Bisphosphonate-related Osteonecrosis Of Jaw Research Articles

Bisphosphonate related osteonecrosis of jaw: A case report

Bisphonates are used widely to treat osteoporosis, hyperglycemia of malignancy, bone metastasis of solid tumors. However a relationship has been reported between the use of bisphosphonates and osteonecrosis of jaw. Clinical presentation of bisphosphonates related osteonecrosis of jaw (BRONJ) includes gingival ulceration with exposed necrotic bone in the oral cavity involving either maxilla or mandible that has persisted for 6-8 weeks. And in severe cases it may cause spontaneous pain, tooth mobility, pathological fracture. Though treatment recommendation's exists, no definitive standard of care has been established for BRONJ and surgery was previously reported as capable of exacerbating bone exposure. The present study shows a case report of patient of BRONJ treated as conservatively as possible. Patient was managed with observation, oral antibacterial rinse, analgesics for pain control. After follow up of 18 months, healing of the lesion was achieved and patient became symptom free.

Prevention of bisphosphonate-related mandibular fractures.

SUMMARYMandibular fracture is usually the clinical end of bisphosphonate-related osteonecrosis of the jaw. This is a painful complication and patients cannot feed as usual, with a worsening of their quality of life. The goal of treatment in bisphosphonate related osteonecrosis of jaw (BRONJ) patients is to slow progression of bone necrosis. We present a novel technique for treatment of severe mandibular BRONJ in stage 3 patients that present with a high risk to develop fracture, since they have a residual unaffected mandibular bone height less than 6 mm. We treated 10 patients in this clinical situation with an extra-oral application of a reconstructive plate superficial to the platysma, to keep the plate separated from the infected site to avoid contamination and consequent need of removal, followed by an intraoral approach for active curettage of mandibular necrosis. The preservation of blood supply to the mandible and avoidance of direct contact of the infected site with the reconstructive plate are some advantages of this technique. This plate allows enhancement of mandibular strength, allowing proper treatment of the BRONJ site on the oral side without fear of causing a mandibular fracture when the residual mandible is thin. This technical solution guarantees these patients an extended disease-free period since it is effective in preventing mandibular fractures in patients with low mandibular residual height left after the BRONJ onset.

Are there any differences in mandibular morphology of patients with bisphosphonate-related osteonecrosis of jaws?: a case-control study.

The aim of this study was to compare the morphological differences in the mandible between patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) and healthy individuals and to detect the correlation between these parameters on panoramic radiography and CBCT. The CBCT and panoramic images of patients with BRONJ (n = 32) and control groups (n = 32) were included in the study. All the comparisons were analyzed between the osteonecrosed and healthy sides of patients with BRONJ and control group. The panoramic radiographs were used to measure the values of the condyle angle, gonial angle, antegonial angle, antegonial depth, condylar height and ramal height. The mandibular cortical index (MCI) and bone quality index (BQI) were also examined on cross-sectional scans of CBCT images. There were significant differences in the MCI (p = 0.014) and BQI (p = 0.021) between the left and right side of the BRONJ group and also between the osteonecrosed side of the BRONJ and control group (p < 0.0001). No significant difference was found in other comparisons. The outcomes of the present study indicate that bisphosphonates influenced some internal morphological changes in the mandible. These changes may be a reason of BRONJ. But, these changes are not reflective of the measured values obtained using panoramic radiographs on the external morphology of the mandible.

Simultaneous Application of Bone Morphogenetic Protein-2 and Platelet-Rich Fibrin for the Treatment of Bisphosphonate-Related Osteonecrosis of Jaw.

Simultaneous Application of Bone Morphogenetic Protein-2 and Platelet-Rich Fibrin for the Treatment of Bisphosphonate-Related Osteonecrosis of Jaw.

Genetic investigation of bisphosphonate-related osteonecrosis of jaw (BRONJ) via whole exome sequencing and bioinformatics.

Complications associated with the use of bisphosphonate (BP) have risen over the years due to an increase in the prescription of BP. BP-related osteonecrosis of jaw (BRONJ), one of the complications linked to the consumption of BP, greatly affects patients with minor dental trauma, incurring a long healing period. While BRONJ afflicts only a minority of patients prescribed with BP, BRONJ is a multigenic disease affected both by environmental and genetic factors having a distinctive phenotype. This study aims to discover genetic biomarkers associated with BRONJ via whole exome sequencing (WES) followed by statistical analysis. Sixteen individuals who had been prescribed with bisphosphonate medication and diagnosed as BRONJ were chosen and each individual’s saliva sample was collected for WES. 126 randomized subsamples from the GSK project representing 109 male and 17 female Koreans were used as a control data set. Fisher’s exact test was carried out to assess the significance of genetic variants in BRONJ patients. Gene set enrichment analysis (GSEA) (DAVID Bioinformatics Resource 6.7) was used to perform a cluster analysis of variants found from Fisher‘s exact test. The results from this study suggest that BRONJ-inducing factors are genetically associated and BRONJ occurs due to the malfunctioning of post-translational modification in osteoclast leading to the impairment of cell morphology and adhesion.

Surgical treatment with hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of jaw

The first preliminary report of bisphosphonate(BP)-related osteonecrosis of jaw (BRONJ) was published by Marx in 2003, and many patients suffering from severe BRONJ have since been identified. Hyperbaric oxygen (HBO) is recognized as useful to treat post-radiation osteonecrosis of the jaw, but few recommendations currently exist for the use of HBO to treat BRONJ, and opinions regarding efficacy are conflicting. Freiberger et al. conducted a randomized controlled study, but lacked the statistical power to show a significant difference between using and not using HBO in complete healing (ref.

The usefulness of FDG-PET for monitoring hyperbaric oxygen therapy in treatment of bisphosphonate-related osteonecrosis of jaws (BRONJ)

The usefulness of FDG-PET for monitoring hyperbaric oxygen therapy in treatment of bisphosphonate-related osteonecrosis of jaws (BRONJ)

Low-level laser therapy supported surgical treatment of bisphosphonate related osteonecrosis of jaws: a retrospective analysis of 11 cases.

The aim of this study is to evaluate and report on low-level laser therapy (LLLT) supported medical-surgical treatment outcomes of 11 patients with bisphosphonate related osteonecrosis of the jaws (BRONJ) lesions. BRONJ is a severe clinical condition, which adversely affects patients' lives. Even though various treatment modalities have been proposed, the ideal approach still remains to be debated. LLLT stands out among supportive approaches because of its favorable effects on tissue healing. Eleven patients diagnosed with Stage II or III lesions (American Association of Oral and Maxillofacial Surgeons [AAOMS] classification) were included in the study. All patients received LLLT applications during the postoperative period in addition to medical and surgical treatment. Laser applications covering the entirety of the surgical site were performed with GaAlAs diode laser with the following parameters: 808 nm wavelength, 0.5 W power, continuous wave, noncontact mode at 0.5-1 cm distance from the oral mucosa, spot size 0.28 cm(2) (R=6 mm), for 3 sec per point (10 sec per cm(2)), and energy density of 5 J/cm(2) (energy per point,1.4 J). Elimination of previously recorded symptoms and a stable mucosal closure was achieved in all patients. Primary healing was achieved in seven patients and secondary healing course was observed in four patients. Permanence of obtained positive outcomes was noted in follow-up periods. Treatment of advanced BRONJ lesions with a combination of antibiotic therapy, surgical removal of the lesion, and consecutive low-level diode laser applications provided favorable results in all patients. In consideration of our findings, it can be assumed that LLLT may serve as a safe and effective adjunct to medical-surgical treatment of BRONJ lesions.

Successful strategy of treatment used to rhBMP-2 and LFA-collagen scaffold for BRONJ

Bispbosphonates are a class of pharmaceutic agents, which induce apoptosis of osteoclast as well as impair osteoclastic activity to suppress bone resorption. Thus, bisphophonates are effectively used to treat osteoporosis, multiple myeloma and to prevent bone metastases of malignant cancer. However, recently dental disease have been reported associated with Bisphosphonates. Thus, there are a number of discussions about proper prevention and treatment of bisphosphonate-related osteonecrosis of jaw(BRONJ). Marshall R. Urist in 1965 made the seminal discovery that a specific protein, BMP(bone morphogenetic protein), found in the extracellular matrix of demineralized bone could induce bone formation newly when implanted in extraosseous tissues in a host. BMPs are multi-functional growth factors which are members of the transforming growth factor-beta super family and their ability is that plays a pivotal roll in inducing bone. About 18 BMP family members have been identified and characterized. Among of them, BMP-2 and BMP-7 have significant importance in bone development. In this study, patients of BRONJ were recieved who visited Department of oral and maxillofacial surgery, school of dentistry, Wonkwang university for past 3 years from 2011 to 2013. We focused on the results of the surgical intervention. We suggest that new strategy of treatment used to rhBMP-2 and LFA(Lidocaine-Fibrinogen-Aprotinin)-collagen scaffold for patients of BRONJ. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on rhBMP-2 and LFA collage scaffold.

비스포스포네이트 관련 악골괴사(BRONJ)의 병기 2기에서의 외과적, 보존적 치료에 대한 비교 연구

Purpose: This study evaluated the prognosis of conservative and surgical treatment according to the staging of bisphosphonate-related osteonecrosis of jaw (BRONJ) by American Association of Oral and Maxillofacial Surgeons and American Society for Bone and Mineral Research. Methods: We evaluated 53 patients of BRONJ who visited Department of Dentistry, Ajou University School of Medicine from May 2007 to February 2013. Twenty eight patients in stage 2, were divided into surgical and conservative groups with cessation of bisphosphonate therapy. Fifteen patients belonged to the conservative treatment group, in which mouth rinsing and antibiotics medication were done. Thirteen patients were treated with debridement or sequestrectomy, in the surgical treatment group. Each study list was analyzed by SPSS ver. 14.0 (SPSS Inc., USA) software and the favorable rate was verified by the Fisher exact test. P-values less than 0.05% were deemed significant. Results: Clinical outcome was evaluated on the basis of both clinical and radiographic findings. Of all the 28 patients of stage 2, 15 patients underwent conservative treatment and 13 patients received surgical treatment. In the surgical group, 9 of 13 (69.2%) showed good prognosis, 4 of 13 (30.7%) showed recurrence. In the conservative group, 13 of 15 (86.6%) showed no change duting the follow-up period. Two of 15 patients even showed a bad prognosis, such as pain and pus discharge, which are criteria for stage 3. P-value was 0.067 (>0.05). Conclusion: The results of the present study suggests that surgical intervention is good choice against the conservative treatment, after proper drug holidays period, while further investigation is needed for a definite solution to BRONJ.

Bisphosphonate-Related Osteonecrosis of Jaw in the Adjuvant Breast Cancer Setting: Risks and Perspective

Bisphosphonate-Related Osteonecrosis of Jaw in the Adjuvant Breast Cancer Setting: Risks and Perspective

Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine

Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ.

Bisphosphonate-related Osteonecrosis of Jaw (BRONJ) in Japanese Population: A Case Series of 13 Patients at Our Clinic

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) affects quality of life and is an important problem for dentists. A Japanese position paper on BRONJ was published in 2010. The purpose of this study was to review clinical data on the treatment of BRONJ obtained at the Clinic of Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba Hospital to further our understanding of this disease. A total of 13 patients (6 men and 7 women) were included. All the patients included in this study had received Bisphosphonate (BP) therapy and had BRONJ. Five of them (38.5%) had received oral BP therapy for osteoporosis, while the remaining 8 (61.5%) had received parenteral BP therapy for bone metastases from breast or prostate cancer. Osteoporosis patients were treated with risedronate or alendronate. Breast or prostate cancer patients were treated with zoledronate. Two patients with rheumatoid arthritis were treated with corticosteroid. Three patients had diabetes mellitus. Eleven patients were treated with antibiotics, while 5 underwent surgical treatment. Discontinuation of BP was recorded in 7 patients during dental treatment. Sequestration was observed in 6 patients during an 11-month follow-up. Eventually, healing and improvement of the oral mucosa were observed in 3 patients. The current standard treatment for BRONJ does not always provide good results. It is necessary to accumulate further clinical data to establish more effective treatment strategies for BRONJ.

Bisphosphonate-related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect

Recently, bisphosphonates (BPs) have been widely used in medical practice as anti-resorptive agents owing to their anti-osteoclatic action. In addition, these compounds are also used for their analgesic action and their potential anti-tumour effect. Patients treated with BPs may subsequently develop osteonecrosis of the jaw or maxillary bone after minor local trauma including dental work, recently labelled as bisphosphonate osteonecrosis of jaw (BRONJ). However, the etiopathogenic mechanisms of this pathological condition are poorly understood. Although, several pathways have been proposed for BRONJ occurrence, no single model can explain all morphological changes observed at the macro- and microscopic level. Recent research suggests that BPs may promote an anti-angiogenic effect which contributes directly to the clinical features associated with BRONJ. Remarkably, the anti-angiogenic effect promoting BRONJ might be in keeping with the anti-neoplastic action of BPs. The current review, presents clinical diagnostic criteria. In addition, based on our own experience we describe the histopathological criteria for diagnosis of BRONJ and the possible pathways which may lead to this frustrating pathological condition.

Bisphophonates related osteonecrosis of the jaw.

Objective:With sporadic reporting of BPs related osteonecrosis of jaw and in absence of definitive guidelines regarding the management of such patients, the dentists and the oral and maxillofacial surgeons need to be updated about this issue. The objective of this article was to produce an updated bibliographic review of BPs related ONJ. This paper reviews the literature regarding the same for better understanding of the problem and its management.Background:Bisphosphonates (BPs) are potent inhibitors of bone resorption and are widely used in the treatment of osteoporosis and other diseases that cause bone mass loss, such as Paget's disease, bone metastases, and multiple myeloma, to prevent pathological fractures. With increasing use, evidence is emerging that patients taking BP drugs are at risk of developing osteonecrosis of the jaws (ONJs), sometimes occurring spontaneously, but more commonly following dental extractions or oral bone surgery.Materials and Methods:A bibliographic search was carried out using PubMed, Medline, and search engines ending in April, 2013. The search terms used were: Oral BPs, dental implants, and osteonecrosis.Conclusion:On the basis of available literature, the management of patients on bisphosphonates requiring dental treatment is classified according to the duration of BPs treatment, method of administration of BPs etc. Dental treatments when planned carefully in such patients have a fair to good prognosis.

Bisphosphonates: An update to the general dentist

Bisphosphonates (BP), included under host modulation therapy are drugs that inhibit bone resorption and commonly prescribed to prevent skeletal related changes in malignant diseases of bone and bone diseases such as osteoporosis. The sudden rise of this group of drugs is unfortunately because of the serious complication of osteonecrosis of jaws called Bisphosphonate related osteonecrosis of jaws which leads to many dental related complications. This literature review is undertaken to review the general recommendations to the dentist and clinical implications of BP's. The implications of BP's use in dentistry are still being determined.

Quantification by energy dispersive x-ray spectroscopy of alendronate in the diseased jaw bone of patients with bisphosphonate-related jaw osteonecrosis

Recently, specific in vitro bisphosphonate concentrations have been established for reaching a toxic threshold that could result in the induction of bisphosphonate-related osteonecrosis of the jaw (BRONJ), but these data have not been validated in vivo. The purpose of this study was to quantify the concentration of bisphosphonates (BPs) in the diseased jaw bone of patients experiencing BRONJ. We hypothesized that if the average natural nitrogen content of mammalian bone is known, the excess of nitrogen in the jaw bone of BRONJ patients is likely to reflect the concentration of amino-BP. To test our hypothesis, jaw bone specimens from patients with BRONJ were acquired after sequestrectomy and analyzed by energy-dispersive X-ray spectroscopy (EDS). The EDS analysis of the bone demonstrated a highly linear correlation between increasing concentrations of BP and the increasing percentage of nitrogen measured at the bone surfaces (R(2) = .9851, P = .0149). SEM/EDS can be a valuable tool for assessing BP concentration in jaw bone and provides important insight into BP pharmacokinetics and BRONJ.

Bisphosphonate-related osteonecrosis of jaw (BRONJ): an anti-angiogenic side-effect?

Bisphosphonates are recommended in the treatment of osteoporosis and some cancers, in which case they prevent the appearance of bone metastasis. The patients taking bisphosphonates are at increased risk of developing bisphosphonate-related osteonecrosis of jaw (BRONJ) which is characterised by the presence of an un-healing wound after dental surgery. BRONJ might represent an anti-angiogenic side effect. However, the real number of patients with BRONJ might be higher than currently recorded. Considering the differential diagnosis which includes various primary and secondary cancers, a correct histopathological diagnosis is very important. The morphological criteria for diagnosis of BRONJ are highlighted in this material.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1813972972323288

Osteonecrosis of jaw (onj): impact of italian patients, and role of italian physicians, dentists, and researchers in the growing evidence of a “new” disease

Purpose: Osteonecrosis of jaw (ONJ) is an uncommon but severe complication observed mostly in patients treated with bisphosphonates (BPs) for bone metastases, myeloma, osteoporosis (so called BRONJ, Bisphosphonate-Related Osteonecrosis of Jaw), but also with other drugs (bevacizumab, sunitinib, denosumab). The number of cases observed in Italy appears high in comparison with other countries and we present a review of several aspects of ONJ in Italy and the role of Italian health professionals and researchers on increasing knowledge and adequate reporting of ONJ phenomenon; Methods: Literature review about osteonecrosis of jaw (ONJ) with selection of Italian authors and publications, on year 2003-2011, by research on international electronic journal databases, Italian language journals, congress acta, web sources; Results: at October 2011, among 1272 papers published worldwide on ONJ issue, 128 (10%) were from Italian Authors; Conclusions: relevant articles by Italian groups were published about pathogenesis hypotheses, animal models, biology studies, risk factors, preventive measures, dental extraction protocols in BP-exposed patients, laser therapy, ozone therapy, surgical treatment. Experience of Italian patients suffering from ONJ, together with work of Italian dentists, physicians and researchers, appears of paramount importance in order to study ONJ and minimize a possible severe side-effect of efficacious medical treatments.

Skeletal Biodistribution of Fluorescently Labeled Bisphosphonate is Anatomic Site-Dependent

Objectives. Long-term administration of bisphosphonates has been associated with bisphosphonate-related jaw osteonecrosis (ONJ). A potential etiologic factor is disproportionate concentration of bisphosphonate in the jaws, but it is unclear if regional biodistribution and bioavailability of bisphosphonates is site-dependent. We tested in rats the hypothesis that skeletal biodistribution and release of pamidronate (a nitrogen-containing bisphosphonate) is anatomic site-dependent.