Giovanni Mergoni

Surgery-triggered and non surgery-triggered Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ): A retrospective analysis of 567 cases in an Italian multicenter study

Invasive local procedures are often reported in clinical history of patients suffering from Bisphosphonates-Related Osteonecrosis of the Jaws (BRONJ) but over 40% of spontaneous forms have been also described in literature. We compared age, gender, underlying bone disorders, bisphosphonate therapy, clinical features and surgical outcome of 205 cases (36.2%) of BRONJ non surgery-triggered (group 1) with 362 (63.8%) cases of surgery-triggered forms (group 2). Differences between group 1 and 2 were analysed using Mann-Whitney U and χ(2) tests. Statistical analysis was performed using STATA 8. Zoledronate was the most used type of bisphosphonate (63.4% versus 69.0%) and the mandible was the most frequently involved site (63.9% versus 63.4%) in both groups. BRONJ in group 1 was more frequently multicentric (9.3% versus 5%, p<0.05), had a lower clinical stage (45.9% versus 13.8% in stage 1, p<0.01) and had a better outcome after surgical therapy (improvement in 74.1% versus 58.6%, p<0.05). The high prevalence of non surgery-triggered forms of BRONJ should be considered by oncologists, haematologists and general physicians who are advised to inform their patients regarding the importance of preventive dental protocols to control the possible causes of osteonecrosis not related to dental invasive procedures.

Conservative Surgical Management of Stage I Bisphosphonate-Related Osteonecrosis of the Jaw

Purpose. To report the efficacy of conservative surgical treatment for stage I bisphosphonate-related osteonecrosis of the jaw (BRONJ). Materials and Methods. This study reports the clinical outcomes of 63 patients treated for BRONJ stage I (according to Ruggieros staging system) at the Oral Pathology and Laser-Assisted Surgery Unit of the University of Parma between January 2004 and January 2011. Surgical interventions were performed, under local analgesia, in patients unresponsive for a period of six months to noninvasive treatments such as cycles of local or systemic antibacterial therapy combined or not to low level laser therapy, ozone therapy, or Hyperbaric Oxygen Therapy. All interventions were performed after the consultation of oncologist or physician. Results. In our experience, conservative surgical treatment is associated with the highest number of BRONJ healed sites in stage I disease. Complete healing was observed in 92.6% of sites surgically treated. Conclusions. This study confirms that treatment of patients affected by minimal bone exposition, (stage I of BRONJ), through conservative surgical strategies, possibly with laser, may result in a high control of the disease in the long term.

Peripheral ossifying fibroma: A clinicopathologic study of 27 cases and review of the literature with emphasis on histomorphologic features

Context: The peripheral ossifying fibroma (POF) is a relatively uncommon, reactive gingival overgrowth usually composed of cellular fibroblastic tissue containing one or more mineralized tissues, namely bone, cementum-like material, or dystrophic calcification. The aetiology and pathogenesis of POF are yet not clear, but some authors have hypothesized a reaction originating from the periodontal ligament, as a result of irritating agents such as dental calculus, plaque, orthodontic appliances, and ill-fitting restorations. Aims: The aim of our study was to report the clinicopathologic features of a case series of POF from a single Italian institution. Materials and Methods: A total of 27 cases were collected over an 18-year period. Detailed relevant medical history, clinical and histological information were recorded for each patient. Results: The age range of patients (m = 6; f = 21) was 17.2-80.1 years with a mean of 42.9 ± 18.1 years. Occurrence of the lesion in the mandibular and maxillary arches was similar, and 67.0% occurred in the incisor-cuspid region. The lesions ranged in size from 0.3 to 5.0 cm (mean, 1.3 cm ± 1.1 cm). All the different types of mineralization were present, with higher prevalence of lamellar bone. The lesions were treated by surgical excision and four lesions in three patients recurred after surgery. Conclusions: Surgeons should consider the high recurrence rate of POF and remove the lesion down to the bone involving also the adjacent periosteum and the periodontal ligament. Professional prophylaxis should precede any surgical procedure, and periodical dental hygiene recalls are important in order to remove any possible irritating factor.

Osteonecrosis of the Jaw (ONJ) in Osteoporosis Patients: Report of Delayed Diagnosis of a Multisite Case and Commentary about Risks Coming from a Restricted ONJ Definition

Osteonecrosis of the jaws (ONJ) in osteoporosis patients has been defined as rare, but the number of reported cases is increasing. We report a case of delayed ONJ diagnosis in a patient, who was being treated with alendronate, developing bone alterations both in maxilla and in mandible. Underestimation of ONJ incidence and missed or delayed ONJ diagnosis in osteoporosis patients might derive from lack of awareness of health providers as well as from an ONJ definition that is too restricted. The more recent definition of medication-related osteonecrosis of the jaws (MRONJ) released in 2014 by the American Association of Oral Maxillofacial Surgeons (AAOMS) accept fistula, besides bone exposure, as a major sign of disease, but it seems to be insufficient since it excludes all cases of ONJ disease without bone exposure. A new MRONJ definition is needed to avoid missing or delayed diagnosis.

Prevalence of Candida Species in Endodontic Infections: Systematic Review and Meta-analysis

Introduction: Candida in endodontic infections has been investigated in a large number of studies, but its role as an endodontic pathogen is still debatable. The aim of this study was to systematically review the literature on the prevalence of Candida species in root canal infections. Methods: Extensive literature research was performed in the most important electronic biomedical databases, and additional studies have been identified from references from relevant articles. Studies were critically appraised using a modified version of the Joanna Briggs Institute Critical Appraisal Checklist. Results: From 2225 unique records, 2118 were excluded on the basis of title and abstract. Of the remaining 107 studies, 50 were excluded after full‐text review, and 57 were included for qualitative and quantitative analysis. The overall prevalence of Candida spp. in root canal infections was 8.20% (95% confidence interval, 5.56%–11.21%). Candida albicans was the most frequently isolated species. Significant heterogeneity among studies was observed (P < .001, I2 = 86.07%). Subgroup analyses revealed a higher prevalence of Candida spp. from African samples. All studies considered, a high or unclear risk of bias was prevalent regarding 6 out of the 8 items considered in the critical appraisal. Conclusions: Candida spp. occurred in a small proportion of root canal infections. Further and better designed research is needed to investigate the real contribution of Candida spp. to the microbial ecology in infected root canals.

A 5-year retrospective longitudinal study on the incidence and the risk factors of osteonecrosis of the jaws in patients treated with zoledronic acid for bone metastases from solid tumors

Background The aim of this study was to evaluate the incidence and the risk factors of osteonecrosis of the jaw (ONJ) in a group of patients treated with zoledronic acid (ZA) for bone metastases from solid tumors and enrolled in a preventive dental program. Material and Methods This 5-year retrospective longitudinal study included all consecutive oncological patients who underwent at least one infusion with ZA between 2004 and 2011 for bone metastases due to solid neoplasms. Results Of the 156 patients enrolled in the study, 17 developed ONJ (10.89%). At the multivariate analysis, severe periodontal disease (P=0.025), tooth extraction (P<0.0001) and starting the preventive dental program after the beginning of ZA therapy (P=0.02) were the only factors which showed a significant association with the occurrence of ONJ. Conclusions This study demonstrated the importance of beginning dental prevention before zoledronic acid exposure in reducing ONJ occurrence, especially in the long term. The results of this research show that control of periodontal disease and an increase in the time between tooth extraction and the first ZA administration are recommended in order to reduce the risk of ONJ development. Key words:Osteonecrosis of the jaw, dental prevention, zoledronic acid, incidence.

Effect of Nd:YAG laser light on post-extractive socket healing in rats treated with zoledronic acid and dexamethasone

Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Material and Methods Thirty male Sprague-Dawley rats were divided in 4 groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10) and treatment plus laser group (T+L, n = 10). Rats of group T and T+L received zoledronate 0,1 mg/Kg and dexamethasone 1 mg/Kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks the first maxillary molars were extracted in all rats. Rats of groups L and T+L received laser therapy (Nd:YAG, 1064 nm, 1.25W, 15Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4 and 6 after surgery. At 8 days from extraction, the sockets were clinically assessed with a grading score and the wound area was measured with a dedicate software. Histomorphometric evaluation and western blot analysis of osteopontin and osteocalcin expression were performed. Results Group T+L showed a trend toward a better clinical grading score compared to group T (grade I 22% Vs 28 % - grade II 56% Vs 28% - grade III 22% Vs 44%, respectively). The average wound area was similar among the groups. Inhibition of osteoclastic alveolar bone resorption was found in groups T and T+L (P<0.001). Rats of groups L and T+L showed a significant higher expression of osteocalcin compared to rats of groups C and T (C=0.3993; L=1.394; T=0.2922; T+L=1.156; P=0.0001). The expression of osteopontin did not show significant differences in the groups treated with Nd:YAG compared to the ones that did not receive laser irradiation. Conclusion Our findings suggest that laser irradiation after tooth extraction can promote osteoblast differentiation, as demonstrated by the higher expression of osteocalcin. Thus, laser irradiation could be considered a way to improve socket healing in conditions at risk for MRONJ development.

Erratum to: Advantages of new technologies in oral mucosal surgery: an intraoperative comparison among Nd:YAG laser, quantic molecular resonance scalpel, and cold blade.

The aim of this study is to evaluate the possible intraoperative advantages of Nd:YAG laser and quantic molecular resonance (QMR) scalpel in oral soft tissue surgery. One hundred sixty-three interventions were evaluated. Group 1 (G1) included 77 interventions performed with Nd:YAG laser, group 2 (G2) 45 with QMR scalpel, and group 3 (G3) 41 with cold blade. Parameters analyzed were as follows: speed of incision, time of intervention, intraoperative bleeding, number of stitches, patient compliance, and operator comfort. Data were analyzed using software STATA 12 (StataCorp LP, College Station, TX, USA). Mean speed of incision was 0.54 mm/s in G1, 2.83 mm/s in G2, and 1.58 mm/s in G3, Nd:YAG laser being the slowest. However, no significant differences among times of intervention were found. In particular, interventions in G1 (221.15 ± 220.89 s) have a mean duration lower than G2 (280.56 ± 248.31 s) and G3 (316.10 ± 248.69 s). Intraoperative bleeding occurred in 29.9 % (n = 23/77) of interventions in G1, 97.8 % (n = 44/45) in G2, and 97.6 % (n = 40/41) in G3 (p < 0.0001). Mean number of stitches in G1 was statistically lower (G1, 0.10; G2, 2.07; G3, 2.29; p < 0.0001). No differences with regard to patient compliance were detected. Operator comfort was higher in G1 (p < 0.0003). Nd:YAG laser and QMR scalpel give several advantages in oral mucosal surgery: Nd:YAG laser cuts tissue slowly, but it provides a good visibility and excellent hemostasis. QMR scalpel allows a very rapid cutting with no considerable temperature increase, but there is major risk of bleeding and need for sutures with lower operator comfort.

Mitochondrial potential changes induced by treatment with a 915 nm GaAs diode laser

Several reports have shown that low level laser therapy (LLLT) stimulates several metabolic activity at cellular level that could enhance wound healing. Laser irradiation seems to modulate various biological process in cell culture. LLLT could affect cell proliferation, differentiation and viability; besides some recent papers suggest that the mechanism of bio-stimulation may occur through mitochondrial photoactivation. The aim of our study was to visualize by time lapse confocal microscopy the effects of 915 nm diode laser on mitochondrial transmembrane potential (ΔΨm) of human dermal fibroblasts. We have compared two modes of irradiation (pulsed and continuous) at different power doses: 5, 15, 45 J/cm2. Cells were loaded with tetramethylrhodamine methyl ester (TMRM), a semi-quantitative marker of ΔΨm. After baseline signal acquisition, cells were irradiated and real time changes of fluorescence were recorded. At time 0 the cells showed the typical mitochondrial network and a negative nucleus. Irradiation with 5J/cm2 in pulsed mode, caused a rough 10% signal increase after 60 sec followed by a fluorescence recovery to baseline after 250 sec. Stimulation in continuous mode with the same dose induced an opposite behaviour characterized by a 5% signal decrease 120 sec after irradiation with a return to baseline after 250 sec. At higher doses, 15J/cm2 and 45J/cm2, both irradiation modes produced a drop of TMRM fluorescence. At 15J/ cm2 the recover after the initial, 10% signal decrease was faster in pulsed (220 sec) rather than continuously irradiated cells (400 sec). 45J/cm2 dose caused a 20% signal decrease in both modes but once again the pulsed irradiated cells recovered faster, 260 and 550 sec respectively. Our results suggest that low intensity (5J/cm2), pulsed 915nm laser have a stimulatory effect on mitochondrial metabolism whereas higher doses (45 J/cm2) irradiation, especially if repeated, could exert a toxic effect on cell, explicated by mitochondrial depolarization.