• Restorative Dentistry and Endodontics
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• v.44 no.4
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• pp.42.1-42.16
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• 2019

Antiresorptive drugs (ARDs), such as bisphosphonates or denosumab, that prevent bone resorption are widely used in patients with osteoporosis or with cancer that has metastasized to the bones. Although osteonecrosis of the jaw (ONJ) is a well-documented complication of ARD use, the benefits ARDs outweigh the complication. Thus, research has focused on finding ways to prevent or reduce the risk of developing ONJ. Dentists, as part of a multi-professional team, have a critical role in preventing ONJ. However, many dentists tend to hesitate to provide dental care to patients with ONJ, or tend to think that it is a problem to be dealt with by oral surgeons. This review gives an overview of ARD-related ONJ and provides the guidelines for dental care in patients taking ARDs to lower the risk of developing ONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.39 no.1
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• pp.9-13
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• 2013

Objectives: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. Materials and Methods: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. Results: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was $70.0{\pm}10.1$ years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. Conclusion: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.41 no.6
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• pp.332-337
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• 2015

Dental infections and maxillary sinusitis are the main causes of osteomyelitis. Osteomyelitis can occur in all age groups, and is more frequently found in the lower jaw than in the upper jaw. Systemic conditions that can alter the patient's resistance to infection including diabetes mellitus, anemia, and autoimmune disorders are predisposing factors for osteomyelitis. We report a case of uncommon broad maxillary osteonecrosis precipitated by uncontrolled type 2 diabetes mellitus and chronic maxillary sinusitis in a female patient in her seventies with no history of bisphosphonate or radiation treatment.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.26.1-26.7
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• 2019

Background: The aim of this study was to investigate clinical and pharmacoepidemiologic characteristics of medicationrelated osteonecrosis of the jaw. Methods: The study population is comprised of 86patients who were diagnosed with ONJ at Ewha Womans University Mokdong Hospital from 2008 to 2015. Factors for epidemiologic evaluation were gender, age, location of lesion, and clinical history. The types of bisphosphonates, duration of intake, and the amount of accumulated dose were evaluated for therapeutic response. Clinical symptoms and radiographic images were utilized for the assessment of prognosis. Results: Among the 86 patients, five were male, whereas 81 were female with mean age of 73.98 (range 45-97). Location of the lesion was in the mandible for 58 patients and maxilla in 25 patients. Three patients had both mandible and maxilla affected. This shows that the mandible is more prone to the formation of ONJ lesions compared to the maxilla. ONJ occurred in 38 cases after extraction, nine cases after implant surgery, six cases were denture use, and spontaneously in 33 cases. Seventy-six patients were taking other drugs aside from drugs indicated for osteoporosis. Most of these patients were diagnosed as osteoporosis, rheumatic arthritis, multiple myeloma, or had a history of cancer therapy. Higher weighted total accumulation doses were significantly associated with poorer prognosis (P < 0.05). Conclusion: Dose, duration, route, and relative potency of bisphosphonates are significantly associated with treatment prognosis of osteonecrosis of the jaw.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.6
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• pp.470-476
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• 2011

Introduction: The incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) has increased gradually in patients who have undergone surgical treatment for osteomyelitis. In this study, a retrospective analysis of BRONJ patients was carried out using the data of osteomyelitis patients treated surgically. Materials and Methods: Osteomyelitis patients, who underwent curettage, sequestrectomy, saucerization or decortications, and partial mandibulectomy at Seoul National University Dental Hospital from 2004 to 2010 were enrolled in this study. The patients were classified and categorized into two groups based on the surgical records and progress notes. One group comprised of patients with osteomyelitis and osteoporosis, and the other group included patients with osteomyelitis only. The epidemiological data of the BRONJ patients was analyzed to identify any trend in the incidence of BRONJ in osteomyelitis patients. Results: Among 200 patients who underwent surgical intervention for osteomyelitis, 64 (32.0%) were identified as having osteoporosis as the underlying disease. In these 64 patients, more than 81.3% had been prescribed bisphosphonates. Females were far more affected by BRONJ than males. The incidence of BRONJ also increased with age. The posterior part of the mandible was affected more frequently by BRONJ. Conclusion: Although the availability of potent antibiotics and increased oral hygiene care can reduce the overall incidence of osteomyelitis, BRONJ can increase the total incidence. To prevent BRONJ, it is recommended that an oral examination be performed before prescribing bisphosphonates. Moreover, the patients should be educated about the potential risks of dental procedures that might be causal factors for BRONJ. Furthermore, patient swho take bisphosphonates for the treatment of osteoporosis should undergo periodic follow up oral examinations to prevent BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.1-8
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• 2011

Introduction: The utility of the C-terminal cross-linking telopeptide test (CTX) as a method for staging Bisphosphonate-related osteonecrosis of the jaws (BRONJ) and its healing process was examined. Materials and Methods: A total 19 patients who were diagnosed with BRONJ underwent a fasted morning CTX test, were enrolled in this study. The serum CTX values ranged from 50 to 630 pg/mL (mean 60). The risk assessment was rated according to the CTX values of the individual patient (minimal risk, ${\geq}$ 150 pg/mL, moderate, 100 to 150 pg/mL, high, ${\leq}$100 pg/mL). The BRONJ scores were then calculated according to the number of BRONJ lesions and their stage. The operation was done as soon as possible, regardless of BORNJ stage. Results: The mean duration of bisphosphonate therapy was 4.1 years. Of the 19 patients, 15, 2 ans 2 received alendronate, risedronate and zoledronate, respecively. Of the 19 patients who underwent a sequestrectomy, saucerization and smoothing, 15 healed after the initial surgery, 1 patient healed after one more surgical procedure, 3 patients did not heal completely but showed improvement in symptoms. Therefore, 17 out of the 19 patients healed completely with complete mucosal coverage and the elimination of pain. The risk assessment using the CTX value and disease severity were not correlated (r=-0.264, P=0.275). In addition, the risk assessment using CTX value and healing after surgery were not correlated (r=-0.147, P=0.547). Conclusion: The serum CTX should be considered carefully by clinicians as part of overall management. Early surgical intervention is of benefit in the treatment of stage II BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.6
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• pp.397-402
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• 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.

• Journal of Periodontal and Implant Science
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• v.50 no.2
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• pp.121-131
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• 2020

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 ㎍/kg of zoledronate once a week for 6 weeks and 30 ㎍/kg PTH after implant installation. The OVX-Z group included ovariectomized rats administered 60 ㎍/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/㎣ vs. 2.2±0.19/㎣) (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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.6
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• pp.365-369
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• 2016

Objectives: To determine the prevalence and oral characteristics of cancer patients treated with bisphosphonates in the oncology and maxillofacial prosthesis departments of the General Hospital of Mexico between 2011 and 2013. Materials and Methods: This cross-sectional study included patients who received prior treatment with bisphosphonates; an intraoral examination was performed by 2 standardized examiners. Results: The prevalence of bisphosphonate-related necrosis in 75 patients was 2.6%; the most common malignancy was breast cancer (84.0%), followed by prostate cancer (16.0%). Exostosis was present in 9.3% of patients and the mean Decayed, Missing, Filled Teeth index was 4.64; 44.0% of the study group had a Community Periodontal Index value between 2 and 2.9 (mean, 0.60). Conclusion: A detailed intraoral assessment must be performed before initiating treatment with bisphosphonates to identify risk factors for osteonecrosis.

• Journal of Korean Dental Hygiene Science
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• v.3 no.2
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• pp.59-66
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• 2020

Dental hygienists handle periodontal tissue every day. Since periodontal tissue contains hard and soft tissue, dental hygienists need to cultivate scientific knowledge about bone tissue. This study introduces recent research results on cells and cytokines related to bone tissue. Recently, bisphosphonate-related osteonecrosis of the jaw has been reported, therefore we would like to present osteoporosis and osteoporosis treatment drugs and their side effects in this study.