BACKGROUND: It is well-known that oral surgical procedures pose a high risk for medication-related osteonecrosis of the jaw in patients taking bisphosphonates. Although some position papers and guidelines have been published with regard to its treatment, few studies have investigated prevention methods. This study investigates the effectiveness of methenolone enanthate, an anabolic steroid, for the prevention of medication-related osteonecrosis of the jaw.
METHODS: Thirty-six Wistar rats were divided into three groups. Two experimental groups, Z and ZM, took zoledronic acid for 6 weeks prior to extraction of the left maxillary first molar. The Group ZM also was given methenolone enanthate continuously for 1 week before and 4 weeks after the extraction. The control group was not given any medication. The rats were euthanized 5 weeks after extraction. The extraction socket was evaluated clinically for bone exposure and histologically for inflammation, hyperemia, collagen fibers, epithelialization, number of osteoclasts, and empty lacunae.
RESULTS: Six rats died during the experimental research. The bone exposure rate, mean numbers of attached osteoclasts (in 40× magnification), and empty lacunae (in 100× magnification) were 0%, 4%, and 0.8% in Group C; 75%, 1%, and 8% in Group Z; and 10%, 2.1%, and 3% in Group ZM, respectively. Significant differences exist between all groups regarding the number of empty lacunae. There were significant differences between Group C/ZM and Group Z in terms of bone exposure rate, inflammation, hyperemia, collagen fiber organization, and epithelialization.
CONCLUSIONS: In our tested preclinical model, methenolone enanthate has shown potential for preventing medication-related osteonecrosis of the jaw.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with prolonged bisphosphonate therapy. Increasing evidence shows that mucosal damage plays an important role in the pathogenesis of MRONJ. This study investigates the combinatorial effects of hydroxyapatite with Tualang honey on cell viability and wound healing in MRONJ.
METHODS: The incorporation of Tualang honey into hydroxyapatite was assessed using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and field emission scanning electron-energy dispersive X-ray analysis microscopy (FESEM-EDX). The effect of hydroxyapatite combined with Tualang honey on cell viability was determined by WST-1 assay and wound healing was assessed by scratch assay.
RESULTS: The incorporation of Tualang honey into hydroxyapatite altered the functional groups, structure, size, morphology, and components of the crystal as evidenced by FTIR, XRD and FESEM-EDX analysis. High concentrations of pamidronic acid inhibit oral fibroblast viability and wound healing. Low and high concentrations of hydroxyapatite demonstrate non-toxicity towards fibroblast cells. Furthermore, hydroxyapatite reversed the action of pamidronic acid on the cells; it increased fibroblast viability but did not close the wound. Tualang honey promotes fibroblast viability and wound closure. However, the addition of Tualang honey is unable to overcome the inhibitory effects of pamidronic acid on fibroblasts. The addition of Tualang honey and hydroxyapatite improved the cell viability and accelerated wound closure of fibroblast exposed to pamidronic acid.
CONCLUSIONS: These findings demonstrated that the combination treatment protects oral fibroblasts by preventing bisphosphonate toxicity.

OBJECTIVE: The aim of this study was to examine particular single-nucleotide polymorphisms (IL-1A-889 C/T - rs1800587, IL-1B +3953 C/T - rs 1143634) of interleukins 1A and 1B in the development and prognosis of medication-related osteonecrosis of the jaw.
METHODS: DentiGen Parodontitis Tests were applied for collecting samples. This test is suitable for sampling oral mucosa cells in order to detect interleukins 1A and 1B single nucleotide polymorphisms (IL-1A-889, IL-1B+3953). Genetic samples were evaluated in the Istenhegyi Genediagnostic Center using the DNA-hybridization method. Genetic samples were collected in the patient group and the control group. The role of gene polymorphisms in the development of the disease was investigated by comparing the genetic results for the patient and control groups. The investigation of gene polymorphisms in disease prognosis is based on stage improvement, recovery, and relapses following treatment.
RESULTS: In total, 91 patients with MRONJ and 59 healthy controls were included in the study. 51 patients in the patient group and 37 controls had unfavorable allelic variants. No association (Mp = 1.42, SDp = 0.496, Mc = 1.35, SDc = 0.482, p = 0.52) was found between unfavorable polymorphisms and the development of the MRONJ. In the patient group, surgical therapy was required in 79 cases. Stage improvement was detected in 78 cases, recovery in 67 cases, and relapse in 33 cases. No stage improvement was found in one case, recovery in nine cases, or relapse in 34 cases. Of the 79 patients requiring surgical therapy, 49 had unfavorable allelic variants. No connection was found between the polymorphisms examined and stage improvement (Mp = 1.37, SDp = 0.486, Mnp = 2, SDnp = -, p = 0.800) or recovery (Mp = 1.39, SDp = 0.491, Mnp = 1.44, SDnp = 0.527, p = 0.990). However, a significant association (Mp = 1.21, SDp = 0.415, Mnp = 1.58, SDnp = 0.502, p < 0.001) was found between relapses and the presence of unfavorable allelic variants.
CONCLUSIONS: Within the possible limitations of this study, it can be assumed that the analysis of certain single-nucleotide polymorphisms of interleukin-1 may have the potential to help define the risk stratification of MRONJ after surgical therapy.

UNASSIGNED: The aim of this study was to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time.
UNASSIGNED: A total of 38 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs. The study group (n = 13) had segmental resection of the mandible and free bone flap reconstruction due to medication-related osteonecrosis of the jaw (MRONJ). The control group (noMRONJ, n = 25) comprised segmental mandibular resections and free bone flap reconstructions due to tumors, chronic osteomyelitis, or trauma without any radiation. Ossification time and influencing factors were evaluated.
UNASSIGNED: Both duration of surgery (346 ± 90 min. vs. 498 ± 124 min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in the MRONJ group compared to the noMRONJ group. Ossification after mandibular reconstruction was significantly faster in the MRONJ study group [224 days, interquartile range (IQR) 175-287] compared to the control group (288 days, IQR 194-445; p < 0.001). Moreover, good initial contact between the segments resulted in faster ossification (p < 0.001) in the MRONJ group. Ossification rate between original and grafted bone or between grafted bone segments only did not differ in both the study and control groups (MRONJ, p = 0.705 vs. control, p = 0.292). The type of antiresorptive agent did not show any significance for ossification. The rate of wound healing disturbances did also not differ between the study and control groups (p = 0.69).
UNASSIGNED: Advanced MRONJ (stage 3) can be resected and reconstructed safely with free microvascular bone flaps. Antiresorptive agents enhance the ossification of the bone segments. Optimal initial contact of the bone segments accelerates bone healing. Surgery and hospitalization are markedly shortened in this vulnerable group of MRONJ patients compared to oncologic patients.

BACKGROUND: 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.
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.

BACKGROUND: Exodontia is commonly considered as a risk factor for the development of medication-related osteonecrosis of the jaw (MRONJ) in individuals exposed to bone modifying agents. This study was aimed at assessing the efficiency and safety of a gaseous oxygen-ozone mixture as an adjuvant to a standard exodontia to reduce the risk of MRONJ development.
METHODS: A randomized, open-label, phase II, single-center clinical trial involving 117 patients at risk of MRONJ was conducted. The study protocol tested injections of an oxygen-ozone mixture in the post-extraction site. Participants were randomly assigned to two groups: oxygen-ozone therapy, and standard tooth extraction protocol. Post-extraction wound healing was assessed using the Inflammatory Proliferative Remodeling (IPR) Wound Healing Scale.
RESULTS: The oxygen-ozone therapy group exhibited a significant improvement in wound healing post-extraction during the inflammatory and proliferative phases, as indicated by the IPR scale scores at 3-5 days (p = 0.006) and 14 days (p < 0.001) respectively.
CONCLUSIONS: Oxygen-ozone therapy shows promise in improving post-extraction healing in patients at risk of MRONJ. Future studies with larger sample sizes and multicenter collaborations are recommended to confirm the validity of these findings and explore the long-term efficacy of ozone therapy.

BACKGROUND: The long time required for bone uptake of radiopharmaceutical material after injection for bone scintigraphy is a burden for patients with poor health. Thus, to assess whether the uptake time could be reduced for single-photon emission computed tomography (SPECT) of the jawbone, this study evaluated differences in maximum standardized uptake values (SUVmax) within patients using SPECT imaging at 2 and 3 hours after radiopharmaceutical injection.
METHODS: A total of 33 patients undergoing treatment or in post-treatment follow-up for medication-related osteonecrosis of the jaw, who visited our hospital between July 2020 and August 2021 and could receive SPECT twice on the same day, were enrolled in the study. Patients were injected with technetium-99 m hydroxymethylene diphosphonate (Tc-99 m HMDP) intravenously. The SUVmax for healthy parietal bones and jawbone lesions were calculated from the SPECT images using quantitative analysis software, and the SUVmax were compared between 2- and 3-hour uptake times.
RESULTS: After exclusion, 30 patients were included in the study. In the 2-hour and 3-hour images, the median SUVmax of the parietal bones were 1.90 and 1.81, respectively, and those of the jawbone lesions were 9.25 and 9.39, respectively. The limits of agreement (LOA) ranged from - 0.33 to 0.25 in the parietal bones, and the %LOA ranged from - 9.8 to 17.3% in the jawbone lesions, showing high equivalence between the two uptake durations. The SUVmax showed no clinical differences between the 2- and 3-hour uptake durations for Tc-99 m HMDP SPECT of the jawbone.
CONCLUSIONS: The results of this study justify a 2-3-hour uptake window when performing quantitative SPECT of the jawbone. Therefore, the minimum uptake time can potentially be reduced to only 2 hours.

Introduction: To properly combine osteoporosis treatment with dental treatment and to prevent medication-related osteonecrosis of the jaw (MRONJI), a system of communication between health providers can be smoothly made within a short time is required. With the recent increase in the possibility of telemedicine being introduced in Korea, it is expected that the introduction of teleconsultation between health providers treating osteoporosis will reduce the discomfort of patients and health providers and improve satisfaction. In this study, a survey was conducted on the knowledge and experience of MRONJ to find out the willingness of dentists treating osteoporosis patients for teleconsultation. Methods: An online questionnaire-based survey was conducted to investigate the intention for teleconsultation for MRONJ with a total of 516 dentists between September and October 2021. Results: Two-thirds of the respondents had experience of requesting consultation other dentists or doctors for the osteoporosis or MRONJ patients. They answered that the referral letter was the most used consultation request method and that it took a long time to get a reply. As for the intention of teleconsultation, 70% of the respondents answered that they were willing. The more experienced or the higher the educational level, the higher the intention for teleconsultation. Although the intention of dentists for teleconsultation was high, satisfaction with the cost of teleconsultation was low. Discussion: Although dentists\' intention to use teleconsultation was high, satisfaction with the cost of medical care for teleconsultation was low, so it seems that this should be coordinated.

OBJECTIVE: Dental implant treatment is considered contraindicated in patients with cancer on high-dose antiresorptive medication (HDAR). The aim of this prospective, feasibility study was to evaluate implant treatment in patients with cancer on HDAR, in terms of implant survival, implant success, and oral health-related quality of life (OHLQoL) after 2 years of loading.
METHODS: Implants were inserted in three groups of HDAR patients: (1) Previous tooth extraction, no medication-related osteonecrosis of the jaw (MRONJ), (2) Previous MRONJ, now healed, (3) Existing MRONJ, planned surgical resection. Implants were placed without adjunctive bone or soft tissue argumentation. Abutment operation was performed after ≥12 weeks. Prosthetic treatment was initiated ≥14 weeks. Survival and success rate were determined, and OHLQoL was analyzed with OHIP-49 and QLQ-H&N35 questionnaires. Patients were seen for 6 months, 1- and 2 years follow-up.
RESULTS: Twenty-two patients, 39 implants, completed the implant-based prosthetic treatment. Implant-supported crowns and overdentures were fabricated. Thirteen patients (59%) with 23 implants (59%) completed 2 years follow-up. Overall implant survival and success rate after 2 years of loading were 100% and 97.4%, respectively. OHLQoL for the patients increased in all groups after the treatment, a substantial increase was seen in group 3. Two patients developed MRONJ, but not related to the implant treatment.
CONCLUSIONS: Dental implant treatment, with high survival and success rate and increased post-treatment OHLQoL, is feasible in HDAR patients after 2 years of loading. Caution with general recommendations should be exercised.

Medication-related osteonecrosis of the jaws (MRONJ) is a challenging situation in clinics. Previous studies have shown that pentoxifylline combined with tocopherol proved to be beneficial in patients with osteoradionecrosis, due to their antioxidant and antifibrotic properties. The aim of this randomized study was to evaluate the effect of pentoxifylline and tocopherol in patients that had developed MRONJ after tooth extractions. The study population consisted of 202 Stage I MRONJ female patients with an average age of 66.4 ± 8.3 years, who were divided into two groups. The test group (n = 108) received a pharmacological protocol with pentoxifylline and tocopherol (2 months pre-operatively and 6 months post-operatively). The control group (n = 94) had sequestrectomy operations without any pharmacological preparation. The main outcomes were clinical healing of the mucosa after 1 month, and clinical and radiographic healing of the bone lesion at 6 months. In the test group all patients had mucosal healing and there was only one relapse within 6 months. In the control group, in 17% of the patients the mucosa did not heal, 71% of the patients relapsed within two months, and 7% developed infectious complications (such as abscess or phlegmon). After 6 months, the control group patients with persisting issues were prescribed pentoxifylline and tocopherol, as in the test group. At a subsequent follow-up, all those patients healed completely. Patients were monitored for a period of 7.8 ± 0.3 years, during which no relapse or additional problems were reported. As a conclusion, pentoxifylline and tocopherol protocol seems to be beneficial in the management of MRONJ patients.