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(a) Patient with medullary thyroid cancer, before and after conservative treatment. Patient just performed brushing exposed bone with stick or spatula with chlorhexidine 0,12% solution. Significant improvement (b). Panoramic radiography (c) and cone beam computer tomography rolled out bone sequestrum. (d) Scanora 3Dx device (On Demand Software Cybermed, Seoul, Korea.)
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This retrospective cohort study aims to describe characteristics of patients with MRONJ, to identify factors associated with MRONJ development, and to examine variables associated with favourable outcome. Totally 32 patients were followed and observed: 21 females and 11 males, in the age range 35-84 in the period from 2009 to 2018. Clinical, radiol...
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Purpose:
The purpose of this study was to investigate pre-extraction variables associated with spontaneous space closure of the perma- nent second molar (PSM) following early extraction of the permanent first molar (PFM), and test an existing prediction model for the mandibular arch as the rates of spontaneous space closure are significantly lower...
Citations
... These adjuvant therapies have shown faster and more comfortable postoperative healing. Additionally, studies have demonstrated the effectiveness of conservative management and antibiotics in MRONJ treatment [48,49,54,24,61,65,67,70,25]. "Conservative surgery combined with adjuvant procedures (i.e., ozone, LLLT or blood component + Nd:YAG laser treatment) can contribute to partial or total healing in all stages of MRONJ, with improved results and variables (from symptoms to clinical and radiological signs). ...
Background and Aims: Medication-related osteonecrosis of the jaws (MRONJ) is a significant and potentially debilitating side effect caused by antiresorptive and antiangiogenic drugs, which can lead to bone exposure in the oral cavity. However, the management of this condition remains controversial, with adjuvant therapies being employed despite limited scientific evidence. This systematic review aimed to identify effective therapeutic procedures for treating MRONJ. Methodology: A literature search was conducted without any temporal limitations. The PRISMA protocol was followed. To identify relevant studies, we developed electronic search strategies for various bibliographic databases, as Cochrane, Embase, PubMed, Scopus, and Web of Science. It was conducted a comprehensive analysis of 30 studies involving 2,079 patients from 35 countries to evaluate the effectiveness of various treatment approaches for MRONJ. Results: The systematic review revealed that long-term use of Zoledronic acid for approximately 452.04 months (±27.41; 12-102) exposed many patients (n=772) to the risk of MRONJ. Similarly, Alendronate use for approximately 104.4 months (±60.16; 6-180) also posed a risk, affecting 650 patients, while Pamidronate use for about 20.74 months (±4.94; 6-96) was associated with MRONJ risk in 121 patients. Among the treatment approaches, conservative surgical management was the most frequently employed (27.92%), followed by local debridement (13.57%) and conservative treatment (11.21%). Treatment complications were observed in 13.03% of cases, with the most frequent complications being resistant or worsening clinical stage of osteonecrosis, followed by incomplete mucosal healing or dehiscence and mental nerve injury. Conclusion: While conservative surgical management, local debridement, and conservative treatment are commonly utilized approaches, the treatment of MRONJ lacks a standardized consensus due to the scarcity of scientific evidence. Further research and comprehensive studies are imperative to establish effective therapeutic strategies for managing this condition.
... This is identified by the mandibular area displaying exposed necrotic bone, which often lasts for eight or more weeks [19]. In contrast to oral-intaking treatment, patients having BPs intravenously had a higher risk of suffering from medication-related osteonecrosis of the jaw (MRONJ) or implant removal [20]. ...
An aberrant growth of plasma cells in the bone marrow characterizes the hematological neoplasm known as multiple myeloma, which is typically accompanied by increased bone pain and skeletal-related events such as pathological fractures and/or spinal cord compression. Changes in the bone marrow microenvironment brought on by increased osteoclastic activity and/or decreased osteoblastic activity as a result of myeloma bone disease have a detrimental effect on quality of life. Bone-modifying medications such as bisphosphonates or denosumab are used to treat myeloma bone disease. These substances can lessen bone pain and the chance of pathological fracture, but they do not stimulate the growth of new bone or heal already damaged bone. In order to conduct this study, we searched the PubMed, Google Scholar, and Cochrane databases for complete free papers published in English and studied people over the previous five years, starting in 2018. The search covered randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and conventional reviews. Twenty-five publications are picked after using quality evaluation techniques to determine the type of study. These papers' full-text articles are investigated, examined, and tallied. We spoke about the various treatments for bone damage in multiple myeloma. It was discovered that bisphosphonates lessen the frequency and severity of bone problems. However, we are unsure of their contribution to survival.
Although these medicines enhance life quality, it is unknown if they also increase overall survival. The focus of this study is on several kinds of bone-modifying drugs, their processes of action, the point at which therapy is started, how long it lasts, and any possible mortality advantages.
... 3 This effect is enhanced depending on the time of application, the presence of amino groups and the route of administration of this drug. 4 Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript. ...
... Among the possible complications, bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most worrisome conditions due to its difficult resolution. 5 BRONJ is characterized by the presence of exposed bone in the jaws for more than eight weeks in patients undergoing BF therapy without a history of head and neck radiotherapy. 4,5 This complication is usually triggered by local trauma and is associated with surgical procedures (e.g., tooth extractions and implant placement). 4,6 Some therapies or combinations of therapies have been proposed for the treatment or prevention of BRONJ, such as systemic antibiotic therapy, 7 local irrigation with bioactive agents, 8 surgical debridement and resection, 9 platelet concentrates, 10 and hyperbaric oxygen therapy. ...
... 4,5 This complication is usually triggered by local trauma and is associated with surgical procedures (e.g., tooth extractions and implant placement). 4,6 Some therapies or combinations of therapies have been proposed for the treatment or prevention of BRONJ, such as systemic antibiotic therapy, 7 local irrigation with bioactive agents, 8 surgical debridement and resection, 9 platelet concentrates, 10 and hyperbaric oxygen therapy. 11 However, there is still no agreement on a definitive and completely effective treatment for BRONJ. ...
Abstract This study evaluated the effect of photobiomodulation therapy (PBMT) with a red or infrared laser on the repair of post extraction sockets in rats administered alendronate (ALN). Forty male rats were randomly allocated into four groups: Control Group (CTR): subcutaneous administration of saline solution throughout the experimental period; Alendronate Group (ALN): subcutaneous administration of alendronate during the entire experimental period; Alendronate/Red Laser Group (ALN/RL): administration of ALN and irradiation with a GaAlAs laser (λ 660 nm); and Alendronate/Infrared Laser Group (ALN/IRL): administration of ALN and irradiation with a GaAlAs laser (λ 830 nm). The first lower molars were extracted 60 days after the beginning of the administration of the drugs. The PBMT was applied after tooth extraction (7 sessions with intervals of 48 hours between sessions). Thirty days after tooth extraction, the animals were euthanized. Micro-CT and histometric analysis were performed to assess the bone healing and soft tissue repair of the tooth socket. The ALN group presented with more bone than the CTR; however, most of this bone was necrotic. ALN does not affect the bone microarchitecture. On the other hand, PBMT with IRL enhances the bone density due to the increase in the number and reduction in the spacing of the trabeculae. The amount of vital bone and connective tissue matrix was higher in the ALN/RL and ALN/IRL groups than in the ALN and CTR groups. PBMT enhanced the healing of the post extraction sockets in rats subjected to ALN administration. Furthermore, IRL improved the new bone microarchitecture.
... 5e8 While the exact etiopathogenesis of MRONJ is still not fully understood, a number of predisposing factors have been suggested including, among others, duration and route of antiresorptive medication, dentoalveolar surgery, age, underlying systemic conditions such as diabetes mellitus, and medications use such as corticosteroids. 1,2,7 MRONJ is a serious complication that gravely impairs the daily oral functions and impacts the patients' quality of life. 9 The management of MRONJ is quite challenging, and requires a multidisciplinary approach. ...
Background/purpose
Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication among dental patients undergoing treatment with antiresorptive medications such as bisphosphonate and denosumab. The present survey investigated the awareness and practice of dentists in the Gulf Cooperation Council (GCC) countries regarding MRONJ.
Materials and methods
This questionnaire-based study was conducted among dental practitioners in all six GCC countries. A questionnaire was designed and distributed among all potential participants via different social media platforms. SPSS version 22 was used for data analysis, and P-value <0.05 was considered statistically significant.
Results
Overall, 1685 dentists from the six GCC countries participated in the present study. The surveyed dentists revealed relatively fair practices and awareness regarding MRONJ and its prevention, with the majority reported asking their patients about history of anti-osteoporotic medications (67.8%), recording name of the medication (73.1%) and duration of treatment (75.5%). However, the majority of the participants were unconfident about the duration of drug holiday prior to dental surgical interventions (70.6%) and the overall good level of knowledge/practice related to MRONJ was just 50.6%. The regression analysis revealed that previous exposure to MRONJ cases and attending a seminar, course, meeting, or conference about osteonecrosis of the jaw were independent predictors for positive awareness/good practice regarding MRONJ (P < 0.05).
Conclusion
The results show inadequate awareness and practices of dentists practicing in GCC countries regarding MRONJ, with significant variations among the countries. Therefore, appropriate interventions such as periodic continuous education courses are required to improve dentists’ knowledge and practices regarding MRONJ.
... Several studies suggested that MRONJ may be secondary to alteration of bone remodeling in a skeletal structure in which microtrauma, inflammation, and mucosa damage are present. [5,6] In addition, in concordance with the antiangiogenic (AA) effect of the bisphosphonates, the vasculature has been hypothesized to play a major role in the development of MRONJ. This AA activity is supported by the fact that biphosphonates highly decreased the vascular endothelial growth factor (VEGF). ...
Aim:
The aim of this preliminary study was to evaluate in an oncological population the association risk of antiangiogenic (AA) agents to antiresorptive (AR) agents on the incidence and the severity of medication-related osteonecrosis of the jaw (MRONJ).
Materials and methods:
In this prospective study, we reviewed the medical records and clinical variables of 59 consecutive oncologic patients who developed MRONJ. For all patients, we retrieved the following variables: age, gender, alcohol and tobacco use, type of cancer, use of corticosteroids for >3 months, history of diabetes, MRONJ staging, combination of AR and AA agents, dental history (surgery, prosthesis) or spontaneous, site of MRONJ, delay between AR and AA first intake, and MRONJ development. Patients were divided into two groups according to drugs therapy they underwent: group 1 (G1) including patients treated with AR agents alone and group 2 (G2) including patients receiving antiresorptive-antiangiogenic drugs (AR+AA). The degree and the therapeutical success were defined as primary outcomes and the number, the localization, and the delay in onset of the lesions as secondary outcomes. In order to identify predictive factors of osteonecrosis-free interval time, univariate and multivariate Cox regression was performed. Statistical tests were carried out using the IBM® SPSS® Statistics software. All reported P-values are two-tailed and were considered to be significant when less than 0.05.
Results:
Among the 47 patients who received AR agent alone (group 1), the mean treatment duration before diagnosis of MRONJ was 39.2 months. In the second group (n = 12), patients developed MRONJ with a comparable mean time of 55 months (P = 0.16). According to the staging of MRONJ at the time of diagnosis, no significant difference (P = 0.736) was observed between the two groups. Moreover, the treatment applied was not statistically different in both the groups and was successful in 36.17% of the patients in group 1 and 58.33% of the patients in group 2. No statistically difference was reported in both the groups (P = 0.16). After statistical analysis, no significant difference in terms of MRONJ localization (P = 0.13) was observed. Finally, the incidence of spontaneous MRONJ was comparable in both the groups. Statistical analysis revealed that total time of treatment was the only factor associated with poor osteonecrosis-free interval time (hazard ratio 0.99; P = 0.001). Interestingly, the combination of an AA and AR agent was not a significant predictor factor of the interval time before the diagnosis of osteonecrosis. Additionally, corticosteroid use, diabetes mellitus, and dental consultation before treatment were not statistically related to poorer osteonecrosis-free interval time rates.
Conclusion:
In our preliminary study, neither the mean treatment time duration before the diagnosis of MRONJ nor the dose delivered was different in both the groups (AR vs. AR+AA). Moreover, no significant difference was observed between both the groups regarding the localization and the staging of MRONJ at the time of diagnosis. Interestingly, our results demonstrated that the risk of spontaneous MRONJ is statistically comparable in the AR and AR-AA groups. Additionally, the addition of an AA agent did not influence the treatment applied in the two groups of patients.
... Kyrgidis et al. 5 also reported that a history of tooth extraction during zoledronic acid treatment increased the risk of developing MRONJ by 16-fold in 20 MRONJ patients with breast cancer. Similarly, there are many reports that tooth extraction is a risk of developing MRONJ [12][13][14][15][16][17][18] . ...
Tooth extraction has been avoided since it has been considered a major risk factor for medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may also develop from tooth that is an infection source. This study aimed to clarify whether tooth extraction is a risk factor for the development of MRONJ in cancer patients receiving bone-modifying agents (BMAs). This retrospective observational study included 189 patients (361 jaws) from two hospitals. The risk factors of MRONJ were identified by comparing patient characteristics between those who did and did not develop MRONJ. Furthermore, the effect of tooth extraction during BMA therapy was analyzed after adjusting for confounding factors using the propensity score matching method. MRONJ occurred in 33 patients jaws. A longer duration of BMA administration, fewer number of teeth, presence of symptoms of local infection, and infected teeth were independent risk factors of MRONJ. However, tooth extraction during BMA therapy did not increase the risk. Propensity score matching analysis showed that tooth extraction significantly lowered the risk of MRONJ development. Teeth that can be an infection source increases the risk of MRONJ, and thus, they need to be extracted even during BMA administration.
... Most of the analyzed studies introduced the use of therapy defined as "additional" in association with surgery. Specifically, additional therapy is referred to as non-invasive treatments, such as cycles of local or systemic antibacterial therapy combined or not, to low level laser therapy, ozone therapy (O3), HBO (Hyperbaric Oxygen therapy), the use of APCcs APCs (Autologous Pletelet Concentrates, such as PRP,PRGF or PRF), AF-GBS/TF-GBS (Auto/ DISCUSSION Despite progress in the prevention of BRONJ, a specific widely accepted and utilized treatment protocol to manage MRONJ is still missing, as the literature shows (43)(44)(45)(46)(47)(48). Summarizing, the MRONJ treatments are referrable to surgical and non-surgical treatments (49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). ...
Medication-related osteonecrosis of the jaw (MRONJ) is a major disease under study for over the last twenty years. Different classifications have been proposed and many therapies for the different stages have been applied. The evolution of treatments lead to an increasingly conservative approach. Numerous adjuvant treatments have been proposed in the last decade. All these complementary treatments have been proposed mainly to resolve or reduce the painful stress, predominantly caused by bacterial infection, simplifying the wound healing process and improving patients' compliance. Nowadays "secondary" treatments, such as autologous platelet concentrates (APCs, more specifically PRP, PRGF or PRF), hyperbaric oxygen (HBO), Auto/tetracycline fluorescence-guided bone surgery (AF-GBS/TF-GBS), medical drugs like teriparatide or the combination between pentoxifylline and tocopherol, fluorodeoxyglucose positron emission tomography (FDG-PET), laser and/or low-laser therapy and ozone therapy are more or less well documented and known considering their clinical effectiveness. The aim of the present review is the evaluation of the quantity and quality of scientific studies concerning this specific topic.
... Most of the analyzed studies introduced the use of therapy defined as "additional" in association with surgery. Specifically, additional therapy is referred to as non-invasive treatments, such as cycles of local or systemic antibacterial therapy combined or not, to low level laser therapy, ozone therapy (O3), HBO (Hyperbaric Oxygen therapy), the use of APCcs APCs (Autologous Pletelet Concentrates, such as PRP,PRGF or PRF), AF-GBS/TF-GBS (Auto/ DISCUSSION Despite progress in the prevention of BRONJ, a specific widely accepted and utilized treatment protocol to manage MRONJ is still missing, as the literature shows (43)(44)(45)(46)(47)(48). Summarizing, the MRONJ treatments are referrable to surgical and non-surgical treatments (49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). ...
Medication-related osteonecrosis of the jaw (MRONJ) is a major disease under study for over the last twenty years. Different classifications have been proposed and many therapies for the different stages have been applied. The evolution of treatments lead to an increasingly conservative approach. Numerous adjuvant treatments have been proposed in the last decade. All these complementary treatments have been proposed mainly to resolve or reduce the painful stress, predominantly caused by bacterial infection, simplifying the wound healing process and improving patients' compliance. Nowadays "secondary" treatments, such as autologous platelet concentrates (APCs, more specifically PRP, PRGF or PRF), hyperbaric oxygen (HBO), Auto/tetracycline fluorescence-guided bone surgery (AF-GBS/TF-GBS), medical drugs like teriparatide or the combination between pentoxifylline and tocopherol, fluorodeoxyglucose positron emission tomography (FDG-PET), laser and/or low-laser therapy and ozone therapy are more or less well documented and known considering their clinical effectiveness. The aim of the present review is the evaluation of the quantity and quality of scientific studies concerning this specific topic.
... [19] Studies have also reported that the risk of developing MRONJ is higher in cases with intravenous administration of BPs. [20,21] Also, patients with cancer have a higher risk of MRONJ in comparison with patients with osteoporosis [7] The receptor activator of nuclear factor-kappa ligand (RANKL) inhibitor denosumab is very effective in minimizing bone loss associated with breast and prostate cancers, menopause, osteoporosis, and giant cell tumor. [22] Denosumab in fewer doses contributes to MRONJ. ...
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic medication. MRONJ is considered when a patient has exposed bone in the jaw for more than 8 weeks and has a history of antiresorptive and antiangiogenic medication with a negative history of radiotherapy. Antiresorptive and antiangiogenic medication do not independently cause necrosis of bone. Various systemic and local risk factors like dentoalveolar trauma and extraction play an important role in the development of MRONJ. MRONJ can be prevented by proper dental evaluation and by performing the required treatment before commencing antiresorptive and antiangiogenic medication.
Objective
This study evaluated the effectiveness of a submental island flap in closing advanced mandibular medication‐related osteonecrosis of the jaw (MRONJ) wounds in patients with malignant tumors.
Subjects and methods
A total of 85 patients with stage II and III MRONJ of mandible with malignant tumor as their primary disease were retrospectively analyzed. All patients underwent surgical treatment, and the soft tissue wound closure was performed either with a submental island flap (SIF) or mucoperiosteal flap (MF). Univariate and multifactorial models were applied to analyze the factors influencing patients' prognosis.
Results
Univariate analysis ( p = 0.004, OR 0.075–0.575, 95% CI) and binary logistic regression ( p = 0.017, OR 0.032–0.713, 95% CI) suggested that the surgical prognosis of SIF wound closure was significantly better than that of MF.
Conclusion
Closure of wound after resection of mandibular MRONJ lesions in patients with malignant tumors using SIF had a better clinical prognosis compared with MF.
