Bisphosphonate-related Osteonecrosis Of The Jaw Stage Research Articles

Zoledronic Acid Deteriorates Soft and Hard Tissue Healing of Murine Tooth Extraction Sockets in a Dose-Dependent Manner.

The pathophysiology, histopathology, and immunopathology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) Stage 0 remain unclear. The aim of this study was to investigate the effects of high-dose bisphosphonates on tooth extraction socket healing by creating a murine model of BRONJ Stage 0-like lesions using 8-week-old female C57BL/6J mice. Zoledronic acid (Zol) was administered subcutaneously twice a week for 7weeks at doses of 0.1mg/kg/week (moderate dose; Zol-M), 0.5mg/kg/week (high dose; Zol-H1), and 1.0mg/kg/week (higher dose; Zol-H2). Saline was used as a control (VC). Both maxillary first molars were extracted 3weeks after drug treatment. Maxillae, long bones, and sera were collected 4weeks post-extraction (n = 7 mice/group). Microcomputed tomography, histological, immunohistochemical, and ELISA analyses were performed. A ceiling effect for Zol was noted at the Zol-H1 dose. Osseous healing of extraction sites was significantly impaired with increased necrotic bone and the number of empty lacunae in a Zol dose-dependent manner. Zol significantly decreased epithelial thickness, due to a decrease in thickness of the stratum spinosum, in both Zol-H1 and Zol-H2. Both Zol-H1 and Zol-H2 significantly suppressed the distribution of F4/80+ macrophages in the connective tissue of tooth extraction sockets, although gross healing appeared to be normal. Intriguingly, both Zol-H1 and Zol-H2 significantly increased the numbers of TRAP+ mononuclear cells and detached osteoclasts in the connective tissue and bone marrow of extraction sites compared to VC and Zol-M, correlated with serum TRAcP5b levels. The created murine model of BRONJ Stage 0-like lesions becoming more severe in a dose-dependent manner may help to understand the pathophysiology and histopathology of BRONJ Stage 0 in humans.

National Survey on Bisphosphonate-Related Osteonecrosis of the Jaws in Japan

From 2011 to 2013, a nationwide retrospective cohort study was conducted by the Japanese Society of Oral and Maxillofacial Surgeons and the Japanese Society of Dentistry for Medically Compromised Patients to assess the development of bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ) and to elucidate the outcomes and factors associated with remission. A written questionnaire, including clinical characteristics, management, and outcomes of patients with BRONJ, was sent to 501 institutions. This large-scale study included 4,797 cases with a female preponderance. BRONJ occurred twice as often in the mandible as in the maxilla. Most patients had BRONJ stage 2 (61.4%), followed by stage 1 (20.7%) and stage 3 (16.8%); stage 0 was excluded. The most common primary disease was malignant neoplasm (46.5%), followed by osteoporosis (including prevention; 45.3%). The proportion of patients on oral BPs increased, with the incidence approaching that of patients receiving parenteral BP. Surgical therapy rates of patients with BRONJ stages 1, 2, and 3 were 14.0, 37.6, and 53.5%, respectively. Outcome assessment for 936 patients with BRONJ stage 2 who underwent surgical therapy indicated remission in 46.3% of cases, improvement in 30.6%, disease progression in 5.4%, and no change in 6.1%. Good prognosis (remission or improvement) was seen in 76.9% of cases and poor prognosis (disease progression or no change) was seen in 11.5%. Analysis showed that risk factors for onset of BRONJ (P=.031), surgical procedure (P<.024), condition of the wound (P=.017), and discontinuation of BP (P<.001) were factors affecting prognosis. The number of patients with BRONJ has increased in Japan. Attention to oral BP and proper treatment is required to minimize the number of cases. Surgical therapy seems to be effective for BRONJ stage2.

Relationship between disease stage and renal function in bisphosphonate-related osteonecrosis of the jaw.

ObjectivesBisphosphonate is the primary cause of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are eliminated from the human body by the kidneys. It is anticipated that bisphosphonate levels in the body will increase if the kidney is in a weak state or if there is systemic disease that affects kidney function. The aim of this study was to analyze the relevance of renal function in the severity of BRONJ.Materials and MethodsNinety-three patients diagnosed with BRONJ in Pusan National University Dental Hospital from January 2012 to December 2014 were included in this study. All patients underwent a clinical exam, radiographs, and serologic lab test, including urine analysis. The patient's medical history was also taken, including the type of bisphosphonate drug, the duration of administration and drug holiday, route of administration, and other systemic diseases. In accordance with the guidelines of the 2009 position paper of American Association of Oral and Maxillofacial Surgeons, the BRONJ stage was divided into 4 groups, from stage 0 to 3, according to the severity of disease. IBM SPSS Statistics version 21.0 (IBM Co., USA) was used to perform regression analysis with a 0.05% significance level.ResultsBRONJ stage and renal factor (estimated glomerular filtration rate) showed a moderate statistically significant correlation. In the group with higher BRONJ stage, the creatinine level was higher, but the increase was not statistically significant. Other factors showed no significant correlation with BRONJ stage. There was a high statistically significant correlation between BRONJ stage and ‘responder group’ and ‘non-responder group,’ but there was no significant difference with the ‘worsened group.’ In addition, the age of the patients was a relative factor with BRONJ stage.ConclusionWith older age and lower renal function, BRONJ is more severe, and there may be a decrease in patient response to treatment.

Bisphosphonate-related osteonecrosis of the jaws: Cohort study of surgical treatment results in seventy-four stage II/III patients.

Bisphosphonates are used in the treatment of osteoporosis and bone metastases. They inhibit osteoclast function, thereby decreasing bone resorption. A side effect of these drugs is bisphosphonate-related osteonecrosis of the jaw (BRONJ), which can be difficult to treat. The purpose of this study was to evaluate the surgical treatment protocol used in our hospital for BRONJ patients. The patients were retrospectively analyzed and followed-up at the Leiden University Medical Center. All patients who were referred to our hospital with therapy-resistant BRONJ between 2003 and 2014 were seen. At first presentation, the clinical features, medical and dental history, bisphosphonate use, and the use of other medications were recorded. Patients underwent surgical intervention, performed by senior surgeons, following the principles of our previously published protocol. Seventy-four patients were followed-up for 6-96 months. Curation was successful with this surgical approach in 93.2% of the patients. All the patients were cured with our surgical protocol, for up to 5 years after surgery. We conclude that this treatment protocol has a high success rate in treating all stages of BRONJ.

Surgical management of bisphosphonate-related osteonecrosis of the jaw stages II and III

The value of surgery in advanced stages of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still controversial. Hence, we evaluated the effect of surgical therapy in BRONJ stages II and III in combination with a standardized perioperative adjuvant treatment. We included 39 patients who presented with BRONJ in a total of 47 locations and stages II (n = 23) and III (n = 24). All patients had exclusively received a monthly intravenous application of zoledronic acid. Surgical therapy consisted of complete removal of the necrotic jaw, accompanied by a standardized perioperative adjuvant treatment including intravenous antibiotic prophylaxis, gastric feeding, and an antimicrobiologic mouth rinsing. Overall, 35 (74.5%) of the 47 BRONJ sites were treated successfully, with success defined as complete mucosal healing of the exposed jaw (n = 24) or as relative healing when surgical therapy downscaled BRONJ II or III to asymptomatic BRONJ stage I (n = 11). Interestingly, perioperative adjuvant treatment or bisphosphonate therapy parameters showed no statistical effect on the treatment outcome. The results of the present study prove the effectiveness of surgical therapy for BRONJ stage II or III.

Value of nonsurgical therapeutic management of stage I bisphosphonate-related osteonecrosis of the jaw

There is still controversy about the best treatment strategy for patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) stage I. Therefore, the aim of the present study was to analyse the effect of a nonsurgical treatment protocol in patients with BRONJ stage I.During the study period we included 17 patients (11 male; 6 female) who presented with a total of 24 separate areas of BRONJ, stage I. All patients were exclusively treated with a monthly intravenous regime of zoledronic acid due to an underlying malignant disease. All patients were treated using a standardized nonsurgical protocol consisting of antimicrobial mouth rinsing with chlorhexidine (CHX) (0.12%) three times a day, and daily CHX gel application.In 11 patients (45.8%) the surface area of the exposed jawbone was completely healed by nonsurgical treatment. In seven patients (29.2%), nonsurgical treatment reduced the size of the exposed bone area by a mean of 64.7% (range 20.0–96.8%). None of the patients showed an increase in size of the area of exposed jawbone, or a worsening of the BRONJ from stage I to stages II or III. However, the duration of nonsurgical treatment or the duration of intravenous bisphosphonate therapy did not significantly influence the treatment outcome (p = 0.6628, p = 0.6077, respectively).The results of the present study support the beneficial role of nonsurgical treatment in patients presenting with BRONJ stage I. Surgical therapy of BRONJ should be restricted to patients with advanced stages with clinical symptoms and local signs of infection.

Usability of surgical treatment in cases of bisphosphonate-related osteonecrosis of the jaw stage 2 with sequestrum.

Objective:This retrospective study was conducted to reveal usability of surgical treatment in the cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) stage 2 with sequestrum.Patients and Methods:Study subjects included 18 patients having BRONJ stage 2 with sequestrum and 12 non-BRONJ patients with nearly equal clinical states of BRONJ stage 2. Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results were compared between BRONJ group and non-BRONJ groups. In addition, correlation between treatment methods (conservative therapy, sequestrum curettage, and sequestrectomy) and treatment results and correlation between the administration route of bisphosphonates (BPs) (oral or intravenous) and treatment results were examined statistically. The Student's t-test and Fisher's exact test were performed for statistical analysis.Results:Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results showed no significant differences between the two groups. In the BRONJ group, treatment result of sequestrectomy was significantly better than conservative therapy/sequestrum curettage (P < 0.001), however, no significant difference was observed in the non-BRONJ group. No significant difference was found in correlation between the administration route of BPs and treatment results in the BRONJ group.Conclusion:Treatment outcome of sequestrectomy was better than conservative therapy/sequestrum curettage in BRONJ stage 2 cases with sequestrum.

Non-exposed variant of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with a plasmacytoma: A rare case report

Bisphoshonate-related osteonecrosis of the jaw (BRONJ) is an avascular osteo-chemonecrosis of the jaw which results after administration of the group of drugs called as bisphosphonates. Bisphosphonates are given to prevent bone resorption in osteolytic diseases such as Paget's, osteoporosis, osteogenic carcinoma, and other carcinomas where there could be metastasis and bone resorption. Incidence of BRONJ is reported to be high in western literature and is found to be more after intravenous route compared to oral route of administration. There are various clinical stages of BRONJ as per the American Association of Oral and Maxillofacial Surgeons (AAOMS). Here, we present a rare case of a 60-year-old lady who presented with a complaint of a painless swelling in the alveolus and gingiva in the left maxillary posterior region. This patient was on intravenous Zolendronate for more than 4 years. Thorough examination with detailed investigations revealed BRONJ along with a coexisting second primary tumor, plasmacytoma. Metastasis to distant site is a common feature of malignancy. A metastatic lesion usually occurs within 6 months to 1 year after treatment of a primary lesion. Any fresh neoplasm beyond 1 or 2 years after detection of a primary can be regarded as a second primary tumor. Solitary bone plasmacytoma is a localized form of plasma cell tumor. Diagnosis is based on the presence of the following: Malignant proliferation of plasma cells in biopsy, absence of osteolytic bone lesion, absence of Bence Jones proteins, low concentration of monoclonal proteins, elevated IgG and gamma globulin levels.

Characteristics of the early stages of intravenous bisphosphonate-related osteonecrosis of the jaw in patients with breast cancer

Objective. The clinical features of the early stages of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients with breast cancer remain unclear. A retrospective cohort study was conducted of patients with breast cancer who received intravenous bisphosphonate (BP) treatment in a single center in order to clarify the status of the early stages of BRONJ. Materials and methods. A BRONJ oral monitoring program was established in 247 breast cancer patients given intravenous BP treatment at the institution. The differences in age, BP treatment period, number of remaining teeth, oral hygiene status, presence of regular oral monitoring and the existence of suspected BRONJ (stage 0) among eight BRONJ and 36 non-BRONJ subjects who completed oral examinations were then compared. Results. BRONJ was observed in 0.4% of subjects on the first visit to the oral surgery clinic and in 3.2% of subjects during the follow-up period. Logistic regression analysis revealed that the odds ratio for identifying patients with BRONJ during follow-up by the presence of stage 0 at first visit was 24.0 (95% confidence interval [CI] = 3.6–161.7). The area under the receiver operating characteristic curve for identifying subjects with BRONJ by the presence of stage 0 was 0.82 (95% CI = 0.63–1.00). Conclusion. The results suggest that patients with stage 0 BRONJ on the first visit may progress to advanced BRONJ during the follow-up period. The oral monitoring program may contribute to the early detection of BRONJ.

Outcomes of osseous free flap reconstruction in stage III bisphosphonate-related osteonecrosis of the jaw: Systematic review and a new case series

IntroductionThere is currently no gold standard for the treatment of Stage III bisphosphonate-related osteonecrosis of the jaw (BRONJ). The question remains whether osseous reconstruction can offer an additional gain in outcome given the theoretical risk of non-union at the resection margins and recurrence in the osseous free flap. The objective was to conduct a systematic review of articles describing outcomes of osseous microsurgical reconstruction in cases of BRONJ with a minimum follow-up of 12 months, and to present the long-term outcomes of a new case series of three patients. Material and methodsA multi-database QUORUM-based single-reviewer systematic review identified eight papers that fulfilled the selection criteria. There are only case series and case reports available (Level 4 of the Oxford Evidence-based medicine scale). A total of 31 patients were analysed including the cases described in this article. ConclusionThe limited overall rate of non-union at the resection margins and the 6.5% recurrence rate of BRONJ in the transplant counters the theoretical objections and advocates for considering osseous free flap reconstruction in the treatment of refractory BRONJ Stage III lesions. However, additional data derived from larger case series or case-control studies are imperative to support this hypothesis.

Oxidative stress in bisphosphonate‐related osteonecrosis of the jaws

To analyze whether oxidative stress (OS) changes are present in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus controls. Oxidative stress was analyzed in serum and unstimulated saliva of three groups: Group 1 consisted of 24 patients who had been treated with intravenous bisphosphonates (ivBPs) and developed BRONJ, group 2 consisted of 20 patients who had received ivBPs and did not develop BRONJ, and group 3 comprised 17 control subjects. Reduced glutathione (GSH), malondialdehyde (MDA), oxidized glutathione (GSSG), and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) levels, as well as the GSSG/GSH ratio, were measured. Mean serum and saliva levels of MDA, GSSG, and 8-oxo-dG and the GSSG/GSH ratio were significantly higher in patients with BRONJ than in controls. We found no significant difference in OS according to BRONJ stage, sex, or location in the jaws. Logistic regression analysis revealed that the GSSG/GSH ratio was a significant factor predicting the development of BRONJ (P=0.01). Oxidative stress was detected in patients with BRONJ, and the GSSG/GSH ratio was the most significant OS variable found; it was a significant factor predicting the development of BRONJ.

A simple evaluation method for early detection of bisphosphonate-related osteonecrosis of the mandible using computed tomography

ObjectivesThe aim of this study was to establish a simple method for the early detection of bisphosphonate-related osteonecrosis of the jaw (BRONJ) using computed tomography (CT). Materials and methodsCT images of the mandible were obtained from a total of 20 patients with BRONJ and 20 control subjects. BRONJ was classified into 2 groups, with bone exposure (Stage 1–3 BRONJ) or without (Stage 0 BRONJ). In each patient, 15 transaxial CT images were selected and 30 configured regions of interest (ROI) were identified. The ANOVA test was applied to test the relationship between the severity of systemic risk factors. ResultsRegarding the local status of the mandible, significant differences were observed among the Stage 0 BRONJ, Stage 1–3 BRONJ, non-BRONJ and control groups in the cancellous bone CT radiodensity values, but there were no significant differences between the Stage 0 and Stage 1–3 BRONJ groups. In the cortical bone widths, significant differences were observed only between BRONJ and the controls. ConclusionsMeasuring cancellous bone CT radiodensity value has the potential to be a simple and quantitative method to detect the early stages of BRONJ.

Conservative surgical management of stage I bisphosphonate-related osteonecrosis of the jaw.

Purpose. To report the efficacy of conservative surgical treatment for stage I bisphosphonate-related osteonecrosis of the jaw (BRONJ). Materials and Methods. This study reports the clinical outcomes of 63 patients treated for BRONJ stage I (according to Ruggiero's staging system) at the Oral Pathology and Laser-Assisted Surgery Unit of the University of Parma between January 2004 and January 2011. Surgical interventions were performed, under local analgesia, in patients unresponsive for a period of six months to noninvasive treatments such as cycles of local or systemic antibacterial therapy combined or not to low level laser therapy, ozone therapy, or Hyperbaric Oxygen Therapy. All interventions were performed after the consultation of oncologist or physician. Results. In our experience, conservative surgical treatment is associated with the highest number of BRONJ healed sites in stage I disease. Complete healing was observed in 92.6% of sites surgically treated. Conclusions. This study confirms that treatment of patients affected by minimal bone exposition, (stage I of BRONJ), through conservative surgical strategies, possibly with laser, may result in a high control of the disease in the long term.

Prevalence of bisphosphonate-associated osteonecrosis of the jaw after intravenous zoledronate infusions in patients with early breast cancer

The definite incidence rate of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is still unknown. The aim of this study was to investigate prevalence of BRONJ in a group of breast cancer patients applying the classification of the Association of Oral and Maxillofacial Surgeons 2009. Between 2000 and 2008, 63 premenopausal early breast cancer patients who were free of metastases were treated with 4 mg zoledronic acid every 6 months over 3 years as participants of a multicenter, randomized, controlled, adjuvant breast cancer medication trial. Patients were not informed about the risk of jaw necrosis. None reported tooth or jaw complaints during the breast cancer follow-up examinations. In 2010, 48 patients of this cohort were investigated concerning BRONJ by clinical and radiological examinations. No advanced stages (AAOMS 2009)were detected. However, five patients (10.4%) presented purulent (2) and nonpurulent (3) fistulas and radiological signs correlating to BRONJ stage 0. Although no case of advanced BRONJ was detected, the study revealed a high prevalence of BRONJ stage 0. This supports the need for tight cooperation between dentists and medical specialists prescribing bisphosphonates including dental pre-therapeutic and follow-up examinations. Adaption of the BRONJ classification taking account to bone exposure via fistulas is recommended. BRONJ is said to be a complication linked to high-dosage bisphosphonate therapy. The study demonstrates that even after application of zoledronate in a low-dose protocol, early BRONJ occurred. Radiological signs solely are not sufficient to confirm BRONJ; clinical signs are mandatory.

PP113: Sinus mucosal involvement in patients with bisphosphonate-related osteonecrosis of the jaw

Purpose Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a clinically significant complication of bisphosphonates (BP). The purpose of this study was to investigate whether BP induces alterations in sinus mucosa and concerning clinical symptoms and imaging features may presage development of BRONJ. Material and methods This retrospective study included 32 patients referred to the Maxillofacial Department of the tertiary centre with a diagnosis of BRONJ. The patient had to confirm the definition of BRONJ as defined by the AAOMS (Ruggiero et al., 2009). Indication for bisphosphonate therapy, type, dose, frequency, therapy duration and discontinuation, primary disease, comorbidities, and dental history were collected and analysed along with BRONJ signs, symptoms, location, stage, treatment, evolution and radiographic data. Special notice was given as to whether or not there was any involvement of the maxillary sinus (sinusitis or mucosal thickening) during the disease. All 32 patients with BRONJ underwent orthopantomography and Computed Tomography (CT). Results A total of 32 patients suffering from BRONJ were identified. Ten male and 22 female, and their age ranged from 47 to 89 years (mean: 69.03; 95% CI: 65.3–73.5). Indications of BPs were breast carcinoma (five cases, 15.6%), multiple myeloma (seven cases, 21.9%), prostate cancer (five cases, 15.6%), kidney cancer (two cases, 6.3%), cervix cancer (one case, 3.1%) and osteoporosis (12 cases, 37.5%). Sinus involvement was observed in CT in 20 patients (62.5%). Seven of the 20 patients with sinus involvement had homolateral maxillary BRONJ, but we found a thickening of the mucosa of the maxillary sinus in 13 patients (40.6%) without affecting of the underlying bone. These patients had BRONJ areas in the jaw or contralateral maxilla. Three of them had bilateral sinus involvement with BRONJ located in the left maxilla. Conclusions BRONJ patients have a high percentage of involvement of the mucosa of the maxillary sinuses.

The outcomes of conservative and surgical treatment of stage 2 bisphosphonate-related osteonecrosis of the jaws: a case series

The purpose of the current retrospective chart review is to describe the outcomes of conservative or surgical treatment of stage 2 bisphosphonate-related osteonecrosis of the jaws (BRONJ). 14 charts (mean patient age 69.07±10.37 years) describing 19 BRONJ stage 2 sites were identified. According to the treatment protocol, all patients received conservative treatment. Surgical treatment was delivered only to sites that did not respond to conservative treatment. Conservative treatment alone was delivered to 11 sites in 8 patients (mean postoperative follow-up 17.6±9.4 months). Surgical treatment was delivered to 8 sites in 6 patients (mean postoperative follow-up 10.0±6.1 months). Bisphosphonate exposure ranged from 1 to 8 years. In most cases, tooth extractions and wearing dentures were reported as triggers for BRONJ. At the last follow-up, BRONJ stage 0 was noted in 7 sites that received conservative treatment and 5 sites that received surgical treatment. Within the limitations of the current chart review, the results showed that although conservative treatment for BRONJ stage 2 can provide favourable outcomes, surgical treatment represents a suitable alternative in non-responsive cases.

Bisphosphonate-related osteonecrosis of the jaws: Study of the staging system in a series of clinical cases

The aim of this study was to validate the classification of bisphosphonate-related osteonecrosis of the jaws (BRONJ) published in 2009(17) in a series of cases. This retrospective clinical study included a series of 102 cases (81%) of intravenous BRONJ (iBRONJ, group 1) and 24 cases (19%) of oral BRONJ (oBRONJ, group 2). We recorded all patients' symptoms and clinical findings and classified each patient into a BRONJ stage (0-3; stage 0=non-exposed BRONJ). Most BRONJ cases (n=120, 95.2%) could be classified according to the proposed stages. Exposed necrotic areas of bone were more prevalent in group 1 than in group 2 (p<0.05). In contrast, we observed more BRONJ cases without areas of exposed bone in group 2 (n=12, 50%) than in group 1 (n=14, 13.7%; p<0.05). We could not assign six cases to any of the proposed stages. These cases had no areas of exposed necrotic bone, but had mandibular fractures, extra-oral fistula or affected maxillary sinuses. In our series, iBRONJ cases showed more advanced stages of BRONJ than did oBRONJ cases. We found few cases that could not be classified into any proposed stage because they had findings associated with stages 0 and 3 but lacked exposed necrotic bone.

Clinical investigation of bisphosphonate-related osteonecrosis of the jaws in patients with malignant tumors

Objectives This study evaluated bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients diagnosed with malignant bone tumors. Demographic findings, laboratory, and radiographic analyses were performed to characterize disease severity and progression. Materials and Methods Patients who had been diagnosed with BRONJ (2005-2010) at the authors' hospital according to the American Association of Oral and Maxillofacial Surgeons were investigated. Twenty-one patients (12 with multiple myelomas, 7 with breast cancer, and 2 with prostate cancer) who had been treated with bisphosphonates (BPs) for malignant bone tumors were included. Radiographic evaluations with a panorama, computed tomography, whole body bone scan, and laboratory findings were evaluated for erythrocyte sedimentation rate (ESR), c-reactive proteins (CRPs), and c-terminal cross-linked telopeptides (CTXs). Results The average age of the patients was 64.3 (range 51-80), and they were treated with BPs for an average of 35±19 months before BRONJ was diagnosed. Types of BPs were zolendronic acid (81%, intravenous [IV]), pamidronate (4.8%, IV), zoledronic acid+pamidronate (4.8%, IV), alendronate (4.8%, per os [PO]), and ibadronate (4.75%, PO). Extraction (67%) and persistent irritation of dentures (20%) were the most common triggering factors. BRONJ in the mandible was reported in 62% of the cases, in the maxilla 24%, and both 14%. BRONJ occurred more frequently in patients with multiple myelomas (n=12, 57.1%). Most of the patients revealed an advanced BRONJ stage; Stage I (n=2, 9%), Stage II (n=13, 62%), and Stage III (n=6, 29%). Conclusion The differences of the ESR, CRP, and CTX values between the BRONJ-recurring and non-recurring patients after the treatment were not evident. Later stage BRONJ patients showed lower CTX levels. A drug holiday after the diagnosis of BRONJ did not remarkably influence the surgical outcomes. However, the limited number of patients in the study should be considered.

Bisphosphonate related osteonecrosis of the jaw – Manifestation in a microvascular iliac bone flap

Bisphosphonate related osteonecrosis of the jaw (BRONJ) is a side effect that may emerge due to a long-term bisphosphonate therapy. Although the timely diagnosis and initiation of treatment are associated with good outcome results, extended cases require whole parts of the jaw to be resected. A possible treatment option is the bony reconstruction of the jaw using microvascular bone flaps. We report, for the first time, the development of a bisphosphonate related osteonecrosis in a microvascular iliac bone graft, a reconstruction that was performed following a partial mandibulectomy due to BRONJ stage III. The observation of BRONJ manifestation in an osseous microvascular transplant is a novel finding that sheds new light on current pathogenesis theories that surround this entity. Furthermore, it is hypothesized that BRONJ is able to progress to adjacent bone. In addition, bone reconstruction in patients suffering from BRONJ may be seen more critically.

Management of Bisphosphonate-related Osteonecrosis of the Jaw in an Elderly Lebanese Female

The use of bisphosphonates (BP) in the treatment of osteopenia and osteoporosis, other than in cancer patients, has been described now for several years. Medical and dental literature in the last decade described the emergence of a new disease, bisphosphonate related osteonecrosis of the jaw (BRONJ), after dental surgical intervention in patients on bisphosphonates. The pathogenesis and complete mechanisms of BRONJ are still unclear, and there is still no all-inclusive understanding of the stages of BRONJ. In this paper, we will describe the treatment of a Lebanese elderly female who had BRONJ after surgical dental treatment. This specific case did not follow the stages set by AAOMS in 2009, and calls for a better understanding of BRONJ and its mechanisms. Better patient education and documentation must be undertaken to decrease the risk of developing BRONJ due to dental procedure.