Surgical treatment of medication-related osteonecrosis of the upper jaw: Case series.

PURPOSE: The management of maxillary medication-related osteonecrosis of the jaw (MRONJ) is challenging. Therefore, identifying the proper treatment is important. This study aimed to evaluate the surgical treatment of maxillary MRONJ using single-layer closure with mucoperiosteal flap and double-layer closure with buccal fat pad flap (BFPF) and mucoperiosteal flap and to find the outcomes after rehabilitation with obturators. METHODS: A retrospective analysis was conducted and included all surgically treated and followed-up maxillary MRONJ cases in a single center. Demographics and clinical data, stage of MRONJ, surgical treatment, and treatment outcome were collected. RESULTS: Seventy-nine lesions were included. Removal of necrotic bone was followed by coverage with mucoperiosteal flap in 60 lesions and BFPF in 14 lesions. Seven lesions (five primarily and two following unsuccessful treatment with BFPF) underwent necrectomy and were reconstructed with obturators. Complete mucosal healing was achieved in 76.7% of the lesions covered with mucoperiosteal flap. BFPF led to complete mucosal healing in 85.7% of the lesions. No complications were observed in the defects rehabilitated with obturators. CONCLUSION: Removal of necrotic bone followed by closure with mucoperiosteal flap is reliable for MRONJ treatment. BFPF is effective for closure of MRONJ-related oroantral communications (OACs).

Photodynamic Inactivation of Actinomyces naeslundii in Comparison With Chlorhexidine and Polyhexanide--A New Approach for Antiseptic Treatment of Medication-Related Osteonecrosis of the Jaw?

PURPOSE: Local antimicrobial therapy is a fundamental principle in the treatment of lesions of medication-related osteonecrosis of the jaw. Antimicrobial photodynamic therapy (aPDT) as a local application for the treatment of microbial infections has become more widely used in recent years. In the mouth, the bone surface is in constant contact with saliva and thus cannot be kept sterile, making the development of strategies for disinfection even more important. Different methods currently in use include local rinses with chlorhexidine (CHX), polyhexanide (PHX), or aPDT. This study compared the efficiency of these 3 methods. MATERIALS AND METHODS: The in vitro activity of 3 different agents against slowly growing Actinomyces naeslundii isolated from a patient with osteonecrosis was evaluated. PHX 0.04% solution, CHX 0.12% solution, and methylene blue (MB) based dye with a laser light of 660-nm wavelength (aPDT) were compared. RESULTS: The decrease in colony-forming units by each method was measured using an in vitro killing assay based on a water-exposed surface in a well plate. MB dye with laser (10 seconds) decreased the bacterial load by more than 4 orders of magnitude and was superior to PHX and CHX exposure for 60 seconds. CONCLUSION: Laser exposure alone and MB dye exposure alone decreased bacterial loads slightly, but less efficiently than 60-second exposure to PHX or CHX. The most effective means of decreasing colony-forming units was achieved by a combination of laser light and dye, which also can be used clinically.

Fluorescence-guided bone resection in bisphosphonate-related osteonecrosis of the jaws: first clinical results of a prospective pilot study.

PURPOSE: Surgical debridement is the therapy of choice in advanced stages of bisphosphonate-related osteonecrosis of the jaws (BRONJ). However, the therapy is currently only loosely standardized because no suitable imaging modalities exist. This study aims to redress this by exploring the suitability and reproducibility of applying a fluorescence-guided bone resection to patients with BRONJ. PATIENTS AND METHODS: This prospective pilot study comprised 15 patients with 20 BRONJ lesions (only stages II and III) with a history of intravenous bisphosphonate treatment for metastatic bone diseases. Before surgical treatment, each patient received a 10-day administration of doxycycline. Fluorescence-guided resection of necrotic bone was performed by means of a certified fluorescence lamp. Success of the procedure was proclaimed if mucosal closure was observed and symptoms were absent 4 weeks postoperatively. RESULTS: The 4-week postoperative follow-up identified a mucosal closure in 17 of 20 BRONJ lesions (85%). These patients were free of any symptoms. Failure as defined by mucosal dehiscence and exposed bone was observed in 3 of 20 BRONJ lesions (15%). CONCLUSION: The success rate of this surgical regimen of BRONJ was respectable, and thus fluorescence-guided bone resection can be considered an effective treatment for stage II and stage III BRONJ. Furthermore, the reproducibility of the technique offers an opportunity to standardize the surgical therapy. Further studies are called for that compare the fluorescence-guided bone resection with conventional surgical approaches, as well as surgical versus conservative treatment in the early stages (stages 0 and I) of BRONJ.

Bisphosphonate-related osteonecrosis of the jaw: is pH the missing part in the pathogenesis puzzle?

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy, primarily diagnosed in patients with cancer and metastatic bone disease and receiving intravenous administrations of nitrogen-containing bisphosphonates. If diagnosis or treatment is delayed, BRONJ can develop to a severe and devastating disease. Numerous studies have focused on BRONJ, with possible pathomechanisms identified to be oversuppression of bone turnover, ischemia due to antiangiogenetic effects, local infections, or soft tissue toxicity. However, the precise pathogenesis largely remains elusive and questions of paramount importance await to be answered, namely 1) Why is only the jaw bone affected? 2) Why and how do the derivatives differ in their potency to induce a BRONJ? and 3) Why and when is BRONJ manifested? The present perspective reflects on existing theories and introduces the hypothesis that local tissue acidosis in the jaw bone offers a conclusive pathogenesis model and may prove to be the missing link in BRONJ.

The role of inferior alveolar nerve involvement in bisphosphonate-related osteonecrosis of the jaw.

PURPOSE: Hypesthesia or anesthesia of the lower lip (Vincent's symptom) is a common sign in patients with osteomyelitis of the mandible, especially in severe cases. PATIENTS AND METHODS: We observed an involvement of the inferior alveolar nerve in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Surprisingly, we found Vincent's symptom also in patients with limited and early stages of BRONJ. RESULTS: These patients were successfully treated by surgical removal of the necrotic bone combined with preoperative and postoperative administration of antibiotics. We report on the occurrence and management of an involvement of the inferior alveolar nerve in patients with BRONJ and discuss possible causes. CONCLUSION: We conclude that impairment of inferior alveolar nerve function can be an important early symptom or even the presenting symptom of BRONJ that is also easily detectable by bisphosphonate-prescribing physicians. Concerning the management of BRONJ, we conclude that surgical removal of necrotic bone combined with antibiotics is an adequate treatment in patients with osteonecrosis of the jaw.

Pathologic fractures in bisphosphonate-related osteonecrosis of the jaw-review of the literature and review of our own cases.

Background Bisphosphonates are powerful drugs used for the management of osteoporosis and metastatic bone disease to avoid skeletal-related complications. Side effects are rare but potentially serious such as the bisphosphonate-related osteonecrosis of the jaws (BRONJ). BRONJ impairs the quality of life and can even lead to pathologic fractures of the mandible. Management of BRONJ is difficult per se. If complicated with pathologic mandibular fractures in advanced stages, the treatment options are controversially discussed. This review delineates the epidemiology and pathogenesis of BRONJ to put the various modalities for the treatment of pathologic mandible fractures into perspective. Methods Various case reports and case series in the literature were reviewed. Cases were reviewed of patients suffering from pathologic fracture due to bisphosphonate-related osteonecrosis of the jaw treated in the Department of Oral and Maxillofacial Surgery (Ludwig-Maximilians-University of Munich) from 2003 to 2010. Of 140 patients suffering from BRONJ, four were identified with pathologic fracture of the mandible. Results Management of pathologic mandibular fractures in patients suffering from BRONJ is an unsolved issue. At present there is a paucity of information to establish reliable therapy guidelines. The published strategies range from conservative treatment to major bone resections with or without internal or external fixation and with or without autogenous reconstruction. There is no evidence for the superiority of a single therapeutic mode, however. Conclusion Further understanding of BRONJ is mandatory to establish a sound rationale for the treatment of associated mandibular fractures.

Bisphosphonate-related osteonecrosis of the jaws - characteristics, risk factors, clinical features, localization and impact on oncological treatment.

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is a serious side-effect of intravenous nitrogen-containing bisphosphonate therapy frequently used in the treatment of malignant diseases. Despite numerous case series published so far studies with detailed investigations into risk factors, the precise localization of ONJ and impact of ONJ on the oncological treatment remain sparse. PATIENTS AND METHODS: This single-centre study collated medical records (2003-2009) of all patients that suffered from ONJ within the Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Germany. In total, 126 patients fulfilled the case criteria of ONJ and were examined clinically. The complete medical history including detailed questionnaires was collected of 66 patients, focussing in particular on the identification of underlying risk factors, clinical features, ONJ localization as well as the impact on the oncological treatment. RESULTS: The majority of ONJ cases occurred in patients suffering from malignant diseases (n=117; 92.8%), in particular breast cancer (n=57; 45.2%), multiple myeloma (n=37; 29.4%) and prostate cancer (n=13; 10.3%), all received nitrogen-containing bisphosphonates intravenously. ONJ was also diagnosed in 9 patients (7.1%) suffering from osteoporosis or rheumatoid arthritis. The most prevalent clinical feature was exposed necrotic bone (93.9%) in the oral cavity which was accompanied in 78.8% of cases by pain. A predilection for the mandible and in particular for molar and premolar regions in both jaws was shown. Although no recommendation concerning the oncologic treatment was made, the manifestation of ONJ resulted (in a significant proportion of the patients) in a change of medication and schedule. The most frequent co-medications were steroids and anti-angiogenetic drugs, such as thalidomide. DISCUSSION: The predilection for mandibular molar and premolar regions, and the infectious conditions that often precede the onset of ONJ support recent pathogenesis theories stating that local inflammation and associated pH-changes may trigger the release and activation of nitrogen-containing bisphosphonates ultimately resulting in necrosis. CONCLUSION: The development of ONJ has a multi-factorial aetiology and the clinical presentation can vary markedly. ONJ cannot only impair the quality of life but also the treatment of the underlying disease.