Medication-related Osteonecrosis Of The Jaw Patients Research Articles

Unveiling Medication-Related Osteonecrosis of the Jaw: A Rapid Review of Etiology, Drug Holidays, and Treatment Strategies

This rapid review critically evaluates recent advancements in the management of medication-related osteonecrosis of the jaw (MRONJ) from 2022 to 2023, employing a specific article selection protocol to focus on the latest literature. Initially screening 262 articles and ultimately selecting 22 based on their relevance and uniqueness, the process involved meticulous screening, methodological evaluation, and data extraction by the authors. The findings, organized into epidemiology, treatment effectiveness, and drug holidays, are synthesized following rapid review guidelines. The review addresses the risk of MRONJ associated with tooth extraction in patients undergoing antiresorptive medication therapy, such as bisphosphonates (BPs) and denosumab (DS), and evaluates the effectiveness of drug holidays in reducing this risk. Recent studies suggest that drug holidays may not effectively mitigate MRONJ risks as previously believed. Furthermore, it highlights that conservative treatment can benefit asymptomatic early-stage MRONJ patients, whereas surgical intervention is more effective for those in advanced stages. Ultimately, this review synthesizes current findings to enhance clinical practice, suggesting that while drug holidays may not significantly reduce MRONJ risks, treatment strategies should be tailored, ranging from conservative approaches in early stages to surgical interventions in advanced stages, thereby guiding evidence-based clinical decisions.

Analysis of SIRT1 Gene SNPs and Clinical Characteristics in Medication-Related Osteonecrosis of the Jaw.

Certain genetic factors, including single-nucleotide polymorphisms (SNPs) in the SIRT1 gene, have been linked to medication-related osteonecrosis of the jaw (MRONJ). This study examined four SNPs in the SIRT1 gene and implemented multivariate statistical analysis to analyze genetic and clinical factors in MRONJ patients. Genomic DNA was isolated from peripheral blood samples of 63 patients of European origin treated for MRONJ, and four SNP genotypes in the gene encoding the SIRT-1 protein were determined by Sanger sequencing. The allele frequencies measured in the MRONJ population were compared with allele frequencies measured in the European population in the National Center for Biotechnology Information Allele Frequency Aggregator (NCBI ALFA) database. Genetic and clinical factors were examined with multivariate statistical analysis. A C:A allele distribution ratio of 77.8:22.2 was measured in the rs932658 SNP. In the ALFA project, a C:A allele distribution ratio of 59.9:40.1 was detected in the European population, which was found to be a significant difference (p = 4.5 × 10-5). Multivariate statistical analysis revealed a positive correlation (0.275) between the genotype of SNP rs932658 and the number of stages improved during appropriate MRONJ therapy. It is concluded that allele A in SNP rs932658 in the SIRT1 gene acts as a protective factor in MRONJ.

THE USE OF PERIOSTEAL FLAP IN MANDIBLE PRIMARY RECONSTRUCTION AFTER SEGMENTAL RESECTION IN MEDICATION-RELATED OSTEONECROSIS PATIENT: CASE REPORT

Background: The treatment of medication-related osteonecrosis of the jaws is challenging. Mandible segmental resection is the main treatment method for advanced stage 2 and stage 3 medication- related osteonecrosis of the mandible. This brings to the large continuity defects of the mandible, decreasing the life quality of the patients. Method: In this study, a modified technique of mandible defect reconstruction, after segmental resection, with only a reconstruction plate, is described. In this technique, the periosteal flap is used for double-layer closure of the intraoral wound. Double-layer isolation of the reconstruction plate from the oral cavity prevents intraoral wound dehiscence and plate exposure. Also, for the bone fragments fixation, prebended 2.3mm reconstructive plate on the 3D-printed individual model of the patient’s mandible was used. The use of a prebended plate reduces the operation time and increases the precision of fixation of mandible fragments in the correct position. Results: After intraoral sutures removal on 14 days, there was a dehiscence of a few intraoral sutures on mucoperiosteal flaps. There was partial exposure of the periosteal flap, which secured the underlying reconstructive plate. Exposed periosteal flap spontaneously epithelialized during 1 month. The postoperative follow-up period was nine months. During this period no complications were noted Conclusion: Within the limitations of the study, this method can be used as an effective and predictable method for the primary reconstruction of the mandible with only a reconstruction plate in medication-related osteonecrosis of the jaws patients.

Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ. A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized. Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation. While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.

Risk factors of medication-related osteonecrosis of the jaw: A clinical investigation

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable condition caused by drugs such as bisphosphonates and denosumab. This study investigated the changes in the incidence of MRONJ in the previous 10 years and examined the poor prognostic factors during surgery in at-risk patients. We compared 57 and 64 patients diagnosed with MRONJ at our hospital between January 2012 and December 2016 and January 2017 and December 2021, respectively. The disease stage and triggers at the time of initial diagnosis in eligible patients were investigated. Additionally, the adverse prognostic factors were examined in 166 patients at risk of MRONJ who underwent tooth extraction at our department during these 10 years. The results indicated that there was no change in the proportion of patients with osteoporosis and malignancy among those with MRONJ. The number of cases after tooth extraction decreased, and those after dental infections increased on comparing the recent 5 years and the preceding 5 years. The number of MRONJ patients receiving denosumab also increased. Denosumab was a significant post-extraction prognostic factor for delayed healing in the 166 patients at risk of MRONJ. The findings suggest that patients receiving denosumab should be closely monitored when undergoing surgery to prevent MRONJ.

Is maxillary sinusitis and radiographic maxillary sinus opacification associated with an altered microbiology of MRONJ?

ObjectiveMaxillary sinusitis can be a sequela of medication-related osteonecrosis of the jaw (MRONJ). This study aims to characterize the microbiome of maxillary MRONJ with concurrent maxillary sinusitis and radiographic maxillary sinus opacification to determine if there is a relationship between the microbiome of MRONJ and sinus disease. Study DesignThis retrospective case series was conducted using electronic health records from the University of Pennsylvania and affiliated hospitals. The target population was surgically managed maxillary MRONJ patients. The primary predictor variables were tissue culture results. The primary outcomes were maxillary sinusitis or maxillary sinus opacification. Statistical analysis was performed using chi-squared tests at the 95% confidence interval. ResultsThirty-nine subjects were selected: 25 had sinus opacification and 11 had sinusitis. Resident bacteria were present in 90% of subjects, non-resident bacteria in 74%, and opportunistic organisms in 15%. There were significantly more subjects with chronic sinusitis microbes (79%) than without. There were significantly more gram-positive anaerobes, specifically Propionibacterium, as well as the gram-negative facultative anaerobe, Capnocytophaga, in subjects with concurrent sinusitis. ConclusionsMaxillary MRONJ with concurrent maxillary sinusitis may be associated with gram-positive anaerobic species, Propionibacterium, and Capnocytophaga colonization. Maxillary MRONJ patients may benefit from sinus evaluation and concurrent surgical intervention.

Comparative Analysis of the Oral Microbiome of Medication-Related Osteonecrosis of the Jaw Patients

Comparative Analysis of the Oral Microbiome of Medication-Related Osteonecrosis of the Jaw Patients

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.

Outcomes of a Pharmacological Protocol with Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Randomized Study on 202 Osteoporosis Patients.

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.

Maximum and mean standardized uptake values of medication-related osteonecrosis of the jaw with bone SPECT/CT: comparison of mandibular pathologies, control and temporomandibular joints.

Recently, single-photon emission CT/CT (SPECT/CT) plays an important role in assessing patients with medication-related osteonecrosis of the jaw (MRONJ). The aim of this study was to investigate maximum and mean standardized uptake values (SUVs) of MRONJ with bone SPECT/CT, especially comparison of mandibular pathologies, control and temporomandibular joints. 61 mandibular patients with MRONJ who underwent bone SPECT/CT were included in this study. The maximum and mean SUVs of the lesion, right and left sides of the lesion, opposite side of the lesion as control, right and left temporomandibular joints were analyzed using a workstation and software. The SUVs of MRONJ were analyzed using one-way analysis of variance with Tukey's honestly significant difference test. Patient characteristics with MRONJ and SUVs were analyzed using Mann-Whitney U test. P-values less than 0.05 were considered to indicate statistical significance. The maximum and mean SUVs for opposite side of the lesions (4.4 ± 2.0 and 1.8 ± 0.7) were significantly lower than those for mandibular lesions (18.3 ± 8.1 and 6.3 ± 2.8), right side of the lesions (8.1 ± 3.9 and 2.9 ± 1.3) and left side of the lesions (8.1 ± 3.9 and 2.8 ± 1.4), respectively. The maximum and mean SUVs for right and left sides of the lesions, and opposite side of the lesions, right and left temporomandibular joints were not significant difference. Furthermore, the maximum SUVs of the mandibular lesions were a significant difference for age and staging. The maximum and mean SUVs with SPECT/CT can be useful in the quantitative management of MRONJ patients.

Oral Health-Related Quality of Life and Mental Health Impairment in Patients Affected by Medication-Related Osteonecrosis of the Jaws: A Case-Control Pilot Study.

In the present case-control study, the impact of medication-related osteonecrosis of the jaws (MRONJ) on patients' oral health-related quality of life (OHRQoL), overall quality of life (QoL), and psychological status was evaluated using a set of questionnaires. These questionnaires included the Oral Health Impact Profile-14 (OHIP-14), the Short Form 36 Health Survey Questionnaire (SF-36), and the hospital anxiety and depression scale (HADS). A total of 25 MRONJ patients and 25 controls were included in the study. The results showed that MRONJ patients had a significantly poorer OHRQoL (OHIP-14 score p-value: 0.003) and lower general QoL, particularly in the domains of "physical functioning", "physical role", "body pain", "general health", and "vitality" in the SF-36 questionnaire (p-values: 0.001, 0.001, 0.013, 0.001, and 0.020). Although there were no significant differences between the groups in the SF-36 domains of "social functioning", "emotional role", and "mental health", the mean sub-scores of the HADS, specifically the depression and anxiety scores (HADS-D and HADS-A), were significantly higher in MRONJ patients (p-values: 0.002 and 0.009). However, the "mental health" domain of the SF-36 questionnaire showed a correlation with both HADS-A and HADS-D scores (p-values: 0.003 and 0.031). Therefore, a comprehensive clinical examination of MRONJ patients should include the assessment of OHRQoL, overall QoL, and psychological profile using different questionnaires. This approach aims to gather detailed information about patients' physical and psychological well-being, enabling the development of tailored treatments.

Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts

BackgroundLong-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients.MethodsThe clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket.ResultsPatients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib.ConclusionOur findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw.

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is multifactorial and there is a substantial consensus on the role of antiresorptive drugs (ARDs), including bisphosphonates (BPs) and denosumab (Dmab), as one of the main determinants. The time exposure, cumulative dose and administration intensity of these drugs are critical parameters to be considered in the treatment of patients, as cancer patients show the highest incidence of MRONJ. BPs and Dmab have distinct mechanisms of action on bone, but they also exert different effects on immune subsets which interact with bone cells, thus contributing to the onset of MRONJ. Here, we summarized the main effects of ARDs on the different immune cell subsets, which consequently affect bone cells, particularly osteoclasts and osteoblasts. Data from animal models and MRONJ patients showed a deep interference of ARDs in modulating immune cells, even though a large part of the literature concerns the effects of BPs and there is a lack of data on Dmab, demonstrating the need to further studies.

Spontaneous Osteogenic Potential of Periosteum after Segmental Mandibulectomy in Patients with Medication-Related Osteonecrosis of the Jaw (MRONJ): A Retrospective Study of 14 Cases

Medication-related osteonecrosis of the jaw (MRONJ) has chiefly involved patients receiving medications for the treatment of bone-related malignancies. The surgical methods are now cautiously recommended as the treatment option for MRONJ. The purpose of this retrospective study was to report new bone formation and examine possible factors influencing spontaneous bony bridge formation by using an R-plate for reconstruction without any graft material after segmental mandibulectomy in patients with MRONJ. A cohort of 54 patients who underwent mandibulectomy between 2017 and 2022 by a single operator were included. Of them, 14 MRONJ patients (12 females and 2 males) were selected based on the inclusion criteria. Data on new bone formation, bony bridge formation, R-plate fracture, patient age, and type and duration of medication were collected. The mean age of the patients was 74.8 ± 9.3 years. All patients showed new bone formation, and 71.4% showed bony bridge formation within a year after surgery. The older the patient, the lower was the tendency for bony bridge formation in the defect (p = 0.035). Statistical analysis was performed using Fisher’s exact test. Preservation of the periosteum might be one of the most important contributing factors to new bone formation, serving as an optimal treatment option for reconstruction after segmental mandibulectomy in patients with MRONJ.

Clinical values of serum Semaphorin 4D (Sema4D) in medication‑related osteonecrosis of the jaw

BackgroundBisphosphonates (BPs) are widely used in clinical practice to prevent and treat bone metabolism-related diseases. Medication-related osteonecrosis of the jaw (MRONJ) is one of the major sequelae of BPs use. Early prediction and intervention of MRONJ are of great significance.MethodsNinety-seven patients currently on treatment with BPs or with a history of BPs usage and 45 healthy volunteers undergoing dentoalveolar surgery were included in this study. Participants' serum Semaphorin 4D (Sema4D) levels were measured and analyzed before participants underwent surgery (T0) and after a 12-month follow-up (T1). Kruskal–Wallis test and ROC analysis were used to examine the predictive effect of Sema4D on MRONJ.ResultsSema4D levels in serum of patients corresponding to confirmed MRONJ were significantly lower at both T0 and T1 time points compared to non-MRONJ and healthy controls. Sema4D has a statistically predictive effect on the occurrence and diagnosis of MRONJ. Serum Sema4D levels were significantly reduced in MRONJ class 3 patients. MRONJ patients who received intravenous BPs had significantly lower Sema4D levels than those who received oral BPs.ConclusionSerum Sema4D level has predictive value for the onset of MRONJ in BPs users within 12 weeks after dentoalveolar surgery.

Novel modified quantitative index for cone-beam CT assessment of medication-related osteonecrosis of the jaw - comparative analysis with original index

PurposeThe main research goal was to address the critical need for an objective and quantitative index to describe the nature and extent of radiographic features of medication-related osteonecrosis of the jaw (MRONJ) lesions and complement the descriptive radiographic interpretation of the lesion and its clinical assessment. Method and MaterialsA retrospective review of MRONJ patients assessed at our institution was performed to compare the Composite Radiographic Index (CRI), identified from a prior scoping review, with a proposed modification, the Modified CRI index (‘Mod-CRI’). The Mod-CRI index was weighted to assign a higher score for diffuse radiographic involvement of a given lesion, and delineated MRONJ lesions into those with ‘high’ and ‘low’ severity. Twenty-two MRONJ cases imaged with CBCT were retrospectively assessed with both CRI and Mod-CRI indices and the two indices were compared for their ability to quantitatively describe cone-beam computerized tomography (CBCT) radiographic features and complement the clinical staging of the MRONJ lesion. ResultsThere was a statistically significant association between increased clinical stage and higher mod-CRI score (p = 0.040).The Mod-CRI index sorted the patients who scored intermediate scores with the CRI (n = 15) into either the low (n = 8) or high categories (n = 7). ConclusionThe Mod-CRI index eliminated the ambiguous intermediate-category-scores in the previously published CRI index and provided greater clarity to the interpretation of a given index score. Adopting the Mod-CRI could improve MRONJ assessment and enhance communication between the radiologist and the clinician.

A nested case-control study of factors contributing to the development of medication-related osteonecrosis of the jaw in patients using bone resorption inhibitors in Mishima City.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by necrosis of the jawbone with intraoral bacterial infection and has a significant negative impact on oral health-related quality of life. Risk factors for the onset are unknown, and definitive therapeutic approaches have not yet been defined. A case-control study at a single institution in Mishima City was conducted. The purpose of this study was to examine in detail the factors that contribute to the development of MRONJ. Medical records of MRONJ patients who visited Mishima Dental Center, Nihon University School of Dentistry, during the period 2015-2021 were extracted. Counter-matched sampling design was used to select participants matched for sex, age, and smoking for this nested case-control study. The incidence factors were statistically examined by logistic regression analysis. Twelve MRONJ patients were used as cases and 32 controls were matched. After adjustment for potential confounders, injectable bisphosphonates (aOR = 24.5; 95% CI = 1.05, 575.0; P < 0.05) were significantly associated with the development of MRONJ. High-dose bisphosphonates may be a risk factor for the development of MRONJ. Patients who use these products require careful prophylactic dental treatment against inflammatory diseases, and dentists and physicians should maintain close communication.

Effect of pentoxifylline and tocopherol for MRONJ patients: A systematic review

MRONJ (medication related osteonecrosis of the jaw) is a disease characterized by necrosis of the jaw that occurs after administration of anti-resorptive or anti-angiogenic drugs. However, etiology and effective treatment methods of MRONJ are not yet clearly identified. In this study, a systematic review was conducted to investigate the effects of pentoxifylline and tocopherol on MRONJ. A total of 5 clinical studies using pentoxifyllie and tocopherol in MRONJ patients among the papers registered in Pubmed/medline were reviewed. Pentoxifyllie and tocopherol were used for therapeutic purposes in 32 patients, and the mean age was 68 years for men and 74.21 years for women. Of the 32 patients, 20 patients were stage 2, 11 patients were stage 3, and one patient was stage 0. In the most cases, the triggering factor was extraction. All patients com-plained of pain in the lesion area before drugs administration. The average follow-up period was 10.6 months. After drugs administration, 29 patients (90.6%) showed improvement in symptoms in terms of bone exposure and pain. Administration of pentoxifylline and tocopherol in MRONJ may improve symptoms of pain and bone exposure. However, it seems that additional studies on the appropriate use and dose, timing and duration of administration are needed.

Oral-Health-Related Quality of Life in Patients with Medication-Related Osteonecrosis of the Jaw: A Prospective Clinical Study.

Medication-related osteonecrosis of the jaw (MRONJ) represents an adverse side effect of antiresorptive and antiangiogenic medications. It is associated with impaired quality of life, oral health, and oral function and can be classified into various stages. The purpose of this prospective clinical study is to evaluate the impact of stages I and II MRONJ on oral-health-related quality of life (OHRQoL) and related parameters. Patients’ OHRQoL, satisfaction with life, oral discomfort, and oral health were assessed using the German version of the Oral Health Impact Profile (OHIP-G49), visual analog scales (VAS), and Satisfaction with Life Scale (SWLS) at baseline (T0), 10 days (T1), and 3 months after treatment (T2) in 36 patients. Data were analyzed using Kolmogorov–Smirnov test, two-way mixed ANOVAs, and follow-up Mann–Whitney U tests. The impact of treatment effects on the original seven OHIP domain structures and the recently introduced four-dimensional OHIP structure were evaluated using linear regression analysis. Thirty-six patients received surgical MRONJ treatment. Before treatment, patients’ perceived OHRQoL, oral discomfort, oral health, and satisfaction with life were negatively affected by MRONJ. Surgical treatment significantly improved OHRQoL and related parameters (all p ≤ 0.012). This improvement was greater in patients with higher impairment at T0. OHRQoL and oral restrictions were still impaired after treatment in patients who needed prosthetic treatment. The four-dimensional structure revealed valuable information beyond the standard seven OHIP domains. Increased awareness of MRONJ risks and an interdisciplinary treatment approach for MRONJ patients are needed.

Ozone Infiltration for Osteonecrosis of the Jaw Therapy: A Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction, mainly due to bone-modifying agents (BMA), and it is a potentially painful and debilitating condition. To date, the literature has reported a 90% rate of successful outcomes for MRONJ patients undergoing surgical treatment. Particularly for patients with advanced disease stages who are unsuitable for surgery, prolonged medical treatment is required, with a consequent risk of the overuse of antibiotics and antibiotic resistance. The aim of this study is to evaluate the efficiency and safety of ozone, via oral mucosal infiltrations, in seven cancer patients with MRONJ, who are not eligible for surgery. The protocol (OZOPROMAF) consists of intratissue injections of an oxygen ozone (O2O3) mixture, which is applied until formation of a sequestrum and clinical healing. Follow-up was scheduled to confirm the healing of MRONJ and radiological evaluations by CBCT were planned. In order to assess the level of pain, a questionnaire including the Numeric Rating Scale for Pain (NRS Pain) was administered on the first visit, one day after treatment, and one week after treatment. After an application of OZOPROMAF, all patients reported discomfort for some hours, probably due to soft tissue pressure around the infiltration site. Thereafter, the discomfort subsided within 6–8 h. Complete mucosal healing of MRONJ occurred within a number of cycles ranging from 7 to 16. Complete resolution with an improvement in bone condition was observed in all patients. The MRONJ lesions of all patients healed after 18–24 months. The authors of this study contend that these preliminary results suggest the efficiency and safety of the O2O3 mixture. However, further research is required to confirm the efficacy of the O2O3 mixtures in MRONJ treatment, at least for patients who are unsuitable for surgery.