Bisphosphonate-related Osteonecrosis Of Jaw Research Articles

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.

Bisphosphonates modulate the expression of OPG and M-CSF in hMSC-derived osteoblasts

Bisphosphonates have been known to suppress osteoclast activity, survival, and recruitment. In this study, we tested effects of BPs on expression of two critical genes for osteoclastogenesis, M-CSF, and OPG in the process of osteoblast differentiation from hMSC. (1) The cells were cultured in osteogenic induction medium together with 0 (control group) and 10-8 M alendronate, pamidronate for up 2 and 3 weeks (for real-time PCR) and 3 and 4 weeks (for ELISA). (2) The real-time PCR protocol for M-CSF, OPG, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) consist of 40 cycles. (3) Enzyme-linked immunosorbent assay (ELISA): the amounts of M-CSF and OPG in the culture medium were determined using commercially available ELISA kits for M-CSF and OPG. Treatment of differentiating cells with alendronate or pamidronate, nitrogen-containing BPs increase the expression of OPG, which suppresses osteoclastogenesis, whereas it decreases the expression of M-CSF, which enhances preosteoclast formation. These results suggest a new mechanism by which BPs inhibit osteoclastogenesis. Results support hypothesis that progressive accumulation of bisphosphonate in jaws causes imbalance in osteogenesis and bone absorption and collateral osteoclast-osteoblast interaction. Bisphosphonate-related osteonecrosis of jaw (BPONJ) is one of the most serious complications of bisphosphonate (BP) therapy. However, the mechanism behind the this process of BPONJ is still unclear and there are so many hypotheses. Among many hypotheses, we focused on osteoclast-osteoblast interaction in this study. The findings of this study show new light on the present BPONJ occurrence theory based on the osteoclastic activity of BPs. Also, a more advanced and developed theory for BRONJ occurrence may be obtained by combining the osteoclast inhibition mechanism and the effects on osteoblastic differentiation by BPs.

Bisphosphonate-related osteonecrosis: laser-assisted surgical treatment or conventional surgery?

Bisphosphonates (BSPs) are used for the treatment of multiple myeloma, metastatic breast and lung cancer, Paget's disease, osteoporosis, hypercalcemia due to malignancy, and many other skeletal diseases. BSPs reduce osteoclastic functions, which result in bone resorption. Bisphosphonates-related osteonecrosis of jaws (BRONJ) is a newly developed term that is used to describe the significant complication in patients receiving bisphosphonates. BSPs are known to exhibit an anti-angiogenetic effect that initiates tissue necrosis of the hard tissue. There is currently no consensus on the correct approach to this issue. The aim of this retrospective study is to compare the effects of laser surgery with biostimulation to conventional surgery in the treatment of BSP-induced avascular bone necrosis on 20 patients who have been treated in our clinic. BRONJ was evaluated in patients with lung, prostate, and breast cancer under intravenous BSP treatment. Twenty patients in this study developed mandibular or maxillary avascular necrosis after a minor tooth extraction surgery or spontaneously. Bone turnover rates were evaluated by serum terminal C-telopeptide levels (CTX) using the electrochemiluminescence immunoassay technique and patients were treated with laser or conventional surgical treatments and medical therapy. Ten patients were treated with laser surgery and biostimulation. An Er:YAG laser (Fotona Fidelis Plus II® Combine laser equipment, Slovenia) very long pulse (VLP) mode (200 mJ, 20 Hz) using a fiber tip 1.3 mm in diameter and 12 mm in length was used to remove the necrotic and granulation tissues from the area of avascular necrosis. Biostimulation was applied postoperatively using an Nd:YAG laser. Low-level laser therapy (LLLT) was applied to the tissues for 1 min from 4 cm distance using an Nd:YAG laser (Fotona-Slovenia) with a R24 950-µm fiber handpiece long-pulse (LP) mode, 0.25-W, 10 Hz power/cm(2) from the mentioned distance the spot size was 0.4 cm(2), and power output was 2.5 J. Energy density from the mentioned distance was calculated to be 6.25 J/cm(2). The other ten patients were treated with conventional surgery. Treatment outcomes were noted as either complete healing or incomplete healing. There were no statistically significant differences between laser surgery and conventional surgery (p > 0.05). CTX values also did not affect the prognosis of the patients. Treatment outcomes were significantly better in patients with stage II osteonecrosis than in patients with stage I osteonecrosis. Our findings suggest that dental evaluation of the patients prior to medication is an important factor in the prevention of BRONJ. Laser surgery is a beneficial alternative in the treatment of patients with this situation. Further randomized studies with larger patient numbers may also improve our understanding of treatment protocols for this situation.

Diagnosis and Management of BRONJ(bisphosphonate related osteonecrosis of jaw)

BRONJ(Bisphosphonate Related Osteonecrosis of Jaws) is not easy to be managed because it responds less predictably to established surgical treatment algorithms for osteomyelitis or osteoradionecrosis. The guidelines recommend that any kind of surgery should be delayed if possible. In the latest stage-dependent recommendations of the AAOMS in 2009, a conservative regime with antibiotics, antibacterial mouthe rinses and pain control in stages 0 to II. Some investigators have described the benefits of early osteotomy with primary wound closure. However, there are only a few publications with a standardized surgical concepts. In this reviews, various aspects of diagnosis and management of BRONJ will be discussed.

Bisphosphonate related osteonecrosis of jaw

Bisphosphonates are widely used in the management of osteoporosis patients. Many reports and clinical studies have published a relationship between necrotic bone lesions localized to the jaw and the use of chronic bisphosphonate therapy. This osteonecrosis named bisphosphonate-related osteonecrosis of the jaw(BRONJ). This article described the mechanism, chemical structure, indication, risk factor of the bisphosphonate.

Bisphosphonate-Related Osteonecrosis of Jaws in 3 Osteoporotic Patients With History of Oral Bisphosphonate Use Treated With Single Yearly Zoledronic Acid Infusion

Bisphosphonate-Related Osteonecrosis of Jaws in 3 Osteoporotic Patients With History of Oral Bisphosphonate Use Treated With Single Yearly Zoledronic Acid Infusion

Bisphosphonate-related osteonecrosis of jaws and the relationship with actinomyces organisms

<h3>Background</h3> Actinomyces species are part of the normal oral flora. They may also be found in association with non-vital bony sequestra in suppurative osteomyelitis, osteoradionecrosis and bisphosphonate-related osteonecrosis of jaws (BRONJ). <h3>Methods</h3> Sixty-two cases of histologically diagnosed chronic suppurative osteomyelitis affecting the jawbones were retrieved from the archives at the ICPMR, Westmead Hospital. The haematoxylin and eosin-stained slides and the available clinical notes were reviewed. <h3>Results</h3> In 23 cases, a history of bisphosphonate use was established. Most cases presented in elderly females and the mandible was the most commonly affected site. Bacterial colonies with the morphological appearance of Actinomyces species were identified in 12 cases diagnosed as BRONJ (12 of 23 cases) while only four cases of non-specific suppurative osteomyelitis demonstrated these organisms (4 of 34 cases). The remaining five cases were diagnosed as osteoradionecrosis. <h3>Discussion</h3> Cervico-facial actinomycosis is a chronic bacterial infection of the soft tissue and jaws caused by the saprophytic Gram-positive, anaerobic bacteria Actinomyces species. In this study, Actinomyces species were frequently associated with BRONJ. As in cervico-facial actinomycosis, long-term use of an appropriate antibiotic, such as penicillin, may play a role in improving the outcome for these patients.

Retrospective study on the bisphosphonate-related osteonecrosis of jaw

J Korean Assoc Oral Maxillofac Surg 2011;37:470-6) Retrospective study on the bisphosphonate-related osteonecrosis of jaw Yoon-Sic Han, In-Woo Lee, Ho Lee, Jin-Won Suh, Soung-Min Kim, Hoon Myoung, Soon-Jung Hwang, Jin-Young Choi, Jong-Ho Lee, Pill-Hoon Choung, Myung-Jin Kim, Byoung-Moo Seo Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Korea Introduction: The incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) has increased gradually in patients who have undergone surgical treatment for osteomyelitis. In this study, a retrospective analysis of BRONJ patients was carried out using the data of osteomyelitis patients treated surgically. Materials and Methods: Osteomyelitis patients, who underwent curettage, sequestrectomy, saucerization or decortications, and partial mandibulectomy at Seoul National University Dental Hospital from 2004 to 2010 were enrolled in this study. The patients were classified and categorized into two groups based on the surgical records and progress notes. One group comprised of patients with osteomyelitis and osteoporosis, and the other group included patients with osteomyelitis only. The epidemiological data of the BRONJ patients was analyzed to identify any trend in the incidence of BRONJ in osteomyelitis patients. Results: Among 200 patients who underwent surgical intervention for osteomyelitis, 64 (32.0%) were identified as having osteoporosis as the underlying disease. In these 64 patients, more than 81.3% had been prescribed bisphosphonates. Females were far more affected by BRONJ than males. The incidence of BRONJ also increased with age. The posterior part of the mandible was affected more frequently by BRONJ. Conclusion: Although the availability of potent antibiotics and increased oral hygiene care can reduce the overall incidence of osteomyelitis, BRONJ can increase the total incidence. To prevent BRONJ, it is recommended that an oral examination be performed before prescribing bisphosphonates. Moreover, the patients should be educated about the potential risks of dental procedures that might be causal factors for BRONJ. Furthermore, patient swho take bisphosphonates for the treatment of osteoporosis should undergo periodic follow up oral examinations to prevent BRONJ.

Extraction socket healing in rats treated with bisphosphonate: Animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patients

The aim of this study is to replicate both clinical and histological presentation of bisphosphonate induced osteonecrosis of the jaws (BONJ) in an animal model of the disease state. Successful recapitulation of a BONJ-like indication in an animal model will be useful for studying pathogenesis, as well as prevention and treatment strategies for BONJ. Eighty (80) rats were prospectively and randomly divided into two groups; control group(40) and study group(40). All animals in study group, injected with a dose of 1 mg/kg dexamethasone (DX) subcutaneously on day 7, 14, or 21; and 1, 2, or 3 doses of 7.5 µg/kg zoledronic acid (ZA) subcutaneously administered to coincide with the last day of DX. Half of the animals from each group underwent extraction of the left mandibular molars and the remaining animals underwent extraction of the left maxillary molars under pentobarbital-induced general anesthesia. All animals were euthanized twenty-eight (28) days following tooth extractions. The amount of new bone trabecules as significantly decreased in bisphosphonate-dexamethasone (BP-DX) treated sockets. Difference between both groups was found statistically significant (p=0,0001). There's no foreign body reaction in sockets of both groups and no significance difference observed for fibrosis (p=0,306). The necrosis scores were significantly higher in BP-DX treated sockets (p=0,015). The inflamation scores were significantly higher for study group (p=0,0001). This study provides preliminary observations for the development of an animal model of BONJ. But we think that there is need for other studies have only BP treated group and larger study population.

Low-level laser therapy supported teeth extractions of two patients receiving IV zolendronate

BRONJ (bisphosphonate-related osteonecrosis of jaws) is a frequently encountered disease, particularly in the maxillofacial region, and a consequence of bisphosphonate use. Treatment of BRONJ remains controversial, as efficiency of medical and surgical approaches as well as a combination of these methods with supportive treatments have not been clearly demonstrated in the literature. In recent years, laser usage alone or in combination with the main therapy methods, has become popular for the treatment of bisphosphonate-related osteo-necrosis of jaws. In this article, we present the successful management of two dental patients who had high potentials for BRONJ development as a result of chemo and radiotherapy combined with IV zoledronic acid application. Multiple consecutive teeth extractions followed with primary wound closure and LLLT applications were performed under high doses of antibiotics prophylaxis. Satisfactory wound healing in both the surrounding soft and hard tissues was achieved. LLLT application combined with atraumatic surgical interventions under antibiotics prophylaxis is a preferable approach in patients with a risk of BRONJ development. Adjunctive effect of LLLT in addition to careful infection control on preventing BRONJ was reported and concluded.

Bisfosfonati e osteonecrosi dei mascellari: protocolli clinici per igienisti dentali

Objectives To suggest protocols to dental hygienists about the prevention and treatment of biphosphonate-related jaw osteonecrosis according to the type, the way, and the duration of bisphosphonates administration. Materials and methods By reviewing the scientific literature and according to their experience, the authors show the protocols developed together with haematologists, oncologists, urologists, rheumatologists, and physical therapists. Results The authors report a reduced rate of cases observed. Conclusions Dental hygienists play a very important role in preventing bisphosphonate-related jaw osteonecrosis by both educating patients in self oral care to prevent dental and periodontal diseases and performing professional oral hygiene and periodically monitoring the oral health of patients at risk.

Clinical feature and treatment of bisphosphonate-related osteonecrosis of jaw about oral bisphosphonate administrated patients: case reports

Bisphosphonates are used effectively for many medical conditions, such as multiple myeloma, Paget ’ s disease, osteoporosis, etc. However, recently, osteonecrosis of the jaw was observed in patients receiving long-term bisphosphonate therapy, including oral administration. Th is osteonecrosis is refractory, and complete recovery is not guaranteed despite a standard treatment protocol being established by many association s related to oral and maxillofacial surgery. The treatment outcome of oral bisphosphonate-related osteonecrosis of jaw (BRONJ) is reported with a rev iew of the relevant literature.

Result of surgical treatment of bisphosphonate-related osteonecrosis of jaw—report of 18 cases

Result of surgical treatment of bisphosphonate-related osteonecrosis of jaw—report of 18 cases

Imaging Findings in Bisphosphonate-Related Osteonecrosis of Jaws

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-described clinical condition with consistent radiographic findings. The purpose of this report was to review these findings in an attempt to offer important diagnostic, prognostic, and therapeutic information associated with BRONJ. The findings of studies assessing the radiographic landmarks on plain films, intraoral films, orthopantograph, computed tomography, magnetic resonance imaging, and nuclear bone scans in patients with BRONJ were analyzed. The radiographic findings in patients with BRONJ include osteosclerosis, osteolysis, dense woven bone, a thickened lamina dura, subperiosteal bone deposition, and failure of postsurgical remodeling. Consistent imaging findings are noted in the BRONJ patient. Imaging is an essential part of the clinical assessment of the BRONJ patient and might be an additional tool for tracking the progression of the disease.

Ozone Therapy in Extractive Surgery on Patients Treated With Bisphosphonates

It is certain that oral extractive surgery is a remarkable trigger to avascular osteonecrosis of the jaw in patients treated with pyrophosphate analogous. This acquisition limits the use of endo-oral surgery in those patients, even when they have already developed the lesions. In this study, we present the results obtained in a group of 15 patients deriving from a 33-patient cluster with osteonecrosis of the jaw in treatment at our department with a new protocol based on ozone therapy. The object of this article is to demonstrate how dental extraction becomes possible in a patient with avascular bisphosphonate-related jaw osteonecrosis or in those who simply received pyrophosphate analogous when proper treatment with ozone therapy has been done.

Ozone Therapy in the Treatment of Avascular Bisphosphonate-Related Jaw Osteonecrosis

Avascular osteonecrosis of the jaw (ONJ) may occur as a consequence of several conditions, even including chemotherapy treatment in patients affected by tumors or osteoporosis. We report our clinical experience in treating bisphosphonate-induced ONJ with a therapeutic methodology that includes ozone therapy as a new and original approach for the clinical management of maxillary necrotic lesions. Of 58 patients with ONJ observed at our department, 33 gave their informed consent to be part of the research and were treated according to a therapeutic approach, which included noninvasive surgery associated with pre- and postsurgical cycles of ozone therapy consisting of eight sessions lasting 3 minutes each besides antibiotic and antifungal therapies. Outcomes showed how ozone therapy increases the benefits of surgical and pharmacologic treatments, increasing the complete healing of the lesions with the disappearance of symptoms and brings cases of lesion progression down to zero. In conclusion, ozone therapy is a reliable presidium in treatment of ONJ; its benefits are remarkable and improve significantly the outcomes of the surgical approach.

Possible Association between Diabetes and Bisphosphonate-Related Jaw Osteonecrosis

Bisphosphonate-related osteonecrosis (BON) of the jaws is a newly identified condition for which the exact mechanism involved in its pathogenesis remains obscure. The objective of the study was to evaluate whether diabetes mellitus (DM) may be a contributing factor in the development of BON. From 2004 to 2006, 31 patients were diagnosed with BON. The diagnosis of BON was based on the medical and dental history of each patient as well as the observation of clinical signs and symptoms of this pathological process. DM was based on two consecutive fasting blood glucose levels above 7 mmol/liter. The study was completed in the Hebrew University-Hadassah Hospital referral center. Of the 31 patients with BON, 18 (58%) were found to have DM or impaired fasting glucose. The proportion of diabetic patients was much higher than expected relative to the incidence of DM in the general population (14%) and compared with the proportion of diabetic patients in a control group of oncological patients treated with bisphosphonates and without BON (12%) (P = 0.00003). This finding indicates that DM may be a risk factor for BON and that DM patients treated with bisphosphonates should be carefully monitored. We discuss here the bone metabolic pathways characteristic of DM patients and the way in which these pathways can augment the effects of bisphosphonates.