Bisphosphonate-related osteonecrosis of the jaws

The purpose of this paper is to highlight an emerging phenomenon of osteonecrosis of the jaws that occurs in some patients who are on long-term bisphosphonate therapy. The condition can appear spontaneously or as a result of trauma, and is difficult to treat. Dental surgeons must be aware of patients who are at risk and institute appropriate preventive care. It is also important to recognize the condition when it does appear and refer appropriately. We present the first local case series of the condition showing varied clinical presentations and treatments.     

Bisphosphonate-related osteonecrosis of the jaws

Bisphosphonates are a class of agents whose efficacy in treating and preventing the skeletal complications associated with osteoporosis and malignant bone metastases has been well established. Despite this benefit, osteonecrosis of the jaws is a significant complication in a subset of patients receiving these drugs. Based on a growing number of case reports and institutional reviews, bisphosphonate therapy may cause bone to become exposed and necrotic. Currently, this phenomenon is isolated to the jaw. This complication usually presents following simple dentoalveolar surgery. The pathogenesis for this complication appears to be related to the profound inhibition of osteoclast function and bone remodeling. This article serves to alert ists and dental specialists about the potential complication of jaw necrosis in patients receiving bisphosphonate therapy, and proposes a guideline for diagnosis, staging and management.     

Bisphosphonate-related osteonecrosis of the jaws

Bisphosphonate-related osteonecrosis of the jaws is a complication which can occur in patients treated with bisphosphonates. The pathogenesis is still poorly understood. Risk factors are invasive oral treatments with tooth extraction as a leading cause. Because of the complexity of the treatment of osteonecrosis of the jaws, prevention is of the utmost importance. Invasive oral treatments needed, should be performed before starting the treatment with bisphosphonates. Since osteonecrosis of the jaws is presenting relatively rare, it is understandable that guidelines with respect to prevention and treatment are not evidence-based.     

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.     

Bisphosphonate-related osteonecrosis of the jaws (Bronj)

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an extremely therapy resistant osteomyelitis-like disease exclusively involving the jaw bones of patients in treatment with bisphosphonates (BPs). Objectives: The aim of this study was to evaluate the radiological and clinical findings and management of 51 patients with BRONJ diagnosed from 2004 to 2009 in our Reference Center. Study Design: A prospective study was performed. The patients were examined every 2-6 months, depending on their clinical conditions. Outcome variables were the resolution of symptoms, persistence of bone exposure and /or fistula and the status of the lesional mucosa. Results: The higher prevalence of the disease was noted in 2006 and 2007 and at the time of diagnosis 90% of patients had been treated with iv BPs. The main precipitating event leading to BRONJ was an invasive dental procedure in 61% of patients while no traumatic event could be identified in 16% of patients. The median time of follow-up was 19 months (range: 2-57), during which 31% of patients healed and 39% succumbed. In 78% of patients the therapy was medical, in 16% it consisted in surgical deep curettage and only in 6% it was necessary to perform an osteotomy to avoid a mandibular pathological fracture. All the patients in treatment with oral BPs healed from BRONJ with a median time of conservative treatment of 19 months. Conclusions: Prevention has lead to a progressive reduction in the prevalence of BRONJ. In our experience medical treatment is often sufficient to keep the disease under control and to lead to the healing of the lesions by spontaneous loss of the sequestrum. This approach seems to be very effective in patients who were in treatment with oral Bps preparations; BRONJ seems to have a more benign clinical behaviour in these patients. Key words:Bisphosphonates, osteonecrosis, treatment, follow-up.     

Bisphosphonate-related osteonecrosis of the jaws: a comprehensive review

BACKGROUND: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) presents the clinician with significant management dilemmas. The purpose of this study was to distil information related to this disorder by comprehensively reviewing the literature. METHODS: The structure and function of bisphosphonates, and their role in the development of BRONJ will be discussed, as will the possible mechanisms through which this pathology develops. A review of cases presented in the literature will be undertaken, and suggestions offered as to the management of this pathology in terms of surgical and conservative approaches. RESULTS: Presentation of BRONJ is currently more common in patients taking intravenous forms of bisphosphonates, but there is a fear that the long-term cumulative effects of oral bisphosphonates may see BRONJ increasingly occurring in this patient group. CONCLUSIONS: Prevention is superior to treatment, and the establishment of meticulous oral hygiene and pre-emptive surgical treatment prior to commencement of bisphosphonate therapy is recommended.     

Bisphosphonate-related osteonecrosis: genetic and acquired risk factors

The objectives of this study were to review epidemiological, clinical and biological aspects associated with the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in multiple myeloma (MM) patients, with special emphasis on the genetic aspects. A detailed review of previously described risk factors as well as recent genetic findings mostly comprises this work. The most recent meeting abstracts and relevant articles published in journals covered by the Science Citation Index and Medline are also examined. The review pays special attention to the genetic component of BRONJ. A total of 15 series and 14 guidelines or revisions were selected to fit the aims of the review. Gene variability was reviewed in depth to give a clinical illustration on the genetic aspects of BRONJ. Crude prevalence and 5-year cumulative incidence were considered as the most important end points for predictive purposes. Several acquired factors were recognized as predictors for BRONJ in MM, especially intravenous bisphosphonates, dental trauma and advanced age. Among genetic factors, polymorphisms on CYP2C8 gene arise as a promising risk factor. Bisphosphonate-related osteonecrosis of the jaw can be predicted with a conjunction of genetic and environmental risk factors.     

双膦酸盐相关性颌骨坏死:病例报道及文献复习

该文报道了因食道癌骨转移使用双膦酸盐治疗而导致下颌骨坏死的病例1例,通过介绍其临床表现及治疗过程,复习文献探讨其临床特征、治疗及预防。患者停用药物,漱口液含漱,接受清创术及抗生素治疗后,预后良好。     

Bisphosphonate-related osteonecrosis of the jaw: clinical correlations with computerized tomography presentation

The aim of this study was to correlate clinical and computerized tomography (CT) features of bisphosphonate-related osteonecrosis of the jaws (BRONJ). All ONJ patients for whom there was complete CT scan imaging were eligible. Selected clinical parameters retrieved from their medical records were analyzed for correlation with CT parameters. The clinical presentation of BRONJ was supported by findings in CT imaging in 78.3%. The lesion’s size on CT correlated with the presence of purulent secretion (p?=?0.03). When sequestrum was present, the median lesion’s size on CT was relatively big (28 mm, range 21–43 mm). The mandibular canal cortex was never breached. CT has reasonable detection competence for diagnosing BRONJ. Purulent secretion indicates the likelihood that a more extensive involvement will be displayed on CT. A large lesion on CT should raise the index of suspicion for sequestrum. The CT appearance of a continuous cortex of the mandibular canal may serve as a differential parameter between BRONJ and metastasis to the jaw.     

双膦酸盐性颌骨坏死：病例报告及文献复习

双膦酸盐类药物临床用于治疗骨质疏松症、变形性骨炎和其他代谢性骨病、多发性骨髓瘤以及与肿瘤转移相关的骨骼疾病。该类药物通过抑制破骨细胞介导的骨吸收而产生临床治疗作用。然而,双膦酸盐类药物,尤其是静脉用双膦酸盐类药物有致颌骨骨坏死的危险。目前,国内尚未有该类药物致下颌骨坏死的报道。作者报告1例口服双膦酸盐类药物阿仑膦酸钠（Alendronate,商品名福善美,Fosamax）致下颌骨骨坏死病例,并结合文献对双膦酸盐性颌骨坏死的发病机制、临床表现及其预防和治疗进行讨论。     

Hyperbaric oxygen and postradiation osteonecrosis of the mandible

The clinical and dental records of 26 patients with the clinical diagnosis of postradiation osteonecrosis (PRON) managed with hyperbaric oxygen (HBO) were reviewed to determine the efficacy of HBO. 19 patients were male and 7 were female; age at the first HBO session ranged from 28 to 80 years (median 57.5 years). All but 8 patients reviewed had some form of surgical management; 7 had mandibulectomy for PRON. As part of management, a total of 9–84 HBO sessions (median 35 sessions) was administered. 18 of the 26 patients ultimately achieved persistent mucosal and cutaneous coverage 1–84 months (median 24 months) after the first HBO session. 13 of the 26 patients met strict criteria for resolution of their disease; fully 21 of 26 patients had improved PRON status following HBO therapy. HBO treatment as part of a comprehensive managment plan is safe and effective in the management of PRON.     

Bisphosphonate-related osteonecrosis of the jaw in four Nordic countries and an indication of under-reporting

Abstract

Objective. To assess reported cases of bisphosphonate-related osteonecrosis of the jaw (BONJ) to Medicines Agencies (MAs) in four Nordic countries and to compare the Norwegian MA data with BONJ cases retrieved through an e-mail survey to Oral and Maxillofacial Surgeons (OMS) in Norway. Material and methods. BONJ cases reported to the national MAs in each country from January 1st 2003 to September 30th 2010 were collected. An e-mail survey was sent to all active members of the Norwegian Association of Oral and Maxillofacial Surgeons (n = 54) included questions on total BONJ cases seen in practice and route of drug administration during January 1st 2003 to December 31st 2009. Results. In total, 253 BONJ cases were reported to the MAs; 39 in Denmark, 44 in Finland, 51 in Norway and 119 in Sweden. These figures result in cumulative incidences (multiplied by 100,000) of 0.7, 0.8, 1.1 and 1.3, respectively. Intravenous administration was reported in 169 of the cases. The e-mail survey resulted in 35 responses reporting 214 BONJ cases, 4-times more cases than reported to the MA. Conclusions. Cumulative incidence of cases reported in this study differs to some degree in the four Nordic countries (Denmark < Finland < Norway < Sweden). In Norway, almost the same number of BONJ cases were reported through the questionnaire by OMS as in all four countries together (214 by OMSs vs 254 to MAs) and included a high number after per oral administration. The present results indicate a notable under-reporting in Norway and most likely in other Nordic countries.     

二膦酸盐相关的颌骨骨坏死——2例病例报告及预防与处置策略

报告2例二膦酸盐相关的颌骨骨坏死病例，1例发生在上颌，另1例发生在下颔。对患者进行了长疗程的抗生素治疗及最小量的外科清创．而未进行大型的切除性手术。概括当前的文献．对该类病损的预防与处置提出了一些临床建议。     

双膦酸盐相关性颌骨坏死并发腕部舟状骨骨髓炎1例

双膦酸盐类药物可以抑制破骨细胞功能,使颌骨骨密度升高,血流减少,发生骨坏死。双膦酸盐类药物相关性骨坏死多发于颌骨。本文报道1例双膦酸盐相关性颌骨坏死并发腕部舟状骨骨髓炎,并结合文献讨论双膦酸盐药物性颌骨坏死的发病机制、治疗与预防等。