Oral health and atherosclerotic cardiovascular disease: A review.

Periodontal disease (PD) is common in the US and globally. Evidence suggests that poor oral health is associated with atherosclerotic cardiovascular disease (ASCVD); however, this relationship has not been a major focus in clinical cardiology. This manuscript will review the growing evidence linking PD to ASCVD, including pathophysiologic mechanisms and coexistent risk factors. Public health considerations with a focus on disparities, social determinants, preventive strategies, and a call to action to reduce the burden of coincident ASCVD and PD are also reviewed.

Protective Measures against COVID-19: Dental Practice and Infection Control.

The onset of the Coronavirus 2019 (COVID-19) pandemic has challenged the worldwide healthcare sector, including dentistry. The highly infectious nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and risk of transmission through aerosol generating procedures has profoundly impacted the delivery of dental care services globally. As dental practices with renewed infection control strategies and preventive measures are re-opening in the "new normal" period, it is the responsibility of healthcare professionals to constantly analyze new data and limit the spread of COVID-19 in dental care settings. In the light of new variants of SARS-CoV-2 rapidly emerging in different geographic locations, there is an urgent need to comply more than ever with the rigorous public health measures to mitigate COVID-19 transmission. The aim of this article is to provide dental clinicians with essential information regarding the spread of SARS-CoV-2 virus and protective measures against COVID-19 transmission in dental facilities. We complied and provided guidance and standard protocols recommended by credible national and international organizations. This review will serve as an aid to navigating through this unprecedented time with ease. Here we reviewed the available literature recommended for the best current practices that must be taken for a dental office to function safely and successfully.

Mandibular Reconstruction with Free Fibula Flap for Medication-related Osteonecrosis of the Jaw in Patients with Multiple Myeloma.

While bisphosphonates are the cornerstone for management of multiple myeloma, they are associated with medication-related osteonecrosis of the jaw (MRONJ). There are many controversies in the management of MRONJ in this patient population. In this article, we describe a representative case and, along with a literature review, we report the outcomes of our 3 cases with multiple myeloma who underwent mandible reconstruction with vascularized fibula bone grafts after segmental mandible resection for Stage 3 MRONJ over a 3-year period. All patients were male with a mean age of 59 years. All patients had undergone therapy with bisphosphonates and had no other identifiable cause of mandible osteonecrosis. All patients had pathologic mandible fractures associated with intraoral fistulae and exposed bone. Nonsurgical management was attempted in all patients. One patient also underwent debridement of the mandible without resolution of the disease. Mandible reconstruction with an osteocutaneous free fibula flap after segmental mandible resection was performed in all 3 cases without major complications or donor site morbidity. Different bacteria were isolated from the intraoperative tissue cultures in all cases. Computed tomographic imaging revealed bony union without hardware complications in all cases. Mean follow-up was 28 months. In conclusion, we demonstrated that patients with multiple myeloma and advanced MRONJ lesions of the mandible can be managed successfully and safely by segmental resection and reconstruction with vascularized fibula bone graft.

Use of Intraoperative Biplanar Fluoroscopy for Minimally Invasive Retrieval of a Broken Dental Needle.

This report describes a case of needle breakage during a left-sided inferior alveolar nerve block to perform restorative dentistry on a 56-year-old male patient. The needle was removed in conjunction with interventional neuroradiology using biplanar fluoroscopy.

Management of stage 0 medication-related osteonecrosis of the jaw with hyperbaric oxygen therapy: a case report and review of the literature.

The definition of medication-related osteonecrosis of the jaw (MRONJ) includes a stage 0 presentation where exposed bone, the hallmark of this condition, is absent. Numerous management strategies have been recommended for MRONJ including hyperbaric oxygen (HBO2) therapy. This report describes a 64-year-old woman with stage 0 MRONJ of the bilateral mandible, refractory to clindamycin and local debridement, who was subsequently managed successfully with amoxicillin/clavulanate and HBO2 therapy. The authors also explore the current literature on the pathophysiology of MRONJ and the potential role of hyperbaric oxygen in its treatment.

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.

Does Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography Facilitate Treatment of Medication-Related Osteonecrosis of the Jaw?

PURPOSE: There is considerable controversy over the treatment of medication-related osteonecrosis of the jaw (MRONJ) and growing interest and debate related to the timing, type, technique, and goals of surgical intervention. The specific aim was to evaluate the predictive value of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) on healing outcomes in patients undergoing surgery for MRONJ of the mandible. MATERIALS AND METHODS: A retrospective cohort study of 31 patients with 33 MRONJ lesions of the mandible who had undergone surgery using FDG PET-CT was conducted. Data were collected on FDG uptake patterns, healing, follow-up, demographics, lesion characteristics, antiresorptive therapy, and adjunctive therapy. Panoramic and/or periapical radiographs were used to identify non-restorable teeth and PET-CT images were used to identify sequestra and FDG uptake. Above the mandibular canal, surgery consisted of marginal resection and/or debridement of clinically involved bone and exposure of clinically uninvolved bone identified by FDG uptake. Below the mandibular canal, mobile segments of bony sequestra were removed, but areas of clinically uninvolved bone with FDG uptake were not. Patients who did not heal underwent segmental resection and reconstruction with rigid fixation and a local or regional soft tissue flap or free fibular flap. The primary predictor variable was the FDG uptake pattern for each patient. The outcome variable was postoperative healing defined by mucosal closure without signs of infection or exposed bone at the time of evaluation. RESULTS: Two risk groups were identified based on FDG uptake pattern. The low-risk group, type A, included 22 patients with activity limited to the alveolus, torus, and/or basal bone superior to the mandibular canal. The high-risk group, type B, included 11 patients with type A FDG activity with extension inferior to the mandibular canal. Treatment of type A MRONJ lesions was more successful than treatment of type B MRONJ lesions (100 vs 27%; P < .001). Seven of the type B failures were successfully retreated by segmental resection and reconstruction (1 patient refused further treatment). CONCLUSION: These results showed that low-risk FDG PET-CT findings predicted successful healing with surgery above the mandibular canal. In contrast, high-risk FDG findings were associated with a greater than 50% risk of failure for treatment that extended below the mandibular canal. Although these failures suggest that FDG uptake indicates infected tissue, further research is needed to identify which high-risk patients are most likely to benefit from a conservative treatment protocol.

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw.

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts (n=30); patients with periodontal disease without a history of BP therapy (Control, n=10), patients with periodontal disease having history of BP therapy but without ONJ (BP, n=5) and patients with BRONJ (BRONJ, n=15). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ (71.6%), BP (70.3%) and Control (59.1%). Significant differences (P<0.05) in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay (ELISA) results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix-loop-helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

Fluorodeoxyglucose positron emission tomography with computed tomography detects greater metabolic changes that are not represented by plain radiography for patients with osteonecrosis of the jaw.

PURPOSE: Imaging is important to identify subclinical changes and for treatment planning in patients with osteonecrosis of the jaw (ONJ) exposed to antiresorptive therapy. The aim of this study was to compare the findings at radiography with those at fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) for patients with ONJ related to antiresorptive therapy. MATERIALS AND METHODS: A cross-sectional retrospective analysis of patients with clinically identified ONJ lesions of the mandible was performed. Two imaging modalities were evaluated for each patient: plain radiography (ie, panoramic or periapical) and FDG PET/CT with 1-mm sections. Outcome variables for the radiographic findings were osteolytic and osteosclerotic bone changes. Outcome variables for FDG PET/CT images were localization of FDG uptake. Maximum standard uptake values (SUVmax) of abnormal FDG jaw uptake were recorded, in addition to the mean SUV of the contralateral normal mandible, and used to calculate the target-to-background ratio. Radiographic changes and FDG uptake were classified as local (ie, corresponding to exposed cortical bone) or diffuse (ie, local changes and changes extending beyond the margins of exposed bone) for each imaging technique. Local and diffuse changes detected by each imaging modality were described and the difference in detection was compared with the McNemar test. RESULTS: Twenty-three patients with 25 clinically identified ONJ lesions were analyzed using radiography and FDG PET/CT. Differences were found in how radiography and FDG PET/CT detect local and diffuse changes associated with ONJ. Radiography showed local changes in 17 patients (68%), diffuse changes in 3 patients (12%), and no changes in 5 patients (20%), whereas FDG PET/CT imaging showed local changes in 17 patients (68%) and diffuse changes in 8 patients (32%). The McNemar test indicated that FDG PET/CT imaging was less likely to miss a lesion (P < .001). Mean SUVmax was 6.59, and the mean target-to-background ratio was 5.37. CONCLUSION: The results of this study show that FDG PET/CT detects local and diffuse metabolic changes that may not be represented by plain radiography for patients with ONJ related to antiresorptive therapy. The target-to-background ratio allowed the discrimination between ONJ lesions and background changes. Future studies are necessary to determine whether FDG PET/CT can determine risk and facilitate management of ONJ.

Metastatic cancer identified in osteonecrosis specimens of the jaws in patients receiving intravenous bisphosphonate medications.

PURPOSE: The aim of the present study was to investigate the microscopic presence of metastatic cancer in jaw specimens clinically and histologically diagnosed as having osteonecrosis in patients receiving intravenous bisphosphonate medications. PATIENTS AND METHODS: A retrospective cohort multicenter study was designed. Patients from the University of Tennessee Medical Center, New York University Medical Center, and New York Center for Orthognathic and Maxillofacial Surgery were enrolled who had been treated with intravenous bisphosphonate medications for an underlying diagnosis of cancer and who had been clinically diagnosed with bisphosphonate-related osteonecrosis of the jaws (BRONJ). The institutional review boards approved the present study. The primary predictor variable was the clinical presence of BRONJ. The primary outcome variable was the microscopic presence of metastatic cancer in the osteonecrotic jaw specimens. RESULTS: A total of 744 sites of BRONJ were clinically diagnosed. Of these sites, 552 (74%) were diagnosed in patients who had received intravenous bisphosphonate medications. Of these 552 sites, 357 (65%) underwent microscopic evaluation through biopsy, sequestrectomy, or resection with curative intent. Of the 357 sites of BRONJ subjected to microscopic analysis, 19 (5.3%) sites were diagnosed with 20 cancers in 16 patients. CONCLUSIONS: Albeit rare, the presence of cancer in a BRONJ specimen represents 1 explanation for the development of osteonecrosis in patients exposed to intravenous bisphosphonate medications in whom a clinical diagnosis of BRONJ has been applied. Additional molecular information is needed to provide an explanation for this observation.

Osteonecrosis of the jaw onset times are based on the route of bisphosphonate therapy.

PURPOSE: Osteonecrosis of the jaw (ONJ) has been reported to be associated with patients receiving bisphosphonate (BP) therapy. There are many reports that suggest that the time of exposure to BPs is a significant risk factor for ONJ and that the greatest risk occurs after dentoalveolar surgery. The aim of this study was to retrospectively investigate the duration of BP therapy and related events before the onset of ONJ based on an intravenous (IV) or oral route of administration. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients referred to our institution to identify the onset of ONJ based on the exposure to BP therapy and associated triggers (ie, dentoalveolar surgery or spontaneous occurrence) based on the route of BP administration. Demographic data (ie, age, gender, and race), medical diagnosis related to BP therapy, and information as to whether the BP therapy was continued at the time of ONJ diagnosis were also collected. RESULTS: We reviewed the records for 114 patients with a history of ONJ. We divided patient cohorts by route of BP administration, with 76 patients having a history of IV BP therapy and 38 patients having a history of oral BP therapy. The overall onset of ONJ was earlier in the IV BP group (median, 3 years) compared with the oral BP group (median, 5 years). There was no statistical difference in the duration to occurrence of ONJ associated with dental extraction compared with spontaneous occurrence for both the IV and oral BP groups. CONCLUSIONS: The median onset of ONJ for patients undergoing IV BP therapy occurs earlier than the median onset for patients undergoing oral BP therapy, and there was no difference in onset occurring spontaneously and after dental extraction. The significance of these findings suggests that patients who receive IV BP therapy should be closely evaluated after the initiation of BP therapy. The lack of evidence suggesting greater onset after dental extraction may provide clinical support for dentoalveolar surgery that is indicated for patients with a history of BP therapy. Research focusing on the clinical circumstances and physiologic events during early antiresorptive therapy may provide insight as to the critical risk factors.

Concentration dependent effects of tobacco particulates from different types of cigarettes on expression of drug metabolizing proteins, and benzo(a)pyrene metabolism in primary normal human oral epithelial cells.

The ability of tobacco smoke (TS) to modulate phase I and II enzymes and affect metabolism of tobacco carcinogens is likely an important factor in its carcinogenicity. For the first time several types of TS particulates (TSP) were compared in different primary cultured human oral epithelial cells (NOE) for their abilities to affect metabolism of the tobacco carcinogen, (BaP) to genotoxic products, and expression of drug metabolizing enzymes. TSP from, reference filtered (2RF4), mentholated (MS), reference unfiltered, (IR3), ultra low tar (UL), and cigarettes that primarily heat tobacco (ECL) were tested. Cells pretreated with TSP concentrations of 0.2-10 µg/ml generally showed increased rates of BaP metabolism; those treated with TSP concentrations above 10 µg/ml showed decreased rates. Effects of TSPs were similar when expressed on a weight basis. Weights of TSP/cigarette varied in the order: MS≈IR3>2RF4>ECL>UL. All TSPs induced the phase I proteins, cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1), phase II proteins, NAD(P)H dehydrogenase quinone 1 (NQO1), and microsomal glutathione S-transferase 1 (MGST1), and additionally, hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2), as assessed by qRT-PCR. The pattern of gene induction at probable physiological levels favored activation over detoxification.

Predicting risk for bisphosphonate-related osteonecrosis of the jaws: CTX versus radiographic markers.

BACKGROUND AND OBJECTIVE: The most common risk factor for bisphosphonate-related osteonecrosis of the jaws (BRONJ) is dentoalveolar surgery. It has been suggested that reduced serum C-terminal telopeptide (CTX) can determine the degree of osteoclast suppression and may predict the development of BRONJ after dentoalveolar surgery. Although there are many radiographic appearances associated with BRONJ, there are little data that describes changes preceding dentoalveolar surgery. The objective of this retrospective study was: 1) to investigate if reduced serum CTX values (i.e., <150 pg/mL) were associated with BRONJ after dentoalveolar surgery; and 2) to determine if specific radiographic changes are associated with teeth that develop BRONJ after extraction. STUDY DESIGN: A retrospective review of radiographic and/or serum CTX data was performed for 68 patients with a history of bisphosphonate therapy who either underwent dental extraction or were diagnosed with BRONJ in the Department of Oral and Maxillofacial Surgery during the period 2007-2009. Postoperative healing was assessed for 26 patients with reduced serum CTX levels (<150 pg/mL) who either underwent dental extraction or treatment for BRONJ. Preoperative radiographs were evaluated for 55 patients who either healed normally or developed BRONJ after dental extraction. RESULTS: All 26 patients (100%) who had serum CTX levels <150 pg/mL healed successfully after dentoalveolar surgery (20 patients) or after treatment for BRONJ (6 patients). Among the 55 patients who underwent radiographic evaluation, 24 patients (83%) with BRONJ exhibited periodontal ligament (PDL) widening associated with extracted teeth, whereas only 3 patients (11%) who healed normally demonstrated PDL widening. CONCLUSION: These data suggest that radiographic PDL widening may be a more sensitive indicator than CTX testing in predicting risk of BRONJ. Current guidelines that recommend minimal surgical intervention may need to be revised to include alternative strategies for the elimination or management of this pathology.

Current trends in the treatment of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a condition of partial or complete upper airway obstruction leading to increased resistance to airflow and potential cessation of breathing during sleep. Effective treatment of OSA is challenging and there has been greater recognition by the medical and dental disciplines. By understanding the rationale, indications, benefits, risks and success of the various treatment options available, clinicians will be able to make more informed treatment recommendations in patient management.

Increased EMMPRIN (CD 147) expression during oral carcinogenesis.

Gene expression profiling of oral premalignant (OPM) cells and normal oral epithelial (NOR) cells showed that EMMPRIN expression was markedly upregulated in OPM cells compared to NOR cells. We used an oral squamous cell carcinoma (OSCC) progression model composed of cell lines, organotypic cultures and tissue specimens to characterize EMMPRIN expression patterns by microarray analysis, qRT-PCR, Western blotting and immunohistochemistry. EMMPRIN levels are elevated in OPM and primary and metastatic OSCC cells as compared to NOR. EMMPRIN was detected as high and low glycosylated forms in the OPM and OSCC cellular extracts and was released in the media by OSCC cells but not by OPM cells. EMMPRIN expression in an organotypic culture model of normal and OPM mucosae mirrored the expression patterns in the respective tissues in vivo. EMMPRIN expression was limited to basal cells of normal, benign hyperkeratotic and inflammatory (lichen planus) oral mucosa. EMMPRIN expression is increased in dysplastic leukoplakias spreading to more superficial layers, and its expression levels correlated significantly with the degree of dysplasia. Primary and metastatic OSCC showed strong cell surface expression of EMMPRIN. These results suggest that EMMPRIN overexpression occurs at a very early stage of oral carcinogenesis and plays a contributing role in OSCC tumorigenesis.