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The aim of this prospective study was to estimate the effects of Erbium substituted: Yttrium Aluminium Garnet (Er:YAG) laser, compared with traditional scalpel, on the early postoperative sequelae of nondysplastic oral lesion removal.There is limited evidence that laser surgery could exhibit advantages over scalpel in oral mucosal surgery.The investigators studied a cohort of 344 patients; 394 lesions were randomized and treated. Outcome statistically evaluated variables were: age, gender, the site and size of investigated lesions, visual analogue score (VAS) of pain, the Oral Health Impact Profile questionnaire (OHIP-14) and the Quality of Life test (QOL), and number of analgesics taken in the 1st week after surgery.Significant differences were found if considering the surgical time, VAS, and QOL and OHIP-14 questionnaires; regarding those data, the Er:YAG laser appeared to be faster and less painful than traditional scalpel (p 0.05). For bigger lesions, patients statistically took more painkillers if they had undergone traditional surgery. Considering the site of the treated lesions, Er:YAG laser was less painful, especially in the gingiva and palate (p 0.05).This is the first randomized controlled surgical trial reported for the management of nondysplastic oral lesions with the use of an Er:YAG laser. With many limitations, the present report identifies significant difference in the immediate postoperative surgical period between the two treatments, meaning that the Er:YAG laser seemed to be less painful, and better accepted by patients, than traditional scalpel.

Background Salivary and serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have previously been studied in oral cancer with conflicting results. Methods We designed a controlled study to assess the correlation between pretreatment salivary and serum levels of IL-6 and IL-8, and all-cause survival and cancer recurrence in oral cancer patients. Results Fifty-two oral cancer patients and 52 healthy control cases were selected. In univariate analysis, salivary IL-6 and IL-8 seemed to be more expressed in cases (pConclusions To date, this is the largest prospective controlled study that has analyzed the pretreatment salivary and serum levels of IL-6 and IL-8 in oral cancer patients, suggesting salivary IL-6 as a possible prognostic biomarker. But further validation in a larger sample is still necessary.

Objective To perform a randomized, placebo-controlled, double-blind study, with a follow-up period of 6 months, for the use of topical clobetasol in cases of symptomatic oral lichen planus (OLP). Subjects and methods Thirty-two participants were analyzed, with the aims of: (I) to compare the usefulness of topically applied clobetasol propionate 0.05% (mixed with 4% hydroxyethyl cellulose gel) and 4% hydroxyethyl cellulose gel alone (considered as placebo) in the management of OLP; (II) to describe which of them is quicker in decreasing signs and reported symptoms, and (III) which is able to give the proper longer remission in the follow-up. Results Symptoms improved in all clobetasol-treated patients during the first 2 months of therapy, while only 50% of placebo control group (p = .005) displayed similar results; of the remaining half, 12.5% did experienced a worsening while 37.5% remained stable. Regarding clinical signs, 87.5% of clobetasol-treated patients improved, while only 62.5% of the placebo-treated patients had a positive response (p = .229). Conclusions It is possible to report that clobetasol, at this dosage, has been more effective than a placebo at provoking symptoms improvement in subjects affected by atrophic-erosive oral lesions.

Objectives Lichen planus has been recently associated with an increased risk of cardiovascular diseases (CVDs). The oral manifestations can be divided into white hyperkeratotic lesions (WL) and atrophic erosive lesions (RL). The aim of this report was to compare the presence of CVDs between patients affected by WL or RL, to test the hypothesis that RL are associated with an increased incidence of CVDs. Subjects And Methods Patients were analysed through a complete collection of all the risk factors for CVDs. The primary endpoint was the occurrence of a cardiovascular event -acute coronary syndrome (ACS), any revascularization or stroke/TIA. A multivariable logistic regression model, adjusted for age at diagnosis, body mass index, smoking, alcohol consumption, diabetes, hypertension, CVDs familiarity and periodontitis was performed. Results A prospective cohort of 307 patients has been evaluated; 185 (60.3%) had WL and 122 RL (39.7%). Twenty-four patients had a CVD. ACS occurred more frequently in RL (adjusted odd ratio 5.83; 95%CI: 1.16-29.39), mainly due to the higher risk of it after the histological diagnosis of OLP (odd ratio 4.23; 95%CI: 0.66-27.23). Conclusion Patients with RL could possibly have a higher risk of developing ACS. Further analysis on larger cohort are however warranted. This article is protected by copyright. All rights reserved.

Presence of epithelial desquamation, erythema, and erosions on gingival tissue is usually described in the literature as desquamative gingivitis (DG). A wide range of autoimmune/dermatologic disorders can manifest as DG, although the two more common are oral lichen planus and mucous membrane pemphigoid. The aim of this study is to investigate prevalence of 11 periodontopathogenic microorganisms in patients with DG and to compare it with the microbiologic status of individuals affected by plaque-induced gingivitis (pGI).Cross-sectional clinical and microbiologic data were obtained from 66 patients (33 in each group). Subgingival plaque samples were analyzed using semiquantitative polymerase chain reaction analysis.Statistically significant difference, but with little clinical significance, was observed in gingival conditions between the two groups, probably due to the worse home control hygiene of patients with DG. Prevalence and levels of Aggregatibacter actinomycetemcomitans, Eikenella corrodens, and Fusobacterium nucleatum/periodonticum were statistically higher in samples from patients with DG than in those with pGI. In multivariate regression models, subgingival colonization of A. actinomycetemcomitans and F. nucleatum/periodonticum was not statistically associated with DG, whereas, high levels of E. corrodens were associated with 13-fold increased odds for DG.Microbiologic differences were found in subgingival plaque for patients with DG and pGI. This may suggest possible association between periodontal pathogens and DG.

Oral lichen planus (OLP) is an inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical. However, to date, the most commonly employed and useful agents for the treatment of OLP are topical corticosteroids. The study objective was to detail the clinical effectiveness of low-level laser therapy (LLLT) for the management of OLP unresponsive to standard topical therapy. The authors studied a prospective cohort of 30 patients affected by OLP, who received biostimulation with a 980-nm gallium-aluminum-arsenide (GaAIAs) diode laser (DM980, distributed by DMT S.r.l., Via Nobel 33, 20035, Lissone, Italy). Outcome variables, statistically evaluated, were: the size of lesions; visual analogue score of pain and stability of the therapeutic results in the follow-up period. Eighty-two lesions were treated. We reported significant reduction in clinical scores of the treated lesions and in reported pain. No detailed complications or therapy side effects were observed during the study. As previously reported by our group with a preliminary report, this study suggests that LLLT could be a possible treatment choice for patients with unresponsive symptomatic OLP, also reducing the possible invasiveness correlated with other therapies.

Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure.A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards.The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P 0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P = 0.001]. Based on multivariate analysis, baseline HIV RNA50 copies/mL ( P 0.001), genotypic susceptibility score ≤2 ( P = 0.001), lower nadir CD4 cell count ( P = 0.003) and not being in the adherent group ( P = 0.029) were independent predictors of HIV RNA50 copies/mL at 48 weeks.The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions.

Objectives The aim of this study was to make an initial estimation on the effects of a sodium bicarbonate and xylitol spray (Cariex®), associated with non-surgical periodontal therapy, in participants with primary Sjogren's syndrome. Background Sjogren's syndrome (SS) is a multisystem autoimmune disease that predominantly involves salivary and lachrymal glands, with the clinical effect of dry eyes and mouth. Materials and methods A prospective cohort of 22 women and two men has been evaluated. They were randomized into three groups (eight patients each): Group A) those treated once with non-surgical periodontal therapy, education and motivation to oral hygiene, associated with the use of Cariex®; Group B) treated only with Cariex®; Group C) treated only with non-surgical periodontal therapy, education and motivation to oral hygiene. Clinical variables described after treatment were unstimulated whole salivary flow, stimulated whole salivary flow, salivary pH, reported pain (using Visual Analogue Scale) and the Periodontal Screening and Recording index. Results Salivary flow rate improved in all groups, but the difference was statistically significant only in those treated with Cariex®, alone or in combination with periodontal therapy. Gingival status improved in participants who underwent periodontal non-surgical therapy while remained unchanged in those only treated with Cariex®. Reported pain decreased in all groups, showing the best result in participants treated with periodontal therapy together with Cariex®. Conclusions We propose a practical approach for improving gingival conditions and alleviating oral symptoms in patients with SS. Future randomized and controlled trials are however required to confirm these results as well as larger population, and also assessing other parameters due to oral dryness, possible oral infections and more comprehensive periodontal indices.

Mucous membrane pemphigoid (MMP) describes a group of chronic, inflammatory, sub epithelial blistering diseases that manifest a heterogeneous pattern of oral, ocular, skin, genital, nasopharyngeal, oesophageal, and laryngeal lesions. MMP is histologically characterizedby lineardepositionof IgG, IgA,or C3 along the epithelial basement membrane zone (BMZ). Autoantibodies against various epithelial BMZ components probablyplaya role in thepathogenesisof thisgroupofdiseases [1, 2].MMPdoesnothaveapredictablenatural history. In some patients, the disease is localized and has a slowly progressive course without complications; in others, it is devastating, with severe morbidity. There have been no large-scale, wellcontrolled studies regarding therapy for MMP and most of the therapeutic experience is from studies on cutaneous bullous pemphigoid [3].The choice of agents for its treatment ismainly based upon the sites of involvement, clinical severity, and disease progression [3].Usually, limited oral lesions are treated with topical immunosuppressive drugs. Low-level laser therapy (LLLT) is a novel approach increasingly used in medicine, which has potential biostimulating effects when applied to oral tissues thus improving wound healing [4, 5]. The basic principle of LLLT is based upon the biostimulation or the biomodulation effect: irradiation at a specific wavelength is able to alter cellular behavior. Laser biostimulationcanobtaindifferent intracellular biological reactions to stimulate regenerative abilities, without undesired adverse effects, reducing also the pharmacological support [6–8]. To date, two MMP cases have been described in literature to have been successfully treated with LLLT but in addiction with systemic [9] and topical [10] immunosuppressive therapy. We have reviewed our experience of treating three patients with MMP using only LLLT.

To cite this article: Int J Dent Hygiene 10, 2012; 138–141 DOI: 10.1111/j.1601-5037.2010.00527.x Arduino PG, Lopetuso E, Carcieri P, Giacometti S, Carbone M, Tanteri C, Broccoletti R. Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients. Abstract: Objectives: The aim of this prospective case series was to assess the clinical efficiency of an oral hygiene protocol in patients affected by mucous membrane pemphigoid (MMP) with specific gingival localization, before starting any medical treatment. Methods: Patients received oral hygiene instruction followed by non-surgical periodontal therapy including oral hygiene instructions in a 3-week cohort study. Clinical outcome variables were recorded at baseline and 5 weeks after intervention and included, as periodontal parameters, full mouth plaque (FMPS) and bleeding (FMBS) scores and patient-related outcomes (visual analogue score of pain). Results: A total of 12 patients were recruited. The mean age at presentation was 59.5 ± 14.52 years. Five weeks after finishing the oral hygiene and periodontal therapy protocol, a statistical significant reduction was observed for FMPS (P = 0.001), FMBS (P = 0.022) and reported pain (P = 0.0028). Conclusions: Professional oral hygiene procedures and non-surgical periodontal therapy are connected with improvement of gingival status and decrease in gingival-related pain, in female patients affected by MMP with specific gingival localization.

Oral Diseases (2011) 17 (Suppl. 1), 58–72 Objectives: Human papillomavirus (HPV) in oral carcinoma (OSCC) and potentially malignant disorders (OPMD) is controversial. The primary aim was to calculate pooled risk estimates for the association of HPV with OSCC and OPMD when compared with healthy oral mucosa as controls. We also examined the effects of sampling techniques on HPV detection rates. Methods: Systematic review was performed using PubMed (January 1966–September 2010) and EMBASE (January 1990–September 2010). Eligible studies included randomized controlled, cohort and cross-sectional studies. Pooled data were analysed by calculating odds ratios, using a random effects model. Risk of bias was based on characteristics of study group, appropriateness of the control group and prospective design. Results: Of the 1121 publications identified, 39 cross-sectional studies met the inclusion criteria. Collectively, 1885 cases and 2248 controls of OSCC and 956 cases and 675 controls of OPMD were available for analysis. Significant association was found between pooled HPV-DNA detection and OSCC (OR = 3.98; 95% CI: 2.62–6.02) and even for HPV16 only (OR = 3.86; 95% CI: 2.16–6.86). HPV was also associated with OPMD (OR = 3.87; 95% CI: 2.87–5.21). In a subgroup analysis of OPMD, HPV was also associated with oral leukoplakia (OR = 4.03; 95% CI: 2.34–6.92), oral lichen planus (OR = 5.12; 95% CI: 2.40–10.93), and epithelial dysplasia (OR = 5.10; 95% CI: 2.03–12.80). Conclusions: The results suggest a potentially important causal association between HPV and OSCC and OPMD.

J Oral Pathol Med (2010) 40: 510–515 Objective: To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ). Methods: Test subjects were 30 Italian female patients with BRONJ (Group A). Control subjects were 30 female patients with a history of intravenous bisphosphonate use without any evidence of osteonecrosis (Group B) and 125 unrelated healthy volunteers (Group C). Three single-nucleotide polymorphisms were investigated: −634 G>C, occurring in 5′ untranslated region (UTR); +936 C>T, occurring in 3′ UTR; and −2578 C>A of the promoter region. Results: The frequency of the VEGF CAC (+936/−2578/−634) haplotype was increased in patients with BRONJ, compared with female disease-negative controls [odds ratio (OR) = 2.76, 95% CI = 1.09–4.94, P = 0.039; corrected P value: Pc = 0.117], and was also increased compared with female healthy controls (OR = 2.11, 95% CI = 1.14–3.89, P = 0.024; corrected P value: Pc = 0.072). The CC homozygotes of −634G>C of VEGF gene and AA homozygotes of −2578C>A have also been significantly correlated in female patients who developed BRONJ compared with healthy controls (OR = 2.04, 95% CI = 1.12–3.70, P = 0.008; corrected P value: Pc = 0.024). Conclusions: These results suggest a possible haplotype effect of VEGF polymorphisms expression in BRONJ Italian female patients. Studies with different and larger populations possibly using TagSNP to represent all haplotypes within the VEGF gene are needed to further delineate the genetic contribution of this gene to BRONJ.

J Oral Pathol Med (2011) 40: 214–217 Purpose: To test the hypothesis that cigarette smokers develop oral potentially malignant disorders or carcinomas in preferential anatomical subsites. Methods: The association of smoking habit with the presence of oral lesions in specific anatomical subsites was assessed in 123 patients using the odds ratio analysis. Results: When compared to all the other subsites, the relative frequency of smokers with lesions was higher in the buccal mucosa and in the floor of the mouth (FOM) (P = 0.002 and P = 0.005), while it was lower in the tongue (P

Oral Diseases (2010) 17, 90–94 Objective: To evaluate the periodontal status of mucous membrane pemphigoid (MMP) patients and compare it with that of healthy controls. Methods: A prospective study was undertaken to examine the impact of gingival MMP lesions on the human periodontium of 29 patients. Parameters evaluated included full mouth plaque score (FMPS), full mouth bleeding upon probing scores, probing depths (PD), gingival recession, clinical attachment level (CAL), mobility score, furcation involvement, number of missing teeth and Machtei criteria. Results: All periodontal parameters recorded were increased in cases when compared to controls in univariate statistics. The mean differences between groups in PD (0.8 ± 0.2 mm, 95% CI 0.3–1.3), CAL (1.3 ± 0.4 mm, 95% CI 0.4–2.2), FMPS (41.0 ± 6.2%, 95% CI 28.7–53.4), FMBS (16.2 ± 6.6%, 95% CI 3.0–29.4) and tooth loss (2 ± 1 teeth, 95% CI 1–3) were all statistically significant (P

Objectives The aim of this study was to evaluate the 2-year success rate of management of patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ). Study design A prospective study was performed. Positive outcome variables were the resolution of symptoms and the status of the mucosa. Results A total of 37 patients are described. The precipitating event was a dental extraction in 22 cases (59.5%). Thirteen patients (35.1%) underwent surgery, and 24 (64.9%) underwent antimicrobial therapy alone. After 2 years, 20 patients (54.1%) presented with soft tissue closure over previously exposed bone, and there were no statistical differences in gender, age, bisphosphonate treatment, or treatment modalities. Spontaneous lesions seemed to have a worse prognosis (P = .001). Conclusions Initial antimicrobial treatment, and later surgery for unresponsive patients, might be a feasible treatment modality for BRONJ. Because these results are not conclusive, it would be very interesting to know if this statement would be the same with a greater number of patients.

The aim of this study was to evaluate the therapeutic benefit of minocycline in mucous membrane pemphigoid (MMP) predominantly involving the oral cavity. A descriptive, open clinical study with no control group, including 9 patients, was developed. The diagnosis was confirmed by histopathological examination and direct and salt-split-skin indirect immunofluorescence analysis. Target antigens were sought by immunoblotting. Patients received minocycline (200 mg/day) for a variable period.. All patients were followed up for at least 2 years after initial diagnosis. Therapeutic response was assessed by clinical improvement in three categories: major response, minor response and no response. A major response was observed in 3 patients (33%), a minor response in 4 (44%) and 2 (22%) patients showed no improvement. Two of the 3 patients with a major response showed no immunoblot reactivity; 80% of patients with circulating autoantibodies (autoAb) against BP180 had a minor or no response. Permanent remission of signs with no relapse was only obtained in one patient. 5 patients (55%) stopped the drug because of adverse effects, such as vertigo and gastralgia. The results revealed temporary clinical benefits in MMP predominantly involving the oral cavity with minocycline, although frequently side effects led to drug withdrawal.

Cell-cell and cell-matrix interactions regulate important cellular functions; they involve a number of specialised molecules and the corresponding receptors, among which a key role is played by cadherins and the associated catenins. Deregulation of these molecules has been associated with tumour progression in many human malignancies. While catenins expression has been extensively studied in many human cancers, including oral carcinoma (OSCC), less is known about their expression in oral epithelial dysplasia. The objective of this study was to evaluate the expression of these proteins in a large group of displastic lesions of the oral mucosa and their relation with subsequent malignant transformation. Expression of beta- and gamma-catenin was investigated by immunohistochemistry using specific monoclonal antibodies in 49 cases of oral epithelial dysplasia and 10 samples of normal oral mucosa. The presence and absence of beta- and gamma-catenin staining was expressed differently in relation to dysplasia grade; while the degree of dysplasia became more severe, we observed a statistically significant loss and/or reduction of catenins expression, the loss of the exclusive membranous expression and a cytoplasmic delocalisation. Progression to OSCC occurred in 10 out of our 49 cases (20.4%); all of them, except one, showed a concurrent and concordantly located beta- and gamma-catenin staining even, if no statistically significant differences were found between cases progressed to invasive OSCC or not. Catenins physiology alterations may be involved in the transformation process; however, the role of catenins expression as possible prognostic markers in precancerous oral lesions seems to be limited. Nonetheless, further studies on larger series of samples are necessary in order to clarify the role of catenins expression in oral carcinogenesis from both a biological and clinical point of view.

Objectives: To undertake a retrospective inspection of the general features, clinical presentation and outcome of 808 Italian patients with oral lichen planus (OLP), followed up from 6 months to 17 years. Results: The mean age was 61 years for women (n = 493) and 58 years for men (n = 315). More than 20% of the total cases had liver abnormalities (n = 164) of which 83.5% infected with hepatitis C virus (n = 137). The reticular and plaque form were the predominant type, affecting almost 60% of patients. 12.3% of patients had also extraoral manifestation, taking into account the skin (n = 63) and genital (n = 24). Symptoms were present in 40% of the total patients. Only less than 2.47% of patients underwent remission, whereas 78% still had oral lesions at the end of the follow-up period. Treatment was directed towards almost 42% of the patients, mainly using topical corticosteroids. Oral squamous cell carcinoma developed in 15 patients, commonly arising on the lateral border of the tongue. Conclusion: This is one of the largest groups of OLP patients with such long a follow-up ever reported. We confirm the chronic nature of this disorder, rarely remissive and the treatment intend for alleviating symptoms. OLP is established to be a disease with small frequency of malignant transformation.

Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical and do not have adequate control groups or correct study designs. However, to date, the most commonly employed and useful agents for the treatment of LP are topical corticosteroids. A randomized, double-blind, placebo-controlled trial has been designed to compare the efficacy and safety of two different formulations of clobetasol, a very potent topical steroid, in the topical management of OLP and to evaluate which gives the longest remission from signs and symptoms. Thirty-five consecutive patients were divided into two groups: the first received clobetasol propionate 0.025% and the second was given clobetasol propionate 0.05%. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Anti-mycotic prophylaxis was also added. After the end of therapy, patients received a 2-month follow-up. In all, 14 of the 15 clobetasol 0.025% patients (93%) and 13 of the 15 clobetasol 0.05% patients (87%), had symptoms improvement after 2 months of therapy (P = 0.001 in both groups). Also, 13 of the 15 clobetasol 0.025% patients (87%) and 11 of the 15 clobetasol 0.05% patients (73%) had clinical improvement after 2 months of therapy (P < 0.05 in both groups). No statistical differences were found in comparing the two different formulations. A larger concentration of the active molecules cannot further improve the therapeutic findings or optimize the obtained results in a significant manner.

Patients affected by polycythemia vera (PV), a myeloproliferative neoplasm characterized by an elevated red blood cell mass, are at high risk of vascular and thrombotic complications. Conventional therapeutic options aim at reducing vascular and thrombotic risk; low-dose aspirin and phlebotomy are first-line recommendations, for patients at low risk of thrombotic events, whereas cytoreductive therapy, usually hydroxyurea (HU) or interferon alpha, is recommended for high-risk patients. In the present study, we report the case of a patient with persistent oral ulcerations, possibly related to long-lasting HU treatment, firstly treated with topic and systemic corticosteroids and then more effectively with the addition of low-level laser therapy. Laser photobiomodulation has achieved pain control and has contributed to the healing of oral ulcers without any adverse effect; this has permitted a reduction in the dose of systemic corticosteroids and the suspension of the use of the topic ones, due to the long-term stability of oral health, even after the interruption of low-level laser therapy sessions.

Comparison between low-level laser therapy (LLLT) and clonazepam for treating burning mouth syndrome (BMS) patients has never been documented; the aim of this study was to assess the effects of LLLT photobiomodulation versus medical therapy with clonazepam on BMS. Thirty-three patients (25 female, 8 male, mean age = 67.12) were randomly allocated to two different groups: the first one (group A, 18 patients) underwent two laser irradiation sessions weekly for 5 weeks, whereas the second one (group B, 15 patients) received topical clonazepam therapy [half a tablet (2 mg) in the mouth without swallowing for 3 min, three times a day for 21 days]. LLLT was delivered with a continuous wave 980-nm aluminum gallium arsenide (AlGaAs) diode laser and the output of 300 mW, delivering a Fluence of 10 J/cm(2), using a "spot technique," with an average power density of about 1 W/cm(2). The laser probe was held perpendicularly at a distance of about 2 mm from the mucosa. Visual analogue scale (VAS), McGill Pain Questionnaire, present pain intensity (PPI), and Oral Health Impact Profile (OHIP-49) assessed sensation of pain. Hospital Anxiety and Depression Scale and Geriatric Depression Scale assessed levels of anxiety and depression. Twelve weeks after the end of treatment, patients treated with LLLT experienced a decrease in pain sensation reported for all the parameters analyzed: VAS (P = 0.004), McGill Pain Questionnaire (P = 0.002), PPI (P = 0.002), and OHIP-49 (P = 0.010). The group treated with clonazepam had less favorable results for VAS (P = 0.33), McGill Pain Questionnaire (P = 0.005), PPI (P = 0.013), and OHIP-49 (P = 0.25). Levels of anxiety and depression did not change statistically in any groups (P > 0.05). Comparing the two groups, LLLT appeared to be superior in improving pain perception, but statistically only at 8 weeks after the end of the protocol proposed (P = 0.026). Based on this preliminary trial, LLLT is capable of reducing the symptoms of patients with BMS with a constant and long-lasting effect, experienced since the end of the first applications.

Herpes Simplex Virus Type 1 (HSV-1) is a nuclear replicating enveloped virus, usually acquired through direct contact with infected lesions or body fluids (typically saliva). The prevalence of HSV-1 infection increases progressively from childhood, the seroprevalence being inversely related to socioeconomic background. Primary HSV-1 infections in children are either asymptomatic or following an incubation period of about 1 week gives rise to mucocutaneous vesicular eruptions. Herpetic gingivostomatitis typically affects the tongue, lips, gingival, buccal mucosa and the hard and soft palate. Most primary oro-facial HSV infection is caused by HSV-1, infection by HSV-2 is increasingly common. Recurrent infections, which occur at variable intervals, typically give rise to vesiculo-ulcerative lesions at mucocutaneous junctions particularly the lips (herpes labialis). Recurrent HSV-1 infection within the mouth is uncommon in otherwise healthy patients, although in immunocompromised patients, recurrent infection can be more extensive and/or aggressive. The diagnosis of common herpetic infection can usually be based upon the clinical history and presenting features. Confirmatory laboratory diagnosis is, however, required when patients are, or may be, immunocompromised.

Mucous membrane pemphigoid (MMP) comprises a heterogenous group of autoimmune subepithelial bullous diseases very frequently having oral involvement. Very few studies have investigated the immunological status of a subset of MMP, termed oral pemphigoid (OP), presenting with exclusive oral lesions. In this study we show that 75% of 20 OP patients without scarring phenotype possessed circulating autoantibodies against the BP180 molecule, indicating a prominent role of this protein as a target antigen in OP. Of note, the frequency of reactivity against BP180 ectodomain epitopes in OP was similar to that previously reported for MMP with cicatricial phenotype, while the lack of significant recognition of BP180 intracellular domain appears to characterize OP with respect to other diseases of the pemphigoid group. Finally, the combined use of sensitive techniques allowed the detection of circulating autoantibodies in 90% of OP patients, supporting the usefulness of this approach in the diagnosis of MMP disease.

Herpes simplex virus type 1 (HSV-1) gives rise to a variety of clinical disorders and is a major cause of morbidity and mortality worldwide. HSV-1 infections are common in oral and perioral area. The aim of the present report was to critically examine the published literature to evaluate the advantages and limitations of therapy of HSV-1 infection in both immunocompetent and immunocompromised patients. Systemic antiviral therapy has been widely accepted as effective for primary herpetic gingivostomatitis. Aciclovir (ACV) 5% cream seems to be the accepted standard topical therapy for herpes labialis, being both effective and well tolerated, although penciclovir 1% cream has been proposed as a potentially useful treatment. Systemic ACV may be effective in reducing the duration of symptoms of recurrent HSV-1 infection, but the optimal timing and dose of the treatment are uncertain. Aciclovir and famciclovir may be of benefit in the acute treatment of severe HSV-1 disease in immunocompromised patients. There is also evidence that prophylactic oral ACV may reduce the frequency and severity of recurrent attack of herpetic infection in immunocompromised patients, but the optimal timing and duration of treatment is uncertain and can vary in different situations.

Summary Background Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, especially in the atrophic and erosive forms. Several drugs have been used with varying results, but most treatments are empirical, and do not have adequate control groups or correct study designs. Objectives To compare the effectiveness of clobetasol and ciclosporin in the topical management of OLP and to evaluate which is more cost-effective and which gives the longest remission from signs and symptoms. Methods A randomized, comparative, double-blind study was designed. Forty consecutive patients were divided into two groups to receive clobetasol propionate or ciclosporin for 2 months. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Antimycotic prophylaxis was also given. After the end of therapy, patients underwent a 2-month follow-up. Results Eighteen of 19 clobetasol-treated patients (95%) improved after 2 months of therapy, while 13 of 20 ciclosporin-treated patients (65%) had a clinical response (P = 0·04). Symptomatology improved in 18 clobetasol-treated patients (95%) and in 17 ciclosporin-treated patients (85%) (not statistically significantly different). Two months after the end of therapy, 33% of clobetasol-treated patients and 77% of ciclosporin-treated patients were stable (P = 0·04). Clobetasol produced significantly more side-effects than ciclosporin (P = 0·04). The daily cost of ciclosporin treatment was 1·82 € compared with 0·35 € for clobetasol therapy. Conclusions Clobetasol is more effective than ciclosporin in inducing clinical improvement, but the two drugs have comparable effects on symptoms. Conversely, clobetasol gives less stable results than ciclosporin when therapy ends and has shown a higher incidence of side-effects. The daily cost of ciclosporin is more than five times higher than clobetasol.

Most lymphocytes in the lamina propria of oral lichen planus (OLP) lesions express and secrete interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), whereas they do not secret interleukin-4 and -10 or transforming growth factor-beta. We analyzed whether the polymorphisms of several cytokines may influence the susceptibility to OLP. Cytokine typing was performed by a sequence-specific PCR assay. Thirteen cytokine genes with 22 single-nucleotide polymorphisms were studied. IFN-gamma UTR 5644 genotype frequencies showed a significant increase in number of T/T homozygotes in OLP patients compared with controls (40.9 vs. 22.9%; p=0.0022). Moreover, in OLP patients, the frequency of the -308A TNF-alpha allele was higher than in the controls (21.6 vs. 9.3%; p0.05) causing a significantly increased frequency of the genotype G/A in OLP (43.2 vs. 14.3%; p=0.0002). Because in patients with mucocutaneous lichen planus (LP), the frequency of the -308A TNF-alpha allele was more than double the values in the pure OLP patients (40.9 vs. 15.1%; p=0.003), the -308G/A TNF-alpha genotype showed a significantly higher frequency in patients with mucocutaneous LP than in patients with pure OLP (81.8 vs. 30.3%, p=0.003). In conclusion, we suggest that genetic polymorphism of the first intron of the promoter gene of IFN-gamma may be an important risk factor to develop oral lesions of LP, whereas an increase in the frequency of -308A TNF-alpha allele may best contribute to the development of additional skin involvement.

Sjogren's syndrome (SS) is a multisystem autoimmune disease characterized by hypofunction of the salivary and lacrimal glands, frequently relieved with symptomatic treatments, such as saliva substitutes, eye lubricants, and cholinergic stimulators. The aim of this pilot randomized placebo-controlled study was to estimate the effects of laser acupuncture on salivary flow rates in patients with severe hyposalivation due to SS. A prospective cohort of 26 female patients affected by SS has been evaluated. The laser therapy equipment used was the Pointer Pulse, emitting light in the red visible spectrum (650 nm), with a power of 5 mW and an irradiation time of 120 s per acupoint, in an area of 3.14 mm(2) (fluence = 19.2 J/cm(2), power density = 0.16 W/cm(2), total dose = 0.6 J). The following acupuncture points were stimulated bilaterally: LI 2 Erjian, ST 5 Daying, ST 6 Jiache, ST 7 Xiaguan, SI 19 Tinggong, and BL 13 Feishu. True laser acupuncture led to a significantly higher amount of saliva production, measured after the end of the protocol (5 weeks), and during the 6-month follow-up period. The results are stable from the end of the protocol until the 3rd month of follow-up; during the last control, a slight but significant decrease in production has also been shown. This preliminary study proposes laser acupuncture as a possible treatment for improving salivary flow rates in patients with SS, but further validation on a larger sample is still necessary.

A 55-year-old man with a history of acute myeloid leukaemia treated with hematopoietic stem cell transplantation and with a 5-year history of bisphosphonate-related osteonecrosis of the jaws, following 12 cycles of intravenous zoledronic acid therapy, presented in December 2009 with a history of increasingly severe unilateral lower jaw pain. Oral examination revealed, as previously, exposed bone in the left mandible, but also a new exophytic mass on the lower-left buccal mucosa. Biopsy confirmed a diagnosis of oral squamous cell carcinoma. To the best of our knowledge, this is the first report of an oral squamous cell carcinoma that appeared adjacent to an area of osteochemonecrosis.

Objectives Current recommendations for safe and effective dental management are less than optimal for some medical conditions because of limited evidence, conflicting conclusions, or both. This review (1) compiled and evaluated dental management recommendations for select medical conditions; (2) summarized recommendations and their assigned levels of evidence; (3) identified areas of conflict, ambiguity, or both; and (4) identified issues that warrant future research, enhanced consensus statements, or both. Study Design Systematic literature searches were performed for guideline publications, systematic and narrative reviews, and opinion documents containing recommendations for (1) medication-related osteonecrosis of the jaw (MRONJ); (2) cardiovascular diseases (CVDs); (3) prosthetic joints (PJs); and (4) systemic steroid therapy (SST). Results The search yielded the following numbers of publications that met the inclusion criteria: MRONJ – 116; CVDs – 54; prosthetic joints – 39; and systemic steroids – 12. Conclusions Very few of the compiled recommendations were assigned or linked to levels of evidence by their authors. Key conclusions include the following: MRONJ–expert recommendations trend toward proceeding with dental treatment with little to no modification in osteoporotic patients on bisphosphonates; CVDs–current recommendations are primarily directed to general surgery and applied to dentistry; PJs–routine antibiotic prophylaxis is not indicated for dental treatment; and SST–steroid supplementation is not indicated for most patients undergoing dental procedures under local anesthesia.

The surgical removal of mandibular third molars is frequently accompanied by significant postsurgical sequelae, and different protocols have been described to decrease such adverse events. The aim of this study was to investigate the performance of piezosurgery compared with traditional rotating instruments during mandibular third molar removal.A single-center, randomized, split-mouth study was performed using a consecutive series of unrelated healthy patients attending the Oral Surgery Unit of the University of Turin for surgical removal of bilateral mandibular third molar teeth. Each patient was treated, at the same appointment, using bur removal on 1 side of the mandible and a piezoelectric device on the contralateral side. The primary outcomes reported were postoperative pain, objective orofacial swelling, and surgical duration; secondary outcomes were gender, age, and possible adverse events. Analysis of variance or paired t test was used as appropriate to test any significant differences at baseline according to each treatment subgroup, and categorical variables were analyzed by χ(2) test.The study sample consisted of 100 otherwise healthy patients. The mean pain evaluation reported by patients who underwent surgery with piezosurgery was significantly lower than that reported after bur (conventional) removal, reaching statistical difference after 4 days (P = .043). The clinical value of orofacial swelling at day 7, normalized to baseline, was lower in the piezosurgery group (P.005). The average surgical duration was significantly shorter in the bur group than in the piezosurgery group (P.05). Three patients having bur removal developed short-term complications (2 dry sockets and 1 temporary paraesthesia), which totally resolved by 4 weeks.To date, this prospective investigation is the largest reported split-mouth study on piezosurgery for lower third molar tooth removal. This study also compared surgeons with different degrees of experience. It is evident that using a piezoelectric device can enhance the patient experience and decrease postoperative pain and swelling.

Background: Oral lichen planus (OLP) is a chronic inflammatory disease, affecting nearly 1-2% of the population; Proposed therapies are usually symptomatic and numerous drugs have been used, but recently, it has been published that there is insufficient evidence to support the effectiveness of any specific treatment as being superior. To the best of our knowledge, direct evaluation of the efficacy of topically applied pimecrolimus and tacrolimus in the treatment of atrophic-erosive OLP, refractory to topical steroids, is still lacking. Objectives: To assess the efficacy and safety of topical calcineurin inhibitors for unresponsive OLP. An 8 week randomized, double-blind controlled trial, followed by a 6 month follow-up period. Patients were treated with either pimecrolimus 1% cream or tacrolimus 0.1% ointment, both mixed with an equivalent amount of 4% hydroxyethyl cellulose gel. The medications were to be applied twice daily for 2 months. Each patient was examined at the beginning of therapy, and then every 2 weeks during the treatment and every 3 months of follow-up. Main outcome measures were: (i) to compare the effectiveness of topically applied pimecrolimus and tacrolimus; (ii) to evaluate which is more cost-effective; (iii) to determine which drug is faster in reducing signs and symptoms and (iv) which gives the longest remission. Results: Thirty patients were involved in the study. Both drugs were effective at inducing clinical improvement, with no statistical difference. Pimecrolimus creams revealed a significantly better stability of the therapeutic effectiveness (P = 0.031). Conclusion: Both medications would currently appear to be a treatment of choice for patients with unresponsive atrophic-erosive OLP. Pimecrolimus seemed to be more effective in providing long-term resolution of signs and symptoms. Future efforts are however needed to obtain more objective evidence of the benefit of these medications in the treatment of immunologically mediated oral mucosal lesion. © 2013 European Academy of Dermatology and Venereology.

The aim of this randomized two-center study was to compare quantic molecular resonance scalpel (QMRS) with traditional scalpel (TS) for the surgical treatment of labial mucoceles, in terms of impact on quality of life and postoperative pain (primary outcomes) and postsurgical lip paresthesia and recurrence of the lesion (secondary outcomes).Eighty-five consecutive patients with labial mucoceles were randomized to receive traditional (46) or QMRS surgery (39) in two Italian University Hospital Centers. Patients were asked to complete three different forms during the first week after surgery to evaluate quality of life and postoperative pain. Periodic follow-up examinations were conducted at 1 week, 1 month, and 3 months after surgery, in order to detect recurrence of lesion and/or lip paresthesia.Regarding the symptoms reported during the first week after surgery, questionnaires given to the patients and the mean painkiller consumption did not demonstrate any statistically significant differences within the two groups. Women treated with QMRS reported a worse experience than women treated with TS (P.05). Among all the mucoceles treated, during the follow-up period of 3 months, one that had been eliminated with the cold scalpel was seen to relapse, versus none of those treated with the QMRS (P = 1.0). We reported a localized and terminal paresthesia of the labial mucosa close to the surgical site in 10.58% of the total patients. Comparing the QMRS with TS, we observed a greater incidence of neurologic complications with the latter technique (P = .035).This is the first prospective randomized study to report outcome data and 3-month follow-up of a cohort of patients suffering from labial mucoceles. QMRS for surgical removal of labial mucoceles seems to be comparable to traditional scalpel in terms of postoperative quality of life, pain, and postsurgical lip paresthesia.

Objectives. The aim of this pilot study was to describe the clinical efficacy of a conservative oral hygiene protocol in patients affected by gingival pemphigus vulgaris (PV) applied in a case series.Methods. Subjects suffering from PV with gingival localisation and slightly responsive to conventional treatment with systemic corticosteroids and immunosuppressive drugs were selected among individuals treated in the Unit of Oral Medicine Section of the University of Turin. Five subjects received nonsurgical periodontal therapy, over a 7-day period, including oral hygiene instructions; patients were instructed about domiciliary oral hygiene maintenance and instructions were reinforced at each visit and personalised if necessary. Clinical outcome variables were recorded at baseline (before starting) and 16 weeks after intervention, including full mouth plaque score (FMPS), bleeding scores (FMBS), probing pocket depth (PPD), oral pemphigus clinical score (OPCS), and patient related outcomes (visual analogue score of pain).Results. Five patients were treated and, after finishing the proposed therapy protocol, a statistical significant reduction was observed for FMBS (P=0.043) and OPCS (P=0.038).Conclusions. Professional oral hygiene procedures with nonsurgical therapy are related to an improvement of gingival status and a decrease of gingival bleeding in patients affected by PV with specific gingival localization.

Purpose The aim of this prospective hospital-based study was to refine a surgical protocol for tooth extractions in patients with a history of intravenous use of a potent bisphosphonate by modifying a previously reported protocol to produce a significantly shortened operating time. Patients and Methods Prospective patients with a follow-up of at least 4 months were included. Tooth extractions were performed without a vestibular split-thickness flap; healing was stimulated by filling the extraction site with autologous plasma rich in growth factors (PRGF System, BTI Biotechnology Institute, Vitoria, Spain). Local and systemic infection control was obtained with dental hygiene and antibiotic therapy. Results Sixty-three patients participated in the study. Two hundred two tooth extractions were performed. Differences between the present and previous protocols (the previous protocol used a vestibular flap) were analyzed and the surgical time proved significantly shorter for the present approach ( P = .00). Conclusions The proposed surgical protocol appears to be a better choice for patients treated with intravenous bisphosphonates who need tooth extraction, because it seems to be faster and simpler than the previously reported successful protocol.

Xerostomia is a frequent salivary complaint, especially in elderly people, typically caused by Sjogren’s syndrome, uncontrolled diabetes mellitus, radiation to the head and neck, chemotherapy, and different medications. Above all, drugs are the most common reason of reduced salivation, and the medications most commonly implicated are tricyclic antidepressants, antipsychotics, atropinics, beta-blockers and antihistamines. Nizatidine is a histamine H2-receptor antagonist used in the treatment of peptic ulcer and gastro-esophageal reflux disease. In the past, salivary secretion has been reported to increase when nizatidine was administered to healthy volunteers, patients with dry mouth and patients with primary Sjo¨ gren’s syndrome. In the present study, we tried to analyze the efficacy of nizatidine on both dry mouth symptoms and salivary secretion in patients affected by idiopathic xerostomia.

Bisphosphonates are used in the treatment of hypocalcaemia, mainly in cancer and osteoporosis. Some patients experience adverse events, such as BP-related osteonecrosis of the jaw (BRONJ). DNA methylation plays a key role in gene regulation in many tissues, but its involvement in bone homeostasis is not well characterized, and no information is available regarding altered methylation in BRONJ. Using the Illumina Infinium HumanMethylation27 BeadChip assay, we performed an epigenome-wide association study in peripheral blood samples from 68 patients treated with nitrogenous BP, including 35 with BRONJ. Analysis of the estimated cumulative BP exposure distribution indicated that the exposure of the case group to BP was slightly higher than that of the control group; more severely affected cases (i.e., with BRONJ in both mandible and maxilla) were significantly more exposed to BP than were those with BRONJ only in the mandible or maxilla (one-sided Wilcoxon rank sum test, p=0.002). Logistic regression analysis confirmed the positive association between cumulative bisphosphonates exposure and risk of BRONJ (OR 1.015 per mg of cumulative exposure, 95% CI 1.004-1.032, p=0.036). Although no statistically significant differences were observed between case and control groups, methylation levels of probes mapping on three genes, ERCC8, LEPREL1 and SDC2, were strongly associated with cumulative BP exposure levels (p1.31E-007). Enrichment analysis, combining differentially methylated genes with genes involved in the mevalonate pathway, showed that BP treatment can affect the methylation pattern of genes involved in extracellular matrix organization and inflammatory responses, leading to more frequent adverse effects such as BRONJ. Differences in DNA methylation induced by BP treatment could be involved in the pathogenesis of the bone lesion.

Plasma cell gingivitis (PCG) is a rare, benign inflammatory condition of unclear etiology with no definitive standard of care ever reported to our knowledge. The aim of this case series is to ascertain the clinical efficacy of professional oral hygiene and periodontal therapy in younger individuals with a histologically confirmed diagnosis of PCG.All patients received non-surgical periodontal therapy, including oral hygiene instructions, and thorough supragingival scaling and polishing with the removal of all deposits and staining combined with the use of antimicrobials in a 9-week cohort study. Clinical outcome variables were recorded at baseline and 4 weeks after the intervention and included, as periodontal parameters, full-mouth plaque scores (FMPS), full-mouth bleeding scores (FMBS), the clinical extension of gingival involvement, and patient-related outcomes (visual analog score of pain).A total of 11 patients (six males and five females; mean age: 11 ± 0.86 years) were recruited. Four weeks after finishing the oral hygiene and periodontal therapy protocol, a statistically significant reduction was observed for FMPS (P = 0.000), FMBS (P = 0.000), reported pain (P = 0.003) and clinical gingival involvement (P = 0.003).Standard, professional oral hygiene procedures and non-surgical periodontal therapy including antimicrobials were associated with a marked improvement of clinical and patient-related outcomes in pediatric cases of PCG.

To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ).Test subjects were 30 Italian female patients with BRONJ (Group A). Control subjects were 30 female patients with a history of intravenous bisphosphonate use without any evidence of osteonecrosis (Group B) and 125 unrelated healthy volunteers (Group C). Three single-nucleotide polymorphisms were investigated: -634 GC, occurring in 5' untranslated region (UTR); +936 CT, occurring in 3' UTR; and -2578 CA of the promoter region.The frequency of the VEGF CAC (+936/-2578/-634) haplotype was increased in patients with BRONJ, compared with female disease-negative controls [odds ratio (OR) = 2.76, 95% CI = 1.09-4.94, P = 0.039; corrected P value: P(c) = 0.117], and was also increased compared with female healthy controls (OR = 2.11, 95% CI = 1.14-3.89, P = 0.024; corrected P value: P(c) = 0.072). The CC homozygotes of -634GC of VEGF gene and AA homozygotes of -2578CA have also been significantly correlated in female patients who developed BRONJ compared with healthy controls (OR = 2.04, 95% CI = 1.12-3.70, P = 0.008; corrected P value: P(c) = 0.024).These results suggest a possible haplotype effect of VEGF polymorphisms expression in BRONJ Italian female patients. Studies with different and larger populations possibly using TagSNP to represent all haplotypes within the VEGF gene are needed to further delineate the genetic contribution of this gene to BRONJ.

To evaluate the periodontal status of mucous membrane pemphigoid (MMP) patients and compare it with that of healthy controls.A prospective study was undertaken to examine the impact of gingival MMP lesions on the human periodontium of 29 patients. Parameters evaluated included full mouth plaque score (FMPS), full mouth bleeding upon probing scores, probing depths (PD), gingival recession, clinical attachment level (CAL), mobility score, furcation involvement, number of missing teeth and Machtei criteria.All periodontal parameters recorded were increased in cases when compared to controls in univariate statistics. The mean differences between groups in PD (0.8±0.2mm, 95% CI 0.3-1.3), CAL (1.3±0.4mm, 95% CI 0.4-2.2), FMPS (41.0±6.2%, 95% CI 28.7-53.4), FMBS (16.2±6.6%, 95% CI 3.0-29.4) and tooth loss (2±1 teeth, 95% CI 1-3) were all statistically significant (P0.01 for all). Substantial differences in domiciliary oral hygiene routines were observed (P0.0001). In multivariate models when FMPS was included as covariate the difference between groups in all clinical periodontal parameters was no longer statistically significant.Our results showed that periodontal status is worse in MMP patients if compared with healthy controls due to a substantial difference in oral hygiene. Oral health should be promoted in MMP.

Purpose More cases of osteonecrosis of the jaws in patients treated with intravenous bisphosphonates have been reported. The aim of this prospective hospital-based study was to detail a surgical protocol for teeth extraction in such patients. Patients and Methods Prospective patients with a follow-up of at least 4 months were included. A surgical procedure using an ultrasonic surgical apparatus (Mectron Piezosurgery Device, Mectron Medical Technology, Carasco, Italy) was undertaken. Healing was stimulated by filling the extraction site with autologous plasma rich in growth factors (PRGF System, BTI Biotechnology Institute, Vitoria, Spain). Local and systemic infection controls were also obtained with antibiotic therapy. Results Sixty-four patients took part in the study. Two hundred twenty teeth extractions were performed in a surgical setting. Bisphosphonate-related osteonecrosis of the jaw occurred in 5 postextraction sites (2.27%); no statistical differences could be reported regarding age, gender, duration of bisphosphonate treatment, concomitant corticosteroid therapy, mean surgical time, and patients' underlying diseases. In contrast, the mandible appeared to be at greater risk than the maxilla to develop bisphosphonate-related osteonecrosis of the jaw (P = .0342). Conclusions Even with many limitations, the proposed surgical protocol appears to be a possible choice for patients treated with intravenous bisphosphonates who need teeth extraction. Further prospective, possibly randomized studies are necessary to determine if this statement would be the same with larger patient samples in different clinical settings.

Purpose To report a case series of patients with the nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw—a form of jaw osteonecrosis that does not manifest with necrotic bone exposure/mucosal fenestration. Methods Among 332 individuals referred to 5 clinical centers in Europe because of development of jawbone abnormalities after or during exposure to bisphosphonates, we identified a total of 96 patients who presented with the nonexposed variant of osteonecrosis. Relevant data were obtained via clinical notes; radiological investigations; patients' history, and referral letters. Results The most common clinical feature of nonexposed osteonecrosis was jaw bone pain (88/96; 91.6%); followed by sinus tract (51%), bone enlargement (36.4%); and gingival swelling (17.7%). No radiological abnormalities were identified in 29.1% (28/96) of patients. In 53.1% (51/96) of the patients; nonexposed osteonecrosis subsequently evolved into frank bone exposure within 4.6 months (mean; 95% confidence interval; 3.6-5.6). Conclusions Clinicians should be highly vigilant to identify individuals with nonexposed osteonecrosis, as the impact on epidemiological data and clinical trial design could be potentially significant. Although the present case series represents approximately 30% of all patients with bisphosphonates-associated osteonecrosis observed at the study centers, further population-based prospective studies are needed to obtain robust epidemiological figures.