Olga Di Fede

Oral manifestations in patients with gastro-oesophageal reflux disease: a single-center case-control study

OBJECTIVE To assess the occurrence of oral pathological changes and symptoms in patients affected by gastro-oesophageal reflux disease (GERD). PATIENTS AND METHODS 200 patients with GERD and 100 matched healthy controls were studied. Thorough visual examination of the dental and oral mucosal tissues was performed and medical history relevant to oral symptoms was collected. The primary outcome was defined as a statistically significant difference, between the study group and controls, in the presence of the following indicators: soft/hard palate and uvula erythema, tooth wear, xerostomia, oral acid/burning sensation, subjective halitosis and dental sensitivity. Statistical analysis included chi-squared test, and crude odds ratio with 95% CI. RESULTS Univariate analysis showed that xerostomia, oral acid/burning sensation, subjective halitosis, and soft and hard palate mucosa and uvula erythema were more common in patients with GERD than matched controls (P < 0.05). CONCLUSIONS This study failed to find any significant association between GERD and dental erosions, whereas some symptoms and other objective oral mucosal changes were found to be significantly associated with GERD.

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.

Osteoporosis, jawbones and periodontal disease

The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa. Hypothetical models linking the two conditions exist: in particular, it is supposed that the osteoporosis-related bone mass density reduction may accelerate alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions such as bone loss in the jaws, periodontal diseases, and tooth loss. Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk. Key words:Osteoporosis, periodontitis, oral bone loss, tooth loss, edentulism, bone mineral density.

Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed.

Recent data suggest that the traditional definition of bisphosphonate-associated osteonecrosis of the jaw (ONJ) may exclude patients who present with the non-exposed variant of the condition. To test the hypothesis that a proportion of patients with ONJ remain undiagnosed because their symptoms do not conform to the traditional case definition, we did a secondary analysis of data from MISSION (Multicentre study on phenotype, definition and classification of osteonecrosis of the jaws associated with bisphosphonates), a cross-sectional study of a large population of patients with bisphosphonate-associated ONJ who were recruited in 13 European centres. Patients with exposed and non-exposed ONJ were included. The main aim was to quantify the proportion of those who, according to the traditional case definition, would not be diagnosed with ONJ because they had no exposed necrotic bone. Data analysis included descriptive statistics, median regression, and Fishers exact test. A total of 886 consecutive patients were recruited and 799 were studied after data cleaning (removal or correction of inaccurate data). Of these, 607 (76%) were diagnosed according to the traditional definition. Diagnosis in the remaining 192 (24%) could not be adjudicated, as they had several abnormal features relating to the jaws but no visible necrotic bone. The groups were similar for most of the phenotypic variables tested. To our knowledge this is the first study in a large population that shows that use of the traditional definition may result in one quarter of patients remaining undiagnosed. Those not considered to have ONJ had the non-exposed variant. These findings show the importance of adding this description to the traditional case definition.

Mucoadhesive Polymers for Oral Transmucosal Drug Delivery: A Review

The oral mucosa offers an interesting site for the application of dosage forms that release drugs within/throughout the oral mucosa, by assuring a high drug bioavailability for topic and systemic effects. However, the relative permeability of the oral mucosa and the washing effect related to the oral fluids and mechanical stresses must be considered in the formulation of oral dosage forms. Since a sustained drug release can be guaranteed only if dosage forms remain in contact with the oral site of absorption/application for a prolonged time, the development of mucoadhesive dosage forms is mandatory. The mucoadhesion is a complex phenomenon and the mucoadhesive bond consists of two different parts, the mucoadhesive polymers and the mucous substrate. In addition to factors related to the oral mucosa and oral environment features, the physical-chemical characteristics of mucoadhesive polymers must be also considered as factors influencing the mucoadhesive bonds. While it is not possible to modify the mucosal features or it is possible to modify or inhibit only in part certain mucosal processes, the knowledge of polymer properties influencing mucoadhesive bonds allows to modify or to control these properties in developing increasingly effective mucoadhesive systems. The aims of this review are to discuss the several mechanisms and factors behind the phenomenon of mucoadhesion with particular reference to the features of the oral environment, oral mucosa, and polymeric compounds influencing mucoadhesion process. Finally, a brief mention to the main mucoadhesive dosage forms designed for oral transmucosal drug delivery is made.

Topical therapies for oral lichen planus management and their efficacy: a narrative review.

Oral Lichen Planus (OLP) is a chronic inflammatory condition implicating T cell-mediated cytotoxicity, and involving oral mucosal surfaces. Several therapeutic regimens have been evaluated to treat OLP and pain related, but often without high level of evidence. Topical formulations are the favourite for the majority of cases; bioadhesive formulations have been considered very useful and practical for local drug delivery in oral mucosa, due to the increased residence time on the oral mucosa of the dosage forms and better therapeutic efficacy. In this narrative review, authors try to illustrate the current topical managements for OLP from the accessible literature on this topic. Steroids are very helpful in discomfort and making better quality of life: they are considered the first-line treatment even if they could cause secondary candidosis, and sometimes bad taste, nausea, dry mouth, sore throat or swollen mouth. Other substances or devices by topical administration are adopted especially when the first line approach is refractory. This is the case when retinol with its synthetic and natural analogues (retinoids), hyaluronic acid, or Aloe Vera are chosen. Recent topical applications for OLP therapy include phototherapy and low/high energy pulsing light; the treatment with extracorporeal photochemotherapy is also reasonable and promising. Finally, calcineurin inhibitors (i.e. cyclosporine, tacrolimus and pimecrolimus), antioxidant and biologics (i.e alefacept, efalizumab, basiliximab, TNF-α inhibitors - infliximab, rituximab) may be alternative approaches when OLP does not respond to the standard protocols. In this scenario, there are several studies on molecules different from glucocorticosteroids, but not sufficient or statistically adequate to justify their evidence-based use in OLP; large randomized placebo controlled trials are required to evaluate the safety and effectiveness of these non conventional therapies. In conclusion, since OLP is a chronic disease and requires long-term management, the dental/medical practitioner, who treats OLP patients, needs to know the natural history of OLP, how to monitor, and how to treat, taking in account all of the available modalities conventional and not, with pros and cons.

Osteonecrosis of the Jaw in Patients with Metastatic Renal Cell Cancer Treated with Bisphosphonates and Targeted Agents: Results of an Italian Multicenter Study and Review of the Literature

Osteonecrosis of the jaw (ONJ) associated with the use of bisphosphonates has been rarely reported in metastatic renal cell cancer (RCC) patients. Since the introduction of combined therapies consisting of nitrogen-containing bisphosphonates (NBPs) and targeted agents, an increasing number of RCC patients were reported to develop ONJ, suggesting that therapeutic angiogenesis suppression might increase the risk of ONJ in NBPs users. We performed a multicenter retrospective study and reviewed literature data to assess the occurrence and to investigate the nature of ONJ in RCC patients taking NBPs and targeted agents. Nine Italian Centers contributed to the data collection. Patients with exposed and nonexposed ONJ were eligible for the study if they had been taking NBPs and were receiving targeted agents at the time of ONJ diagnosis. Forty-four RCC patients were studied. Patients were mostly male (82%), with a median age of 63 years (range, 45-85 years). Zoledronic acid (93%) and sunitinib (80%) were the most frequently used NBP and antiangiogenic agent, respectively. Other agents included Pamidronate, ibandronate, sorafenib, bevacizumab, mammalian target of rapamycin inhibitors. Forty-nine sites of ONJ were encountered, with the mandible being the preferred site of ONJ (52%); both jaws were affected in 5 cases (12%). The most common precipitating event was dental/periodontal infection (34%), followed by tooth extraction (30%). Oral triggers of ONJ were missing in 10 cases (23%). This unexpectedly high number of ONJ cases, in comparison with literature data, suggests that frequency of ONJ in RCC patients might be largely underestimated and suggests a potential role for targeted agents in the incremental risk of ONJ.

Halitosis: could it be more than mere bad breath?

Halitosis is a generic term used to describe unpleasant odor emanating from the mouth air and breath, independent of the source where the odor substances originate. It affects between 50 and 65% of the population, but despite its frequency, this problem is often unaccepted and declared as taboo. Ninety percent of patients suffering from halitosis have oral causes: a small, but important percentage, of oral malodor cases have an extra-oral etiology, very often falling into the category of “blood-borne halitosis”. Several systemic diseases have been found to provoke malodor or to be a cofactor; bad breath may be an early sign of a serious local or systemic condition. A psychogenic halitosis also exists including the variant “pseudo-halitosis”, when the oral malodor does not exist, but the patient believes he or she is suffering severely from it, and the halitophobia, when, instead, there is an exaggerated fear of having halitosis. The aims of this paper are to review both oral and extra-oral causes of halitosis, especially those related to underlying systemic diseases, and to provide the primary care clinician a helpful means for its diagnosis and management. In fact, it is important to determine quickly whether the odor comes from an oral cause or not: if so, it requires referral to a dentist; if not (extra-oral origin alone or combined), its management requires the treatment of the underlying causes. Extra-oral disorders can be the cause in up to 15% of cases.

Adverse drug reactions in the oral cavity

Several drugs may have a number of adverse reactions (ADRs) involving the oro-facial region. The dose of the drug and the time required for the reaction to take place are relevant parameters; nonetheless, ADRs mechanisms are not always known and ADRs are not always predictable since aspects other than drug pharmacodynamics and/or pharmacokinetics, as well as various interacting variables contribute to the final outcome. All tissues and many functions of the oral cavity can be affected. In particular, salivary function is frequently involved and hypo-salivation is the main manifestation; several mucosal lesions with different morphology (ulcerations, vesiculobullous lesions, white lesions, pigmentations, swelling) are also possible. Taste, sensation and trigeminal function alterations have been reported and the recent evidence regarding the occurrence of jawbones osteonecrosis, especially in bisphosphonates treated patients, is increasing. Clinical management may be quite difficult due to the multiplicity of involved classes of drugs and substances (dental materials, foods), the variety of affected tissues and functions, the type of produced lesions and disturbances, the complexity of related pathogenetic mechanisms (if known), the difficulties in assessing causality and managing drug withdrawal and/or dose adjustment, as well as in establishing specific treatments, if any. In this paper the most common and significant oral ADRs, their related aspects and importance (including medico-legal implications) for health care providers will be discussed.

Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein

BackgroundThere is increasing evidence for the role of High Risk (HR) Human PapillomaVirus (HPV) in the pathogenesis of Oral Squamous Cell Carcinoma (OSCC). The E6 and E7 oncogenes from HR HPVs are responsible for the deregulation of p53 and pRB proteins involved in cell cycle and apoptotic pathways. In cell lines experiments, the HPV E7 protein seems to be able to enhance Hypoxia Inducible Factor-1 alpha (HIF-1α) activity, normally involved in the response to hypoxia and able to enhance angiogenesis.ResultsWe studied tumor specimens from 62 OSCC; a higher prevalence of tumors in TNM stage II and also in pT2 class between OSCC infected positive HPV16 DNA than non-infected ones was observed. HIF-1α positivity was detected throughout the analysed fields, not associated with areas of necrosis and also observed in cells immediately adjacent to blood vessels. A significant increase in mean values of the HIF-1α labeling indexes was observed for pT1-T2, as well for stage I-II, in the infected positive HPV16 DNA tumors than non-infected ones. HIF-1α and HPV16 E7 labeling indexes showed a significantly positive correlation which suggested a positive association between HPV16 E7 and HIF-1α expression.ConclusionsIn our specimens HIF-1α immunoreactivity hints for an O2-independent regulatory mechanism in infected positive HPV16 DNA tumors, especially for pT1-T2 and stage I-II tumors, suggesting a very early involvement in the development of HPV-induced OSCC. HIF-1α and HPV16 E7 labeling indexes suggest also a positive association between the two proteins in infected positive HPV16 DNA OSCC.