Accurate Approach in the Treatment of Oral Bisphosphonate-Related Jaw Osteonecrosis

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood and difficult to treat. Even though the occurrence of BRONJ is mainly related to the therapy with intravenous bisphosphonates (BPs), this article reports a case of long-term oral BP use and BRONJ occurrence. In addition, a literature review provides some additional information about BPs, BRONJ, and also a guideline for the prevention and treatment of BRONJ stages. A 79-year-old patient presented intense and persistent pain, purulent secretion, and exposed bone at the right side of the lower jaw. Thus, she was submitted to anamnesis, radiologic and tomographic examinations, and bacterial culture and sensitivity tests. These procedures were followed by surgical debridement of the bone and surrounding tissues/cyst and antibiotic prescription and histopathologic analysis of the fragments. Together, the examinations performed showed the occurrence of stage 2 BRONJ. Moreover, the antibiotic prescription, discontinuation of oral BP, and surgical procedures ensure that the patient had no more symptoms. Therefore, considering the presented case, we believe that an accurate approach is promising to diagnose and treat stage 2 BRONJ and other associated pathologic findings.

Management of Osteonecrosis of the Jaws in Patients With History of Bisphosphonates Therapy

Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. The relation between the use of bisphosphonates and ostenonecrosis of the jaws as an adverse effect of the drug has been intensely discussed during the last few years, and up to this moment, there is no consensus concerning an ideal treatment modality for this condition. Nevertheless, there is an agreement among researchers that the standard goal for controlling jaw osteonecrosis is to prevent it. Otherwise, the rationale for a randomized controlled trial is that current treatment has proven to be suboptimal, and no consensus has been reached yet on the best strategies to repair the exposed bone once bone necrosis is developed. This article is focused on reporting a case of moderate osteonecrosis of the upper jaw induced by bisphosphonates and discusses a possible role for surgical debridement associated to platelet-rich plasma, hyperbaric oxygen therapy, and the cessation of the bisphosphonate use in managing this type of lesion. Moreover, the dentist, the oral surgeon, and the oncologist need to work together to reach better outcomes.

Experimental development of bisphosphonate-related osteonecrosis of the jaws in rodents

Osteonecrosis of the jaw (ONJ) following the use of bisphosphonates has become of increased interest in the scientific community, due in particular to its as-yet-unsolved pathogenesis. An experimental model of ONJ was induced in normal male rats [alendronate (ALN); 1 mg/Kg/day; n = 10] and matched controls (saline solution; n = 10). After 60 days of drug treatment, all animals were subjected to extractions of the left first lower molars and were euthanized at 3 and 28 days postsurgery. The following analyses were performed: (i) descriptive and quantitative (scores) histological evaluation, (ii) stereometry of distal sockets and (iii) biochemical measurement of C-telopeptide cross-linked collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results showed that 28 days postsurgery the animals treated with ALN had areas of exposed and necrotic bone, associated with significant infection, especially in the interalveolar septum area and crestal regions, compared with controls. The levels of CTX, BALP and bone volume, as well as the degrees of inflammation and vascularization, were significantly reduced in these animals. Therefore, analysis of the data presented suggests that ALN therapy is associated with the development of osteonecrosis in the jaws of rodents after tooth extraction. © 2012 International Journal of Experimental Pathology.

Osteonecrose dos maxilares associada ao uso de bisfosfonatos: importante complicação do tratamento oncológico

Os bisfosfonatos são um grupo de medicamentos utilizados no tratamento de doenças malignas metastáticas e em outras doenças ósseas como osteoporose e doença de Paget. A despeito dos seus benefícios, uma importante complicação denominada de osteonecrose dos maxilares vem sendo observada nos pacientes usuários crônicos dos bisfosfonatos que se caracteriza clinicamente por exposições ósseas na região maxilofacial persistente, acompanhadas de osteomielite, geralmente sintomáticas e cujo tratamento é complexo. Este estudo tem por objetivo revisar a literatura sobre a osteonecrose associada ao uso dos bisfosfonatos, em especial, em oncologia, no período de 2003 a 2008. Serão apresentados e discutidos os fatores de risco, aspectos etiopatogênicos, clínicos, imagenológicos, terapêuticos e preventivos desta doença. Devido à dificuldade de tratamento da osteonecrose associada aos bisfosfonatos, o foco deve ser a prevenção, sendo o ideal a eliminação de quadros infecciosos orais antes da terapia com os bisfosfonatos ter sido iniciada e minimizar traumas em boca após o uso destes medicamentos.

Bisphosphonate-related Osteonecrosis Of The Jaw: A Review Of The Literature.

Bisphosphonates (BPs) are a class of drugs used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. The American Society for Bone and Mineral Research defines BRONJ as an area of exposed bone in the maxillofacial region that has not healed within 8 weeks after identification by a healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has not had radiation therapy to the craniofacial region. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) can adversely affect quality of life, as it may produce significant morbidity. The American Association of Oral and Maxillofacial Surgeons (AAOMS) considers as vitally important that information on BRONJ be disseminated to other dental and medical specialties. The purpose of this work is to offer a perspective on how dentists should manage patients on BPs, to show the benefits of accurately diagnosing BRONJ, and to present diagnostic aids and treatments strategies for the condition.

Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients

Osteonecrosis of the jaw (ONJ), previously an entity associated with radiation therapy to the head and neck, has been observed in patients treated with bisphosphonates. Patients with metastatic breast cancer and myelomatous bone disease, commonly treated with high-potency nitrogen-containing bisphosphonates for a prolonged period of time, have the greatest risk of ONJ development. The reported frequency of ONJ ranges from 0.6% to 6.2% in breast cancer and from 1.7% to 15% in patients with multiple myeloma. Osteonecrosis of the jaw has also been observed in patients with other cancers such as prostate cancer and in benign bone disorders such as osteoporosis and Paget`s disease in which the incidence is low. Risk factors associated with the development of ONJ include dental extractions, length of bisphosphonate treatment, and the type of bisphosphonate used. In this review, we summarize the reported incidence and risk factors associated with ONJ.

A Role of Oral Bacteria in Bisphosphonate-induced Osteonecrosis of the Jaw

No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics.

Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate-related osteonecrosis of the jaw

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: Not just a sporadic coincidence - a multi-centre study

Bisphosphonates (BPs) are powerful drugs that inhibit bone metabolism. Adverse side effects are rare but potentially severe such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). To date, research has primarily focused on the development and progression of BRONJ in cancer patients with bone metastasis, who have received high dosages of BPs intravenously. However, a potential dilemma may arise from a far larger cohort, namely the millions of osteoporosis patients on long-term oral BP therapy.

Frequencies and risk factors for bisphosphonate-related osteonecrosis of the jaw in cancer patients: A matched case-control study

Bisphosphonates represent a unique class of drugs that effectively treat and prevent a variety of bone-related disorders including metastatic bone disease and osteoporosis. High tolerance and high efficacy rates quickly ranked bisphosphonates as the standard of care for bone-related diseases. However, in the early 2000s, case reports began to surface that linked bisphosphonates with osteonecrosis of the jaw (ONJ). Since that time, studies conducted have corroborated the linkage. However, as with most disease states, many factors can contribute to the onset of disease. The aim of this study was to determine which comorbid factors presented an increased risk for developing ONJ in cancer patients.^ Using a case-control study design, investigators used a combination of ICD-9 codes and chart review to identify confirmed cases of ONJ at The University of Texas M. D. Anderson Cancer Center (MDACC). Each case was then matched to five controls based on age, gender, race/ethnicity, and primary cancer diagnosis. Data querying and chart review provided information on variables of interest. These variables included bisphosphonate exposure, glucocorticoids exposure, smoking history, obesity, and diabetes. Statistical analysis was conducted using PASW (Predictive Analytics Software) Statistics, Version 18 (SPSS Inc., Chicago, Illinois).^ One hundred twelve (112) cases were identified as confirmed cases of ONJ. Variables were run using univariate logistic regression to determine significance (p < .05); significant variables were included in the final conditional logistic regression model. Concurrent use of bisphosphonates and glucocorticoids (OR, 18.60; CI, 8.85 to 39.12; p < .001), current smokers (OR, 2.52; CI, 1.21 to 5.25; p = .014), and presence of diabetes (OR, 1.84; CI, 1.06 to 3.20; p = .030) were found to increase the risk for developing ONJ. Obesity was not associated significantly with ONJ development.^ In this study, cancer patients that received bisphosphonates as part of their therapeutic regimen were found to have an 18-fold increase in their risk of developing ONJ. Other factors included smoking and diabetes. More studies examining the concurrent use of glucocorticoids and bisphosphonates may be able to strengthen any correlations.^

Bisphosphonate-related osteonecrosis of the jaws: how to manage cancer patients.

Bisphosphonate related osteonecrosis of the jaw (BRONJ) is defined as exposed necrotic bone appearing in the jaws of patients treated by systemic IV or oral BPs never irradiated in the head and neck area and that has persisted for more than 8 weeks. More than 90% of cases of osteonecrosis of the jaw have been in patients with cancer who received IV-BPs. The estimate of cumulative incidence of BRONJ in cancer patients with IV-BPs ranges from 0.8% to 18.6%. The pathogenesis of BRONJ appeared related to the potent osteoblast-inhibiting properties of BPs which act by blocking osteoclast recruitment, decreasing osteoclast activity and promoting osteoclast apoptosis. Dental extractions are the most potent local risk factor. Cancer patients wearing a denture could also be at increased risk of BRONJ. Non-healing mucosal breaches caused by dentures could be a portal for the oral flora to access bone, while the oral mucosa of patients on IV-BPs could also be defective. Whether periodontal disease is a risk factor for BRONJ remains controversial. Preventive measures are fundamental. Nevertheless, some teams have questioned its cost-effectiveness. The perceived limitations of surgical therapy of BRONJ led to the restriction of aggressive surgery to symptomatic patients with stage 3 BRONJ. The evidence-based literature on BRONJ is growing but there are still many controversial aspects.

Oral bisphosphonate-related osteonecrosis of the jaws in rheumatoid arthritis patients: a critical discussion and two case reports

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition characterized by the presence of exposed bone in the maxillofacial region. Its pathogenesis is still undetermined, but may be associated with risk factors such as rheumatoid arthritis (RA). The aim of this paper is to report two unpublished cases of BRONJ in patients with RA and to conduct a literature review of similar clinical cases with a view to describe the main issues concerning these patients, including demographic characteristics and therapeutic approaches applied.Methods: Two case reports of BRONJ involving RA patients were discussedResults: Both patients were aging female taking alendronate for more than 3 years. Lesions were detected in stage II in posterior mandible with no clear trigger agent. The treatment applied consisted of antibiotics, oral rinses with chlorhexidine, drug discontinuation and surgical procedures. Complete healing of the lesions was achieved.Conclusions: This paper brings to light the necessity for rheumatologists to be aware of the potential risk to their patients of developing BRONJ and to work together with dentists for the prevention and early detection of the lesions. Although some features seem to link RA with oral BRONJ and act as synergistic effects, more studies should be developed to support the scientific bases for this hypothesis.