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.

Response of stem cells from different origins to biphasic calcium phosphate bioceramics.

Biphasic calcium phosphate (BCP) bioceramics have been successfully applied in a broad variety of presentation forms and with different ratios of hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP). BCPs have been loaded with stem cells from different origins for bone tissue engineering purposes, but evidence of stem cell behavior on different compositions (various HA/ß-TCP ratios) and physical features of BCPs is limited. We compared the adhesion, proliferation, viability and osteogenic potential of human mesenchymal stem cells (MSCs) on granular BCPs with equal HA/ß-TCP ratio of diverse particle sizes and on porous blocks which had different chemical compositions. In addition, the osteogenic differentiation of MSCs was compared to adipose-derived (ADSC) and dental pulp (DPSC) stem cells, as well as to pre-osteoblasts on a particulate BCP. MSCs growing on granular BCPs demonstrated increased number as compared to MSCs growing on blocks. Cells proliferated to a greater extent on small granular BCPs, while large granular BCPs and blocks promoted cell differentiation. Surprisingly, the expression of genes involved in osteogenesis was upregulated in MSCs on bioceramics in basal medium which indicates that BCPs may have osteoinductive potential. This was confirmed with the upregulation of osteochondrogenic markers, at different time points, when stem cells from various tissues were grown on the BCP. This study demonstrates that BCPs, depending on their physical features and chemical composition, modulate stem cell behavior, and that stem cells from different origins are inherently distinct in their gene expression profile and can be triggered toward osteochondrogenic fate by BCPs.

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.

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.

Esthetic Considerations In Minimally Invasive Orthognathic Surgery.

The success of dental implants has long been considered to be dependent primarily on the quality and quantity of alveolar bone. Bone grafting allows patients with insufficient bone volume to obtain implant-supported prosthetic solutions for treatment of edentulism. While extensive bone grafting procedures have been commonly used to rehabilitate severely atrophic arches, they can be associated with long treatment times, unpredictability, and donor site morbidity. Nongrafting solutions have more recently been employed that maximally utilize the residual highly atrophic alveolar or extra-alveolar bone for implant therapy. With the use of modern diagnostic imaging and 3D printing technology, clinicians are able to provide individualized, subperiosteal implants that fully adapt to the patient's remaining alveolar bone. Other "graftless" implants, including zygomatic implants, utilize the patient's extraoral facial bone outside the alveolar process and have been shown to provide predictable results. This article discusses the rationale for graftless solutions in implant therapy and the data supporting the use of various graftless protocols as alternatives to grafting and conventional dental implant therapy.

Graftless Implantology as a Forward-Looking Clinical Concept for Highly Atrophic Maxillary Arches.

For many decades the success of dental implants has been considered to be dependent predominantly on the quality and quantity of the patient's alveolar bone. Building on the high success rates of implants, bone grafting eventually was implemented, allowing patients with insufficient bone volume to obtain implant-supported prosthetic solutions for treatment of partial or complete edentulism. Extensive bone grafting procedures have been commonly used to rehabilitate severely atrophic arches but are associated with long treatment times, unpredictability, and donor site morbidity. More recently, nongrafting solutions that maximally utilize the residual highly atrophic alveolar or extra-alveolar bone for implant therapy have been reported to have success. The emergence of diagnostic imaging and 3D printing technology has allowed clinicians to provide individualized, subperiosteal implants that can adapt precisely to the patient's remaining alveolar bone. Furthermore, paranasal, pterygoid, and zygomatic implants that utilize the patient's extraoral facial bone outside the alveolar process can provide predictable and optimal results with no or minimal bone grafting with less treatment time. This article considers and evaluates the rationale for graftless solutions in implant therapy as well as the data supporting the use of various graftless protocols as alternatives to grafting and conventional dental implant therapy.

How Patient-Centered Medical Homes Integrate Dental Services Into Primary Care: A Scoping Review.

Integrated care delivery is at the core of patient-centered medical homes (PCMHs). The extent of integration of dental services in PCMHs for adults is largely unknown. We first identified dental-medical integrating processes from the literature and then conducted a scoping review using PRISMA guidelines to evaluate their implementation among PCMHs. Processes were categorized into workforce, information-sharing, evidence-based care, and measuring and monitoring. After screening, 16 articles describing 21 PCMHs fulfilled the inclusion criteria. Overall, the implementation of integrating processes was limited. Less than half of the PCMHs reported processes for information exchange across medical and dental teams, referral tracking, and standardized protocols for oral health assessments by medical providers. Results highlight significant gaps in current implementation of adult dental integration in PCMHs, despite an increasing policy-level recognition of and support for dental-medical integration in primary care. Understanding and addressing associated barriers is important to achieve comprehensive patient-centered primary care.

Clinical Validation of an Alternative Specimen Collection Kit for SARS-CoV-2 Testing at Fox Chase Cancer Center.

Background: Supply chain disruptions during the COVID-19 pandemic have affected the availability of components for specimen collection kits to detect SARS-CoV-2. Plastic injection molding offers a rapid and cheap method for mass production of swabs for upper respiratory tract sampling. Local production of virus transport medium increases flexibility to assemble sample collection kits if the medium provides appropriate stability for SARS-CoV-2 detection. Methods: A locally produced virus transport medium and a novel injection molded plastic swab were validated for SARS-CoV-2 detection by reverse-transcription quantitative polymerase chain reaction. Both components were compared to standard counterparts using viral reference material and representative patient samples. Results: Clinical testing showed no significant differences between molded and flocked swabs. Commercial and in-house virus transport media provided stable test results for over 40 days of specimen storage and showed no differences in test results using patient samples. Conclusions: This collection kit provides new supply chain options for SARS-CoV-2 testing.

The Challenges and Rewards of Teledentistry.

On March 15, 2020, routine dental care in New York State paused due to the COVID-19 pandemic. The pause lasted 10 weeks in part to preserve critical supplies of personal protective equipment (PPE). This interruption of access to dental care led to an overall deterioration of oral health, an increase in prescribing and use of antibiotics and analgesic medications, especially opiates, and a rise in visits to hospital emergency centers. New York University's College of Dentistry, an academic ambulatory dental center, normally sees over 1,000 patient visits per day. Most visits are patients who require urgent care or are in the process of treatment to restore debilitating oral health problems. NYU Dentistry responded to the State pause by creating a nascent teledentistry service that began operations on March 17, 2020.

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.

Controlled phase III clinical trial of diclofenac potassium liquid-filled soft gelatin capsule for treatment of postoperative dental pain.

PURPOSE: The purpose of the present study was to assess the safety and efficacy of oral diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) that uses ProSorb dispersion technology (Xanodyne Pharmaceuticals, Inc, licensed from AAIPharma, Wilmington, NC), to treat adult patients with acute pain after third molar extraction. PATIENTS AND METHODS: In the present multicenter, randomized, double-blind, placebo-controlled trial, patients experiencing a baseline level of pain (≥ 50 mm on a 100-mm visual analog scale within 4 hours after surgery) were randomized to receive a single dose of DPSGC at 25, 50, or 100 mg or placebo. Pain intensity and relief were assessed for 6 hours after dosing. The efficacy endpoints included the summed pain intensity difference, total pain relief, and the median time to the onset of perceptible and meaningful pain relief (using the 2-stopwatch method). RESULTS: A total of 249 randomized patients had a significant increase in the summed pain intensity difference and total pain relief values at 3 and 6 hours across all DPSGC-treated groups compared with the placebo group (P < .0001). The onset of perceptible and meaningful pain relief was significantly faster in all DPSGC groups than in the placebo group, including the DPSGC 25-mg group (25 minutes [P = .0002] and 52 minutes [P < .0001] for perceptible and meaningful pain relief, respectively). Significantly fewer patients in the DPSGC groups required rescue medication compared with those in the placebo group (P < .0001). The global evaluation scores were significantly greater for the patients who received DPSGC than for those who received placebo (P < .0001), and more than 65% of DPSGC-treated patients rated the medication as good, very good, or excellent compared with 18% of the placebo-treated patients. DPSGC was generally well tolerated, and no serious adverse events were reported. CONCLUSIONS: The results from the present single-dose study of postoperative dental pain suggest that DPSGC offers significant pain relief compared with placebo and that the study medication provided was well tolerated by patients who required pain relief after third molar extraction.

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.

The recognition, physiology, and treatment of medication-induced methemoglobinemia: a case report.

Dapsone is a leprostatic agent commonly prescribed for the management of leprosy, malaria, and the immunosuppression-induced infections of Pneumocystis carinii and Toxoplasma gondii. In susceptible patients, methemoglobinemia, a potentially life-threatening event, can occur. We report a case of dapsone-induced methemoglobinemia which was observed during general anesthesia for the management of a fractured mandible. The pathophysiology, diagnosis, and management of dapsone-induced methemoglobinemia will be discussed.

Dental management of the gravid patient.

Gravidity is defined as the development of the young in utero. It initiates hormonal, psychological and physiological changes in the female patient, providing the dentist with many questions about the management of these patients. These physiologic alterations, as well as the embryologic development of the fetus, will be discussed along with the treatment alterations that should be considered. The changes are often subtle, but can lead to disastrous complications if proper precautions are not taken. Conversely, appropriate management of routine and dental emergencies can be denied by the practitioner because of misconceptions about pregnancy and fetal tolerance. Anesthetic and pharmacology of agents used in dentistry in treating the pregnant patient will be reviewed.

Clinical implications of cyclo-oxygenase-2 inhibitors for acute dental pain management: benefits and risks.

UNLABELLED: BACKGROUND; Cyclo-oxygenase-2 inhibitors (COX-2i) demonstrate analgesic efficacy for patients who require gastrointestinal safety. The authors discuss the potential benefits and risks of these novel, but expensive, analgesics when used in dentistry. METHODS: The authors conducted a MEDLINE search focused on the subject headings of common analgesic drugs and COX-2i, using peer-reviewed journals limited to the English language. They selected for review 127 articles that met the criteria. They also tried to identify any randomized controlled trials pertinent to dentistry and indicative of evidence-based medicine. RESULTS. When comparing COX isoforms (COX-1 and COX-2), the authors found that overlapping and mutually exclusively properties coexist. COX-2i originally were developed to minimize interference with the gastroprotective properties of the COX-1 isoform, while selectively preventing prostanoid synthesis expressed solely at sites of bodily trauma or other inflammation. COX-2i were found to provide pain relief equal to or slightly exceeding that offered by many mild narcotics. They may avoid some of the serious side effects that can occur with even short-term use of nonselective nonsteroidal anti-inflammatory drugs. CONCLUSIONS: The pharmacodynamics of COX-2i reveal an agent that includes analgesic, anti-inflammatory and gastroprotective properties but also allows for an undesirable disruption of the delicate hemodynamic balance. CLINICAL IMPLICATIONS: Symptomatic and asymptomatic gastroparietic patients who do not have severe cardiovascular, cerebral or renal ischemic disease benefit from use of COX-2i. Long-term use of these agents in medically compromised patients may prove disastrous.

Allelic loss at the GPx-1 locus in cancer of the head and neck.

Glutathione peroxidase is a selenium-containing, antioxidant enzyme previously implicated in the risk and development of lung and breast cancer, in part the result of allelic loss at the GPx-1 locus. This study examined allelic loss at the same locus in squamous cell carcinomas of the head and neck. The frequency of a polymorphism at codon 198 resulting in either a leucine or a proline at that position was surveyed by comparing 133 DNA samples obtained from head and neck tumors and 517 samples obtained from cancer-free individuals. Tumor DNAs exhibited fewer pro/leu heterozygotes as compared to DNA obtained from the cancer-free population. Fewer GPx-1 heterozygotes were verified by determining the frequency of highly polymorphic alanine repeat sequences in the same gene. The analysis revealed an approximately 42% reduction in heterozygosity in the DNA from the tumor samples. In order to assess loss of heterozygosity (LOH) at the GPx-1 locus, DNA was genotyped from peripheral lymphocytes, tumor tissue, and microscopically normal tissues adjacent to the tumor, derived from the same patients. These studies indicated LOH at the GPx-1 locus in each of the three tumor/normal tissues sample sets examined. Furthermore, LOH in the microscopically normal tissues at the tumor margin occurred in two of the three sample sets examined. These data implicate GPx-1 in the development of squamous cell carcinoma the head and neck and suggest that allelic loss of this gene, or one tightly linked to it, is an early event in the development of this type of malignancy.