Medication-related Osteonecrosis Of The Jaw Research Articles

Teriparatide-induced alleviation of medication-related osteonecrosis of the jaw: Potential molecular mechanisms

Medication-related osteonecrosis of the jaw (MRONJ) is a significant side effect of drugs such as bone modifying agents (BMA) or angiogenesis inhibitors. The incidence has been rising but the clinical prognosis is dismal. Teriparatide (TPTD), a synthetic derivative of parathyroid hormone (PTH), is occasionally demonstrated to efficiently reduced the clinical incidence of MRONJ in particular patients. However, the precise signaling mechanisms involved in TPTD-induced MRONJ repair are unknown. Currently, MRONJ progression is involved with decreased expression of the Wnt/β-catenin signaling pathway, inhibition of angiogenic function, and up-regulated inflammatory cytokines (IL-1β, TNF-α, and IL-6). Notably, in animal model experiments, TPTD increased β-catenin expression in alveolar bone and skeletal muscle; similarly, TPTD was able to reduce the area of cerebral infarction, restore cerebral blood flow, and improve neovascularization by increasing the number of blood vessels in bone tunnels and enlarging the diameter of blood vessels in the bone marrow. Furthermore, TPTD can also treat osteoarthritis in animals by suppressing inflammatory markers such as TNF- and IL-6. Thus, we propose that TPTD can cure MRONJ by dynamically modulating various signaling pathways (stimulation of the Wnt/β-catenin signaling pathway, promotion of angiogenesis, and down-regulation of inflammatory markers).

Zoledronate treatment exerts sex-independent effects on bone and dental physicochemical properties in mice jaw necrosis.

Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Menaquinone-4 prevents medication-related osteonecrosis of the jaw through the SIRT1 signaling-mediated inhibition of cellular metabolic stresses-induced osteoblast apoptosis.

Long-term usage of bisphosphonates, especially zoledronic acid (ZA), induces osteogenesis disorders and medication-related osteonecrosis of the jaw (MRONJ) in patients, thereby contributing to the destruction of bone remodeling and the continuous progression of osteonecrosis. Menaquinone-4 (MK-4), a specific vitamin K2 isoform converted by the mevalonate (MVA) pathway in vivo, exerts the promotion of bone formation, whereas ZA administration suppresses this pathway and results in endogenous MK-4 deficiency. However, no study has evaluated whether exogenous MK-4 supplementation can prevent ZA-induced MRONJ. Here we showed that MK-4 pretreatment partially ameliorated mucosal nonunion and bone sequestration among ZA-treated MRONJ mouse models. Moreover, MK-4 promoted bone regeneration and inhibited osteoblast apoptosis in vivo. Consistently, MK-4 downregulated ZA-induced osteoblast apoptosis in MC3T3-E1 cells and suppressed the levels of cellular metabolic stresses, including oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and DNA damage, which were accompanied by elevated sirtuin 1 (SIRT1) expression. Notably, EX527, an inhibitor of the SIRT1 signaling pathway, abolished the inhibitory effects of MK-4 on ZA-induced cell metabolic stresses and osteoblast damage. Combined with experimental evidences from MRONJ mouse models and MC3T3-E1 cells, our findings suggested that MK-4 prevents ZA-induced MRONJ by inhibiting osteoblast apoptosis through suppression of cellular metabolic stresses in a SIRT1-dependent manner. The results provide a novel translational direction for the clinical application of MK-4 for preventing MRONJ.

Medication-related osteonecrosis of the jaw: the radiologist’s role

In recent decades, the dreaded adverse effect of bisphosphonates, osteonecrosis of the jaw, has been widely reported and described in detail. Osteonecrosis of the jaw consists of the destruction of part of the maxilla as a consequence of these antiresorptive drugs. In recent years, new drugs that can also cause osteonecrosis of the jaw (e.g., some monoclonal antibodies or antiangiogenic drugs) have come on the market. For this reason, the term “bisphosphonate-related osteonecrosis of the jaw” has been replaced with “medication-related osteonecrosis of the jaw (MRONJ).This review aims to describe the radiologic characteristics of MRONJ that, although nonspecific, radiologists need to recognize in the appropriate clinical context.

Group 3 ITI Consensus Report: Materials and antiresorptive drug-associated outcomes in implant dentistry.

The aim of Working Group 3 was to address the influence of both material- and anti-resorptive drug- related factors on clinical and biological outcomes and complications in implant dentistry. Focused questions were addressed on (a) implant materials other than titanium (alloy)s, (b) transmucosal abutment materials and (c) medications affecting bone metabolism were addressed. Three systematic reviews formed the basis for discussion in Group 3. Consensus statements and clinical recommendations were formulated by group consensus based on the findings of the systematic reviews. Patient perspectives and recommendations for future research were also conveyed. These were then presented and accepted following further discussion and modifications as required by the plenary. Zirconia is a valid alternative to titanium as material for implant and transmucosal components, allowing soft and hard tissue integration with clinical outcomes-identified by implant survival, marginal bone loss and peri-implant probing depths-up to 5-years comparable to titatnium. However, most of the evidence for zirconia implants is based on 1-piece implants limiting the indication range. Furthermore, based on expert opinion, zirconia transmucosal components might be preferred in the esthetic zone. In patients receiving low-dose bisphosphonate therapy, the rate of early implant failure is not increased, while the long-term effects remain poorly studied. Although it has not been sufficiently addressed, similar outcomes can be expected with low-dose denosumab. A drug holiday is not recommended when considering implant placement in patients treated with low-dose ARD. However, the specific therapeutic window, the cumulative dose and the administration time should be considered. Access to peri-implant supportive care is mandatory to prevent peri-implantitis-related medication-related osteonecrosis of the jaw (MRONJ) or implant-related sequestra (IRS). In patients receiving low-dose anti-resorptive drugs (ARD) therapy, the risk of complications related to implant placement is high, and implant procedures in this specific population should be strictly treated in a comprehensive multidisciplinary center. Finally, healthy dental implants should not be removed before low or high-dose ARD. Zirconia implants can be an alternative to titanium implants in selected indications. However, the current state of evidence remains limited, especially for 2-piece implant designs. Administration of low-dose ARD did not show any negative impact on early implant outcomes, but careful follow-up and supportive care is recommended in order to prevent peri-implant MRONJ and IRS. Implant placement in high-dose patients must be strictly considered in a comprehensive multidisciplinary center.

Should Mandibular Tori Be Documented in the Literature as a Known Risk Factor for Medication-Related Osteonecrosis of the Jaw?

Should Mandibular Tori Be Documented in the Literature as a Known Risk Factor for Medication-Related Osteonecrosis of the Jaw?

A Study on the Treatment Period and Bone Turnover Markers According to Application of Teriparatide in the Treatment of Medication-Related Osteonecrosis of the Jaw

A Study on the Treatment Period and Bone Turnover Markers According to Application of Teriparatide in the Treatment of Medication-Related Osteonecrosis of the Jaw

Effects of low dose bisphosphonates treatment on the mandibular bone in rats with and without mini-implants application: an experimental model

Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is a pathological condition observed in patients underwent oral surgical procedures during bisphosphonates treatment. Although several studies have focused on the BRONJ, the exact pathophysiological pathways remain still unclear. In this study we aimed to observe the effects of the low-dose bisphosphonates administration on mandibular bone of rats with and without mini-implants application. For this study we used 28 male Wistar rats, divided in in two groups: 1) control group, treated with saline solution (n = 14 rats); 2) ZA group, treated with low dose zoledronic acid (n=14 rats). After 6 weeks of treatment, the half of each group underwent mini-implant application. All rats were sacrificed and their mandibles were analyzed by light microscopy and scanning electron microscopy (SEM). Our data have shown a healthy bone tissue of control group both with and without mini-implant application. In the treated group empty osteocyte lacunae have been observed and they slightly increase in rats with mini-implant application. Although that, no bone exposition has been observed. By that, during low dose zoledronic acid treatment we can observe the presence of empty osteocytes lacunae, also called “primary lesion”, that not seem to be sufficient alone to determine osteonecrosis of the jaw spontaneously or even after mini-implant application.

Alendronate reduces periosteal microperfusion in vivo

ObjectivesBisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of bisphosphonates on microperfusion; therefore, this study aimed to investigate alendronate-induced microcirculatory reactions in the calvarial periosteum of rats. Study designBone chambers were implanted into 48 Lewis rats. Microhemodynamics, inflammatory parameters, functional capillary density and defect healing were examined after alendronate treatment for two and six weeks using repetitive intravital fluorescence microscopy for two weeks. ResultsMicrohemodynamics remained unchanged. In alendronate-treated rats, inflammation was slightly increased, functional capillary density was significantly reduced (day 10: controls 100.45 ± 5.38 cm/cm2, two weeks alendronate treatment 44.77 ± 3.55 cm/cm2, six weeks alendronate treatment 27.54 ± 2.23 cm/cm2) and defect healing was decelerated. The changes in functional capillary density and defect healing were dose-dependent. ConclusionThe bisphosphonate alendronate has a significant negative impact on periosteal microperfusion in vivo. This could be a promising target for the treatment of MRONJ.

Alloplastic reconstruction of the mandible after subtotal mandibulectomy for medication-related osteonecrosis of the jaw: An update of the method.

Reconstruction of continuity defects following osteonecrosis in multimorbid patients is challenging. In all cases of the predescribed palliative treatment method for alloplastic mandible reconstruction, plate fractures were detected in follow-up. We hypothesized that a modification could avoid these fractures, leading to stable long-term results. This retrospective study compares the original method with a modification using single, laser-sintered CAD-CAM plates instead of manually bent miniplates. The predescribed shuttering technique was used to reconstruct the mandible in its original shape with bone cement. Uneventful wound healing was observed in 86% of the cases after modification of the method. No implant or plate fracture occurred. The presented method should be considered as a treatment option for mandible reconstruction in elderly, multimorbid patients in palliative situations. The results of this study suggest that the modification of the method leads to significantly improved long-term stability. Donor site morbidity is avoided with this method of palliative surgery.

Prevention and management of drug-induced osteonecrosis of the jaws using platelet-rich fibrin: A clinical feasibility study.

Although a standard treatment guideline has not been established to date, various treatment modalities have been described in the literature based on the staging of medication-related osteonecrosis of the jaw (MRONJ). The aim of this case series was to describe the outcomes of surgical intervention of MRONJ cases with the adjunctive use of platelet-rich fibrin (PRF). Thirteen patients under therapy with zoledronic acid, seven of them underwent surgical removal of necrotic bone with debridement, followed by placement of three to four PRF membranes and achieving primary closure. In six patients, PRF was used preventively to avoid MRONJ. The surgical treatment outcomes were successful in all patients, with a follow-up range of 12-48 months. In the presented cases, the intraoral evaluation showed excellent soft tissue healing except for one patient secondary wound healing was reported. Additionally, there was no recurrence of bone exposure in all cases. PRF membranes were comparatively effective in postsurgical pain control. The use of PRF could represent a valuable adjunct in the surgical management for advanced stages of MRONJ cases. This clinical case series describes the use of PRF membranes as a valuable adjunct in the surgical management of MRONJ patients, especially when treating advanced MRONJ cases. Moreover, PRF demonstrates usefulness in preventing such difficult complications from occurring.

Medication-related osteonecrosis of the jaw using periodontitis-induced rat before tooth extraction

ObjectiveThis study aimed to investigate the occurrence of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction due to periodontitis in ovariectomized rats.MethodsTwenty-four osteoporosis-induced rats were administered with zoledronic acid (ZA; ZA group) or saline (CONT group). In both groups, tooth extraction was performed after inducing periodontitis, and all animals were sacrificed 8-week after tooth extraction.ResultsMicro-CT of the tibia showed that the bone volume fraction, bone surface density, trabecular number, and bone mineral density were significantly higher in the ZA group than in the CONT group. Histologically, the proliferative zone on the growth plate was thicker in the ZA group than in the CONT group. Micro-CT of the extraction sites revealed that the bone volume fraction was significantly higher in the ZA group than in the CONT group. Radiologically, the ZA group showed partial healing and delayed healing. Histological analysis revealed normal bone healing status with completely healed epithelium in the extraction sites of the CONT group, whereas abnormal empty osteocytes in the necrotic bone and inflammatory infiltration were observed in the ZA group.ConclusionThe incidence of MRONJ increased in the rats administered with ZA.

Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect.

Background: Medication-related osteonecrosis of the jaw is a serious complication that develops in oncologic patients treated with Zoledronic acid. Although used for over 30years, the influence of Zoledronic acid on bone has been thoroughly investigated, mainly on osteoclasts. While decreasing osteoclast differentiation and function, for many years it was thought that Zoledronic acid increased osteoblast differentiation, thus increasing bone volume. Moreover, despite the influence of soft tissue on the bone healing process, the impact of zoledronic acid on the interaction between soft tissue and bone was not investigated. Aim: Our goal was to investigate the influence of Zoledronic Acid and soft tissue cells on osteogenic differentiation of mesenchymal stem cells (MSCs). Materials and methods: Osteogenic differentiation of MSCs was examined after exposure to Zoledronic Acid. To determine the influence of soft tissue cells on MSCs' osteogenic differentiation, conditioned media from keratinocytes and oral fibroblasts were added to osteogenic medium supplemented with Zoledronic Acid. Proteomic composition of keratinocytes' and fibroblasts' conditioned media were analyzed. Results: Zoledronic Acid decreased osteogenic differentiation of MSCs by seven-fold. The osteogenic differentiation of MSCs was restored by the supplementation of fibroblasts' conditioned medium to osteogenic medium, despite Zoledronic acid treatment. Five osteogenic proteins involved in the TGFβ pathway were exclusively identified in fibroblasts' conditioned medium, suggesting their role in the rescue effect. Conclusion: Oral fibroblasts secrete proteins that enable osteogenic differentiation of MSCs in the presence of Zoledronic Acid.

Medication-related osteonecrosis of the jaw without osteolysis on computed tomography: a retrospective and observational study

Medication-related osteonecrosis of the jaw (MRONJ) is a refractory osteonecrosis caused by antiresorptive agents such as bisphosphonate and denosumab (DMB). In MRONJ surgery, computed tomography (CT) is generally used to determine the extent of bone resection. However, in some recent MRONJ cases, no abnormal findings were detected on CT. Therefore, we aimed to clarify the characteristics of MRONJ without osteolysis. This retrospective and observational study included 18 patients diagnosed with MRONJ between October 2020 and October 2022 at Department of Dentistry and Oral Surgery, Kansai Medical University Medical Center. In four of 18 patients with MRONJ, no abnormal findings such as osteolysis, separation of sequestrum, and periosteal reaction were observed on CT images at the first visit. All four patients with non-osteolytic MRONJ had malignant tumors and received high-dose DMB, and in the four patients there were no preceding dental infections such as apical lesions or periodontal disease and the trigger of MRONJ was unknown. Surgery was performed in three of the four patients. The extent of bone resection was determined using magnetic resonance imaging and intraoperative gross findings. In the future, it is necessary to establish a method for diagnosing non osteolytic MRONJ and determining the extent of bone resection.

Sex difference in the morbidity and pain response with stage 0 of medication-related osteonecrosis of the jaws

ObjectiveMedication-related osteonecrosis of the jaws (MRONJ) is a potentially severe complication associated with antiresorptive or antiangiogenic therapies. Prior studies, including our own clinical data, have indicated a higher incidence of MRONJ among women compare to men. However, robust evidence establishing a relationship between sex and the prevalence of MRONJ is lacking. MethodsWe conducted a meta-analysis and utilized murine models to investigate potential sex-based differences in the morbidity associated with MRONJ. ResultsOur results revealed no significant difference in the incidence of MRONJ between the sexes when using exposed necrotic bone as a diagnostic criterion. However, a histological examination of the murine models identified the presence of stage 0 MRONJ. Notably, pain assessments across all groups revealed that male mice with stage 0 MRONJ displayed less severe pain symptoms than their female counterparts. ConclusionsOur findings suggested that sex does not contribute to the risk of developing MRONJ. However, considering that approximately 50% of stage 0 MRONJ cases progress to more advanced stages, the less pronounced pain in male patients might delay medical consultation and potentially lead to disease progression. Clinicians should be particularly vigilant about the subdued pain response in male patients with stage 0 MRONJ to prevent disease advancement.

Radiographic Evaluation of Medication-Related Osteonecrosis of the Jaw (MRONJ) With Different Primary Cancers and Medication Therapies.

Medication-related osteonecrosis of the jaw (MRONJ) is a condition that affects the jaws and is characterized by exposed bone in the oral cavity that persists for more than eight weeks despite treatment. Additional criteria include that the patient should have a current or past history of antiresorptive drugsand/or in combination with antiangiogenic drugs, absence of metastasis, and no previous radiotherapy to the affected area. The radiographic features of MRONJ in most instances do not have any specific radiographic features. This is because standard radiographs usually show no stark abnormalities in the early stages of the disease. The study aimed to evaluate if any specific radiographic patterns are associated with primary cancers and between medications. The study is an observational case series. A total of 50 cases of possible osteonecrosisfrom June 2010 to June 2013 archives of the Department of Oral and Maxillofacial Radiology were assessed. Based on the history, 12 cases that had a history of medication use that could lead to medication-related osteonecrosis of the jaw (MRONJ) were selected. Cone beam computed tomography (CBCT) scans of these 12 cases were evaluated using the CBCT reconstruction program InVivo Dental version 6 (Anatomage Inc., San Jose, CA, USA). The number of areas showing sequestration, the pattern of osteonecrosis, and the extent were assessed. Primary cancer and the type of medication were also assessed to identify if certain cancers or drugs showed any distinctive pattern of osteonecrosis. Reconstructed panoramic images and true three-dimensional (3D) multi-planar images were assessed to study the condition. An oral and maxillofacial radiology resident in training and a board-certified oral and maxillofacial radiologist assessed the images. Radiographic findings varied among the 12 cases and included generalized sclerosis, osteosclerosis with widened periodontal ligament (PDL) space, bony sequestra, and bony necrosis. However, no specific or distinctive radiographic patterns were observed in any of the cases, regardless of the type of primary cancer or medication used. It is challenging to radiographically distinguish between MRONJ cases with different primary cancer and/or medication. Future studies should include evaluating larger samples with varying primary cancers and medications and combination drug therapies. Cases in an advanced stage of MRONJ do not have distinctive features due to extensive destruction and superimposed infection;it may be valuable to evaluate patients in the early stages of MRONJ to better understand distinguishing radiographic patterns specific to certain primary cancers or medications.

Awareness and Attitude among Physicians Regarding Bisphosphonaterelated Osteonecrosis of the Jaw (BRONJ): A Cross-sectional Study.

An invasive dental procedure is considered one of the risk factors for osteonecrosis of the jaw, especially among patients on bisphosphonates. This study aimed to determine the awareness and perceptions of medical practitioners regarding bisphosphonate-related osteonecrosis of the jaw (BRONJ), and their attitude towards dental referrals of such patients. This cross-sectional questionnaire-based study was conducted among medical practitioners in and around Mysore city, Karnataka, India, who commonly prescribe bisphosphonates. The sample included orthopaedic doctors, physicians, endocrinologists, and oncologists, divided based on the duration of practice and speciality. Data on the type of practice, awareness of BRONJ, referral to a dentist before/during therapy, and patient education about adverse effects, were collected and analyzed. A p-value ≤0.05 was considered statistically significant. Among 58 practitioners, 84.5% (49) were aware of the association between bisphosphonates and BRONJ, while 56.9% (33/58) believed dental procedure to be a risk factor, and 55.2% (32/58) did not recommend screening of the oral cavity by a dentist before initiation of bisphosphonate therapy. A majority (65.5%) of them educated their patients about adverse effects. Mean knowledge scores varied with specialization (post-graduation vs. super specialization = 1.43 vs. 2; p = 0.01) but not with the duration of practice (<= 10 years vs. >10 years= 1.57 vs. 1.4; p= 0.24). The practitioners in our study were oblivious to dental procedures' role in the osteonecrosis of the jaw, highlighting the need for continuing education programs regarding BRONJ for medical and dental professionals. Clinicians updated regarding evidence-based practices and working cooperatively in teams may reduce the incidence of medication-related osteonecrosis of the jaw.

Prosthodontic rehabilitation of a patient with nintedanib-induced osteonecrosis of the jaw: A clinical report

Medication-related osteonecrosis of the jaw results in extensive excision and proves challenging to rehabilitate prosthetically. This article describes the prosthodontic rehabilitation of medication-related osteonecrosis of the jaw induced by nintedanib. A custom-made subperiosteal implant was designed to adapt to the bone, remaining after the excision of the jaw necrosis. The implant followed the anatomic contour of the residual bone and was milled in titanium alloy, allowing the rehabilitation of a patient with a fixed dental prosthesis.

Position Papers on MRONJ(Medication related osteonecrosis of the jaw), What has changed?

Antiresorptives, such as bisphosphonate, denosumab, are widely prescribed drugs for the treatment of osteoporosis, os-teopenia, malignant bone metastases, multiple myeloma and Paget`s disease. They have therapeutic efficacy for controlling bone pain and reducing skeletal related events including the pathologic fractures. However, it was reported that the develop-ment of osteonecrosis of the jaw(ONJ) could be related to antiresorptive treatments. It was first defined as Bisphosphonate-related osteonecrosis of the jaw in 2007 American Association of Oral and Maxillofacial Surgeons(AAOMS) position paper. This was changed to Medication-related osteonecrosis of the jaw(MRONJ) in the AAOMS position paper 2014. Thisposition paper was updated recently in May 2022 and contains revisions to disease definition and management strategies at “AAOMS position paper on MRONJ-2022 update”. The important changes in clinical implications are as follows; 1) In the definition, immune modulators (such as Romosozumab) were included with potential medications related with osteo-necrosis of the jaw (ONJ), 2) Operative therapy was included for all stages (1, 2 and 3) in treatment strategies, 3) Formerly mentioned drug holiday before surgical procedure to prevent MRONJ was not identified in 2022 AAOMS position paper. Most of the statements in AAOMS 2022 position paper were based on strict literature reviews and changes were made if there is little evidence to suggest the specific diagnosis or therapeutic options. Understanding the changes compared to the previous position papers is important in selecting adequate treatment strategies for MRONJ.