Abstract 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.
Summary Objectives: The clinical management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains controversial. Since universally accepted guidelines have not been released yet, ...clinicians usually chose the type of treatment according to position papers based on expert opinion, or on empirical experience. The aim of this systematic review is to identify different therapeutical approaches for BRONJ that have been described in literature and to describe their effectiveness. Materials and Methods: A Medline via Pubmed and Scopus database literature search was conducted and all publications fulfilling the inclusion and exclusion criteria were included in eligibility assessment. The full texts of 146 retrieved articles were then screened and 40 studies were included in the quality assessment process. Results: After quality assessment, 22 full text articles were selected for the final review. 14 articles out of 22 were screened for stage-related outcomes. The overall outcome results and results for every disease stage were the highest when patients were treated with extensive surgery or extensive laser assisted surgery.
The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on ...the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference-held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)-after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.
Background: The aberrant expression of microRNAs (miRNAs) has been associated with several diseases, including cancer, inflammatory, and autoimmune conditions. Interest in salivary miRNAs as ...non-invasive tools for the diagnosis of malignancies and systemic diseases is rapidly increasing. The present systematic review was developed for answering the question: "Are salivary microRNAs reliable biomarkers for diagnosis of cancer and systemic diseases?"
The application of inclusion and exclusion criteria led to the selection of 11 papers. Critical appraisals and quality assessments of the selected studies were performed through the National Institute of Health "Study Quality Assessment Tool" and the classification of the Oxford Center for Evidence-Based Medicine.
Seven studies reported statistically significant correlations between one or more salivary miRNAs and the investigated disease. The critical analysis allowed us to classify only two studies (18.2%) as having "good" quality, the rest being scored as "intermediate" (8; 73%) and "poor" (1; 9%). Evidence exists that salivary miR-940 and miR-3679-5p are reliable markers for pancreatic cancer and that miR140-5p and miR301a are promising molecules for the salivary diagnosis of gastric cancer.
Further studies, possibly avoiding the risk of bias highlighted here, are necessary to consolidate these findings and to identify new reliable salivary biomarkers.
Biological tissues (including oral mucosa) can absorb and re‐emit specific light wavelengths, detectable through spectrophotometric devices. Such a phenomenon is known as “autofluorescence” (AF). ...Several devices evaluating tissue AF have been developed and commercialized in the last two decades. Among these, the VELscope® system has been proposed as a visual diagnostic aid for potentially malignant disorders and malignant lesions of the oral mucosa. In the present pilot study, we investigated which are the main histopathological features possibly related to variations in AF patterns in a set of 20 oral squamous cell verrucous carcinoma. Among all the histological features investigated, only the mean width of keratin was significantly different between hypofluorescent and hyperfluorescent carcinomas. The results of the present study demonstrate that AF features of oral malignant lesions are significantly associated with the width of their keratin layer.
The aim of this study was to evaluate the long-term success rate of oral leukoplakia treatments by using different laser-supported surgical protocols.
Overall, 2347 diagnosed homogeneous oral ...leukoplakias were treated with CO
laser and were included in this study. Different surgical protocols (P) were used: P1 (SV = superficial scanning) was a complete superficial vaporization of the leukoplakia by a scanning mode in two passages respecting an overlapping. Only the visible white area was treated in one surgical session independently of the lesion size. P2 (CR1x1) was a complete excision of the lesions until a tissular depth of 1 mm and 1 mm of surrounding healthy-like tissue were attained. The visible white area was treated in one surgical session independently of the lesion size. P3 (CR1x3) was a complete excision of the lesions until a minimum tissue depth of 1 mm and 3 mm of surrounding healthy-like tissue were obtained. The visible white area was treated in one surgical session independently of the lesion size. P4 (PR1x3) was similar to the third one, but for patient comfort, the large lesions of leukoplakias (lesion size higher than 20 mm), the complete surgical excision of the leukoplakia was performed in multiple sessions that were spaced by 1 month (partial surgical removal of 10 mm per session). All patients were recalled at 2 and 8 weeks after surgery, and then every 2 months during the first year, every 4 months during the second year, and once a year for the follow-up period of 6 years. A biopsy was done once a year during the follow-up period in the surgical site when needed. The control consisted of checking the nature and the aspect of the healed mucosa to exclude an eventual recurrence of leukoplakia.
The percentage of permanent success after 6 years of follow-up was 5.7%, 69.7%, 97.8%, and 71.9%, respectively, for the first surgical protocol (SV), the second (CR 1 × 1), the third (CR 1 × 3), and the fourth (PR 1 × 3). The appearance of malignant transformation after laser treatment (during the follow-up period of 6 years) was 20%, 1%, and 0.2%, respectively, for the groups treated by the following protocols: 1 (SV), 2 (CR 1 × 1), and 4 (PR 1 × 3). Only in the third group CR1x3, no dysplasia or malignant transformation was noted. On the contrary, the appearance of malignant transformation in failed treated cases was 21.21% for the protocol 1 (SV), 3% for the protocol 2 (CR 1 × 1), and 0.6% for the protocol 4 (PR 1 × 3).
The results of this long-term follow-up of treated patients with oral homogeneous leukoplakias pointed out that the surgical laser protocol respecting the complete excision of leukoplakias, in one session, by the removal of a minimum of 1 mm in lesion depth and 3 mm of surrounding healthy-like tissues (CR 1 × 3) offers significantly the highest success rate.
Among the many GIS based multivariate statistical methods for landslide susceptibility zonation, the so called “Conditional Analysis method” holds a special place for its conceptual simplicity. In ...fact, in this method landslide susceptibility is simply expressed as landslide density in correspondence with different combinations of instability-factor classes. To overcome the operational complexity connected to the long, tedious and error prone sequence of commands required by the procedure, a shell script mainly based on the GRASS GIS was created. The script, starting from a landslide inventory map and a number of factor maps, automatically carries out the whole procedure resulting in the construction of a map with five landslide susceptibility classes. A validation procedure allows to assess the reliability of the resulting model, while the simple mean deviation of the density values in the factor class combinations, helps to evaluate the goodness of landslide density distribution. The procedure was applied to a relatively small basin (167 km²) in the Italian Northern Apennines considering three landslide types, namely rotational slides, flows and complex landslides, for a total of 1,137 landslides, and five factors, namely lithology, slope angle and aspect, elevation and slope/bedding relations. The analysis of the resulting 31 different models obtained combining the five factors, confirms the role of lithology, slope angle and slope/bedding relations in influencing slope stability.
Medication-related osteonecrosis of the jaws (MRONJ) is an adverse side effect of several drug therapies, including bisphosphonates (BPs). Osteonecrosis of the jaw specifically related to BP therapy ...is usually referred to using the acronym BRONJ. However, no consensus has yet been reached regarding the most appropriate management of BRONJ. The greatest success rates have been recorded with surgical removal of necrotic bone. In particular, erbium:yttrium-aluminum-garnet (Er:YAG) laser-assisted surgery has shown significantly better results than conventional surgical approaches. According to a position paper reported by the American Association of Oral and Maxillofacial Surgeons in 2007, the identification of necrotic bone margins during osteonecrosis removal can be very difficult. In 2015, a review of treatment perspectives for MRONJ reported that both surgical debridement and resection cannot be standardized owing to the lack of guidance to define the necrotic margins. Recently, the use of autofluorescence (AF) of the bone as a possible suitable guide to visualize necrotic bone during surgical debridement or resection was proposed. It seems that vital bone could be highlighted by its very strong AF. In contrast, necrotic bone loses AF and, thus, appears much darker. The molecular sources of the phenomenon of AF are the specific amino acids of the collagen molecules that show AF when irradiated by ultraviolet or blue light. The use of AF as an intraoperative diagnostic tool is entirely new in the management of MRONJ, although it has been used for several years in other fields (eg, intervertebral disc surgery). The aim of the present report was to describe a case of mandibular BRONJ treated with a new surgical approach performed with an Er:YAG laser and guided by AF. The histopathologic evaluation of the removed hypofluorescent bone block and hyperfluorescent surrounding bone has also been reported in detail.
Photobiomodulation (PBM) is a non-invasive treatment that uses laser or led devices making its effects a response to light and not to heat. The possibility of accelerating dental implant ...osteointegration and orthodontic movements and the need to treat refractory bone lesions, such as bisphosphonate related osteonecrosis of the jaws, has led researchers to consider the effects of PBM on bone for dentistry purposes. The aim of our study was to investigate the effects of 915 nm light supplied with a GaAs diode laser on human osteoblasts in vitro. Osteoblasts were isolated from mandibular cortical bone of a young healthy donor. The irradiation parameters were as follows: doses = 5, 15 and 45 J/cm
2
; power densities = 0.12 and 1.25 W/cm
2
; and irradiation times = 41.7, 125 and 375 s. We performed one irradiation per day for 3 and 6 days to study proliferation and differentiation, respectively. Microscopic analysis showed a greater amount of bone nodules in samples treated with 5 J/cm
2
and 0.12 W/cm
2
compared to controls (56.00 ± 10.44 vs 19.67 ± 7.64,
P
= 0.0075). Cell growth and quantification of calcium deposition did not show any differences when comparing irradiated and non-irradiated samples. Photobiomodulation, with the parameters investigated in the present study, positively modulated the mineralization process in human osteoblasts, inducing the formation of a greater amount of bone nodules, but did not increase cell proliferation.
Background In an era of precision and stratified medicine, homogeneity in population-based cohorts, stringent causative entry, and pattern analysis of datasets are key elements to investigate medical ...treatments. Adhering to these principles, we collected in vivo and in vitro data pointing to an insulin-sensitizing/insulin-mimetic effect of myo-inositol (MYO) relevant to cell regeneration in dentistry and oral surgery. Confirmation of this possibility was obtained by in silico analysis of the relation between in vivo and in vitro results (the so-called bed-to-benchside reverse translational approach). Results Fourteen subjects over the 266 screened were young adult, normal weight, euglycemic, sedentary males having normal appetite, free diet, with a regular three-times-a-day eating schedule, standard dental hygiene, and negligible malocclusion/enamel defects. Occlusal caries were detected by fluorescence videoscanning, whereas body composition and energy balance were estimated with plicometry, predictive equations, and handgrip. Statistically significant correlations (Pearson r coefficient) were found between the number of occlusal caries and anthropometric indexes predicting insulin resistance (IR) in relation to the abdominal/visceral fat mass, fat-free mass, muscular strength, and energy expenditure adjusted to the fat and muscle stores. This indicated a role for IR in affecting dentin reparative processes. Consistently, in vitro administration of MYO to HUVEC and Swiss NIH3T3 cells in concentrations corresponding to those administered in vivo to reduce IR resulted in statistically significant cell replication (ANOVA/Turkey tests), suggesting that MYO has the potential to counteract inhibitory effects of IR on dental vascular and stromal cells turnover. Finally, in in silico experiments, quantitative evaluation (WOE and information value) of a bioinformatic Clinical Outcome Pathway confirmed that in vitro trophic effects of MYO could be transferred in vivo with high predictability, providing robust credence of its efficacy for oral health. Conclusion Our reverse bed-to-benchside data indicate that MYO might antagonize the detrimental effects of IR on tooth decay. This provides feasibility for clinical studies on MYO as a regenerative factor in dentistry and oral surgery, including dysmetabolic/aging conditions, bone reconstruction in oral destructive/necrotic disorders, dental implants, and for empowering the efficacy of a number of tissue engineering methodologies in dentistry and oral surgery.
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