parasite infection, is typically found in the respiratory tract and viscera of the host, including humans. Here, we report for the first time an extremely rare case of intraosseous pentastomiasis in the human maxilla suffering from medication related osteonecrosis of the jaw (MRONJ). A 55-year-old male had continuously visited the hospital for MRONJ which had primarily developed after bisphosphonate and anti-neoplastic administration for previous bone metastasis of medullary thyroid cancer. Pain, bone exposure, and pus discharge in the right mandible and left maxilla were seen. Osteolysis with maxillary cortical bone perforation at the left buccal vestibule, palate, nasal cavity, and maxillary sinus was observed by radiologic images. A biopsy was done at the left maxilla and through pathological evaluation, a parasite with features of pentastome was revealed within the necrotic bone tissue. Further history taking and laboratory evaluation was done. The parasite was suspected to be infected through maxillary open wounds caused by MRONJ. Awareness of intraosseous pentastomiasis should be emphasized not to be missed behind the MRONJ. Proper evaluation and interpretation for past medical history may lead to correct differential diagnosis and therapeutic intervention for parasite infections.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제32권5호
• /
• pp.478-483
• /
• 2010

Bisphosphonates are synthetic analogue and have high affinity on bone remodeling site. Since they have a long half-reduction time, they accumulate at bone and act for a long time. They are widely used in osteo-porosis derived from imflammatory bowel disease or postmenopausal osteoporosis patient for bone mineral density improvement. In addition, they neutralize hypercalcemia owing to bone metastasis of malignancy. However, a jaw bone necrosis was recently reported in some patients who have taken bisphosphonates for a long time. It is called Bisphosphonate Related Osteonecrosis of Jaws (BRONJ). It can come spontaneous-ly, but more often after oral surgery including tooth extraction. In this case, a 80-year-old woman was treated with bisphosphonate (sodium alendronate) for 2 years to improve bone mineral density. She had her left lower second molar tooth extracted at local clinic. After extraction, she had inflammatory symptoms like a pain, a cheek swelling, and a discharge of pus. She was referred to our clinic for treatment. We treated meticulously from dressing to surgery. After following up about 1.5 years, the jaw lesion was successfully healed. So we report this case.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제35권6호
• /
• pp.397-402
• /
• 2009

The purpose of this study is to investigate the effects of alendronate and pamidronate on proliferation and the alkaline phosphatase activity of human bone marrow derived mesenchymal stem cells and to relate the results with bisphosphonate related osteonecrosis of the jaw(BRONJ). With the consent of patients with no systemic disease and undergoing iliac bone graft, cancellous bone was collected to obtain human bone marrow derived mesenchymal stem cells through cell culture. 96 well plate were prepared with a concentration of $10^4$cell/ well. Alendronate and pamidronate were added to each well with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively. Then proliferation capacity of each well was evaluated with the cell counting kit. 24 well plates were prepared with a concentration of $10^5$cell/ml/well and with the bone supplement, alendronate and pamidronate were added with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively on each plate. The plates were cultured for either 24 or 72 hours. Then the cells were sonicated to measure the alkaline phosphatase activity and protein assay was done to standardize the data for analysis. As the concentration of alendronate or pamidronate added to the culture increased, the proliferation capacity of the cells decreased. However, no statistical significance was found between the group with $10^{-10}M$ of bisphophonate and the control group. Pamidronate was not capable of increasing the alkaline phosphatase activity in all trials. However, alkaline phosphatase activity increased with 24 hours of $10^{-8}M$ of alendronate treatment and with 48 hours of $10^{-10}M$ of alendronate treatment. Cell toxicity increased as the bisphosphonate concentration increased. This seems to be associated with the long half life of bisphosphonate, resulting in high concentration of bisphosphonate in the jaw and thus displaying delayed healing after surgical procedures. Alendronate has shown to increase the alkaline phophatase activity of human bone marrow derived mesenchymal stem cells. However, this data is insufficient to conclude that alendronate facilitates the differentiation of human bone marrow derived mesenchymal stem cells. Further studies on DNA level and animal studies are required to support these results.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제38권
• /
• pp.48.1-48.8
• /
• 2016

Background: This study investigates the effect of alendronate-treated osteoblasts, as well as the effect of low-level laser therapy (LLLT) on the alendronate-treated osteoblasts. Bisphosphonate decreases the osteoblastic activity. Various treatment modalities are used to enhance the bisphosphonate-treated osteoblasts; however, there were no cell culture studies conducted using a low-level laser. Methods: Human fetal osteoblastic (hFOB 1.19) cells were treated with $50{\mu}M$ alendronate. Then, they were irradiated with a $1.2J/cm^2$ low-level Ga-Al-As laser (${\lambda}=808{\pm}3nm$, 80 mW, and 80 mA; spot size, $1 cm^2$; NDLux, Seoul, Korea). The cell survivability was measured with the MTT assay. The three cytokines of osteoblasts, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF) were analyzed. Results: In the cells treated with alendronate at concentrations of $50{\mu}M$ and higher, cell survivability significantly decreased after 48 h (p < 0.05). After the applications of low-level laser on alendronate-treated cells, cell survivability significantly increased at 72 h (p < 0.05). The expressions of OPG, RANKL, and M-CSF have decreased via the alendronate. The RANKL and M-CSF expressions have increased, but the OPG was not significantly affected by the LLLT. Conclusions: The LLLT does not affect the OPG expression in the hFOB cell line, but it may increase the RANKL and M-CSF expressions, thereby resulting in positive effects on osteoclastogenesis and bone remodeling.