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.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious condition associated with the use of antiresorptive and antiangiogenic medications. Despite extensive research, the pathophysiology of MRONJ remains poorly understood. Bibliometric analysis provides insights into the academic impact of research, helping identify influential works and emerging trends in this field. This study employed a bibliometric analysis of MRONJ publications indexed in Web of Science from 2003 to 2023. The analysis included English-language articles and utilized the VOSviewer, R Studio Bibliometrix package, and Graphpad to evaluate citation counts, publication trends, and collaboration patterns. This study unveils the current situation of the MRONJ research, addressing well-recognized safety issues of antiresorptive and antiangiogenic agents. Our findings may suggest that the overall trend of the MRONJ research continues to evolve and is not likely to reach its peak or plateau yet. We believe that our work will help to identify gaps in the literature and future research directions, contributing to a better understanding of MRONJ management.

Medication Related Osteonecrosis of the Jaw (MRONJ) has traditionally been mostly attributed to the exposure to antiresorptive agents such as bisphosphonates and denosumab. Nevertheless, following the development of new medications in oncology, the spectrum of drugs associated with MRONJ widened, with, for example, tyrosine kinase inhibitors, mTOR inhibitor, or monoclonal antibodies against VEGF. To date, MRONJ has not been assessed or reported in patients treated with guselkumab so far. Guselkumab is a fully human IgG1λ monoclonal antibody that selectively targets the p19 protein subunit of extracellular human IL-23 and inhibits its intracellular and downstream signalling. It consists of two identical light chains and two identical heavy chains. The four chains are linked together by covalent disulfide bonds and noncovalent protein-protein interactions. The aim of this article is to report a case of a patient with severe psoriasic arhtritis and plaque psoriasis who presented with a clinical condition that could resemble a MRONJ following guselkumab therapy and a dental root extraction.

Medication-Related Osteonecrosis of the Jaw (MRONJ) is a challenging and evolving aspect of Oral and Maxillofacial Surgery. In recent years, several medications apart from those traditionally associated with MRONJ such as bisphosphates (BPs) and Denosumab (DMB) have been implicated in bony necrosis of the jaw. This aim of this report is to demonstrate a significant case of bone necrosis following dental extractions on a patient being treated with infliximab therapy for Crohn\'s disease. Several cases in literature have reported MRONJ associated with infliximab but very few patients have developed as significant a form of the disease as seen in this report. Previous investigators have proposed pathophysiological pathways via which TNF-α inhibitors such as infliximab have a causative mechanism for MRONJ. When osteoclastic activity is restricted via these pathways, bone healing is impaired and MRONJ can occur. However, it remains a diagnostic challenge to differentiate between antiresorptive MRONJ and chronic osteomyelitis with bone necrosis in patients with acquired immunodeficiency. This case aims to illustrate why the antiresorptive effects of TNF-α inhibitors need to be considered as a possible primary driver of bone necrosis in such patients.

Purpose Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of antiresorptive agents such as bisphosphonates (BPs) and denosumab (DMB). We investigated whether a difference exists between BP- and DMB-related osteonecrosis of the jaw (ONJ). Patients and methods Histological images of 30 patients with BP-related ONJ and 13 patients with DMB-related ONJ were observed using hematoxylin-eosin and cathepsin K staining. Moreover, bone metabolism markers in the blood and bone mineral density were measured in 18 patients with BP-related ONJ and five patients with DMB-related ONJ. Furthermore, we conducted a quantitative analysis of local bone metabolism-related genes using surgical specimens through real-time reverse transcription polymerase chain reaction. Additionally, a retrospective study of 298 patients with MRONJ examined the differences in the characteristics of BP- and DMB-related ONJ and the factors associated with treatment outcomes. Results Histological examination revealed that patients treated with DMB had more severe osteoclast suppression than those treated with BP. No significant difference was observed in blood-bone metabolism markers between the two drugs; however, the suppression of local bone metabolism-related genes was stronger in patients treated with DMB. Clinical studies indicate that DMB-related ONJ is more frequently observed without osteolysis. Conclusion BP-associated ONJ and DMB-associated ONJ were shown to differ slightly. Clinical studies indicate that osteolysis is often unclear in DMB-related ONJ, and methods of bone resection during surgery need to be established.

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: Zoledronate (ZA) stands as a highly effective antiresorptive agent known to trigger medication-related osteonecrosis of the jaw (MRONJ). Its clinical dosages primarily encompass those used for oncologic and osteoporosis treatments. While inflammation is recognized as a potential disruptor of mucosal healing processes associated with ZA, prior research has overlooked the influence of varying ZA dosages on tissue adaptability. Therefore, a deeper understanding of the specific mechanisms by which inflammation exacerbates ZA-induced MRONJ, particularly when inflammation acts as a risk factor, remains crucial.
UNASSIGNED: Cell proliferation and migration of human oral keratinocytes (HOK) was analyzed after treatment with different doses of ZA and/or lipopolysaccharide (LPS) to assess their possible effect on mucosal healing of extraction wounds. Mouse periodontitis models were established using LPS, and histological changes in extraction wounds were observed after the administration of oncologic dose ZA. Hematoxylin and eosin (HE) staining and immunofluorescence were used to evaluate mucosal healing.
UNASSIGNED: In vitro, LPS did not exacerbate the effects of osteoporosis therapeutic dose of ZA on the proliferation and migration of HOK cells, while aggravated these with the oncologic dose of ZA treatment by inducing mitochondrial dysfunction and oxidative stress via regulating SIRT1 expression. Furthermore, SIRT1 overexpression can alleviate this process. In vivo, local injection of LPS increased the nonunion of mucous membranes in MRONJ and decreased the expression of SIRT1, PGC-1α, and MnSOD.
UNASSIGNED: Inflammation aggravates oncologic dose of ZA-induced mitochondrial dysfunction and oxidative stress via a SIRT1-dependent pathway, enhancing the risk of impaired mucosal healing in MRONJ. Our study implies that inflammation becomes a critical risk factor for MRONJ development at higher ZA concentrations. Elucidating the mechanisms of inflammation as a risk factor for mucosal non-healing in MRONJ could inform the development of SIRT1-targeted therapies.

This study presents a rare case of an Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) co-existing with medication-related osteonecrosis of the jaw (MRONJ) in the mandible of a 54-year-old Japanese man who complained of painful swelling of the left mandibular gingiva over the past three months. The patient had a history of methotrexate (MTX) and bisphosphonates (BPs) use. Intraoral examination revealed a 35 mm large ulcerative lesion with marginal gingival swelling and bone exposure on the left side of the mandible. A biopsy was performed, confirming the diagnosis of EBVMCU with MRONJ. Due to the enlargement of the bone exposure, marginal resection of the mandible was performed under general anesthesia as a treatment for residual MRONJ. At the two-year follow-up, no evidence of recurrence was observed.

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.