• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.35 no.2
• /
• pp.106-111
• /
• 2009

Bisphosphonates have been approved for Paget's disease, cancer-related hypercalcemia, bone involvement in multiple myeloma or solid tumors and osteoporosis. Although, underlying pathophysiological mechanisms remain unclear, it seems that bisphosphonates inhibit osteoclast precursor cells, modulate migratory and adhesive characteristics and induce apoptosis of osteoclasts. Furthermore impacts on angiogenesis, microenvironment and signal transduction between osteoclasts and osteoblasts. In this report, we present a case of oral bisphosphonates induced osteonecrosis of the mandible in a 84-year-old patient who received for two years. Two tapered screw vent implants(Zimmer, USA) were placed in the area of first and second molar. Two weeks later after crowns restored, some inflammatory signs and symptoms were observed on the second molar area. Sequestrum was formed and the sequestrum was removed with the implant. Frequent follow-up checks and oral hygiene maintenances were done and the first molar implant was restored. There is insufficient evidence suggests that duration of oral bisphosphonate therapy correlates with the development and severity of osteonecrosis. Therefore, dentists should not overlook the possibility of development of bisphosphonate induced osteonecrosis in patients who have taken oral forms of medication for less than three years.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.42 no.6
• /
• pp.365-369
• /
• 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 the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.37 no.1
• /
• pp.54-61
• /
• 2011

Introduction: Bisphosphonates is used widely for the treatment of the Paget's disease, multiple myeloma, bone metastases of malignant tumors with the prevention of pain and their pathological fracture. However, it was recently suggested that bisphosphonates related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate use. Materials and Methods: Twenty-four individuals, who were referred to the Department of Oral and Maxillofacial surgery, Dankook University Dental Hospital, were selected from those who had exposed bone associated with bisphosphonates from January, 2005 to December, 2009 according to the criteria of American Association of Oral and Maxillofacial Surgeons (AAOMS) for BRONJ. The patients group consisted of 7 males and 17 females between the age of 46 to 78 years (average 61.8 years). Each patient had panoramic imaging, computed tomography (CT), whole body bone scanning performed for a diagnosis and biopsy sampling from the necrotizing tissue. C-terminal cross-linking telopeptide of type I collagen (CTX) level of patients who had undergone surgical intervention was measured 7 days before surgery. Results: The main cause of bone exposure was post-extraction (15), chronic periodontitis (4), persistent irritation of the denture (3). Twenty people had undergone BRONJ treatment for two to eight months except for 4 people who had to maintain the bisphosphonates treatment to prevent a metastasis and bone trabecular pain with medical treatment. When the bisphosphonate treatment was suspended at least for 3 months and followed up according to the AAOMS protocols, the exposed necrotizing bones were found to be covered by soft tissue. Conclusion: Prevention therapy, interruption of bisphophonates for at least 3 months and cooperation with the physician for conservative treatment are the essential for treating BRONJ patient with high risk factors. The CTX level of BRONJ patients should be checked before undergoing surgical intervention. Surgical treatments should be delayed in the case of a CTX level <150 pg/mL.

• Imaging Science in Dentistry
• /
• v.47 no.1
• /
• pp.45-50
• /
• 2017

Purpose: The aim of this study was to investigate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after tooth extraction in patients with osteoporosis on oral bisphosphonates in Korea and to evaluate local factors affecting the development of BRONJ. Materials and Methods: The clinical records of 320 patients who underwent dental extraction while receiving oral bisphosphonates were reviewed. All patients had a healing period of more than 6 months following the extractions. Each patient's clinical record was used to assess the incidence of BRONJ; if BRONJ occurred, a further radiographic investigation was carried out to obtain a more definitive diagnosis. Various local factors including age, gender, extraction site, drug type, duration of administration, and C-terminal telopeptide (CTx) level were retrieved from the patients' clinical records for evaluating their effect on the incidence of BRONJ. Results: Among the 320 osteoporotic patients who underwent tooth extraction, 11 developed BRONJ, reflecting an incidence rate of 3.44%. Out of the local factors that may affect the incidence of BRONJ, gender, drug type, and CTx level showed no statistically significant effects, while statistically significant associations were found for age, extraction site, and duration of administration. The incidence of BRONJ increased with age, was greater in the mandible than the maxilla, and was associated with a duration of administration of more than 3 years. Conclusion: Tooth extraction in patients on oral bisphosphonates requires careful consideration of their age, the extraction site, and the duration of administration, and close postoperative follow-up should be carried out to facilitate effective early management.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.37
• /
• pp.18.1-18.7
• /
• 2015

Background: The aim of this study is to develop a rat model of bisphosphonates-related osteonecrosis of the jaw (BRONJ) that would be verified with clinical, radiological and histological examination, and to confirm the influence of concurrent bisphosphonates and steroids use upon the occurrence and aggravation of BRONJ. Methods: Twenty seven rats were divided into 3 groups; Saline group (I), Zoledronate group (II), Zoledronate and Dexamethasone group (III). Rats got weekly intraperitoneal injection for 4 times and extraction of left maxillary and mandibular 1st, 2nd molars were followed. Consecutive injections were performed, and blood sampling for measurements of C-terminal crosslinked telopeptide of type I collagen and tartrate-resistant acid phosphate 5b rats were performed at the time of 2, 4 and 8 weeks. And then, rats were sacrificed and evaluated clinically, radiologically and histologically. Results: 12/18 (66.6 %) of experimental group were diagnosed as BRONJ. There was no significant difference in incidence between zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll). Conclusions: Concurrent use of bisphosphonates and steroids increase incidence of BRONJ compared to saline group (l). Zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll) shows same incidence of BRONJ. Based on this study, the rat treated with bisphosphonates and steroids can be considered a novel, reliable and reproducible model to understand pathology of BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.43 no.2
• /
• pp.120-124
• /
• 2017

Osteonecrosis of the jaw (ONJ) is commonly described as an adverse effect of the use of bisphosphonates. A few cases of ONJ associated with tyrosine kinase inhibitors (sunitinib, imatinib) have been reported in the literature and usually they occurred in patients simultaneously treated with bisphosphonates. We report an atypical case of ONJ related only to imatinib. A 72-year-old male patient was treated with imatinib for metastases from gastrointestinal stromal tumors (GISTs). The patient developed ONJ after 22 months of imatinib only therapy. During his whole life, the patient had never been treated with bisphosphonates or radiotherapy. Microscope examination of the tissues confirmed the clinical diagnosis of diffuse osteonecrosis and showed absence of neoplastic cells. Thus, secondary localisations from GISTs were ruled out. Osteonecrosis of the lower jaw appeared 22 months after initial and exclusive therapy with imatinib. Therefore, imatinib monotherapy can induce ONJ in patients that have never been treated with bisphosphonates or radiotherapy.

• Korean Journal of Clinical Pharmacy
• /
• v.24 no.2
• /
• pp.98-105
• /
• 2014

Purpose: The aim of this study was to compare retrospectively the efficacy of anti-osteoporotic agents (RAL-Raloxifene 60 mg, ALD-weekly alendronate 70 mg, RSD-weekly risedronate 35 mg, AVD3-weekly alendronate 70 mg/vitamin $D_3$ 2800IU, IBD-quarterly IV ibandronate 3 mg/3 ml, ZLD-yearly IV zoledronate 5 mg/100 ml) in postmenopausal patients with osteoporosis or osteopenia. Method: This study retrospectively reviewed medical record and compared the lumbar spine BMD percentage changes of each medicine group one year later from the baseline. 209 patients (27, 50, 60, 30, 35, and 7 patients in RAL, ALD, RSD, AVD3, IBD, and ZLD groups, respectively) are within the inclusion criteria for the study. Results: From baseline to month 12, lumbar spine BMD increased significantly larger with bisphosphonate groups, compared to SERM (p < 0.05). In all bisphosphonate groups, the lumbar spine BMD were increased significantly from baseline. Of the bisphosphonates, the changes from baseline in BMD of IV bisphosphonates were more larger than those of oral bisphosphonates, and yearly, quarterly bisphosphonates yielded significantly greater BMD gains, compared with weekly bisphosphonate groups (p<0.05). In addition, patients receiving 70 mg weekly alendronate+vitamin D3 had greater gains in BMD than alendronate Single preparation (p<0.05). Conclusion: Bisphosphonates yielded significantly greater BMD gains than SERM. Of the bisphosphonates, the changes from baseline in BMD of yearly, quarterly IV bisphosphonates yielded significantly greater BMD gains, compared with weekly oral bisphosphonate groups. In addition, vitamin D3 plays an significant role in BMD gains.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.37 no.6
• /
• pp.470-476
• /
• 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 Periodontal and Implant Science
• /
• v.39 no.1
• /
• pp.1-8
• /
• 2009

Purpose: Bisphosphonates are drugs used to suppress osteoclastic activity and to treat osteoporosis, Paget's disease of bone and bone metastasis. The purpose of this report is to review the literatures on bisphosphonates use that could affect bone healing and cause osteonecrosis of the jaws. Materials and methods: Medline research was carried out to find relevant articles on bisphosphonates and osteonecrosis of the jaw. Results: Oral administration of bisphosphonates is reported to decrease the risk of adverse bone outcomes. On the contrary, IV bisphosphonates is known to significantly increase the risk. Prevention of the osteonecrosis of the jaw is primary concern before usage. If the adverse bone reaction takes place, proper management and treatments are required to alleviate pain of patients and prevent further progression of necrosis. Conclusion: Case reports of bisphosphonates induced osteonecrosis of the jaw are increasing. Dentists and physicians should be aware of the higher frequency of osteonecrosis of the jaw in patients receiving IV bisphosphonates and be prepared to prevent and cope with adverse bone reaction.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.42 no.3
• /
• pp.157-161
• /
• 2016

Although pathophysiology, incidence, and factors associated with the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and management strategies for patients treated with bisphosphonates or patients with BRONJ are well-established, few guidelines or recommendations are available for patients with a history of successfully healed BRONJ. We present a case of successful dental implant treatment after healing of BRONJ in the same region of the jaw, and speculate that implant placement is possible after healing of BRONJ surgery in select cases.