Osteonecrosis of the jaw associated with pembrolizumab.

We report a case of osteonecrosis of the jaw (ONJ) with pembrolizumab, a rare yet possibly emerging complication. In this case, a temporal relationship between the development of ONJ and the patient's treatment regimen suggested an association between pembrolizumab/GVD therapy and the development of ONJ. Thrombocytosis and anatomic factors may also have played a role. The number of patients using pembrolizumab will likely continue to increase. We document this instance in order to better inform dental treatment around cancer patients undergoing pembrolizumab therapy.

Florid Cemento-Osseous Dysplasia with a Concurrent Glandular Odontogenic Cyst.

The presence of non-odontogenic cysts associated with benign fibro-osseous lesions of the jaws has been well documented. However, literature is scant when describing benign fibro-osseous lesions with associated odontogenic cysts. This case report highlights the presence of a concurrent developmental odontogenic cyst, glandular odontogenic cyst with extensive squamous metaplasia, in a patient with florid cemento-osseous dysplasia (COD). The postulated pathogenesis of these synchronous lesions is discussed along with a review of current literature. Surgical treatment is discouraged for florid COD, however, radiological follow-up is recommended, especially in lesions with associated cysts.

ACE Gene Variant Causing High Blood Pressure May Be Associated With Medication-related Jaw Osteonecrosis.

The association of the high blood pressure D variant of the angiotensin-converting enzyme (ACE) gene with medication-related jaw osteonecrosis (MRONJ) is described in two Greek patients. The first patient, a 73-year-old man, took zolendronate, 4 mg/100 ml IV once per month for two years for prostate cancer and bone metastases. Three months after drug discontinuation, extraction of the first premolar was performed. After the intervention, he suffered from osteonecrosis of the mandible. He presented with hypertension and genetic testing revealed that he was homozygous for the high blood pressure D variant of the ACE gene. The second patient, a 65 years old woman, took denosumab, 120 mg subcutaneously once per month for 6 months for possible bone metastases from breast cancer. Three months after extraction of the first molar, she suffered from MRONJ. He also presented with hypertension and genetic testing revealed that she had the high blood pressure D variant of the ACE gene in a heterozygous state, which moderately predisposes to hypertension. To our knowledge, this is the first report indicating that genetic predisposition to hypertension may increase risk for MRONJ.

Comorbid conditions are a risk for osteonecrosis of the jaw unrelated to antiresorptive therapy.

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is commonly associated with antiresorptive therapy. There have been numerous reports of ONJ unrelated to antiresorptive therapy (ONJuat), confounding risk assessment. This study aimed to determine if ONJuat is associated with one or more particular comorbidities. STUDY DESIGN: This was a retrospective case-control study of patients with ONJuat and delayed healing (DH). Each case was matched for patient age and gender, as well as location of ONJuat or DH lesion to a control patient who had a history of dentoalveolar surgery with uneventful healing and no history of antiresorptive therapy. Comorbidity data included medical conditions and smoking. RESULTS: Of the 92 patients identified, 67 (73%) met the criteria for ONJuat and 25 (27%) for DH. The most common trigger for ONJ and DH was extraction (50%). The presence of any comorbidity (i.e., at least 1) was more prevalent in ONJuat than among controls (P = .04), and there were more comorbidities in patients with ONJuat and DH than in controls [M(SD) = 1.94 (1.2) and 2.0 (1.3) vs 1.26 (0.89); both P < .001]. CONCLUSIONS: ONJ and DH are not limited to patients with a history of antiresorptive therapy. More comorbidities may signal increased risk for ONJuat and DH.

Giant cell lesion of the jaw as a presenting feature of Noonan syndrome.

This is a case of a 20-year-old woman who presented with a left jaw mass which was resected and found to be a giant cell granuloma of the mandible. Her history and physical examination were suggestive for Noonan syndrome which was confirmed with genetic testing and the finding of a PTPN11 gene mutation which has rarely been associated with giant cell lesions of the jaw. Given her particular genetic mutation and the presence of a giant cell lesion, we present a case of Noonan-like/multiple giant cell lesion syndrome.

Association Between Marginal Jawbone Loss and Onset of Rheumatoid Arthritis and Relationship to Plasma Levels of RANKL.

OBJECTIVE: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti-citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls. METHODS: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme-linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity. RESULTS: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01-1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL-positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA. CONCLUSION: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL-positive presymptomatic subjects compared with RANKL-negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.

Dental treatments, tooth extractions, and osteonecrosis of the jaw in Japanese patients with rheumatoid arthritis: results from the IORRA cohort study.

This study aimed to evaluate dental treatments, tooth extractions, and osteonecrosis of the jaw (ONJ) in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in our cohort completed self-administered questionnaires, which included questions regarding their dental treatments, tooth extractions by dentists during the past 6 months, and past history of ONJ. The history of ONJ was validated with the patients' medical records. Logistic regression was used to determine the association of variables with dental treatments and tooth extractions during the past 6 months. Among 5695 Japanese patients with RA who responded to the questionnaires (mean age, 61.0 years; 85.6 % female), 2323 patients (40.8 %) and 378 patients (6.6 %) reported having had dental treatments and tooth extractions performed by a dentist within the past 6 months, respectively. In multivariate models, advanced age was significantly (P < 0.0001) associated with both dental treatments and tooth extractions during the prior 6-month period, and ever smoking was significantly (P = 0.023) correlated with tooth extractions during that time. Among patients who reported a history of ONJ, we confirmed five cases of ONJ with patient medical records. The prevalence of ONJ was 0.094 % among all RA patients and 0.26 % among female RA patients ≥65 years of age (n = 1888). Our data suggest that more than a few Japanese patients with RA have dental complications that require care by dentists, and that Japanese rheumatologists and dentists should cooperate to improve dental health in patients with RA.

Management challenges with brown tumor of primary hyperparathyroidism masked by severe vitamin D deficiency: a case report.

BACKGROUND: Hyperparathyroidism is a disease characterized by excessive secretion of parathyroid hormone, the hormone responsible for calcium and phosphate homeostasis in the body. It can be of three types: primary, secondary, or tertiary. It is essential to bear in mind that in any one patient more than one type of hyperparathyroidism may be found, which may create perplexity regarding the etiology of the case. Hyperparathyroidism can become apparent early in its course when a patient presents with symptoms of abdominal pain, recurrent renal calculi, repeated fractures, or behavior changes. It is generally accepted that bone involvement is a late manifestation of primary hyperparathyroidism. It is imperative to consider that some patients, such as our patient described in this report, may be previously asymptomatic clinically and on the basis of laboratory findings and present with only late skeletal manifestations. Brown tumors are one of the mimickers of lytic lesions of the jaw and need to be ruled out early in the course of management. Researchers in several studies published in high-impact journals have recommended the use of high-dose vitamin D as safe in patients with primary hyperparathyroidism without the risk of raising calcium levels significantly. In our patient, we observed considerable hypercalcemia after high-dose vitamin D therapy, and we propose exercising discretion with the use of high-dose therapies. CASE PRESENTATION: We report a case of a 21-year-old Arab woman with a brown tumor who presented with hypocalcaemia. She presented with a mixed picture of primary hyperparathyroidism and severe vitamin D deficiency. CONCLUSIONS: Brown tumors, although thought to be a forgotten entity with the advent of early screening for hypercalcemia, is still prevalent, as a handful of patients may present late in the disease course with no early markers, such as in our patient. We emphasize using a holistic approach for early diagnosis and adopting a restricted attitude to treating these benign entities, especially in the context of cosmesis for sensitive locations such as the face. In addition, we express caution in using daily supplementation with a high vitamin D dose to improve vitamin D status and decrease parathyroid hormone.

[Pneumomediastinum Due to the Fracture of the Maxillary Antrum].

A 47-year-old man was admitted to the emergency room, half a day after having fallen down on his right cheek drunkenly onto a concrete block. Physical examination revealed that the contusion was limited to the right side of his face, only around the cheek, without trauma to the neck, chest or abdomen. But wide ranging tactile crepitus with severe swelling was present on his face and neck due to widely spread emphysema. Computed tomography (CT) scan revealed some fractures of maxillary antrum, facial and cervical emphysema spreading to the lower part of mediastinum. After a conservative treatment, he recovered without any severe systematic complication. It was found that the facial and cervical emphysema and pneumomediastimum completely disappeared on the follow-up CT scan, 18 days after the event.

Secondary jaw aneurysmal bone cyst (JABC)--a possible misnomer? A review of literature on secondary JABCs, their pathogenesis and oncogenesis.

CONTEXT: Aneurysmal bone cysts are rare pseudocysts, commonly seen in long bones and vertebral column. Although a well described and reported lesion, many misconceptions still prevail regarding their etiopathogenesis. Many of the reported cases of jaw aneurysmal bone cysts (JABC) present with another bone pathology. AIMS: The purpose of this review was to evaluate the incidence of neoplastic lesions occurring simultaneously with a JABC (in contrast to primary JABCs). Any pathogenetic and oncogenetic association between primary and secondary jaw ABCs has been reviewed and discussed. SETTINGS AND DESIGN: A methodical narrative review of literature was performed, given the incidence of mostly case reports on this topic. METHODS AND MATERIAL: A methodical electronic search of Pubmed, Pubmed Central, Medline and Cochrane databases was performed for reported cases of JABC. These articles were analysed and segregated into primary and secondary ABC and, if secondary, the lesion it concurrently occurred with. Another search was conducted to yield articles discussing the cytopathogenetic and oncogenetic origins of ABCs. RESULTS AND CONCLUSIONS: About 15% of the ABCs reported were of secondary nature. Amongst the associated lesions, cement-ossifying fibroma and ossifying fibroma were the most common, followed by fibrous dysplasia and central giant cell granuloma. No ABCs were associated with metastatic changes. The search for histopathogenesis pointed to a specific cytogenetic abnormality as the origin of primary ABCs, with USP6 as its main oncogene and spindle cell as the neoplastic cell, unlike with secondary ABCs, suggesting that they are distinct pathological processes.

The 'anatomically difficult' denture case.

UNLABELLED: Complete loss of teeth from one or both arches is a disabling condition which is usually managed by a conventional removable denture. Rehabilitation may be poorly tolerated by patients, particularly in the lower jaw, and is more difficult in situations when the anatomy of the denture-bearing area is less favourable. These situations may require specific prosthodontic or surgical techniques, or a combination of both. Prosthodontic solutions involve special impression techniques and the use of soft linings and it is vitally important to manage patient expectations in such cases. This article describes prosthodontic management options for dealing with the fibrous (flabby) anterior ridge and bony exostoses. CLINICAL RELEVANCE: Although tooth loss in the UK is diminishing, it is nevertheless important that dental practitioners are able to demonstrate good prosthodontic skills for managing an ageing population. Surgical correction of anatomical defects may occasionally be employed.

Diagnosis and treatment of Sagliker syndrome: a case series from Iran.

Sagliker syndrome was introduced in 2004 in patients with end-stage renal disease and severe secondary hyperparathyroidism. This syndrome describes maxillary and mandibular deformities, dental abnormalities, benign soft tissue tumors in mouth, and various kinds of skeletal changes including short stature and fingertip abnormalities. There are a few reports from different regions of the world. The aim of this study is to report 5 cases of the Sagliker syndrome from Iran.

[Complex approach to assessment of condition severity in patients with pyoinflammatory odontogenous diseases].

Dynamics of mean value indices and mean dispersion doesn't exclude the feedback (Mayanskiy D.N., 2008) in process of study the disease according to cooperative processes using system leukocyte-monocyte-lymphocyte (L+M+LM). The authors investigated a dynamic balance between these cell substratums and collagen formation. Acute inflammatory processes in tissues of maxillofacial area accompanied by leukemoid response of peripheral blood in the form of leukocytosis (10 x 10(9)-15 x 10(9)/l and more). The authors completely agree with the opinion of M.M. Solov'yov (2012) and N.K. Artyushenko (2008) that mechanism of this reaction is associated with both the leukocyte redistribution in the inflammation zone and with changes of hematopoietic rostock which aimed to balance the affected compensatory mechanisms of nonspecific resistance.

Risk factors and indices of osteomyelitis of the jaw in osteoporosis patients: results from a hospital-based cohort study in Japan.

BACKGROUND: Several studies have reported osteomyelitis of the jaw (OMJ) as a side effect of bisphosphonates (BPs), and the risk of oral BPs has been recently clarified. However, other systemic risk factors of OMJ remain unclear. Importantly, the possibility of risk classification based on the clinical characteristics of patients has not been explored. Here, we clarified risk factors of OMJ and evaluate the predictive accuracy of risk indices in osteoporosis patients. METHODS: We performed sub-analysis using a database developed for a retrospective cohort study in patients taking medications for osteoporosis at Kyoto University Hospital. Risk indices for OMJ were constructed using logistic regression analysis, and odds ratios (OR) for OMJ cases and 95% confidence intervals (CI) were estimated. Potential risk factors included in the statistical analysis were age; sex; diabetes; use of oral BPs, corticosteroids, cancer chemotherapy, antirheumatic drugs, and biologic agents; and their interactions. Risk indices were calculated by the sum of potential risk factors of an individual patient multiplied by the regression coefficients. The discriminatory power of the risk indices was assessed by receiver operating characteristic (ROC) analysis. RESULTS: In analysis of all patients, oral BPs (OR: 4.98, 95% CIs: 1.94-12.75), age (OR: 1.28, 95% CI: 1.06-1.60) and sex-chemotherapy interaction (OR: 11.70, 95% CI: 1.46-93.64) were significant risk factors of OMJ. Areas under the ROC curves of these risk indices provided moderate sensitivity or specificity regardless of group (0.683 to 0.718). CONCLUSIONS: Our data suggest that oral BP use, age, and sex-chemotherapy are predictors of OMJ in osteoporosis patients. The risk indices are moderately high, and allow the prediction of OMJ incidence.

Morbidity and cost of odontogenic infections.

OBJECTIVE: Cost analysis of deep neck space infections from odontogenic origin and review of the morbidity of potentially preventable complications. STUDY DESIGN: Case series with chart review. SETTING: Level 1 trauma center and academic safety net hospital. SUBJECTS AND METHODS: Patients treated for deep neck space infections due to an odontogenic source between 2001 and 2010 were reviewed. Two hundred patients were included in the study. Ninety-eight patients required inpatient admission. Twelve percent of these patients had difficult airways, and 16% had at least 1 day in the intensive care unit. Cost data were available only for the later 3.5 years of the study period. RESULTS: The overall cost of treatment for these 71 individuals exceeded $1.1 million. CONCLUSION: The cost of treatment for odontogenic infections is staggering. Based on assumptions of the percentage of infections in the metropolitan area captured at Hennepin County Medical Center, extrapolation to the total national cost of inpatient care approaches $200 million annually. This study highlights the importance of access to medical and preventative dental care for the general population and demonstrates the cost benefit that could be achieved through prevention of disease and, therefore, avoidance of its complications.

[Cellular and tissue reactions of the mucous membrane of the maxillary sinus in the patients presenting with odontogenic aspergillous maxillary sinusitis].

The results of this morphological study of the mucous membrane of the maxillary sinuses in the patients presenting with the non-invasive fungal form of odontogenic sinusitis revealed the signs of granulematous inflammation. Epithelium underwent metaplasia into the single-row cubic or prismatic layer. The invasive form of fungal odontogenic sinusitis was characterized by allergic inflammation with intensive infiltration of maxillary sinus mucosa by antigen-representing and effector cells.

Tooth extraction in patients on zoledronic acid therapy.

OBJECTIVES: Surgical management of patients following zoledronic acid therapy is particularly difficult, since the dental extraction is the main cause of BRONJ. METHODS: A case-control study was conducted on 176 patients treated with intravenous (IV) bisphosphonates for oncologic pathologies who also underwent dental extractions. The study was divided randomly into two groups: 91 were treated with Plasma Rich in Growth Factor Plasma (PRGF) (study group) and the other 85 were not treated with the growth factor preparation (control group). RESULTS: Panoramic X-ray and computed tomography were performed both before and 60 months after surgery. By clinical and radiological diagnosis, BRONJ was diagnosed in only 5 patients in the control group at an average of 91, 6 days after tooth extraction. CONCLUSIONS: We hypothesize that Plasma Rich in Growth Factor (PRGF) is important for the successful treatment of patients on bisphosphonates to restore the osteoblast/osteoclast homeostatic cycles via autologous cytokines. Moreover, this protocol reduces the risk of BRONJ when it is necessary to perform dental extractions in patients undergoing IV bisphosphonate treatment.