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Background: Overall survival (OS) and outcome of cancer patients with bisphosphonate-associated osteonecrosis of the jaw (ONJ) using conservative treatment (chlorhexidine 0.12% rinse, intermittent antibiotics, and careful sequestrectomy) are unknown., Design: In all, 33 ONJ patients were studied for OS and ONJ outcome., Results: Median duration of bisphosphonate treatment was 27 months (range 4-115) and was stopped in 25 (76%) patients. Nine (27%) cases presented with stage 1, 21 (64%) with stage 2, and 3 (9%) with stage 3 disease. During median follow-up of 23 months, 11 patients (33%) died (median survival 39 months), with no ONJ-related fatalities. Out of 30 assessable patients, 53% no longer had exposed bone, 37% had stable lesions, and 10% showed progressive necrosis. The hazard ratio for healing with doubling of bisphosphonate exposure was 0.419 [95% confidence interval (CI) 0.178-0.982; P = 0.045], stage 2 versus stage 1 disease 0.216 (95% CI 0.063-0.738; P = 0.015), and stage 3 versus stage 1 disease 0.084 (95% CI 0.008-0.913; P = 0.042). Cessation of bisphosphonate treatment did not influence outcome., Conclusions: Conservative treatment of ONJ leads to mucosal closure in 53% of patients. Doubling the exposure time to bisphosphonates and higher stages of ONJ significantly reduce ONJ healing rates.

Bisphosphonates (BP) have clinically been used as a highly effective drug in the treatment of hypercalcemia of malignancy, multiple myeloma, skeletal events associated with metastatic breast cancer and prostate cancer, and osteoporosis. Despite these benefits, however, the emergence of BP-related osteonecrosis of the jaws (BRONJ) becomes a growing and significant problem in a subset of patients receiving these drugs, especially intravenous preparations. It has also been reported in the patients receiving oral BP, although the incidence is extremely low. Most of BRONJ cases occur after dental treatments such as tooth extraction, periodontal surgery, and dental implants, and are refractory to conventional treatment modalities such as debridement, antibiotics and hyperbaric oxygen therapy. As compared to EU and USA, the number of BRONJ case is still small in Japan, but it is exactly increasing year by year. The ratio of the number of BRONJ in patients receiving oral BP to that in patients receiving intravenous BP is higher in Japan than in EU and USA, speculating due to the difference of time of approval. In this communication, the practical guidelines for prevention, diagnosis and treatment of BRONJ recently released from USA and Canada were introduced. Although no effective therapy for BRONJ is established yet, the importance of oral hygiene, patient education and treatments suitable for clinical stage is emphasized. In addition, it is considered that the survey of incidence of BRONJ in Japan and the preparation of Japanese guideline are urgent need.

Osteonecrosis of the jaw (ONJ) was first reported in the dental literature in 2003. The term was coined to describe a spectrum of dental problems seen in cancer patients treated with high doses of intravenous bisphosphonates for the prevention of skeletal-related events. By consensus, the syndrome is now defined by the presence of exposed bone in the mouth which fails to heal after appropriate intervention over a period of 6 or 8 weeks. It is most common in patients with breast or prostate cancers, or multiple myeloma treated with bisphosphonates, of whom about 5% develop the condition. In patients receiving the much lower drug doses used in osteoporosis, the incidence appears to be approximately 1/100,000 patient-years, probably comparable to that in the general population. It is likely that ONJ results from direct drug toxicity to cells of bone and soft tissue. The bone in ONJ lesions does not appear to be 'frozen' but rather there is very active bone resorption taking place, which is likely to be responsible for the local release at high concentrations of bisphosphonates. Infection probably plays a pivotal role in driving this resorption, so its active management is critical. Obvious abnormalities are apparent with a variety of radiologic modalities, and it is not clear that radiographs are inferior to other approaches. Most authors favor a conservative approach to surgical debridement of the lesions.

Bisphosphonate therapy has been considered standard therapy in the management and care of cancer patients with metastatic bone disease and patients with osteoporosis. The efficacy of these drugs is due to their ability to inhibit osteoclast-mediated bone resorption. However, the postmarketing experience with intravenous and, to a much lesser extent, oral bisphosphonates has raised concerns about potential side effects related to profound bone remodeling inhibition and osteonecrosis isolated to the jaws. We review the risk factors, incidence, pathogenesis, prevention strategies, and management of this new complication.

Intravenous bisphosphonate (BP) therapy has become the standard of care for the treatment of cancers that metastasize to bone. BPs are associated with osteonecrosis of alveolar bones, a condition known as osteonecrosis of the jaw (ONJ). The incidence or pathogenesis of ONJ is largely unknown. The lesions are characterized by areas of exposed necrotic bone that do not heal after 8 weeks in the absence of radiation to the head and neck. ONJ lesions have been recalcitrant to conventional therapies. Lesions in cancer patients treated with BPs develop in association with periodontal disease, tooth extraction and/or in association with increased mechanical force due to partial/complete dentures. We hypothesized that intravenous BPs in cancer patients impair normal bone remodeling, thereby increasing the incidence of osteonecrotic lesions and that these lesions can be detected using cone beam computerized tomography (CBCT). From CBCTs taken at the University of Missouri at Kansas City School of Dentistry, 26 subjects had a cancer diagnosis and were on BP therapy. From these 26 subjects, 18 presented visible, exposed necrotic bone. We observed both sclerotic and radiolucent lesions. Lesions could be detected and measured in reconstructed images where most were found to expand to large areas of the bone. We were able to identify necrotic bodies or 'involucrums' within the ONJ lesions, suggesting that this could be the mechanism for the formation of a clinically visible sequestrum. We propose that CBCT can potentially identify and follow the progression of both pre- and postclinical lesions in ONJ patients, allowing better diagnosis and assessment of disease status., (Copyright 2008 S. Karger AG, Basel.)

Condensing osteitis is defined as pathologic growth of maxillomandibular bones characterized by mild clinical symptoms. The bone thickening reflects the impaired bone rearrangement in response to mild infection of dental pulp. This clinical study describes case reports of patients sent to us with radiological findings and clinical examination that failed to lead to definitive diagnosis. On differential diagnosis, all bone tissue tumors were considered. Based on clinical and radiological findings (bone density and trabeculation of the bone) we settled on the diagnosis of osteitis condensans, which allowed us to remain in conservative therapy in terms of observing the patient (Fig. 3, Ref. 26). Full Text (Free, PDF) www.bmj.sk.

Background: and Overview. In 2005, the American Dental Association (ADA) Council on Scientific Affairs convened an expert panel to develop clinical recommendations for dentists treating patients who are receiving oral bisphosphonate therapy. The Journal of the American Dental Association published the resulting report in 2006. This 2008 advisory statement is the first of projected periodic updates of the 2006 clinical recommendations., Conclusion: This 2008 advisory statement concludes, on the basis of a review of the current literature, that for patients receiving bisphosphonate therapy, the risk of developing bisphosphonate-associated osteonecrosis (BON) of the jaw apparently remains low. It also newly concludes that current screening and diagnostic tests are unreliable for predicting a patient's risk of developing the condition. This statement updates the 2006 recommendations regarding general dentistry, management of periodontal diseases, implant placement and maintenance, oral and maxillofacial surgery, endodontics, restorative dentistry and prosthodontics, and orthodontics.

Objective: To evaluate the literature and discuss the risk factors, mechanisms, pathophysiologic aspects, and recommended management of bisphosphonate-associated osteomyelitis of the jaw (BAOMJ)., Methods: More than 350 published articles, case reports mentioning BAOMJ, and independent histology slides from BAOMJ lesions were reviewed critically. The most pertinent publications are cited and discussed., Results: The incidence of BAOMJ increases after extraction of teeth, dentoalveolar surgical procedures, or recent oral trauma leading to exposed maxillary or mandibular bone. Contributory factors include poor oral hygiene, oral infections, periodontal disease; recent or ongoing corticosteroid administration or chemotherapy; compromised immune status; diabetes or vascular insufficiency; old age; chronic diseases; and malignancies. On average, 1 of every 100,000 patients treated with bisphosphonates orally for osteoporosis or Paget disease of bone may develop BAOMJ-like lesions. Patients with cancer often receive bisphosphonate doses 10 times or higher, and also more frequently, than those used in patients with osteoporosis or Paget disease of bone. Therefore, greater frequency of administration of bisphosphonates, higher dosages, and prolonged use (that is, for more than 2 years) are likely to be factors triggering BAOMJ., Conclusion: The association of bisphosphonate therapy with BAOMJ is rare in noncancer patients and is likely to be a class effect that may occur with use of any bisphosphonate. Whether patients with cancer require such a high frequency of intravenously administered bisphosphonates needs to be investigated. Following established guidelines can decrease the risks of BAOMJ in vulnerable patients. Rather than necrotic bone, current evidence supports an infectious and perhaps immunologic underlying cause for BAOMJ. The estimated incidence of BAOMJ among noncancer patients receiving bisphosphonates is about 0.001%, whereas among patients with cancer receiving intravenous bisphosphonate therapy the incidence is between 0.5% and 4%, depending on the dose, frequency, and duration of therapy (on average, approximately 2%). Nevertheless, the benefits of bisphosphonates far outweigh the risks.

The health history form is a rapid, time-honored method used by practitioners to assess a patient's medical history before treatment. Because of increased reports of bisphosphonate-related osteonecrosis of the jaws (BRONJ), we investigated the percentage of our patients taking oral bisphosphonates who actually reported taking the medication on our health history form. A questionnaire inquiring about bisphosphonate use was sent to 1,400 female patients who had undergone implant placement in the last five years. A total of 500 responses were received; of these, 112 reported they used bisphosphonates. We then reviewed the charts of the 112 patients to determine the percentage of patients who had included bisphosphonate use in their health history form. Only 35% of our patients who were using bisphosphonates had reported taking bisphosphonates on the health history form. With the difficulties in treating BRONJ, we strongly suggest including direct questions concerning bisphosphonate use in the medical history form so practitioners can identify the patient population that is at risk and can modify the treatment plan to avoid potentially disastrous clinical situations.

Goals of the Work: Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonates treatment. Bisphosphonates reduce skeletal adverse events and give a clinical benefit to cancer patients. Therefore, it is necessary to identify appropriate procedures to reduce ONJ injures by using a successful monitoring program. In a retrospective study we analyzed the impact of a prevention program based on clinical oral cavity examination, dentists, and patients' education. The aim of the study was to evaluate if this approach might improve ONJ outcome in patients receiving pamidronate or zoledronate., Materials and Methods: We analyzed retrospectively two different groups of patients treated at our Institution: patients treated from October 2003 to June 2005 (group A) and patients treated from June 2005 to April 2007 (group B). In June 2005 the prevention program started for all our patients., Main Results: One hundred and eighty-six cancer patients with bone involvement, treated with bisphosphonates, were considered. Sixteen of them developed ONJ: eight before and eight after June 2005. We observed a consistent difference in the evolution of the two groups. In the first group, four patients underwent a major surgery (one partial maxillectomy, complicated by septic shock and oronasal communication; two partial mandibulectomies; and one segmental mandibular resection), with an important impairment of their quality of life; while the eight new ONJ cases, diagnosed after June 2005, were successfully treated without aggressive dental interventions, and achieved a good control of symptoms., Conclusions: Bisphosphonates-related ONJ is a frequent adverse event (8.6%). The monitoring program proved very efficient to improve the clinical outcome of ONJ, avoiding an aggressive treatment and using a conservative approach and medical therapy.

Bisphosphonate osteonecrosis, BON, was recently described in the literature. Lack of scientific evidence explaining the pathophysiologic mechanisms involved in the development of this oral complication has generated uncertainties about proper management of patients treated with a bisphosphonate. This manuscript discusses the dental management of two breast cancer patients treated with intravenous bisphosphonates as part of their cancer management and who developed oral disease. Clinical management decisions will be presented as well as the treatment outcomes.

Case Description: A 5-year-old neutered male English Bulldog was evaluated for intermittent closed-mouth jaw locking of approximately 1 week's duration., Clinical Findings: Initial physical examination revealed a nonpainful inability to open the jaw with and without manual assistance; however, manipulation of the jaw after the dog was sedated for diagnostic imaging restored jaw function. Anesthesia was subsequently induced, and computed tomography was performed with the jaw open and closed; contrast agent-enhanced images of the closed jaw were also obtained. No abnormalities of the temporomandibular joints or retrobulbar space were detected. Fluoroscopic examination of movement of the temporomandibular joints revealed a dynamic interference of the rostrodorsal aspect of the coronoid process of the left mandibular ramus with the medial surface of the frontal process of the left zygomatic bone or the left orbital ligament., Treatment and Outcome: Partial excision of the coronoid process of the left mandibular ramus was performed. The dog recovered without complication and was able to open and close its jaw and eat within 6 hours after surgery. No additional episodes of jaw locking were detected during the 6 months after surgery., Clinical Relevance: To the authors' knowledge, closed-mouth jaw locking in animals attributable to dynamic interference of the rostrodorsal aspect of the coronoid process of a mandibular ramus with the medial surface of the frontal process of a zygomatic bone or an orbital ligament has not been described. Surgical excision of the coronoid process of the mandibular ramus appeared to provide a successful outcome in the dog of this report.

Background: The purpose of this study is to describe the nature of cases undergoing temporal artery biopsy (TAB) for suspected giant cell arteritis (GCA)., Methods: A retrospective review of case notes was undertaken for all patients on whom ophthalmologists had performed TAB in 2 teaching hospitals between 1995 and 2001. Presenting symptoms, referring specialty, TAB result, treatment, and discharge diagnosis were recorded., Results: Ophthalmologists performed TAB on 110 patients for suspected GCA. A variety of specialties referred patients to ophthalmology for TAB; presenting symptoms varied with referral source. Of the 110 TABs, 21 (19%) were reported as positive for GCA, 84 (76%) were negative, and 5 (4.5%) were reported as inadequate. The symptoms most commonly associated with a positive TAB were visual disturbance (15/21) and headache (15/21). The odds ratios for having a positive TAB result rather than a negative result were 1.0 for the presence of headache, 4.1 for visual disturbance, and 6.7 for jaw claudication., Interpretation: Physicians were faced with a different population of GCA suspects than ophthalmologists. While physicians should be alert to the significance of visual symptoms or jaw claudication, ophthalmologists should be ready to facilitate prompt TABs when appropriate. TAB should be performed promptly and an adequate length of artery taken for biopsy. An argument can be made that TAB is not needed in cases of suspected GCA. However, a positive result provides firm justification for the use of steroids. We feel that TAB has a useful role and we make reference to methods to maximize its usefulness.

Purpose of Review: Bisphosphonates are used for the management of metastatic bone disease, prevention and treatment of osteoporosis and Paget's disease of bone. An increasing number of reports have associated the use of bisphosphonates with the occurrence of osteoradionecrosis of the jaw. The purpose of this review is to summarize the recent literature in this area, specifically focusing on its management., Recent Findings: Osteoradionecrosis of the jaw mostly results from the use of intravenous bisphosphonates for metastatic bone disease and multiple myeloma; cases from oral treatment for osteoporosis and Paget's disease have also been reported. It mostly affects the posterior maxilla, followed by the posterior mandible. In more than half of the affected patients, there has been preceding dental trauma or procedure. Many treatment modalities have been attempted in order to limit disease progression. Conservative management with antibiotic therapy and mouthwashes seems to be most beneficial. Surgery should be reserved for refractory and symptomatic cases., Summary: It is important for the reconstructive head and neck surgeon to recognize the clinical presentation of bisphosphonate-induced osteoradionecrosis of the jaw and the role of conservative management in consistently achieving good results.

Introduction: Jaw claudication is mostly described as a symptom of giant cell arteritis. However it can also occur in presence of severe bilateral external carotid artery stenosis., Report: An 87-year-old man with extensive cardiovascular history presented with disabling bilateral jaw claudication. Duplex Scan and MR-Angiography showed severe bilateral ostial external carotid artery stenosis. After unilateral carotid endarterectomy, the symptoms disappeared., Discussion: Bilateral jaw claudication as a symptom of carotid atherosclerosis is a rare condition. It can be treated by unilateral carotid endarterectomy.

Objective: Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists., Methods: The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies., Results: RECOMMENDATIONS regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case reports, case series, surveys, retrospective studies, and 2 prospective observational studies., Recommendations: In all oncology patients, a thorough dental examination including radiographs should be completed prior to the initiation of intravenous bisphosphonate therapy. In this population, any invasive dental procedure is ideally completed prior to the initiation of high-dose bisphosphonate therapy. Non-urgent procedures are preferably delayed for 3 to 6 months following interruption of bisphosphonate therapy. Osteoporosis patients receiving oral or intravenous bisphosphonates do not require a dental examination prior to initiating therapy in the presence of appropriate dental care and good oral hygiene. Stopping smoking, limiting alcohol intake, and maintaining good oral hygiene should be emphasized for all patients receiving bisphosphonate therapy. Individuals with established ONJ are most appropriately managed with supportive care including pain control, treatment of secondary infection, removal of necrotic debris, and mobile sequestrate. Aggressive debridement is contraindicated., Conclusion: Our multidisciplinary guidelines, which provide a rational evidence-based approach to the diagnosis, prevention, and management of bisphosphonate-associated ONJ in Canada, are based on the best available published data and the opinion of national and international experts involved in the prevention and management of ONJ.

A review of state-of-the-art maxillofacial imaging is presented. Current imaging techniques include intra-oral radiographs, dental panoramic tomography, multidetector helical computed tomography, cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI). The commonest conditions encountered in clinical radiological practice are reviewed, including maxillofacial deformities, complicated dental impactions, maxillofacial trauma, jaw lesions (cysts, neoplasms, fibro-osseous lesions (FOLs) and infections), and temporomandibular joint pathology. Pre-operative assessment for dental implant placement is also briefly reviewed.

The unique and specialized structures of the oral cavity and jaws give rise to a myriad of diverse developmental, inflammatory, and benign lesions or conditions. This article reviews the imaging of common lesions and their variants, and reviews several rare but important lesions. Guidelines and algorithms for approaching the differential diagnosis are provided.

The roles of the 'classical'Actinomyces spp. as colonizers of oral cavities of man and animals, in development of intra-oral infections and as agents of actinomycosis have been well documented. This mini-review focuses on perceptions of human colonization and infection that have emerged in the past decade, largely as a result of advances in classification, identification and direct detection from clinical material. Arguably, of the greatest importance is the recognition of actinomycosis as a major factor and indicator of poor prognosis in both infected osteoradionecrosis and bisphosphonate-associated osteonecrosis of the jaws. Among recently described species, Actinomyces graevenitzii has been isolated almost exclusively from oral and respiratory sites and may be a causative agent of actinomycosis. Conversely, several other Actinomyces spp. are isolated commonly from superficial soft tissue infections. Members of the genus Actinobaculum, which is closely related to Actinomyces, are strongly associated with urosepsis. Isolation and identification of Actinomyces and related genera by conventional methods remain difficult. Diagnosis is commonly belated and based solely upon histological findings. Development of direct detection methods may aid patient management and further elucidate clinical associations.

The first bisphosphonate (etidronate) was approved by the FDA in 1977; alendronate was approved in 1995 for the prevention and treatment of osteoporosis. Bisphosphonates have emerged as the agents of choice for the treatment of osteoporosis and have proved useful in the treatment of skeletal complications of malignancy (hypercalcemia, bone metastases) and have been used long-term in millions of patients. Osteonecrosis of the jaw (ONJ) is a newly described condition (2003) defined as exposed bone in the maxillofacial area, not associated with radiation or any other known cause and not healing for 8 weeks. Most cases have followed dental extraction, another invasive dental procedure, or poorly fitting dentures. Although most cases are painful and it can be progressive, approximately one-third of cases are painless and some do resolve. Although ONJ occurs exclusively or almost exclusively in patients receiving bisphosphonate therapy, a causal association has not been shown, and the mechanism is not clear. In patients receiving high-dose i.v. bisphosphonates for malignant diseases, ONJ may occur in 5 to 10% over 3 years. It does occur in patients receiving oral or i.v. bisphosphonates for osteoporosis, but is rare in that setting; about 1 case per 100,000. Treatment is conservative (antimicrobial mouthwash, antibiotics for secondary infection, limited debridement). Preventive strategies should include good dental hygiene for all patients and completion of elective invasive dental procedures before initiating high-dose i.v. bisphosphonate therapy for cancer. Patients with osteoporosis receiving lower-dose bisphosphonate therapy do not require special precautions, but should be informed of the low risk of this complication.

Aim: To evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) findings of biphosphonate therapy-associated changes of the mandible and maxilla., Materials and Methods: Thirty-two patients with a clinical history of pain, purulent discharge, and swelling in the mandible or maxilla as well as non-healing dental extraction were examined. All patients had received biphosphonate medication for approximately 33 months. Non-contrast enhanced CT and contrast-enhanced MRI were performed and, subsequently, all patients underwent a surgical removal of the affected bone, the histological diagnosis of which confirmed osteonecrosis. The images were read by two head and neck radiologists in consensus., Results: Osteonecrosis with Actinomyces infection was identified in the mandible of 18 patients, in the maxilla of eight patients, and in both jaws in six patients. The CT images showed predominantly osteolytic lesions and sclerotic regions in the jaws with or without periostal bone proliferation. There was a reduction of the marrow space in the jaws. The T1-weighted MRI signal was hypointense in nearly all cases. The gadolinium-enhanced MRI images revealed intensity changes of the cortical and subcortical bone structures in all patients. The T2-weighted MRI signal was hypointense on the affected side in the majority of the cases (28/32). Pathological gadolinium enhancement was observed in the neighbouring soft tissues, including the masticator space in all patients. Reactive lymphadenopathy was found in all patients in submental and jugulodigastric areas., Conclusion: Biphosphonate-induced osteonecrosis of the jaws presents a wide variety of CT and MRI features that are readily recognized and help to determine the extent of the disease; however, they are not specific for the disease.

Since four years from now on more and more information about bisphosphonate induced osteonecrosis of the jaws is published not only in professional journals, but also in the mass media. The result is a growing uncertainty of patients, but also professionals in dealing with this group of medication. Usually bisphosphonates are prescribed for treatment of severe osteoporosis, but also for treatment of metastatic bone disease and tumor induced hypercalcemia. The following article gives information about bisphosphonates, bisphosphonate induced osteonecrosis of the jaws (BON) and potential risk factors. Additionally it shows the typical clinical picture, necessary diagnostic measures and informs about possible prevention strategies especially for dentists in daily practice.

Intravenous application of bisphosphonates (BP) represents an established therapeutic strategy of tumor-associated bone metastasis and severe hypercalcemia. Patients can develop osteonecrosis of the jaw (ONJ) as a side effect of this therapy. The diagnosis of ONJ is based on three criteria: a) patients have been or are currently treated with BP; b) a deficiency in wound healing, which is in 70-80% associated with necrotic alveolar bone, characteristically exposed, is present for at least 8 weeks and c) no radiotherapy of the head and neck was performed. The suppression of bone turnover, concomitant with high functional load of the alveolar bone, and the subsequent accumulation of microfractures are considered the main pathologic factors of this disease. The cumulative incidence of ONJ lies approximately between 1 and 10% in oncologic patients, being associated with the antiresorptive potency and the respective molecular structure of the BPs. Patients with multiple myeloma develop ONJ more frequently than patients with other oncological diseases such as metastasizing breast- and prostate cancer, a fact that may also be due to the higher transfusion/injection frequency of BP in these patients. Dental treatment strategies are responsible for the occurrence of ONJ in approximately 80% of cases. Based on a clinical staging, patients can be grouped into three categories and should receive the corresponding treatment regime. Prospective clinical studies are required for a better understanding of etiology and pathogenesis of ONJ to make treatment, risk estimation and prognosis of ONJ more accurate.

Bisphosphonates have been prescribed for the treatments of oncologic and metabolic bone diseases to inhibit bone resorption of osteoclasts. However, in recent years, the increased numbers of cases diagnosed with exposed and necrotic bone localized in the jawbones associated with bisphosphonate use have been reported, mostly in patients with multiple myeloma or bone metastases who received long-term intravenous bisphosphonate treatments. The strong association between patients receiving dentoalveolar surgery and the incidence of this complication highlights the need for multidisciplinary approaches and necessitates the close attention from a team of health care personnel. The present review summarizes the current knowledge on etiology, risk factors, clinical presentations, and recommended preventive measures and managements for afflicted patients. In light of recent available data and because stanterdized management strategies have not been well established, prevention seems to be of paramount benefit to this group of patients.

Unlabelled: Osteonecrosis of the jaw (ONJ) is a well-known devastating side effect of bisphosphonate therapy for cancer. Several ONJ cases of patients using oral bisphosphonates have been reported in the literature. The present study analyzed the clinical features, predisposing factors, and treatment outcome of 11 patients with oral bisphosphonates-related ONJ., Introduction and Hypothesis: Osteonecrosis of the jaw (ONJ) is a well-known side effect of parenteral bisphosphonates therapy. Although ONJ has been reported in patients using oral bisphosphonates, documentation of this entity is sparse. It was hypothesized that the clinical features, predisposing factors, and treatment outcome of this population are different from those of oncologic patients., Methods: This retrospective bi-central study involved 98 ONJ patients, 13 of whom were treated with oral bisphosphonates. Two patients were excluded because of previous use of intravenous bisphosphonates. The profiles of 11 patients were analyzed., Results: The mean duration of alendronate use before developing ONJ was 4.1 years. ONJ was triggered by dental surgery in 9 patients and by ill-fitted dentures in 2. Heavy smokers were the most recalcitrant subjects. Among the nine patients with at least 6 months of follow-up, ONJ healed completely in three, partially in four, and not at all in two., Conclusions: ONJ is a rare devastating side effect of oral bisphosphonates associated with patient morbidity and high financial burden. Clinicians must be aware of this entity and inform patients of the risks of dental surgery. The synergistic effect of smoking in the pathogenesis of ONJ should be further investigated.

Purpose of Review: Osteonecrosis of the jaw associated with the use of potent nitrogen containing bisphosphonates is a new and challenging clinical entity with a high impact on quality of life. This review attempts to consolidate the rapidly expanding literature into practical guidelines and provides expert consensus for areas of uncertainty., Recent Findings: Diagnostic criteria and a staging system for osteonecrosis of the jaw have been proposed, and histomorphologic analysis has confirmed osteonecrosis of the jaw as a proper disease, distinctively different from osteoradionecrosis. Various guidelines for the management of osteonecrosis of the jaw have been suggested and further retrospective research has provided new insights into its epidemiology., Summary: Osteonecrosis of the jaw is a distinct entity of uncertain origin that is increasingly being observed in patients treated with potent aminobisphosphonates, although the etiology is probably multifactorial. Recent data confirm the predisposition of multiple myeloma patients to develop osteonecrosis of the jaw. Although various treatment strategies have been reported, conservative management remains the mainstay of therapy.

Eosinophilic granuloma is classified as a Langerhans cell histiocytosis. Although considered a rare pathology, up to 20% of all cases occur in the jaw bones, and radiographically may mimic odontogenic cysts or benign and malignant tumours. Different protocols have been suggested in the literature for treating eosinophilic granuloma. We report a case of polyostotic eosinophilic granuloma in a 34-year-old man showing ill defined mandibular and palatal radiolucencies. Due to the presence of multiple jaw lesions the treatment choice was chemotherapy. The clinical and radiographic feature are described, as well as treatment, complications and patient's follow-up.

In light of recent reports of osteonecrosis of the jaw (ONJ) in cancer patients whose treatment regimens include an intravenous bisphosphonate, Novartis convened an international advisory board of experts in the fields of oral surgery and pathology, medical oncology, metabolic bone disease, and orthopedics to review existing data and provide updated recommendations on the clinical diagnosis, prevention, and management of ONJ in the oncology setting. Recommendations were developed to help guide healthcare professionals in early diagnosis and patient management. It is recommended that patients be encouraged to receive a dental examination prior to initiating bisphosphonate therapy and, if possible, complete any necessary dental procedures (e.g., tooth extraction) prior to initiating bisphosphonate therapy. Patients should receive regular dental visits during bisphosphonate therapy. Patients should be encouraged to practice good oral hygiene and minimize possible jaw trauma. If possible, patients should avoid dental surgery during treatment with bisphosphonates. If exposed bone is observed or reported in the oral cavity at any time (suspected ONJ), refer the patient to a dental professional immediately.

Purpose: To estimate the prognosis of simple bone cyst of the jaws., Subjects and Methods: We reviewed 132 of our own and published cases that received postoperative follow-up until healing or recurrence. The recurrence rate was obtained from treatment outcomes. The time to healing or recurrence was estimated from the distributions of the times of examinations that confirmed healing or recurrence., Results: Simple bone cyst lesions healed in 98 cases and recurred in 34 cases. The overall recurrence rate was 26%. The recurrence rate was 71% and 75% for cases with multiple cysts and cemento-osseous dysplasia, respectively. In most cases, healing or recurrence was confirmed within 3 years, 5 months of surgery. The maximum number of cases with healing and recurrence was observed 12 to 17 months and 2 to 2.5 years after surgery, respectively., Conclusion: The recurrence rate was higher than rates reported previously. We recommend that postoperative examination be continued until complete healing is confirmed radiographically, particularly in cases with multiple lesions or cemento-osseous dysplasia. Healing or recurrence should be confirmed within 3 years of treatment.

Objective: The percentage of negative temporal artery biopsies (TABs) remains very high in patients with suspected giant cell arteritis (GCA). The aim of our study was to identify the clinical predictors of TAB results to improve the effectiveness of this diagnostic procedure., Methods: We performed a cross-sectional study of 125 consecutive patients who underwent TAB in the Department of Internal Medicine of a public tertiary hospital, from January 1997 to March 2002. We compared patients with a positive and a negative biopsy result., Results: Forty-six of the 125 biopsies (36.8%) were positive for GCA and 79 (63.2%) negative. Temporal artery (TA) thickening (8.01), decreased pulse (5.58), jaw claudication (4.87), and scalp tenderness (4.29) presented the highest positive likelihood ratios (LR+). Erythrocyte sedimentation rate (ESR) (0.11), headache (0.39), TA thickening (0.42), and decreased pulse (0.48) had the lowest negative likelihood ratios (LR-). Only TA abnormalities [odds ratio (OR) 12.3] and scalp tenderness (OR 6) were independent predictors of biopsy results. By excluding patients with no evidence of TA abnormalities, scalp tenderness, or jaw claudication, only 48% of the 125 biopsies would have been performed; 59 negative biopsies would have been prevented, but six positive biopsies would have been missed., Conclusion: Careful assessment of patients with clinically suspected GCA to rule out artery abnormalities, scalp tenderness, and jaw claudication can lead to a dramatic decrease in the percentage of negative biopsies. This observation may contribute to improving the physician's decision-making process when contemplating TAB.

Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is encountered predominantly in cancer populations being treated with high-dose intravenous bisphosphonates for skeletal complications such as bone metastases and secondary fracture risk. A minority of BONJ lesions have been observed in patients receiving oral bisphosphonates for management of osteoporosis or osteopenia. In this paper, the current knowledge pertaining to the incidence, definition, and signs and symptoms of BONJ is presented, followed by a discussion of the incidence and consequences of osteoporotic skeletal fracture and the use of oral bisphosphonates to mitigate fracture. The risk of BONJ appears to be very small in patients taking oral bisphosphonates. In addition, the consequences of osteoporotic fracture likely have significantly greater mortality and morbidity than BONJ. Within this context, management concepts and guidelines are presented to help the dental clinician allay concerns about BONJ expressed by patients receiving oral bisphosphonate therapy.

Periodontal disease is a bacteria-induced chronic inflammatory disease affecting the soft and hard supporting structures encompassing the teeth. When left untreated, the ultimate outcome is alveolar bone loss and exfoliation of the involved teeth. Traditional periodontal diagnostic methods include assessment of clinical parameters and radiographs. Though efficient, these conventional techniques are inherently limited in that only a historical perspective, not current appraisal, of disease status can be determined. Advances in the use of oral fluids as possible biological samples for objective measures of current disease state, treatment monitoring, and prognostic indicators have boosted saliva and other oral-based fluids to the forefront of technology. Oral fluids contain locally and systemically derived mediators of periodontal disease, including microbial, host-response, and bone-specific resorptive markers. Although most biomarkers in oral fluids represent inflammatory mediators, several specific collagen degradation and bone turnover-related molecules have emerged as possible measures of periodontal disease activity. Pyridinoline cross-linked carboxyterminal telopeptide (ICTP), for example, has been highly correlated with clinical features of the disease and decreases in response to intervention therapies, and has been shown to possess predictive properties for possible future disease activity. One foreseeable benefit of an oral fluid-based periodontal diagnostic would be identification of highly susceptible individuals prior to overt disease. Timely detection and diagnosis of disease may significantly affect the clinical management of periodontal patients by offering earlier, less invasive, and more cost-effective treatment therapies.

The osteonecrosis of the jaws (ONJ) has been reported occasionally in cancer patients treated with radiotherapy and chemotherapy. However, bisphosphonate (BP)-associated ONJ in patients with cancer such as multiple myeloma, breast cancer and prostate cancer mainly administered with intravenous BPs has been first reported in 2003. Since then, many cases over 2,500 are accumulating worldwide. Since BPs are often used for osteoporosis, cancer-associated hypercalcemia and osteolytic bone metastasis, it is speculated that ONJ cases will increase in Japan where a small number of them were reported until now. Most of ONJ in cancer patients receiving BP administration occur after dental treatments such as tooth extraction, periodontal surgery and dental implants, and do not respond to conventional treatment modalities such as debridement, antibiotic therapy and hyperbaric oxygen therapy. No effective therapy for ONJ is established yet and empirical conservative therapy is recommended in the guidelines for prevention, diagnosis, and treatment of ONJ. Therefore, dentists and oral and maxillofacial surgeons need to recognize ONJ as a serious side effect of BPs and to make informed consent to the patients and a close consultation with medical oncologists for administration of BPs.

Bisphosphonates are a valuable class of drugs with potent anti-resorptive actions that make them ideal for skeletal protection in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget's disease of bone. It has become apparent, however, that these drugs also have the potential to cause a number of adverse effects. While these do not limit bisphosphonate use, the incidence of these adverse events can be minimized if appropriate care is taken with their administration, and by maintaining appropriate surveillance and patient care. We review the range of adverse reactions to bisphosphonate therapy with a particular emphasis on the recently identified association between long-term bisphosphonate treatment and osteonecrosis of the jaw. This is a potentially serious side effect seen mostly in patients with multiple myeloma or breast cancer bone metastases who receive intravenous bisphosphonate treatment. While the etiology is uncertain, a strong association with dental pathology and interventions highlights the need for close attention to dental health in this patient group.

A 60-year-old man with multiple myeloma (MM) (IgG-kappa, stage IIIA) had been treated with minodronate at 6 mg orally as a phase 1 clinical trial for myeloma bone disease for 13 months (total dose, 4032 mg). Then he received incadronate at 10mg intravenously every 1 to 4 weeks (total dose, 350 mg). In July 2005, he complained of mild right mandibular pain, and bone scintigram showed a hot spot at the right side of the mandible. Panoramic radiograph showed osteonecrosis of the jaw (ONJ) and axial and 3-dimensional computed tomography confirmed ONJ. Oral examination showed massive gingival swelling of the right side of the mandible without exposed necrotic bone. He was given clarithromycin in addition to levofloxacin, followed by hyperbaric oxygen (HBO) therapy, which resulted in the complete disappearance of the pain. This is a first reported case of ONJ induced by incadronate. The present case suggests that early detection of ONJ by regular dental check-ups is important in the management of patients with MM who have received bisphosphonate therapy, and HBO in combination with antibiotic therapy is effective in the early stage of ONJ.

The aim of this article is to highlight the link between bisphosphonates and osteonecrotic lesions of the jaws ("osteochemonecrosis") and to alert general practitioners to the implications these drugs may have on their day-to-day practice. We review the use of this class of drug, the indications for which have widened recently, describe their effect on bone metabolism and outline the proposed mechanism for bisphosphonate-induced osteochemonecrosis. Predisposing and initiating factors and management are outlined, and suggestions made as to how the dental profession can help with this increasingly prevalent problem.

For several decades bisphosphonates have been used to reduce skeletal related events in patients with both osteoporosis or bone metastases. Under long term application, besides the known therapy side effects, a new clinical picture has been described within the last few years. This is osteonecrosis of the jaws, which is characterized by its difficulty in treatment. Besides exposed jaw bone, the start of the disease usually lacks any symptoms. The typical clinical symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The X-ray shows persisting tooth sockets after extractions and later cloudy radio-lucency, sequestra or fractures. The patient exposed to bisphosphonate can be grouped according to the risk for osteonecrosis: high risk patients with intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid therapy--predominantly patients with a malignant underlying disease and bone metastases low risk patients with an oral bisphosphonate therapy without additional chemo-, radiation or corticoid therapy--preferably patients with non-corticoid-induced osteoporosis. Before starting a bisphosphonate therapy possible causes of infection should be treated and risk of injuries to the mucosa should be reduced according to the individual risk profile. This is supplemented by information of the patient about the risk of necrosis and the possibilities for prevention. Regular dental recall under bisphophonate therapy is emphasised for early recognition of possible problems. Prophylaxis is recommended for the prevention of periodontal infection combined with a follow up of removable denture for possible ulcera. Generally, conservative treatment measures are preferred to surgical ones. Inevitable operations are carried out non-traumatically using broad spectrum antibiotic prophylaxis until the day of suture removal (not before day 10). Long term follow up examinations are recommended.Patients with dental implants inserted before a bisphophonate therapy should be subject to intensive recall examinations. For patients undergoing or following a bisphosphonate therapy the indication for dental implants should be as strict as for patients following head and neck radiation therapy. In the present for patients with osteonecrosis, even after healing, dental implants are regarded as contra-indication. Therapy of the necrosis often requires general anaesthesia, hospitalisation, naso-gastral feeding tube and intravenous, systemic antiinfective treatment. The necrosis is removed completely and a tension free wound closure with vascularised tissue is intended. A literature review shows the metabolic effect of biphosphonates, the known pathogenesis of the bisphosphonate-induced jaw necrosis. It is essential to develop interdisciplinary communication, aiming at a joint care for this group of concerned patients and involving not only those medical disciplines, which order and use bisphosphonates, but especially dentists and maxillofacial surgeons.

Bone necrosis of the jaws is often related to head and neck radiotherapy, to surgical procedures at maxillary or mandibular level but also to various local and systemic factors such as haematological diseases, haemoglobinopathies and systemic lupus eritematosus; its pathogenesis maybe associated with defects of vascularization. Bisphosphonate are synthetic analogues of pyrophosphate used for the treatment of hypercalcemia in patients with malignancies and bone metastasis and for the treatment of many other disorders such as metabolic bone diseases, Paget's disease, and osteoporosis; their pharmacological activity is related to the inhibition of the osteoclastic function which leads to resorption and reduction of bone vascularization. Since the end of 2003 Bisphosphonate-associated Osteonecrosis (BON) has become an increasing problem and the test of that is the increase of the relative published case report and case series. Here we report 29 cases of bone necrosis of the jaws in patients treated with pamidronate (Aredia), zoledronate (Zometa) and alendronate: 15 underwent surgical procedures and 14 occurred spontaneously. Among these patients (21 females, 8 males; mean age between 45 and 83 years); 14 were treated for bone metastasis, 12 for multiple myeloma and 3 for osteoporosis. Bone necrosis involved only maxilla in 7 patients, only mandible in 20 patients and both in 2 patients. Six patients had multiple osteonecrotic lesions, 3 contemporary lesions and 3 non contemporary. In these patients we performed 3 kinds of therapy, associated or not: medical therapy (with antibiotic drugs, antimycotics and antiseptic mouthwashes), surgical therapy with curettage or sequestrectomy and Nd:YAG laser biostimulation.