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Technetium 99m Bone scintigraphy. Bone scan showing increased radioactive uptake in the body of the mandible (arrow) thought to be metastatic disease.
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Osteonecrosis of the jaw is usually a potential complication of bisphosphonate therapy. In a cancer patient, this disease entity can be misdiagnosed as a metastatic lesion. Our aim is to make clinicians aware of bisphosphonate associated osteonecrosis of the jaw to prevent misdiagnosis and initiate proper treatment at the earliest. We present the c...
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Background: medication related osteonecrosis of the jaw (MRONJ) is a chronic condition of the oral cavity resulting in mucosal ulceration and exposure of underlying necrotic bone, and the ensuing secondary complications. The aim of this study was to evaluate the relationship between vitamin D deficiency and osteonecrosis of the jaw related to bisph...
An 83-year-old woman underwent mastectomy for breast cancer of the right breast in 2008. In addition to hormone therapy and irradiation, zoledronate was started for bone metastasis 6 months postoperatively. Five years after the operation, the patient developed osteonecrosis of the jaw, and underwent sequestrectomy because of uncontrollable pain in...
Background:
With the frequent use of Bisphosphonates (BPs), the morbidity of BP-related osteonecrosis of the jaw (BRONJ) is also increasing. However, the prevention and treatment of BRONJ is faced with enormous challenges. This study aimed to illuminate the influence of BP administration in the rat mandible and explore the feasibility of discrimin...
Medication-related osteonecrosis of the jaw (MRONJ) is an adverse drug reaction that affects the mandible and maxilla of patients exposed to bone-targeting agents (anti-resorptive and anti-angiogenic agents). Bone lesions in multiple myeloma require bisphosphonate treatment. Particularly, the aim of this abstract is to report a successfully treated...
The main aim of the present report is to show the potential utility of bone scintigraphy for the diagnosis of jaw osteonecrosis. We report the history of a 62-year-old woman underwent breast cancer surgery in 2010. Moreover, patient received postoperative radiotherapy and chemotherapy. Intravenous bisphosphonates were also added to the treatment st...
Citations
... Mauceri et al. (48) also described 3 cases of oral SCC presented intraorally as exposed jaw bone mimicking BRONJ in patients receiving per os bisphosphonates, while Arduino et al. (49) reported a case of oral SCC arising adjacent to an area of long-term BRONJ associated with IV zolendronic acid therapy, following hematopoietic stem cell transplantation for acute myeloid leukemia. Vice versa, it should be kept in mind that BRONJ lesions may mimic malignancy, as in the case presented by Bhatt et al. (50) in which a patient with metastatic breast cancer on IV alendronate developed a painful mandibular lesion, which was deemed compatible with metastatic focus on the basis of the clinical and imaging features alone and was initially managed with radiation therapy with lack of response; a subsequent biopsy did not show evidence of metastatic disease and a diagnosis of BRONJ was eventually made. Likewise, Pancholi et al. (51) reported on a case of BRONJ mimicking oral SCC in a female patient on bisphosphonates for metastatic breast cancer, and Tocaciu et al. (52) described two cases of osteolytic lesions in the mandible in patients receiving low dose bisphosphonates causing significant confusion between MRONJ or SCC, before the latter diagnosis was definitively made, but with considerable delay, based on careful histopathologic examination (in one case requiring repeat biopsies and evaluation of the final surgical specimen). ...
Lymphoma is the second most common malignancy in the head and neck area, affecting both nodal and extranodal sites, including oral soft and hard tissues, usually in the form of non-Hodgkin’s lymphoma (NHL). However, lymphomas of the jaws, including diffuse large B-cell lymphoma (DLBCL), the most common type of NHL, are very rare and may cause significant diagnostic challenges resembling common jaw pathologies, such as periapical lesions, osteomyelitis and osteonecrosis. The aim of this paper is to present a rare case of DLBCL in an 84-years-old diabetic male patient on methylprednisolone treatment for autoimmune hemolytic anemia. The lesion appeared clinically as exposed necrotic bone of the maxilla with surrounding soft tissue ulceration and radiographically as an extensive osteolytic lesion with ill-defined borders. Despite the resemblance of the lesion with osteonecrosis or osteomyelitis that could be theoretically related to diabetes and/or systemic use of corticosteroids, histopathologic examination, necessitating a repeat biopsy in order to acquire sufficient tissue, revealed the final diagnosis of lymphoma. The need for increased clinical awareness and vigilance of this possible diagnostic conundrum is emphasized.
Key words:Diffuse large B-cell lymphoma, exposed bone, oral, malignancy, maxilla, jaw osteonecrosis, differential diagnosis.
... However, the risk of complications such as medication-related osteonecrosis of the jaw (ONJ) and atypical femoral fracture increases due to the long skeletal retention time of BPs (3). The incidence of osteonecrosis of the jaw (ONJ) among patients with cancer and metastatic bone disease being treated with bisphosphonates is as high as 10%, which dictates that an understanding of the risk factors, preventative measures, means of early diagnosis, and treatment is critical, despite ONJ occurring in the clinical setting of intravenous bisphosphonates (4,5). ONJ could occur in patients with underlying comorbidities and not receiving BP treatments. ...
Background
A causal relationship of bisphosphonate (BP) exposure with osteonecrosis of the jaw (ONJ) has been reported; however, a definite dose-dependent risk remains to be elucidated beyond current vague recommendations of 4-year oral BP for ONJ risk increase.
Objective
To identify the effect of bisphosphonate cumulative dose on ONJ development in women with osteoporosis.
Methods
A retrospective cohort study was designed using the National Health Insurance Service—National Health Screening database of Korea. Females over the age of 50 were diagnosed with osteoporosis based on the International Classification of Diseases 10th revision (ICD-10) codes (M80, M81, and M82) with bisphosphonate prescriptions. The cumulative dose of bisphosphonate was calculated using defined daily doses (DDD) to provide an accurate BP cumulative effect on ONJ occurrence. Osteonecrosis of the jaw was identified using both ICD-10 codes and related procedure codes. The incidence rates of ONJ and hazard ratios were estimated according to the bisphosphonate cumulative dose.
Results
Among 74,491 included subjects, 190 cases of ONJ were identified. The incidence rate substantially increased after BP cumulative dose over 1 year (25.75 for DDD < 365, which increased to 53.43 for 365 ≤ DDD < 730). Compared to subjects with a cumulative dose of DDD < 365, subjects with a cumulative dose of 365 ≤ DDD < 730 had 2.36-fold hazard for developing ONJ (p < 0.001).
Conclusion
A bisphosphonate cumulative dose of more than 1 year had an increased risk of ONJ development. A gradual, but not sudden, dose-dependent increase in ONJ risk with BP exposure needs to be considered in providing the optimal BP treatment duration.
... [31][32][33][34][35][36][37][38][39][40][41][42][43] List of Excluded Studies 17 studies were initially considered to be potentially eligible for inclusion, but after inspection of the full papers, 4 were excluded for not meeting the inclusion criteria for this review (Figure 1). [44][45][46][47] Study subjects and MRONJ data analysis Where data was present but not clear, this was reported as 'unclear'. Where data was not included, this was reported as 'Not reported'. ...
... Study flow diagram. * The excluded articles were: (n=2) case reports; (n=1) retrospective analysis; (n=1) unclear nature of the study.[44][45][46][47] ...
Introduction
Osteonecrosis of the jaw (ONJ) is reported to be primarily associated with patients receiving bisphosphonate (BP) therapies, but has been found in patients taken a number of other medications. A number of recent reports have noted the presence of metastatic cancers in the histological analysis of osteonecrotic lesions from the jaw. The aim of the present review is to estimate the frequency and the type of metastatic cancer most commonly found in ONJ specimens in patients undergoing antiresorptive and/or antiangiogenic drug therapy.
Material and Methods
A multi-database (PubMed, MEDLINE, EMBASE, and CINAHAL) systematic search was performed. Any studies involving human participants treated with antiresorptive and antiangiogenic drugs were considered. Where study subjects presented with malignant cells within osteonecrotic specimens, further data were collected. Data was presented using descriptive statistics
Results
A total of 13 studies met the inclusion criteria for this systematic review. Thirty-seven study subjects had histological evidence of malignant cells within MRONJ specimens. The most frequent phenotype of malignant cells found within MRONJ specimens were breast cancer variants (n=15). The frequnecy of malignant tumour cells found within the MRONJ specimens was calculated using 4 studies. Out of 604 subjects, the frequency was 4.64% (n=28).
Conclusions
Based on the limited data available in literature, it is plausible that not histologically analysing all ONJ specimens could result in a small amount of undiagnosed and untreated malignant diseases. Additional data based on a larger cohort of study subjects is necessary to understand the role of MRONJ in metastatic spread and the influence of surgical treatment and reoccurrence.
... In cancer patients, receiving intravenous bisphosphonate therapy, ONJ can be easily mistaken for a metastatic lesion due to its clinical presentation and imaging characteristics. [10] The practicing oncologist, the radiologist, the nuclear medicine specialist, and the dental specialist must all be aware of BRONJ as an entity mimicking bone metastasis. Early recognition will facilitate early diagnosis, minimize the need for biopsies, and multiple unnecessary imaging studies, and most importantly, allow appropriate treatment measures to be initiated. ...
Context: Owing to the increasing number of cancer cases, and introduction of newer drugs like bisphosphonates (BP) for the management of metastatic bone disease, complications such as bisphosphonate‑related osteonecrosis of the jaw (BRONJ) have come into light. However, several of the treating physicians are not fully aware of this adverse effect. Aim: This study aimed to assess the knowledge and awareness of physicians regarding BRONJ and practices related to bisphosphonate use. Settings and Design: A cross‑sectional study conducted among health‑care professionals in various medical institutions in Mangalore. Subjects and Methods: A questionnaire was developed to assess the knowledge and awareness of physicians about osteonecrosis of the jaw and practices related to bisphosphonate use, consisting of 21 questions, 12 – knowledge based and 9 – practice based. The questionnaire was validated and distributed among 113 doctors; their responses assigned scores, tabulated and assessed. Statistical Analysis: One‑way analysis of variance and Tukey test. Results: More than 50% of the medical professionals had a score <40%, which shows a lack of knowledge about BP and BRONJ. About 45% of the medical professionals in the study group failed to identify the clinical features of BRONJ, and 67.26% were unaware of the risk associated with tooth extractions and oral surgical procedures in the development of the condition. Conclusion: Bisphosphonate‑related osteonecrosis is almost exclusively seen in the jaws and hence, the diagnosis usually made by a dental practitioner. Lack of awareness of jaw osteonecrosis among the medical practitioners can result in delay in providing the right treatment
... 27 ). For the differential diagnosis of osteonecrosis of the jaw using bisphosphonate therapy or metastasis to the jaw, the use of SPECT/CT is needed 28 . ...
Background:
The increasing incidence of breast cancer worldwide raises the importance of improving imaging techniques for disease stratification after early lesion detection. SPECT/CT imaging is now widely available but its diagnostic potential is not fully utilized for more specific purposes including breast cancer patient stratification.
Methods and results:
A Pubmed search for both original and review articles related to the value of SPECT/CT in breast cancer patients and comparison to other diagnostic methods. 62 articles were found using the key words SPECT/CT, Fusion Image and Breast Cancer. Development of a new generation of SPECT/CT systems and their introduction into practice has changed the old diagnostic algorithm. The increasing importance of SPECT/CT in the detection of bone metastases is confirmed. The diagnostic accuracy of new SPECT/CT instruments in the diagnostics of bone metastases is nearly comparable to PET/CT scans. SPECT/CT is more widely available and costs less than PET. It is able not only to identify a sentinel lymph nodes in atypical localizations but also to detect sentinel lymph nodes non visualized on previous planar scans. SPECT/CT offers precise anatomic localization of sentinel lymph nodes, thereby facilitating surgery. Knowledge of precise sentinel lymph node localization can also be applied in radiotherapy.
Conclusions:
The role of hybrid SPECT/CT imaging in breast cancer patients is changing. It is a powerful modality for skeletal and nodal staging in breast cancer patients with important impact on therapy.
... Diagnosis of ONJ is usually made through history-taking and clinical examination McLeod et al., 2012;Khan et al., 2015). Biopsy is not mandatory but can be useful for excluding other jawbone disorders, such as metastasis (Khosla et al., 2007;Arrain and Masud, 2011;Bhatt et al., 2014). Although there is no specific imaging features for ONJ, it remains helpful in differential diagnosis and disease staging (Khan et al., 2015). ...
Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates. It can cause persistent pain and infection to the jawbones, and is currently considered incurable. ONJ occurs in a subset of individuals exposed to bisphosphonates (≤7%). Although a number of clinical risk factors, such as dentoalveolar surgery and dental infection, can increase the risk of ONJ development, there remains a number of patients who do not present with these clinical risk factors. Therefore, a genetic predisposition has been proposed. Genome-wide association studies (GWAS), widely performed in pharmacogenomics and successful in other drug side effects, have also been attempted in bisphosphonates-associated ONJ. However, possibly due to small cohort sizes (≤30 cases), these studies failed to detect any significant genetic risk factors. The aim of this thesis is to present the results of a large, multicentre GWAS, coupled with detailed analyses of clinical phenotype. 393 ONJ cases were recruited from 23 clinical centres worldwide. All cases were thoroughly phenotyped and adjudicated by specialist multidisciplinary teams. Random effects logistic regressions (Stata v12.1) were used for clinical risk factor analyses. All samples were genotyped using Illumina® Human1M Omni Express Beadchip (1,072,820 probes) and were compared with 2,554 genetically-matched population controls from publicly available sources. Genotype statistical analysis was performed in PLINK. Risk factors including advanced age, longer bisphosphonates duration, other cancers and use of steroids were found statistically significant (p<0.05). With extreme phenotyping, i.e. non-surgery triggered ONJ cases versus the population controls, for the first time, a genome-wide significant single nucleotide polymorphism was identified: rs12440268 at TJP1 gene (p=1.21E-8). Individuals positive for this marker were nearly three times more likely to develop ONJ than those negative for it (OR=2.66). TJP1 encodes protein at the tight junctions, which maintain epithelial integrity. Its polymorphism may contribute to ONJ pathogenesis through impaired mucosal healing.
... Most of them considered that it is associated with a previous radiation therapy to the affected region, as well as a local evidence of malignancy to the affected region. This suggests that most clinical physicians surveyed were confused between the bisphosphonate-related ONJ and two differential diagnoses: the osteoradionecrosis [19] and bone tumors or metastases to the jaw [20,21]. This confusion could be partially explained by the high frequency of this complication among cancer sufferers [15,18,22]. ...
... Most of them considered that it is associated with a previous radiation therapy to the affected region, as well as a local evidence of malignancy to the affected region. This suggests that most clinical physicians surveyed were confused between the bisphosphonate-related ONJ and two differential diagnoses: the osteoradionecrosis [19] and bone tumors or metastases to the jaw [20,21]. This confusion could be partially explained by the high frequency of this complication among cancer sufferers [15,18,22]. ...
Purpose: Bisphosphonate-induced osteonecrosis of the jaw (ONJ) is a potentially destructive complication, particularly encountered in oncology. It is supposed that awareness and good knowledge of this disease by physicians are important factors of its early detection and management. This study aims to evaluate the level of knowledge among a sample of Lebanese physicians with regard to this complication.
Methods: An observational cross-sectional study was conducted at Hôtel-Dieu de France hospital between March and June 2013. Data were collected through a self-administered questionnaire distributed to 190 eligible physicians in the departments involved in prescribing bisphosphonates and managing the ONJ.
Results: A total of 136 valid responses were obtained (response rate 71.6 %). Eighty-six (63.2 %) physicians were treating patients with bisphosphonates: the most prescribed form being the weekly oral bisphosphonates for osteoporosis followed by zoledronate several times yearly for bone malignancies. Fifty-one (37.5 %) participants were unaware of bisphosphonate-relatedONJ. Furthermore, the level of knowledge was relatively poor: the mean score of all participants was 12.42±10.08, while 77 (56.6 %) had a global score more than 16 over 30. There were statistically significant associations between the level of knowledge and physicians’ specialty (p value <0.0001), whether or not they prescribe bisphosphonates (p value=0.039), the most frequently form prescribed (p value=0.048), whether or not they attend patients already on bisphosphonate (p value=0.047), whether or not they have observed (p value=0.004) and treated (p value=0.002) exposed necrotic bone of the jaw.
Conclusions: Our study revealed a deficient knowledge regarding bisphosphonate-related ONJ among Lebanese physicians. Appropriate training strategies to increase their awareness are required.
Los bifosfonatos son un grupo de medicamentos análogos al pirofosfato inorgánico clasificados como antirresortivos. Su mecanismo de acción es inhibir la resorción ósea llevada a cabo por los osteoclastos e inducir su apoptosis. Indicados en la prevención y tratamiento de enfermedades metabólicas óseas (osteoporosis, enfermedad de Paget), enfermedades óseas malignas (hipercalcemia, mieloma múltiple) y metástasis ósea por cáncer de mama y próstata. Los efectos secundarios reportados son: úlceras gástricas, esofagitis, conjuntivitis, uveítis y osteonecrosis de los maxilares. Esta última se define como la exposición de hueso necrótico por más de ocho semanas en pacientes con historial de uso de bifosfonatos y que no han recibido terapia de radiación en cabeza o cuello. En los últimos años se han empleado nuevos agentes antirresortivos y antiangiogénicos relacionados también con la osteonecrosis de los maxilares. La Asociación Americana de Cirugía Oral y Maxilofacial propuso cambiar el nombre de osteonecrosis de los maxilares relacionada con bifosfonatos por osteonecrosis de los maxilares relacionado con medicamentos; aunque los más prescritos actualmente siguen siendo los bifosfonatos. Esta revisión narrativa de la literatura tiene como objetivo describir el diagnóstico, tratamiento y prevención de la osteonecrosis de los maxilares relacionado al uso de bifosfonatos.
