Bisphosphonate-related osteonecrosis of the jaw around dental implants in the maxilla: report of a case

Objective: We describe a patient who developed bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) around implants in the upper molar area.
Patients and methods: The patient was a 54-year-old woman with ulceration of the gum, bone exposure, and severe spontaneous pain around implants in the upper left molar area. She had received BPs intravenously for 2 years to treat bone metastases of breast cancer. She was diagnosed with BP-related ONJ. Sequestrum including implants was resected, and hyperbaric oxygen therapy was performed. Undecalcified ground sections were prepared from the resected bone around the implants and stained with toluidine blue. For the bone around the lesion, decalcified sections were prepared, and examined by histological and immunohistological analysis.
Results: The surgical wound became completely covered with mucosal epithelia, and postoperative pain disappeared. No recurrence of ONJ was noted during a 6-month postoperative follow-up period. However, the patient died from metastatic disease. Although histopathological examination of the resected jaw bone revealed sequestrum, osseointegration of the implant was maintained. In the area around the lesion, there was no progression of bone necrosis, and reactive bone formation, fibrosis, and invasion of lymphoid cells into the marrow cavity were observed.
Conclusion: There is no effective treatment for ONJ caused by BPs, and conservative therapy based on clinicians' experience is recommended. However, if chemotherapy is planned, or if bone necrosis around implants is thought to harbor infection, the option of jaw resection should be considered.     

双膦酸盐及其相关性颌骨坏死的机制和治疗

双膦酸盐相关性颌骨坏死（BRONJ）是长期使用双膦酸盐治疗骨质疏松症,多发性骨髓瘤以及乳腺癌、前列腺癌和肺癌等其他恶性肿瘤骨转移所引起的骨相关性疾病的严重并发症。BRONJ的发生发展与一些因素密切相关,譬如双膦酸盐的效能、用药方式、牙拔除和不良义齿修复等。美国口腔颌面外科协会在2007年对BRONJ进行了定义、分级并颁布其治疗指南,在2009年和2014年进对其行了更新。尽管BRONJ在国际上引起了广泛的重视,但其发病机制仍不完全清楚,治疗措施也存在着较大的争议。本文就双膦酸盐及其相关性颌骨坏死的机制和治疗等研究进展作一综述。     

Bacterial promotion of bisphosphonate-induced osteonecrosis in Wistar rats

Clinically, bisphosphonate-related osteonecrosis (BRON) only occurs in the jaw (BRONJ). We aimed to determine differences between the jaw and other bones, as well as the relationship between periodontal pathogens and BRON. Twelve male Wistar rats were divided into two groups: group Z (n = 6) were subcutaneously injected with zoledronic acid weekly for 4 weeks; group C (n = 6) were injected with saline. One week after the final injection, rats in both groups were divided into three subgroups: Aa subgroup was injected with freeze-dried Aggregatibacter actinomycetemcomitans into bone marrow of the mandibles and femurs, while CFA and saline subgroups were injected with complete Freund's adjuvant (CFA) or saline using the same protocol. Four weeks after those injections, the rats were euthanized. Areas of osteonecrosis were measured histologically. Statistically, rats in group Z showed significantly wider osteonecrosis areas in both mandibles and femurs with each type of local injection than rats in group C. In group Z, mandibles and femurs stimulated with A. actinomycetemcomitans or CFA had significantly wider osteonecrosis areas than those stimulated with saline. We have developed a rat model with BRONJ-like lesions. Our results showed BRON to develop not only in the jaw but also in other types of bone following an inflammatory stimulus.     

晚期药物相关性颌骨坏死的手术治疗

目的 总结晚期（2、3期）药物相关性颌骨坏死（MRONJ）的手术治疗效果。方法 纳入2013年7月—2021年5月就诊于北京大学口腔医学院·口腔医院口腔颌面外科且采用手术治疗的晚期MRONJ患者。回顾性分析患者的临床资料,包括患者的原发疾病、用药情况、病变情况、手术治疗和随访结果等。结果 本研究共纳入104例患者（123处病变）,男性42例,女性62例,平均年龄（64.6±9.1）岁。原发疾病为恶性肿瘤91例,非肿瘤性疾病13例。2期病变43处（35.0%）,3期病变80处（65.0%）。39处（31.7%）病变位于上颌骨,84处（68.3%）病变位于下颌骨。使用唑来膦酸89例（85.6%）,阿仑膦酸钠10例（9.6%）,帕米膦酸钠10例（9.6%）,抗血管生成药物62例（59.6%）。平均药物治疗时长（34.7±25.8）月,平均停药时长（10.1±10.7）月。全部患者均在全麻下完成手术。手术去净死骨后,2期病变以局部黏骨膜瓣关闭创口,3期病变根据具体情况分别采用重建钛板联合下颌下腺转位、血管化腓骨瓣修复、碘仿纱条填塞、带蒂颊脂垫瓣修复等关闭创口。术后随访3个月至6年,81.3%(...     

Bisphosphonate-related osteonecrosis of the maxilla and sinusitis maxillaris

Bisphosphonates (BPs) are widely used as bone-stabilizers, but side effects of BP therapy include bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is resistant to therapy. The aim of this study was to evaluate the outcome of maxillary BRONJ involving sinusitis maxillaris. 21 patients presenting with maxillary BRONJ, from 2005 to 2008, were included in the study. In 18 cases BP had been administered for carcinoma and in 3 cases for osteoporosis, with an average exposure time of 47.4 months. 12 patients spontaneously developed BRONJ. The 10 patients diagnosed with stage III BRONJ presented with concomitant sinusitis maxillaris. Despite treatment, there were six recurrences of BRONJ, four of them with additional sinusitis maxillaris. Whether BRONJ occurred spontaneously or after extraction there was no difference in the outcome. Patients with advanced maxillary BRONJ often suffer from sinusitis maxillaris, both of which are frequently resistant to therapy.     

Survey of Korean dentists on the awareness on bisphosphonate‐related osteonecrosis of the jaws

Aim: This survey evaluates the awareness of bisphosphonate‐related osteonecrosis of the jaws among Korean dentists. Methods: We prepared a questionnaire based on bisphosphonate‐related osteonecrosis of the jaw guidelines, suggested by The American Association of Oral Maxillofacial Surgeons. Among 13 405 dentists, we randomly selected 264 (2%) practitioners. Results: A total of 56.5% of respondents had heard of bisphosphonates asmedication related to osteonecrosis, but only 31.4% routinely recorded bisphosphonate medication history. The cross‐sectional analysis demonstrated that most dentists were unaware of The American Association of Oral Maxillofacial Surgeons’ guidelines. Dentists with <5 years’ clinical experience were significantly more aware than those with >5 years’ experience. Experience with treating osteonecrosis of the jaw patients and recording medication histories were significantly greater in dental hospitals with >300 beds or university hospitals. Awareness of the severity of bisphosphonate‐related osteonecrosis of the jaws was greatest among oral surgeons. Conclusion: Dentists should thoroughly check patients’ medical histories, including bisphosphonate intake. With the exception of oral surgeons, most Korean dentists were not adequately aware of bisphosphonate‐related osteonecrosis of the jaws and its seriousness, making it a potential risk in Korean dentistry. Therefore, it is important to educate clinicians regarding the potential risk of bisphosphonate medication in dentistry through education programs.     

Survey on awareness and perceptions of bisphosphonate‐related osteonecrosis of the jaw in dental hygienists in Seoul

We investigated awareness in dental hygienists of bisphosphonate‐related osteonecrosis of the jaw (BRONJ) in patients with osteoporosis and cancer and assessed the situation in systemic history investigations to broaden the scope of the dental hygienists' BRONJ awareness as a basis for contributing to preventing this disease. The study was carried out through a survey; 217 dental hygienists responded to the survey. They worked at 12 university and general hospitals, 10 dental hospitals and 35 dental clinics, for a total of 57 institutions in Seoul. The survey consisted of 37 questions: general characteristics (J Oral Maxillofac Surg 65: 2007; 369), systemic history investigations (Ruggiero et al. J Oral Maxillofac Surg 62: 2004; 527) and awareness of BRONJ (Park et al. J Korean Dent Assoc 49: 2011; 389). Among them, 79.7% were aware of BRONJ. Recognition was highest among those from 25 to 35 years old (P < 0.05). In terms of work experience, those with 5–10 years experience showed the highest awareness (P < 0.05). In terms of institutions type, dental clinics showed lower awareness than general and dental hospitals (P < 0.05). It was found that 55.3% of the dental hygienists had been educated about BRONJ. Those aged 25–35 years were the most educated. In terms of institutions, dental clinic staff were the least educated. The degree of understanding about BRONJ was analysed with the average score of 6.14 points. According to these results, dental hygienists working in university hospitals and general hospitals had more opportunity to receive training than those working in dental clinics. Thus, it is considered that the development of professional training programs about BRONJ for all dental hygienists is necessary.     

Predoctoral implant dentistry curriculum survey: European dental schools

PURPOSE: In 2002 a survey of European dental schools was conducted. The purpose of the survey was to determine the curricular structure, teaching philosophies and materials used in predoctoral implant dentistry courses. MATERIALS AND METHODS: Fifty-six European dental schools were randomly selected from the Association for Dental Education in Europe representing 33 countries. A questionnaire was mailed to the predoctoral implant dentistry director/chairperson of the selected European dental schools. Of these, 40 schools returned the completed survey, resulting in a response rate of 71%. The mean, median and range of responses were computed where applicable. RESULTS: The results from this survey show that 80% of the responding schools required a course in implant dentistry. Between 1997 and 1999 over a third of responding schools (36%) incorporated a predoctoral implant dentistry course into their curriculum. Eighty-seven per cent of the schools have some prosthodontists teaching the course. Thirty-seven per cent of schools are offering a laboratory course in conjunction with the implant course. Sixty-three per cent of the schools are not restoring implant cases at the predoctoral level. However, 68% of schools reported students are required to be present during implant surgery. Ten per cent of schools require that the implant-related laboratory work be completed by the students. CONCLUSIONS: Predoctoral implant dentistry educational programmes vary from school to school. Yet a large percentage of schools agree on certain topics, including the importance of including implant education in predoctoral dental programmes.