Epidemiology, etiopathogenesis, and management of MRONJ: A European multicenter study.

INTRODUCTION: The purpose of this European multicenter study was to describe the general characteristics and risk factors of MRONJ lesions as well as their clinical diagnosis and management at different European Oral and Maxillofacial Surgery centers, in order to minimize selections biases and provide information about the epidemiology, etiopathogenesis, and the current trends in the treatment of MRONJ across Europe. MATERIALS AND METHODS: The following data were registered for each patient: gender; age at MRONJ diagnosis; past medical history; indication for antiresorptive or antiangiogenic therapy; type of antiresorptive medication; local risk factor for MRONJ; MRONJ Stage; anatomic location and symptoms; treatment; surgical complications; recurrence. RESULTS: A total of 537 patients (375 females, 162 males) with MRONJ were included. Statistically significant associations were found between patients with metastatic bone disease and recurrences (P < 0.0005) and between advanced MRONJ stages (stages 2 and 3) and recurrences (P < 0.005). Statistically significant associations were also found between male gender and recurrences (P < 0.05), and between MRONJ maxillary sites and recurrences (P < 0.0000005). CONCLUSIONS: A longer mean duration of antiresorptive medications before MRONJ onset was observed in patients affected by osteoporosis, whereas a shorter mean duration was observed in all metastatic bone cancer patients, and in particular in those affected by prostate cancer with bone metastases or multiple myeloma. Surgery plays an important role for the management of MRONJ lesions.

Risk of dentoalveolar surgery postoperative bleeding in patients taking direct oral anticoagulants and vitamin K antagonists: A prospective observational study.

The aim of this study was to evaluate whether direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) increase the risk of postoperative bleeding after dentoalveolar surgery. Patients were classified into two groups: one taking DOAC and the other taking VKA with a therapeutic INR range. The control group comprised non-anticoagulated subjects. Participants were matched regarding dentoalveolar procedure. The primary predictor was anticoagulant status. The primary outcome was postoperative bleeding. The DOAC group comprised 77 patients, while the VKA group and control group each consisted of 103 participants. In each group, 103 dentoalveolar surgical procedures were conducted. Postoperative bleeding was recorded in 3/103 (2.9%), 5/103 (4.8%), and 1/103 (0.97%) occasions in the DOAC, VKA, and control groups, respectively, without significant difference (χ2; p = 0.54). The fully adjusted odds ratio for postoperative bleeding was 0.14 (CI 0.01-1.61; p = 0.05) for patients taking DOAC and 0.19 (CI 0.02-1.65; p = 0.285) for those taking VKA compared with non-anticoagulated controls. In conclusion, there was no increase in risk for clinically significant postoperative bleeding after dentoalveolar surgery in patients taking DOAC or VKA compared with non-anticoagulated subjects. Dentoalveolar surgery in patients taking DOAC and VKA can be performed safely without therapy cessation. The study was registered at Clinicaltrials.gov (NCT04505475).

Biocompatibility of mesoporous SBA-16/hydroxyapatite nanocomposite and dentin demineralized particles on human dental pulp stem cells.

In the present work, a biomaterial (SBA-16/HA) based on the growth of hydroxyapatite (HA) particles within an organized silica structure SBA-16 (Santa Barbara Amorphous-16) was developed to evaluate its application to act as a porous microenvironment promoting attachment and viability of human dental pulp stem cells of healthy deciduous teeth (SHED). First, SHED were isolated and their phenotypes were evaluated by flow cytometry. The samples of SBA-16/HA were characterized by X-ray diffraction (XRD), small and wide angle X-ray scattering (SWAXS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) equipped with energy dispersive spectra detector (EDS). Afterward, cells were cultured in the eluates of the above-mentioned biomaterial aged for 24 hr, 7. and 14 days. Bio-Oss® and dentin particles are involved for comparison and cells are cultured in the eluates of these two materials also. Thiazolyl Blue Tetrazolium bromide assay-MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay) was used for the determination of cell viability. The results obtained by all aforementioned characterization methods of SBA-16/HA, revealed a uniform spherical mesoporous structure, an intrinsic characteristic of this material. This material displayed excellent biocompatibility on SHEDs, and even proliferative potential, indicating that SBA-16/HA could potentially serve as a suitable substrate for bone regeneration. Contrary to SBA-16/HA, dentin particles showed low cytotoxicity at all time points, compared to control and Bio-Oss®groups. Our results substantiate the idea that SBA-16/HA has a beneficial effect on SHEDs, thus paving the way toward developing new material for bone replacement.

Scanning electron microscopy analysis of marginal adaptation of mineral trioxide aggregate, tricalcium silicate cement, and dental amalgam as a root end filling materials.

The aim of this research was to examine marginal adaptation of three root end filling materials mineral trioxide aggregate (MTA), Biodentine and amalgam. Ninety single-rooted extracted human teeth of the maxillary intercanine sector were used in the study. After the endodontic treatment and retrograde preparation, teeth were divided into three groups, depending on the root-end filling material. Teeth were cut in longitudinal manner. Measurements of the total width of the marginal gap in micrometers were performed using scanning electron microscopy. The results showed that MTA and Biodentine have better marginal adaptation compared to amalgam expressed through the mean value of the measured edge crack, however without significant difference (p > .05). Mean value of the measured edge crack in Group 1 (MTA) was 8.17 µm, in Group 2 (Biodentine) 8.53 µm, and in Group 3 (amalgam) 9.13 µm. All tested materials show a satisfactory degree of marginal adaptation, but MTA and Biodentine proved to be superior to amalgam.

Dental implant surgery and risk of bleeding in patients on antithrombotic medications: A review of the literature.

OBJECTIVES: This literature review was performed to assess the risk of bleeding in dental implantation procedures in patients taking antiplatelet drugs (APs), oral anticoagulants (OACs) and direct oral anticoagulants (DOACs). STUDY DESIGN: MEDLINE and SCOPUS databases were searched for English language publications through October 2019, using the keywords "dental implants," "dental implantation," "anticoagulants," "platelet aggregation inhibitors," and "hemorrhage." Reference lists of relevant articles were also hand searched. Collected data regarding dental implantation procedures, type of medications (APs, OACs and DOAC), and postoperative bleeding episodes were analyzed. RESULTS: Nine studies were included in the review. Postoperative bleeding occurred in 10 (2.2%) of 456 of cases involving dental implant placements; in all of those cases, bleeding was controlled with the use of local hemostatic agents. The bleeding incidence in patients on antiplatelet medications was 0.4% (range 1 of 253 to 1 of 261). Among those taking oral anticoagulants, the bleeding incidence was 5.7% (range 6 of 105 to 6 of 113), and among those on direct oral anticoagulants, the bleeding incidence was 3.3% (3 of 90). The numbers of more extensive surgical procedures (i.e., sinus lift and bone augmentation procedures) were small, and additional information regarding the surgery, the specific antithrombotic used, or bleeding was often not provided, so further analysis was not possible. CONCLUSIONS: Evidence supports continuing OACs, DOACs, or APs during dental implant surgery.

Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

: Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

Risk factors for bleeding after oral surgery in patients who continued using oral anticoagulant therapy.

BACKGROUND: The authors assessed the incidence of postoperative bleeding in patients who were highly anticoagulated and in patients who underwent extensive oral surgical procedures and who continued using oral anticoagulant therapy. METHODS: The authors placed 125 patients receiving anticoagulant therapy into 1 of 3 groups. Group A had 54 patients who were highly anticoagulated (international normalized ratio [INR] ≥ 3.5) in whom up to 3 teeth were extracted. Group B had 60 patients with INR 2.0 to less than 3.5 in whom higher-risk dentoalveolar surgery (extraction of more than 3 teeth or other oral surgery procedure involving raising a mucoperiosteal flap, osteotomy, or biopsy) was performed. Group C had 11 patients whose INR values were 3.5 or higher and who required higher-risk dentoalveolar surgery. Eighty-five healthy participants who underwent surgical procedures similar to those performed in group A and group B were the control group. RESULTS: Two patients in group A (3.7%), 3 in group B (5.0%), and 2 in group C (18.2%) experienced postoperative bleeding. In the control group, a single bleeding event (1.2%) occurred. All cases of hemorrhage were mild and easily controlled using local hemostatic measures. CONCLUSIONS: Dental extractions in patients who are highly anticoagulated (INR, 3.5-4.2), as well as more extensive oral surgical procedures in patients who are therapeutically anticoagulated, can be performed safely without interruption or modification of the therapy. PRACTICAL IMPLICATIONS: Tooth extractions and even more extensive surgical procedures can be performed safely in patients who continue using anticoagulant therapy if proper local hemostatic measures are used and if no other coagulopathies are present.

Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment.

Our aim was to evaluate the effects of single and dual antiplatelet treatment on postoperative bleeding in patients having dental extractions. The prospective clinical study included 160 patients who were taking antiplatelet drugs. The first group (n=43) were taking 2 drugs, mostly aspirin and clopidogrel, and the second group (n=117) were taking a single antiplatelet drug in the form of aspirin (n=84), clopidogrel (n=20), and ticlopidine (n=13). All patients had simple dental extractions, and local haemostasis was with resorbable collagen sponges, without suturing of the wound. The control group comprised 105 healthy subjects with a similar number of dental extractions. Bleeding was an "event" if it continued for more than 12h, made the patient call or return to the dental practice or emergency department, induced a large haematoma or ecchymosis within the oral soft tissues, or required blood transfusion. A total of 110 teeth were extracted on 59 occasions in the dual drug group, and 232 teeth on 128 occasions in the single drug group. Bleeding was recorded after extraction in only one patient on dual aspirin-clopidogrel treatment, which was mild and easily controlled by local haemostasis. The incidence of postoperative bleeding did not differ significantly among the three groups (χ(2)=4.3, p=0.11). However, the wound was sutured to achieve effective initial local haemostasis in 4/59 (6.8%) and 2/128 (1.6%) occasions of tooth extractions in the dual and single drug groups, respectively, and none in the control group (χ(2)=10.02, p=0.007). Patients taking single or dual antiplatelet drugs may have teeth extracted safely without interruption of treatment using only local haemostatic measures.

Comparison of efficacy of local hemostatic modalities in anticoagulated patients undergoing tooth extractions.

BACKGROUND/AIM: Patients receiving long-term oral anticoagulant therapy pose a clinical challenge during invasive dental procedures. The goal of this study was to compare different local hemostatic modalities after tooth extraction in patients receiving chronic Vitamin-K antagonist therapy. METHODS: Totally 90 patients with International Normalized Ratio (INR) ≤ 3.0 requiring simple extraction of one or two teeth were randomized into three groups, 30 patients in each group. The patients with the mean INR value of 2.35 ± 0.37, in whom extraction wound was sutured comprised the group A. In the group B with the mean INR of 2.43 ± 0.4, local hemostasis was achieved by placing absorbable gelatin sponges into the wound without suturing. The group C consisted of the patients with the mean INR of 2.36 ± 0.34 in whom neither gelatin sponge nor suturing were used for providing local hemostasis. Bleeding was registered as an event if other than initial hemostatic measure was needed or additional oral surgeon intervention required. RESULTS: The obtainded results show that 1 (3.3%) patient in the group A, 2 (6.7%) patients in the groups B and C manifested post-extraction bleeding. All cases of hemorrhage were easily solved with local hemostatic measures and all, except one case, were registered in the first two hours after the procedure until the dismissal. A difference between the groups was not statistically significant (χ2 = .42, p > 0.05). CONCLUSION: In therapeutically anticoagulated patients tooth extractions can be safely performed without altering the dose of anticoagulant medication if efficient local hemostasis is provided. In most cases; in patients with INR ≤ 3.0 after extraction of one or two teeth postoperative bleeding can be controlled with local pressure, without any additional local hemostatic measures.

The effects of combined oral anticoagulant-aspirin therapy in patients undergoing tooth extractions: a prospective study.

BACKGROUND: The authors conducted a study to evaluate the effect of combined oral anticoagulant-aspirin therapy on postoperative bleeding in patients undergoing tooth extractions. METHODS: A total of 213 patients were divided into three groups of 71 participants each. Patients in group A received combined anticoagulant-aspirin (100-milligram prophylactic dose) therapy. Patients in group B received oral anticoagulant therapy. Patients in group C received aspirin therapy (100-mg prophylactic dose). Bleeding was marked as an "event" if it met the following criteria: the bleeding continued beyond 12 hours, patient had to call the surgeon or return to dental practice or emergency department, bleeding resolved with large hematoma or ecchymosis within the oral soft tissues, or required a blood transfusion. RESULTS: Mean international normalized ratio (INR) (standard deviation) was 2.43 (0.61) in group A, and 2.45 (0.60) in group B. Postoperative bleeding occurred in three (4.2 percent) participants in group A, two (2.8 percent) participants in group B and no (0.0 percent) participants in group C. The authors found no statistical significance in postoperative bleeding between these three groups (χ(2) = 2.867, P = .238). All cases of hemorrhage were controlled easily by using local hemostatic measures. CONCLUSION: Tooth extractions can be performed safely while patients continue to receive combined anticoagulant-aspirin therapy. CLINICAL IMPLICATIONS: In patients receiving combined anticoagulant-aspirin therapy, simple tooth extractions can be performed safely without discontinuing either oral anticoagulant or antiplatelet therapy if their INRs are within therapeutic range and appropriate local hemostasis measures are provided.

Safety of local anaesthesia in dental patients taking oral anticoagulants: is it still controversial?

The aim of this study was to investigate the safety of local infiltration techniques and the inferior alveolar nerve block (IANB) in dental patients taking oral anticoagulants. A total of 352 patients were given a total of 560 injections of local anaesthetic (119 IANB and 441 others). The study group comprised 279 patients with therapeutic international normalised ratios (INRs), and the control group 73 patients who were taking oral anticoagulants but had subtherapeutic INR on the day of operation. Blood was aspirated 7 times (7.3%) during the IANB in the study group. However, there were no clinical signs of prolonged haemorrhage into the medial pterygoid muscle or pterygomandibular space after 96 IANB, including those from whom blood had been aspirated. Only two minor haematomas developed after multiple infiltrations in the lingual sulci. The results suggest that bleeding as a result of the use of local anaesthesia in patients with therapeutic INR is unlikely, provided that the IANB is done correctly.

Randomized, prospective trial comparing bridging therapy using low-molecular-weight heparin with maintenance of oral anticoagulation during extraction of teeth.

PURPOSE: To evaluate postoperative bleeding and thromboembolic complications during dental extractions in anticoagulated patients, using 2 different protocols. PATIENTS AND METHODS: In total, 214 anticoagulated patients in need of simple dental extractions were randomized into 2 groups. Group A consisted of 109 patients on continuous oral anticoagulation therapy (OAT), with a mean international normalized ratio (INR) of 2.45 +/- 0.54. Local hemostasis in these patients was achieved with resorbable collagen sponges, without wound suturing. Group B consisted of 105 patients on bridging therapy with low-molecular-weight heparin (nadroparin-calcium), with a mean INR of 1.26 +/- 0.11 on the day of the procedure. Neither local hemostatic agents nor suturing of the wound was used in these patients. RESULTS: Eight (7.34%) patients in group A and 5 (4.76%) patients in group B manifested postextractional bleeding, without statistical significance (chi(2), Yates' = 0.253, P > .05). All cases of hemorrhage were mild and easily controlled using local hemostatic measures. None of the participants in either group experienced thromboembolic complications. CONCLUSIONS: In patients receiving OAT with an INR