Towy Sorel Lazarovici

Bisphosphonate-Related Osteonecrosis of the Jaws: A Single-Center Study of 101 Patients

PURPOSE Osteonecrosis of the jaw (ONJ) is a devastating side effect of long-term bisphosphonate (BP) use. We present the largest case series from a single department. MATERIALS AND METHODS This case series included 101 ONJ patients. Data on demographics, medical background, type and duration of BP use, possible triggering events, mode of therapy, and outcome were recorded. RESULTS ONJ was associated with intravenous BPs in 85 patients and with oral BPs in 16 patients. It was diagnosed after 48, 27, and 67 months of pamidronate, zoledronic acid, and alendronate use, respectively. Long-term antibiotics and minimal surgical procedures resulted in complete or partial healing in 18% and 52% of the patients, respectively; 30% had no response. There was no association between ONJ and diabetes, steroid and antiangiogenic treatment, or underlying periodontal disease. Diagnostic biopsies aggravated lesions without being informative about pathogenesis. A conservative regimen is our treatment of choice. CONCLUSION Solutions for decreasing morbidity and poor outcome of ONJ remain elusive.

Bisphosphonate-related osteonecrosis of the jaw associated with dental implants.

PURPOSE Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-documented devastating side effect of long-term bisphosphonate (BP) use. There is scarce information in the literature on BRONJ associated with dental implants (DIs). The purpose of this study was to present a large series of cases of this association. PATIENTS AND METHODS The files of all patients with BRONJ associated with DIs who were treated in the department of oral and maxillofacial surgery from 2003 to 2009 were reviewed. Data on demographics, medical background, type, and duration of BP treatment before the development of BRONJ, mode of therapy, and therapeutic outcome were retrieved. RESULTS Of the 27 patients enrolled into the study, 11 (41%) developed BRONJ while taking oral BPs and 16 (59%) developed BRONJ associated with intravenous BPs. BRONJ developed after mean periods of 68 months (median, 60), 16.4 months (median, 13), and 50.2 months (median, 35) in patients on alendronate, zoledronic acid, and pamidronate, respectively. Only 6 patients developed BRONJ during the first 6 months after DI placement. When BP treatment had been started before DI placement, there was a mean duration of 16.2 months (median, 11) until the appearance of BRONJ development. Long-term antibiotics and only essential surgical procedures comprised the treatment of choice, and the response rate was considerably better for patients taking the oral type of BPs. There was no significant association between BRONJ and diabetes, steroid intake, or smoking habits. CONCLUSION Patients undergoing BP treatment and who receive DIs require a prolonged follow-up period to detect any development of BRONJ associated with DIs.

Serologic bone markers for predicting development of osteonecrosis of the jaw in patients receiving bisphosphonates.

PURPOSE Osteonecrosis of the jaw is a well-documented side effect of bisphosphonate (BP) use. Attempts have recently been made to predict the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We prospectively investigated the predictive value of serum levels of C-terminal telopeptide of collagen I (CTX), bone-specific alkaline phosphatase, and parathyroid hormone for the development of BRONJ. PATIENTS AND METHODS Data on the demographics, comorbidities, and BP treatment were collected from 78 patients scheduled for dentoalveolar surgery. Of the 78 patients, 51 had been treated with oral BPs and 27 had been treated with frequent intravenous infusions of BPs. Blood samples for CTX, bone-specific alkaline phosphatase, and parathyroid hormone measurements were taken preoperatively. Surgery was performed conservatively, and antibiotic medications were prescribed for 7 days. RESULTS Of the 78 patients, 4 patients taking oral BPs (7.8%) and 14 receiving intravenous BPs (51.8%) developed BRONJ. A CTX level less than 150 pg/mL was significantly associated with BRONJ development, with an increased odds ratio of 5.268 (P = .004). The bone-specific alkaline phosphatase levels were significantly lower in patients taking oral BPs who developed BRONJ. The parathyroid hormone levels were similar in patients who did and did not develop BRONJ. CONCLUSION The incidence of BRONJ after oral surgery involving bone is greater among patients receiving frequent, intravenous infusions of BPs than among patients taking oral BPs. Although the measurement of serum levels of CTX is not a definitive predictor of the development of BRONJ, it might have an important role in the risk assessment before oral surgery.

Is exposure of the jawbone mandatory for establishing the diagnosis of bisphosphonate-related osteonecrosis of the jaw?

o the Editor:—The American Association of Oral and Maxllofacial Surgeons recently updated its position paper on isphosphonate-related osteonecrosis of the jaw (BRONJ). e applaud the efforts that were made in comprehensively eviewing and revising the official position of the organization. We would like to bring to the attention of the journal eaders that the presence of transmucosal exposed bone for period of at least 8 weeks continues to be a required eature for diagnosing BRONJ. Based on our growing exerience with patients with BRONJ and increasing evidence rom other studies, we strongly believe that establishing the iagnosis of BRONJ warrants further consideration. It is undisputed that exposed bone is the hallmark of RONJ and that transmucosal or transcutaneous evidence f necrotic jawbone is observed in most patients with ong-standing BRONJ. Little is known, however, about early linical features and their progression toward frank BRONJ. t is our experience that the disease is characterized by resenting signs other than bone exposure in a significant umber of cases. We recently reported the findings from a ingle-center retrospective review of a large cohort of paients with BRONJ: exposed bone was the presenting sign n only 55.4% of cases (56/101). The remaining 45 patients 44.5%) showed at least one of the following presenting linical features in the absence of macroscopic bone expoure: 1) sinus tract to the oral cavity or facial skin with urulent discharge, 2) gingival swelling or bone expansion, nd 3) jaw pain. Bone exposure did not appear until a few onths later in some, albeit not all, of these cases. Radioraphic findings were normal in some cases but in most atients there was evidence of jaw bone abnormalities comatible with BRONJ. Of note, the updated American Association of Oral and axillofacial Surgeons position paper categorizes patients ith nonspecific clinical features and radiographic findings n the absence of obvious bone exposure as having BRONJ tage 0. Stage 0 refers to an early stage with minimal radioogic changes that can be managed with minimal intervenion and may evolve toward frank bone exposure and more dvanced disease (stages 1 to 3). This is not our experience because the extent of bone ecrosis and infection in some of our cases without bone xposure was severe (eg, leading to pathologic fracture) nd evident by imaging techniques and required intensive anagement including surgical debridement and resection. With the growing awareness of BRONJ, it is likely that atients will be referred for treatment earlier in the course d

Involvement of the Maxillary Sinus in Bisphosphonate-Related Osteonecrosis of the Jaw: Radiologic Aspects

Background The use of bisphosphonates is very common among patients with osteoporosis and multiple myeloma as well as those with bone metastases from various malignancies. The benefits of bisphosphonates are well recognized, but it became evident during the past decade that these medications portend the major adverse effect of osteonecrosis of the jaw, known as bisphosphonate-related osteonecrosis of the jaw. Objective Our aim was to evaluate the specific manifestations of bisphosphonate use on the maxillary sinus in patients with documented bisphosphonate-related osteonecrosis of the jaw. Methods A retrospective review of all the patients diagnosed between October 2003 to August 2014 as having bisphosphonate-related osteonecrosis of the jaw in a large university-affiliated tertiary care medical center. The records of 173 patients diagnosed as having bisphosphonate-related osteonecrosis of the jaw during the study period were retrieved. The available head and neck computed tomographic images were analyzed for cases of involvement of the maxilla. Main Outcome Measures Manifestations of bisphosphonate-related osteonecrosis of the jaw as observed on physical examination and on imaging studies. Results Seventy-one patients (41%) had involvement of the maxilla, 86 patients (49%) had involvement of the mandible, and 16 patients (9%) had involvement of both the maxilla and the mandible. Computerized tomography studies were available for 50 patients with involvement of the maxilla: 36 (72%) had evidence of maxillary sinus opacification (in comparison, the incidence of maxillary sinus opacification as an incidental finding in the general population is reported to be 19%, p < 0.0001). Sixteen patients (32%) had evidence of oroantral fistula, and five patients (10%) had oronasal fistula. Conclusion In addition to its well-established effects on the mandible and maxilla, bisphosphonate-related osteonecrosis of the jaw significantly affected the maxillary sinus. Its radiologic manifestations should be recognized by clinicians and especially by otolaryngologists.

Rapid onset of osteonecrosis of the jaw in patients switching from bisphosphonates to denosumab

OBJECTIVE The aim of this study was to determine whether osteonecrosis of the jaw (ONJ) developed more rapidly in patients who switched from bisphosphonates (BP) treatment to denosumab than in patients who received only denosumab. STUDY DESIGN This was a retrospective cohort study conducted at a tertiary referral center. Thirty-one patients with ONJ met the inclusion criteria. RESULTS Twenty-two patients who had been on BP were switched to denosumab (BP + D), whereas 9 patients received only denosumab. Both groups were similar for the known ONJ risk factors, that is, age, diabetes mellitus, and smoking. The number and cumulative doses of denosumab before the onset of ONJ symptoms were significantly lower among the BP + D group compared with the denosumab-only group (P = .025 and .018, respectively). In the BP + D group, ONJ symptoms developed in 9 patients (41%) following the administration of ≤3 denosumab doses compared with ONJ developing in only 1 patient (11%) who was naïve to BP. ONJ developed spontaneously without any known triggering event in 72.7% of patients in the BP + D group and in 77.8% of patients in the denosumab-only group. CONCLUSIONS Denosumab-induced ONJ might develop rapidly in patients previously treated with BP. ONJ developed spontaneously in most patients treated with denosumab. In light of our sample being small, there is need for further investigation on our conclusions.

Bisphosphonate-Related Osteonecrosis of the Jaw.

Biphosphonate related osteonecrosis of the jaw, (BRON), is a pathological condition that is defined as oral bone exposure for a period greater than 8 weeks, in a patient that has been on biphosphonate medication without a history of exposure to external beam radiation. Most affected patients present the condition after invasive procedures that involve dentoalveolar bone manipulation, although spontaneous exposure of bone has also been observed.

Epidemiology of Medication-Related Osteonecrosis of the Jaw

Osteonecrosis of the jaw is a devastating side effect of long-term bisphosphonate (BP) use. We investigated epidemiological aspects of Bisphosphonate-related osteonecrosis of the jaws (BRONJ/MRONJ).