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Objectives: The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings. Methods: Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical interventions for seven patients. Bone tracer uptake was classified as high, medium, or low, and surgical samples were evaluated using Micro-CT and histomorphometric analysis. Results: CT showed medullary sclerosis in all patients, and MRI revealed gadolinium enhancement in four patients. PET imaging revealed remarkably elevated [18F]fluoride uptake and moderately increased [18F]FDG uptake in MRONJ compared to healthy jawbones, with both differences being statistically significant. [18F]fluoride uptake was associated with necrosis, bacteria, and inflammatory tissue. Micro-CT data did not show significant differences, but histomorphometric analysis revealed higher osteocyte and lacunae densities in the high [18F]fluoride uptake group, and more necrotic bone in the medium [18F]fluoride uptake group. Bacteria were observed in all areas. Conclusions: In summary, [18F]fluoride PET accurately identified MRONJ extent, revealing functional changes in jawbone remodeling not visible on CT. [18F]FDG PET showed differences in bone and soft tissue, though less pronounced. This method aids in evaluating disease activity and guiding treatment planning, requiring further research for optimal surgical approaches based on tracer uptake. [ABSTRACT FROM AUTHOR]

Summary: In this multi-institutional retrospective cohort study, we compared the long-term risk of osteonecrosis of the jaw following the use of denosumab vs. bisphosphonates in osteoporotic patients. After 2-year use, the likelihood of osteonecrosis of the jaw is lower with denosumab compared to bisphosphonates, and the difference increases with time. Purpose: To compare the long-term risk of osteonecrosis of the jaw (ONJ) between osteoporotic patients treated with bisphosphonates (BPs) and denosumab. Methods: This multi-institutional retrospective cohort study included patients aged > 40 years with osteoporosis between January 2010 and December 2018. Patients who met the eligibility criteria were divided into BPs and denosumab groups by propensity score matching (PSM). The risk of ONJ of denosumab vs. BPs was estimated using a Cox proportional hazards model and was described by the cumulative incidence rate using the Kaplan–Meier method. Results: A total of 84,102 patients with osteoporosis were enrolled, among whom, 8962 were eligible for inclusion based on their first-line drug use (denosumab, n = 3,823; BPs, n = 5,139). Following PCM matching (1:1), the BPs and denosumab groups included 3665 patients each. The incidence density of ONJ in the denosumab and BPs matching groups was 1.47 vs. 2.49 events (per 1000 person-years), respectively. The hazard ratio of ONJ in the denosumab vs. BPs group was estimated as 0.581 (95% confidence interval: 0.33–1.04, p = 0.07). The cumulative incidence rates of ONJ in both groups were similar for the first and second years of drug use (p = 0.062), but significantly different from the third year onwards (p = 0.022). The severity of ONJ was not significantly different between the two groups. Conclusion: In osteoporotic patients, after 2 years of use, the likelihood of ONJ being induced by denosumab is lower than that of BPs, and the difference increases with time. [ABSTRACT FROM AUTHOR]

Purpose: To review the mechanisms of action and clinical applications of bisphosphonate drugs, which are widely used in the management of metastatic bone cancer and systemic metabolic bone diseases, as well as the complications related to bisphosphonate treatment, emphasising the occurrence and management of bisphosphonate-related osteo-necrosis of the jaws (BRONJ). Materials and Methods: A search of the medical and dental literature was conducted in Medline and Embase using a combination of the keywords bisphosphonates, jaw, complications, osteonecrosis, osteoporosis and periodontal disease. A manual search of the references of the retrieved articles was also performed. Results: BRONJ predominantly affects cancer patients being treated with high-dose intravenous bisphosphonates and is characterised by the appearance of necrotic bone in the oral cavity either spontaneously or following an invasive surgical procedure such as dental extraction. The severity of this condition warrants a thorough medical and dental history in every patient in order to identify high risk patients. Conclusion: It is important that dental practitioners be aware of the association between bisphosphonate treatment and osteonecrosis of the jaws. Clinicians should perform a thorough oral examination in cancer patients before they begin intravenous bisphosphonate treatment. Optimal oral hygiene and regular dental care can lower BRONJ risk. Further clinical research is necessary to unveil the full therapeutic potential of bisphosphonates, their mechanisms of action and the factors that induce unwanted side-effects. [ABSTRACT FROM AUTHOR]

Just a decade ago, the outlook appeared limitless for the use of bisphosphonates for the treatment of a large number of metabolic bone diseases ranging from osteoporosis to cancer-related bone alterations to oral bone loss. Soon thereafter, however, osteonecrosis of the jaw (ONJ) emerged as a rare but significant condition associated with bisphosphonate treatment. Although many questions remain concerning ONJ, some significant knowledge has been gained over the past decade. Ideas have emerged regarding how to stage and treat the condition, and a number of preclinical models have been developed that will soon begin to speed progress toward understanding the pathophysiology of this condition. Researchers have also discovered that ONJ is not specific to bisphosphonates, as other potent antiremodeling agents have now been associated with the condition. While antiremodeling agents remain essential tools in medicine, ONJ has somewhat slowed the momentum for this drug class, especially as it relates to new and emerging applications. Until more effective prevention or treatment regimens for ONJ are developed, this side effect of remodeling suppression will continue--for better or worse--to have a significant impact on the field. One potential treatment option may be in the form of osteoanabolics. Exciting new data have emerged demonstrating the efficacy of teriparatide (parathyroid hormone) in reversing oral cavity bone loss and even as a potential therapy for ONJ. [ABSTRACT FROM AUTHOR]

Objective: A computer-aided diagnosis of bone scintigraphy using a bone scan index (BSI) has not been applied to a diagnosis of anti-resorptive agents-related osteonecrosis of the jaw (ARONJ). The aim of this study was to validate a diagnostic ability of BSI for early-stage ARONJ.Methods: A total of 44 cancer patients treated with anti-resorptive drugs were evaluated retrospectively. All patients underwent bone scintigraphy and the tracer uptakes were analyzed by BSI. The software BONENAVI (FUJIFILM RI Pharma; EXINIbone, EXINI Diagnostics) could automatically detect abnormal intensities and calculate each regional BSI (rBSI). Among the rBSIs, the largest one in the jaw was manually selected and defined as maximum BSI of the jaw (BSIJmax). Uptake ratio (UR) between the maximum jaw count-to-average forehead count was also calculated. Screening accuracy of ARONJ based on 2 parameters was compared. Receiver operating characteristic analysis and Fisher's exact test were performed.Results: The BSIJmax was significantly higher in patients who developed ARONJ than in those who did not, 3 months before the diagnosis of stage 2 ARONJ (p < 0.0001 and p = 0.02 in the maxilla and mandible, respectively). Using the cutoff values of 0.09% in the maxilla and 0.06% in the mandible, BSIJmax for predicting stage 2 ARONJ showed sensitivity and specificity of 88 and 96%, respectively, in the maxilla and 64 and 89%, respectively, in the mandible at 3 months before the diagnosis. The BSIJmax >0.09% and BSIJmax >0.06% in the maxilla and mandible, respectively, were much more frequently observed in patients who subsequently developed stage 2 ARONJ 3 months after the bone scintigraphy than in those who did not (p < 0.0001 and odds ratio = 182 in the maxilla and p < 0.005 and odds ratio = 14 in the mandible). The UR showed comparable diagnostic ability.Conclusion: The BSIJ provided a new index for evaluating ARONJ. For predicting occurrence of ARONJ, the thresholds of BSIJmax = 0.09 and 0.06% in the maxilla and mandible, respectively, may be used in patients treated with anti-resorptive drugs, and a differential diagnosis including ARONJ is recommended. [ABSTRACT FROM AUTHOR]

The present work aimed to review the literature focusing on the diagnostic criteria for bisphosphonate-related osteonecrosis of the jaw (BRONJ) and its implications regarding the management of the disease. Since the report of the first cases, BRONJ concepts, diagnostic criteria and guidelines have been changed. The presence of bone exposure in the oral cavity was at first a sine qua non condition for diagnosis. However, it seems that the great concern now is the possibility of occurrence of BRONJ without this feature. Some authors warn that the bone exposure criterion leads to late diagnosis and poor response to treatment. Meanwhile, some radiographic features, such as bone sclerosis, have been postulated as early signs of the disease. Criticisms have also been raised about the clinical staging system of BRONJ. While there is no consensus on the subject, common sense recommends treating symptomatic patients taking bisphosphonate as having BRONJ despite the absence of bone exposure; and asymptomatic patients must be kept under dental follow-up, since all of them are at risk for BRONJ. [ABSTRACT FROM AUTHOR]

For patients with malignant disease taking bisphosphonates and denosumab, the incidence of medication-related osteonecrosis of the jaw (MRONJ) is up to 15% in contrast to 0.01% in patients with osteoporosis. Clinical presentation of MRONJ extends from asymptomatic exposure of bone in 94% of patients to severe cases of mandibular fractures in a minority of 4.5%. The strongest risk factors for MRONJ are invasive dental procedures and dental infections. Advances in imaging provide more preoperation information compared with panoramic radiograph. Prevention strategies are the elimination of potential risk factors leading to invasive dental procedures and maintenance of good oral hygiene prior to the administration of antiresorptive agents. Management of MRONJ depends on the underlying disease, extent of the necrosis, and the presence of contributing therapy. Conservative therapies include topical anti-infective rinses and systemic antibiotic therapy. The most important part of surgical therapy is to remove the exposed and necrotic bone. Several options for defect closure are possible from local tissue flaps to microvascular free flap procedures. The development of MRONJ in conjunction with dental implants is a severe side effect and should be avoided if potentially harmful medication has already been administered. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the jaw ( ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non-bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high-dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. As treatment protocols based on randomized controlled trials ( RCTs) do not exist, we critically reviewed the existing data concerning the management of bisphosphonate-related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen. [ABSTRACT FROM AUTHOR]

Nitrogen containing bisphosphonate (N-BP) therapy is used extensively to treat osteoporosis and osteolytic bone lesions. Recently, a special form of osteonecrosis limited to the maxillofacial skeleton has been discovered especially within those patients who are receiving either long-term N-BP therapy alone and/or associated with invasive dental procedure. Bisphosphonates accumulate almost exclusively in maxillofacial skeleton owing to high bone turn over remodeling to maintain the mechanical competence. The pathogenesis and why it commonly appears in maxillofacial skeleton and the fixed treatment strategies remains unknown. The aim of this study was to improve the clinician understanding of N-BPs associated osteonecrosis of maxillofacial skeleton by reviewing the past 10 year literature. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to establish a bisphosphonate-related osteonecrosis of the jaw (BRONJ) rat model and to analyse the effects of teriparatide (TP) on this model. Methods: Sprague-Dawley rats were divided into three groups: I--zoledronic acid (ZA, n = 10); II--ZA and teriparatide (ZA + TP, n = 10); III--control (n = 10). Osteonecrosis was induced by administering zoledronic acid to groups ZA and ZA + TP. A week after the injections, rats underwent extraction of the first left mandibular molar. Following a four week period, TP was administered to the ZA + TP group for 28 days. Upon killing, extraction sockets were examined clinically, radiologically and histopathologically. Results: Clinical examination revealed necrotic bone exposure in none of the animals. MicroCT (µCT) examination showed that bone mineral density of the newly formed bone in the extraction socket was lower in the ZA group than in the ZA + TP group (p < 0.05). Histopathological examination revealed that only the ZA and ZA + TP groups developed osteonecrosis, and the osteonecrotic bone area in the ZA group was larger than that in the ZA + TP group (p < 0.05). Tartrate-resistant acid phosphatase (TRAcP) enzyme histochemistry revealed that the number of detached and large osteoclasts were higher in the ZA group than in other groups, whereas the number of apoptotic osteoclasts in both ZA and ZA + TP groups were higher than in the control group (p < 0.05). Conclusions: Our data indicate that bisphosphonate-related osteonecrosis of the jaw model used in the present study is an attractive model to investigate treatment modalities and that TP might be an effective treatment in BRONJ. [ABSTRACT FROM AUTHOR]

The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-up and the treatment showed favorable prognosis. [ABSTRACT FROM AUTHOR]

Adequate nutrition is imperative for a successful outcome in dialysis patients. Excellent oral hygiene and an efficient mastication can help to correct several metabolic and endocrine disturbances as well as delay initiation of dialysis in patients with chronic renal failure. However, concerns exist about the risk of malnutrition and protein depletion. On the other hand, intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws. This complication occurs either spontaneously or after minor dento-alveolar surgery including extraction of teeth. A malnourished dialysis patient who showed the typical clinical features of bisphosphonate-related osteonecrosis of the jaw (BRONJ) without any obvious radiological changes in his panoramic radiograph is reported. To minimize the risk of BRONJ, patients initiated on bisphosphonates should optimize routine dental care and have their baseline oral health evaluated by both clinical and radiographic examinations before initiation of bisphosphonate therapy. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the magnetic resonance (MR) imaging features of bisphosphonate-related osteonecrosis of the jaw (BRONJ), particularly those in the early stage, through a literature review and case analysis. Methods: Literature on MR imaging of BRONJ was collected, and the MR imaging features were summarized. On MR images of patients with BRONJ, the signal intensity of the bone marrow was evaluated quantitatively by means of the contrast-to-noise ratio (CNR). The relationships of the imaging features with the presence of exposed bone, types and administration routes of bisphosphonates (BP), and duration of symptoms were investigated. Results: Fifteen articles were identified. In the early stages, the region of osteonecrosis displayed decreased signal intensity on T1-weighted images and normal signal intensity on T2-weighted images. In the late stages, the signal intensity of the bone marrow on T2-weighted images was variable: the exposed diseased bone displayed decreased signal intensity, and the unexposed diseased bone displayed increased signal intensity. These changes were also seen in BRONJ cases. There was a significant difference in the CNR between the exposed and unexposed diseased bones on STIR images. There were no significant differences in the CNR among the three groups by types and administration routes of BP, both on T1-weighted and STIR images. Changes in the signal intensity of bone marrow were seen at the early duration of symptoms. In the early stage, the CNR on T1-weighted images had a significant correlation with duration of symptoms. Conclusion: MR imaging may provide visualization of useful features in the early stage of BRONJ. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the possibility of radiographic examination as a tool for differential diagnosis of bisphosphonate-related osteomyelitis of the jaw (BROMJ). Methods: The radiographic findings of the mandibular lesions in 25 BROMJ patients were compared with those in 36 radiation osteomyelitis, 92 suppurative osteomyelitis, and 34 diffuse sclerosing osteomyelitis patients. The diagnostic criterion for BROMJ was osteomyelitis in patients with experience of bisphosphonate therapy. The amount and duration of bisphosphonate administration and presence and term of bone exposure were not considered for diagnosis. Results: BROMJ revealed characteristic radiographic findings. Osteolytic change that started at the superficial layer of bone (cortical bone), followed by extension between the cortical and cancellous bone, large cancellous bone sequestrum formation often accompanied by extensive osteolytic change of the cortical bone or fairly large cortical bone sequestrum formation, and solid-type periosteal reaction formed at a site related to the margin of the remaining cortical bone were found to be pathognomonic, and were observed not only in cases with bone exposure but also in cases without bone exposure. A relationship between lamina dura thickening and the lesion was doubtful. Osteosclerotic change was frequent and remarkable, but not specific. Conclusions: Radiographic examination was considered to be useful for differential diagnosis of BROMJ. Inclusion of the pathognomonic radiographic findings into the definition of BROMJ will make it possible to achieve earlier and more accurate diagnoses. In addition, the active bone remodeling in the lesions confirmed by radiography suggested that osteonecrosis was not the cause, but the result of infection. [ABSTRACT FROM AUTHOR]

This review gives an overview of the factors that may play a role in the development of osteonecrosis of the jaw in patients treated with bisphosphonates ( BPs) and undergoing nonsurgical endodontic treatment as well as some recommendations for its prevention. BPs are a widely prescribed group of drugs for diverse bone diseases. The occasional but devastating adverse effect of these drugs has been described as bisphosphonate-related osteonecrosis of the jaw ( BRONJ). As this condition is debilitating and difficult to treat, all efforts should be made to prevent its occurence in patients at risk. The main triggering event is considered to be dental extraction. Even though nonsurgical endodontic treatment appears to be a relatively safe procedure, care remains essential. After an overview of this class of drugs, the clinical presentation, epidemiology and pathogenesis of BRONJ, as well as the possible risk factors associated with its development after nonsurgical endodontic treatment will be described. Finally, several strategies will be proposed for the prevention of BRONJ during nonsurgical endodontic treatment. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to (1) evaluate the fractal dimension (FD) in regions of the mandible on cone beam CT (CBCT) images of patients with bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) and (2) to select the most suitable region of interest (ROI) for further study on detection of bone alterations associated with bisphosphonates. Methods: CBCT images of patients with BP-ONJ were included with matched controls. Values of FD were compared between groups. Selected ROIs were: ROI-1 --below the mandibular foramen; ROI-2 -- above the mandibular foramen; ROI-3 -- anterior to the mental foramen; ROI-4 -- above the mandibular canal. The area of bone exposure was included as ROI-5. The results were analysed using generalized estimating equations and conditional logistic regression. Results: There were 36 patients (67% female) with a mean age of 60.7 years. The mean FDs were: ROI-1 -- 1.678 for controls and 1.673 for patients (P 5 0.81); ROI-2 -- 1.657 for controls and 1.653 for patients (P 5 0.78); ROI-3 -- 1.661 for controls and 1.684 for patients (P 5 0.17); and ROI-4 -- 1.670 for controls and 1.698 for patients (P 5 0.03). The value of the FD in the area of exposed bone was the highest (1.729). The odds of being a BPONJ patient vs being a control was six times as high for individuals with a higher FD score at ROI-4, although the confidence interval was quite wide owing to the small sample size. Conclusion: In this preliminary study, BP-ONJ patients had higher FD values than controls at regions close to the alveolar process. The results suggest that FD is a promising tool for detection of bone alterations associated with BP-ONJ. [ABSTRACT FROM AUTHOR]

Nitrogen-containing bisphosphonates have been associated with the development of osteonecrosis of the jaws (ONJ), but the lack of reliable epidemiological data and appropriate animal models has restricted our understanding of ONJ pathophysiology and limited its management. The best available information is from histopathologic findings, which implicate bone necrosis and infection, although it is not clear which is primary. However, there are data suggesting that macrophages could well be the central factor in allowing the infection to develop first, followed by local necrosis, which could also account for the development of ONJ in patients treated with denosumab, a human monoclonal antibody to the receptor activator of nuclear factor-κB ligand. This review examines the evidence that macrophages could play a prominent role in development of ONJ and the proposal that it may be more appropriate to view ONJ as a drug and not only a bisphosphonate-related complication. [ABSTRACT FROM PUBLISHER]

Bisphosphonates (BPs) have been widely, efficiently, and safely used for the treatment of osteoporosis, malignant hypercalcemia, bone metastasis of solid cancers, and multiple myeloma bone diseases. Accumulating recent reports describe that surgical dental treatments in patients with cancer or osteoporosis who have been receiving intravenous or oral BPs are associated with osteonecrosis of the jaw (bisphosphonate-related osteonecrosis of the jaw, BRONJ). The accurate incidence, clinical backgrounds, and pathogenesis of BRONJ have been unclear and appropriate approaches for prevention and treatment have not been established to date. To address the current situation of BRONJ in Japan, the "Allied Task Force Committee of Bisphosphonate-Related Osteonecrosis of the Jaw," consisting of physicians specializing in bone biology, orthopedic surgery, rheumatology, obstetrics/gynecology, and medical oncology and dentists specializing in oral surgery, periodontology, dental radiology, and oral pathology, was organized. The committee attempted to propose a standard position paper for the treatment of BRONJ. The committee expects that this proposal will provide objective and correct scientific information on BRONJ and will serve as a reference for conducting dental procedures for patients receiving BPs and in designing prevention and treatment of BRONJ. However, because this position paper is not based on direct clinical evidence, it should be used as a reference, and a decision on treatment in each case should be made after an extensive discussion among physicians, dentists/oral surgeons, and the patients. [ABSTRACT FROM AUTHOR]

It was the aim of the present study to find out which radiological imaging techniques allow assessing the extent of bisphosphonate-associated osteonecrosis of the jaw (BONJ) in an adequate way. Twenty-four patients suffering from BONJ were included in the study. Before surgery, each patient was examined with panoramic radiograph, contrast-enhanced magnetic resonance imaging (MRI) and non-enhanced computed tomography. The detectability of BONJ was assessed for the three imaging techniques. The extent of the jaw region affected by BONJ was determined in MRI and CT scans and compared to the intra-operative situation. The detectability of BONJ lesions was 54% for panoramic radiographs, 92% for MRI scans and 96% for computed tomography (CT) scans. The intra-operatively assessed extent of BONJ correlated significantly with the measurements on CT scans ( p = 0.0004) but did not correlate significantly with the measurements in MRI scans ( p = 0.241). The intra-operatively measured extent of BONJ differed significantly from the CT measurements ( p = 0.00003) but not from the MRI data ( p = 0.137). Although MRI as well as CT have a high detectability for BONJ lesions that exceeds that of panoramic radiographs by far, both techniques show problems with the exact assessment of the extent of BONJ lesions in the individual patients. Therefore, the relevance of MRI and CT for the preoperative assessment of the extent of BONJ lesions is limited. Future research should focus on the identification of imaging techniques that allow assessing the extent of BONJ lesions with a higher accuracy. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 39: 390–396 The aim of this study was to evaluate a novel animal model of bisphosphonates-associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm-diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach. [ABSTRACT FROM AUTHOR]

Abstract  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 ∼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. [ABSTRACT FROM AUTHOR]

Objectives: To determine the extent to which clinical and radiographic features of bisphosphonate-associated osteonecrosis of the jaw (BONJ) are correlated. Design: Retrospective case review. Methods: The records of 39 patients diagnosed with BONJ and examined by panoramic radiography were retrospectively evaluated. The arches were divided into sextants ( n = 234) and evaluated for the following signs: sclerosis, surface irregularity, sockets, fragmentation and lysis. Main outcome measures: The McNemar, Kruskall–Wallis and equivalency tests were performed to analyze the association between clinical and radiographic signs and BONJ severity. Results: Sixty-two out of 234 sextants were abnormal by clinical criteria and 61 out of 234 sextants demonstrated at least one radiographic abnormality. There was agreement between clinical and radiographic detection in 41 sextants. The data showed equivalency between BONJ diagnosis and both sclerosis and surface irregularity. The correlation between number of clinical sites and any radiographic finding was significant in the maxilla ( P < 0.001) but not in the mandible ( P = 0.178). The total number of radiographic signs per patient increased with BONJ stage. Conclusion: Focal panoramic radiographic findings of sclerosis and surface irregularity correlate with clinical sites of BONJ. This may be a useful and reliable tool to detect early changes of BONJ or to confirm a clinical diagnosis. [ABSTRACT FROM AUTHOR]

The article reflects on bisphosphonate-associated osteonecrosis of the jaws (ONJ). It was primarily associated with intravenous bisphosphonates such as zoledronate and palmidronate, used for the control of meta-static cancer to the bones, malignant hypercalcemia and multiple myeloma. However, cases of ONJ have been reported in patients with osteoporosis being treated with oral bisphosphonates such as alendronate, ebandronate and residronate.

Bisphosphonate therapy has been shown to significantly reduce the incidence of skeletal complications in patients with myeloma. Several recent reports have described osteonecrosis of the jaw (ONJ) associated with bisphosphonates. These reports mainly demonstrate an association between ONJ and potent i.v. bisphosphonates. We report a case of ONJ in a patient with myeloma, who had only been treated with oral sodium clodronate. While the degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as clodronate, remains uncertain it would be prudent to consider carefully the indications for the use of these agents to minimise the risk of ONJ. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonate (BP) has the ability to thicken the cortical bone. In addition, it has been reported that the cortical bone thickened by BP has relation to the medication-related osteonecrosis of the jaw (MRONJ). Therefore, the objective of this article is to analyze the ratio as well as thickness of cortical bone in the mandible using computed tomography (CT) and to evaluate it as the predictive factor of MRONJ.Methods: The thickness of the cortical bone was measured on a paraxial view of the CT showing the mental foramen in 95 patients: 33 patients with MRONJ (3 males, 30 females), 30 patients taking BP without MRONJ (2 males, 28 females), and 32 controls (9 males, 28 females). Also, the ratios of the cortical bone to the total bone were obtained using the measured values. Based on these results, we compared the difference of mandibular cortical bone ratio between the three groups.Results: The average cortical bone thickness was measured as 3.81 mm in patients with MRONJ, 3.39 mm in patients taking BP without MRONJ, and 3.23 mm in controls. There was only a significant difference between patients with MRONJ and controls (P < 0.05). On the other hand, the average mandibular cortical bone ratio was measured as 37.9% in patients with MRONJ, 27.9% in patients taking BP without MRONJ, and 23.3% in controls. There was a significant difference between all groups (P < 0.05).Conclusion: The mandibular cortical bone ratio is large in order of patients with MRONJ, patients taking BP without MRONJ, and controls. This result suggests that the mandibular cortical bone ratio would be very useful to predict the development of MRONJ. [ABSTRACT FROM AUTHOR]

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ)/medication-related osteonecrosis of the jaw (MRONJ) include both bisphosphonate-related osteonecrosis of jaw (BRONJ) and denosumab-related osteonecrosis of jaw (DRONJ). The purpose of this study is to study radiological characteristics of ARONJ/MRONJ. These imaging features may serve as one useful aid for assessing ARONJ/MRONJ. CT scans of 74 Japanese patients, who were clinically diagnosed by inclusion criteria of ARONJ/MRONJ, obtained between April 1, 2011 and September 30, 2016, were evaluated. We investigated the CT imaging features of ARONJ/MRONJ, and clarified radiological differentiation between BRONJ and DRONJ, BRONJ due to oral bisphosphonate administration and due to intravenous bisphosphonate administration, BRONJ with respective kinds of medication, BRONJ with long-term administration and short-term administration, BRONJ with each clinical staging respectively. Fisher's exact test, χ2 test, Student's t-test and analysis of variance were performed in the statistical analyses. Unilateral maxillary sinusitis was detected in all patients with upper ARONJ/MRONJ (100%). DRONJ showed large sequestrum more frequently than BRONJ (3/4, 75 vs 3/35, 8.6%, p < 0.05). DRONJ showed periosteal reaction more frequently than BRONJ (4/10, 40 vs 7/65, 10.1%, p < 0.05). Patients of BRONJ resulting from intravenous bisphosphonate administration showed larger and more frequent buccolingual cortical bone perforations than BRONJ resulting from oral bisphosphonate administration (7/8, 87.5 vs 11/30, 36.7%, p < 0.05). There was no significant correlation between CT findings and respective kinds of medication, long/short-term administration, clinical stages of BRONJ. ARONJ/MRONJ has characteristic CT image findings which could be useful for its assessment. [ABSTRACT FROM AUTHOR]