Evaluation of Preventive Role of Systemically Applied Erythropoietin after Tooth Extraction in a Bisphosphonate-Induced MRONJ Model.

Background and Objectives: In this experimental study, the prophylactic effect of systemically administered erythropoietin (EPO) in medication-related osteonecrosis of the jaw (MRONJ) was evaluated. Materials and Methods: The osteonecrosis model was established using 36 Sprague Dawley rats. EPO was systemically applied before and/or after tooth extraction. Groups were formed based on the application time. All samples were evaluated histologically, histomorphometrically, and immunohistochemically. A statistically significant difference in new bone formation was observed between the groups (p < 0.001). Results: When new bone-formation rates were compared, no significant differences were observed between the control group and the EPO, ZA+PostEPO, and ZA+Pre-PostEPO groups (p = 1, 0.402, and 1, respectively); however, this rate was significantly lower in the ZA+PreEPO group (p = 0.021). No significant differences in new bone formation were observed between the ZA+PostEPO and ZA+PreEPO groups (p = 1); however, this rate was significantly higher in the ZA+Pre-PostEPO group (p = 0.009). The ZA+Pre-PostEPO group demonstrated significantly higher intensity level in VEGF protein expression than the other groups (p < 0.001). Conclusions: Administering EPO two weeks pre-extraction and continuing EPO treatment for three weeks post-extraction in ZA-treated rats optimized the inflammatory reaction, increased angiogenesis by inducing VEGF, and positively affected bone healing. Further studies are needed to determine the exact durations and doses.

Could Local Application of Hypoxia Inducible Factor 1-α Enhancer Deferoxamine Be Promising for Preventing of Medication-Related Osteonecrosis of the Jaw?

This experimental study investigates the prophylactic effect of deferoxamine (DFO) on medication-related osteonecrosis of the jaw (MRONJ). Thirty-six female Sprague Dawley rats received zoledronic acid (ZA) for eight weeks to create an osteonecrosis model. DFO was locally applied into the extraction sockets with gelatin sponge (GS) carriers to prevent MRONJ. The specimens were histopathologically and histomorphometrically evaluated. Hypoxia-inducible factor 1-alpha (HIF-1α) protein levels in the extraction sockets were quantified. New bone formation rate differed significantly between groups (p = 0.005). Newly formed bone ratios in the extraction sockets did not differ significantly between the control group and the GS (p = 1), GS/DFO (p = 0.749), ZA (p = 0.105), ZA-GS (p = 0.474), and ZA-GS/DFO (p = 1) groups. While newly formed bone rates were higher in the ZA-GS and ZA-GS/DFO groups than in the ZA group, the differences were not significant. HIF-1α levels differed significantly between groups (p < 0.001) and were significantly higher in the DFO and ZA-GS/DFO groups than in the control group (p = 0.001 and p = 0.004, respectively). While HIF-1α levels were higher in the ZA-GS/DFO group than in the ZA group, the difference was not significant. While HIF-1α protein levels and new bone formation rate were elevated in the DFO-treated group, the effect was not significant. Further large-scale studies are needed to understand DFO's preventative effects on MRONJ and the role of HIF-1α in MRONJ pathogenesis.

Use of Leukocyte-rich and Platelet-rich Fibrin (L-PRF) Adjunct to Surgical Debridement in the Treatment of Stage 2 and 3 Medication-Related Osteonecrosis of the Jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed necrotic bone persisting for more than 8 weeks in the maxillofacial region in patients using antiresorptive or antiangiogenetic drugs for several treatment options like bone metastasis or osteoporosis. There are several treatment options studied in scientific literature, and one of them with promising results is using platelet concentrates adjunct to surgical therapy. The aim of this study is to examine the therapeutic effect of leukocyte and platelet-rich fibrin (L-PRF) on patients with MRONJ. This 2-centered study investigated patients referred to oral and maxillofacial surgery departments of 2 university clinics between the years 2014 and 2020 with the diagnosis of MRONJ. Demographic data, the indication of the drug usage, drug type, duration, administration route, and systemic comorbidities of the patients were recorded. L-PRF was applied to 20 osteonecrotic lesions of 19 patients following surgical debridement. The male/female ratio was 5/14. Except 1 of the patients, all of the indications of medication were neoplasia-related. The mean follow-up period of patients was 27.9±9.2 months. Most common antirezorptive drug was zoledronate (84.2%). Complete resolution was observed in 16 necrosis sites (80%). It could be concluded that the use of L-PRF may represent an important adjunct in the surgical management of MRONJ.

Effect of Residual Bone Height and Implant Macro-Design on Primary Stability in Sinus Floor Elevation: An Ex Vivo Study.

The objective was to evaluate the influence of residual bone height (RBH) and implant macro-design on the primary stability (PS) of implants using a simultaneous sinus floor elevation (SFE) and implant insertion model. Fresh bovine rib samples that resembled type-IV density that were confirmed by computerized tomography were prepared to represent 4 groups of varying RBHs (3, 6, 9, 15 mm). To simulate simultaneous implant insertion with SFE, 120 implants in different macro-designs (group R: NobelReplace; group P: NobelParallel; group A: NobelActive, Nobel Biocare, Gothenburg, Sweden) were randomly inserted at RBHs of 3, 6, 9, and 15 mm in each rib. The implant stability quotient (ISQ) was measured immediately after implant insertion. RBH and implant macro-design have an impact on ISQ values (P < .001). ISQ values were the highest with RBH of 15 mm, followed by RBHs of 9, 6, and 3 mm. (P < .001). There was no statistically significant difference between different implant macro-designs at RBHs of 3 and 15 mm regarding ISQ values (P = .111, P = .551). ISQ values of group P were higher than those of group R and group A at an RBH of 6 mm (P = .049, P = .029). ISQ values were also higher in group P compared to group A at an RBH of 9 mm (P = .006). A higher PS may be expected in sites with higher RBH, regardless of the macro-design. In addition, cylindric implant design may enhance the PS at RBHs of 6 and 9 mm in simultaneous implant insertion with SFE.

Is there any predictive bone parameter for implant stability in 2-dimensional and 3-dimensional radiologic images?

OBJECTIVES: This ex vivo study aimed to compare radiomorphometric parameters between 2-dimensional (2-D) and 3-dimensional (3-D) radiographs and evaluate the influence of preoperative radiologic bone parameters on the clinical outcomes of implant stability. STUDY DESIGN: Implant recipient sites in fresh bovine blocks were evaluated on panoramic radiographs for gray value (GV), fractal dimension (FD), number of connected trabeculae (Co), and density of connected trabeculae (CoD). Cone beam computed tomography (CBCT) scans were evaluated for trabecular thickness (TbTh), cortical thickness (CTh), degree of anisotropy (DA), FD, and Co. Insertion torque (IT) and implant stability quotient (ISQ) were measured. RESULTS: GV was significantly correlated with all parameters in 2-D and 3-D images except FD in 2-D and Co in 3-D, and with all surgical parameters (P ≤ .029). Co and CoD values on panoramic radiographs had significant correlation with TbTh, CTh, and DA values on CBCT images (P < .001). All 2-D parameters and TbTh and CTh in the CBCT data were significantly correlated with IT only (P ≤ .047). Only GV was correlated with ISQ measurements (P ≤ .029). CONCLUSIONS: GV, Co, and CoD values on panoramic radiographs reflect the architecture of trabecular bone and the thickness of cortical bone, and might help predict implant stability in clinical situations.

In vitro tooth-shaped scaffold construction by mimicking late bell stage.

Neogenesis of osseous and ligamentous interfacial structures is essential for the regeneration of large oral or craniofacial defects. However, current treatment strategies are inadequate in renewing supporting tissues of teeth after trauma, chronic infections or surgical resection. Combined use of 3D scaffolds with stem cells became a promising treatment option for these injuries. Matching different scaffolding materials with different tissues can induce the correct cytokines and the differentiation of cells corresponding to that particular tissue. In this study, a hydroxyapatite (HA) based scaffold was used together with human adipose stem cells (hASCs), human bone marrow stem cells (hBMSCs) and gingival epithelial cells to mimic human tooth dentin-pulp-enamel tissue complexes and model an immature tooth at the late bell stage in vitro. Characteristics of the scaffold were determined via SEM, FTIR, pore size and density measurements. Changes in gene expression, protein secretions and tissue histology resulting from cross-interactions of different dental tissues grown in the system were shown. Classical tooth tissues such as cementum, pulp and bone like tissues were formed within the scaffold. Our study suggests that a HA-based scaffold with different cell lineages can successfully mimic early stages of tooth development and can be a valuable tool for hard tissue engineering.

Antibiotic prescribing habits of the clinicians dealing with dental implant surgery in Turkey: a questionnaire study.

PURPOSE: Although various prophylactic and/or postoperative systemic antibiotic regimens have been suggested to minimize failure after dental implant placement and postoperative infection, the role of antibiotics in implant dentistry is still controversial. The purposes of this questionnaire study were to determine the current antibiotic prescribing habits of clinicians in conjunction with dental implant placement and to understand whether any consensus has been reached among implant surgery performing clinicians. METHODS: An electronic questionnaire was sent by electronic mail to all members of the Turkish Dental Society. The questions were related to whether antibiotics were routinely prescribed either pre- or/and postoperatively during routine dental implant placement. The respondents were also asked to specify their workplace and education. The results were analyzed using SPSS software. Descriptive and chi-square analyses were used to compare categorical data; Kruskal-Wallis test was used to compare the quantitative data by category. RESULTS: A total of 429 members responded to the questionnaire. The clinicians having more experience had a greater tendency to prescribe preoperative antibiotics (p < 0.001), but there was no statistically significant difference between the postoperative antibiotic prescription choice of the clinician according to the clinicians' experience (p > 0.05). A total of 175 of the clinicians preferred to prescribe preoperative antibiotics when there was systemic comorbidity; 99 of the clinicians preferred to prescribe antibiotics before every implant surgery. The aminopenicillins were the most commonly prescribed antibiotics by the clinicians. A total of 38.58% of the respondents (n = 130) who were prescribing preoperative antibiotics, 2000 mg aminopenicillin was given 1 h before the surgical procedure. Dentists and solo private practitioners were prescribing more preoperative antibiotics (p < 0,05). CONCLUSIONS: There was no consensus among clinicians regarding the use of antibiotics in association with routine dental implant placement. Aminopenicillins were the most commonly prescribed antibiotics for both pre- and postoperatively. Furthermore, most of the antibiotic regimens being used are not in accordance with the current published data.

Tooth extractions in patients under antiresorptive therapy for osteoporosis: Primary closure of the extraction socket with a mucoperiosteal flap versus application of platelet-rich fibrin for the prevention of antiresorptive agent-related osteonecrosis of the jaw.

PURPOSE: The aim of this study was to compare primary closure of the extraction socket to application of platelet-rich fibrin (PRF) without subsequent primary closure for the prevention of osteonecrosis of the jaw (ONJ) in patients administered antiresorptive therapy for osteoporosis. MATERIALS AND METHODS: Primary closure of the extraction socket was performed with a mucoperiosteal flap and two-layer suturing or PRF was inserted into the extraction socket without subsequent primary closure. In all patients, intra- and postoperative complications as well as the overall treatment outcome were recorded. RESULTS: The patient sample consisted of 77 patients; primary closure with a mucoperiosteal flap was performed in 39 patients (group A), and application of PRF without subsequent primary closure was performed in 38 patients (group B). There were no statistically significant differences (p > 0.05) between the two groups in terms of age and gender, duration and type of antiresorptive therapy, teeth to be extracted (number, location and type) as well as comorbidities. No intraoperative complications occurred in either of the groups. Postoperative complications were found in 6 patients in group A and in one patient in group B. Analyzing risk factors for these complications, the highest OR (6.72 with p = 0.085 in univariate analysis; 12.81 with p = 0.052 in multivariate analysis) was found for the type of procedure (group A/group B). All patients had complete mucosal coverage without any signs of antiresorptive agent-related osteonecrosis of the jaw at the final control examination 90 days postoperatively. CONCLUSION: Based on the results of this study, the use of PRF can be recommended as a preventive measure in patients requiring tooth extractions while being under antiresorptive therapy for osteoporosis.

A city-wide survey of dental students' opinions on undergraduate oral surgery teaching.

PURPOSE: This study aimed to carry out a city-wide survey to evaluate undergraduate students' opinions on their oral surgery training by measuring their self-confidence. MATERIALS AND METHODS: A cross-sectional survey of 383 3rd year, 412 4th year and 363 5th year undergraduate dental students from six dental schools in Istanbul with a mean age of 22.73 ± 1.55 was conducted towards the end of the academic year. A web link to the questionnaire was sent to the contact person at the participating dental schools. The questionnaires were anonymously evaluated. Descriptive statistics were calculated, and Chi-square tests were performed to examine the data. A P-value of <.05 was considered to be statistically significant. RESULTS: In total, 1158 responses were returned, representing 67% of the overall students in the 2018-2019 academic year. The male respondents were significantly more self-confident than females in the general aspects of surgical skills. More than half of the respondents (53%) felt confident in oral surgery knowledge to undertake independent practice. Although 5th year respondents felt more confident in the general aspect of the questionnaire, their ability of differentiation of odontogenic and non-odontogenic pain was lower than their counterparts. The majority (86%) of the participants disagreed that the only knowledge required for oral surgery was that of tooth and jaw anatomy. CONCLUSION: This survey revealed perceived confidence in tooth and retained root extraction. The male respondents were found to be more self-confident. There is a need for improvement in surgical skills, recognition of malignancies and differentiation of the origin of the pain.

Comparison of the effect of postoperative care agents on human gingival fibroblasts: a preliminary study.

PURPOSE: The aim of this study is to compare effects of postoperative care agents; chlorhexidine, octenidine dihydrochloride and hyaluronic acid on human gingival fibroblasts' viability, proliferation, apoptosis and migration. MATERIALS AND METHODS: After cell culturing; chlorhexidine, octenidine dihydrochloride and hyaluronic acid solutions were applied on cells and nothing was applied for control group. The cells were monitored to investigate cytotoxicity; the percentage of apoptotic, living and dead cells at the time of 24, 48, and 72 hours (h). A scratch wound assay was performed to detect cell migration and cells were monitored at baseline, at 24 and 48h. RESULTS: At 24h, chlorhexidine showed statistically lower percentage of total apoptotic cells' than octenidine dihydrochloride (p=0.049), hyaluronic acid (p=0.049) and control (p=0.049). At 48h, hyaluronic acid showed statistically lower percentage than chlorhexidine (p=0.049), and control (p=0.049). All agents were found to have statistically and significantly more cytotoxic than control. However, there was no difference between experimental groups for proliferation rate. Octenidine dihydrochloride showed statistically negative effects on cell migration than chlorhexidine and hyaluronic acid at 24h. Chlorhexidine and hyaluronic acid maintained migration ability of cells than octenidine dihydrochloride at 48h. CONCLUSION: All agents have similar effects on cell behavior such as viability, apoptosis and cell proliferation. However, octenidine dihydrochloride showed statistically negative effects on migration ability than chlorhexidine and hyaluronic acid.

Preventive Effect of Phosphodiesterase Inhibitor Pentoxifylline Against Medication-Related Osteonecrosis of the Jaw: An Animal Study.

PURPOSE: The aim of this experimental study was to investigate the prophylactic effect of pentoxifylline (PTX) on medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: Female Sprague-Dawley rats (n = 33) received zoledronic acid (ZA) for 8 weeks to create an osteonecrosis model. The left mandibular second molars were extracted and the recovery period lasted 8 weeks before sacrifice. PTX was intraperitoneally administered to prevent MRONJ. The specimens were histopathologically and histomorphometrically evaluated. RESULTS: Histomorphometrically, between the control and ZA groups, there was no statistically significant difference in total bone volume (P = .999), but there was a statistically significant difference in bone ratio in the extraction sockets (P < .001). A comparison of the bone ratio of the ZA group with the ZA/PTX group (PTX administered after extraction) showed no statistically significant difference (P = .69), but there was a statistically significant difference with the ZA/PTX/PTX group (PTX administered before and after extraction; P = .008). Histopathologically, between the control and ZA groups, there were statistically significant differences for inflammation (P = .013), vascularization (P = .022), hemorrhage (P = .025), and regeneration (P = .008). Between the ZA and ZA/PTX groups, there were no statistically significant differences for inflammation (P = .536), vascularization (P = .642), hemorrhage (P = .765), and regeneration (P = .127). Between the ZA and ZA/PTX/PTX groups, there were statistically significant differences for inflammation (P = .017), vascularization (P = .04), hemorrhage (P = .044), and regeneration (P = .04). CONCLUSION: In this experimental model of MRONJ, it might be concluded that although PTX, given after tooth extraction, improves new bone formation that positively affects bone healing, it is not prophylactic. However, PTX given before tooth extraction is prophylactic. Therefore, PTX might affect healing in a positive way by optimizing the inflammatory response.