Factors affecting the quality of life of patients with medication-related osteonecrosis of the jaw during treatment: A quality-of-life survey and causal analysis.

This prospective cohort study aimed to investigate the impact of medication-related osteonecrosis of the jaw (MRONJ) on health-related quality of life (HRQOL) and oral health-related QOL (OHRQOL) and the association between the downstaging of MRONJ and OHRQOL. The HRQOL and OHRQOL of 44 patients with MRONJ were assessed using the SF-36v2 and the General Oral Health Assessment Index (GOHAI), respectively. Treatment was performed in accordance with the AAOMS position paper (2014). The SF-36v2 and GOHAI scores at the beginning of the survey were used to evaluate the impact of MRONJ on QOL. Potential confounders affecting the association between downstaging and QOL improvement were selected using directed acyclic graphs. Multiple regression analysis was performed to evaluate causal inferences. HRQOL scale scores declined below the national average. The three-component summary score (3CS), comprising the physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS), revealed that performance status and primary disease significantly affected the PCS and RCS (P = 0.005 and P < 0.001, respectively) and PCS and MCS (P = 0.024 and P = 0.003, respectively). The MRONJ stage did not influence the 3CS; however, OHRQOL declined in a stage-dependent manner (P = 0.005). Downstaging of MRONJ was independently associated with the improvement rate of the total GOHAI scores after adjusting for variables (P = 0.045). The HRQOL of patients with MRONJ declined; however, this may depend on the underlying disease status rather than the MRONJ stage. Improvement of the disease status can potentially predict an improvement in OHRQOL, regardless of the treatment modality.

Sclerotic bone: a sign of bone reaction in patients with medication related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.

Bone pattern changes in post liver transplant patients using bisphosphonates.

OBJECTIVE: To identify radiographic findings suggestive of drug-induced osteonecrosis and evaluate radiomorphometric patterns indicative of changes in bone mineral density in individuals transplanted for liver disorders using bisphosphonates. STUDY DESIGN: The study group included panoramic x-rays of liver transplant patients who are being monitored and who present a clinical status of osteoporosis and use bisphosphonates. The control group was made up of liver transplant patients who did not have osteoporosis. On panoramic radiographs, mental index (MI) and mandibular cortical index (MCI) and the presence of radiographic anomalies suggestive of osteonecrosis were evaluated. RESULTS: There were significant statistical results when comparing the groups in relation to the decrease in bone mineral density (BMD) with MCI-C3 (p = 0.036), however, there were none in relation to MI (p = 0.14). There were no valid statistical results when relating MCI (p = 0.94) and MI (p = 0.66) with reduced BMD and use of bisphosphonates. CONCLUSION: Liver transplant individuals using bisphosphonates present greater radiographic signs of bone sclerosis suggestive of a greater propensity to develop osteonecrosis of the jaw and an increased risk of presenting changes suggestive of reduced bone mineral density on panoramic radiographs when compared to liver transplant individuals not using bisphosphonates.

Surgical and conservative treatment outcomes of medication-related osteonecrosis of the jaw located at tori: a retrospective study.

PURPOSE: Tori and exostoses are considered risk factors for the development of medication-related osteonecrosis of the jaw (MRONJ). The aims of this study were to present the prevalence of MRONJ located at tori in the Copenhagen ONJ Cohort, evaluate the surgical treatment of MRONJ located at tori and explore trauma to tori as an additional risk factor in patients on antiresorptive medication. METHODS: Data from a consecutive series of 506 patients with MRONJ (Copenhagen ONJ Cohort) were reviewed for the presence of tori and MRONJ located at tori. Demographic and medical data were analyzed, and healing outcomes and pain after the prophylactic removal of tori, surgical treatment of MRONJ located at tori, and conservative treatment of MRONJ located at tori were evaluated and compared using Fisher's exact test. RESULTS: MRONJ located at tori was frequent and could be identified in 53% of the patients with tori, which accounts for a prevalence of 5.1% in the entire cohort. Of the 28 surgically treated patients, 27 (96.4%) healed uneventfully with no exposed bone after their first or second revision surgery. Fourteen (41.2%) patients with tori underwent therapeutic removal, eight (23.5%) underwent prophylactic removal, and six (17.6%) underwent both therapeutic and prophylactic removals. Two (33.3%) of the six conservatively treated patients healed spontaneously. Both treatment types resulted in a significant decrease in pain. CONCLUSION: Prophylactic and therapeutic surgical removal of tori are reliable treatments and should be considered if a patient's general health allows surgery. TRIAL REGISTRATION: The study was approved by the Regional Scientific Ethical Committee (H-6-2013-010) on November 20, 2013, and was retrospectively registered.

Use of Leukocyte- and Platelet-Rich Fibrin to Prevent Osteonecrosis of the Jaws Associated with the Use of Bisphosphonate Therapy: A Case Series.

Medication-related osteonecrosis of the jaws (MRONJ) consists of an area of exposed intraoral or extraoral bone that affects patients with a history of use of antiresorptive and antiangiogenic medications, and who have not undergone head and neck radiotherapy. Leukocyte- and platelet-rich fibrin (L-PRF) is an autologous material of great potential, used as an adjuvant in surgical treatments, especially where healing is compromised. The aim of this article is to report three cases of the use of L-PRF in the prevention of MRONJ in three female Caucasian under bisphosphonates therapy. Patient 1, 86 years old, with osteoporosis, complained of intense pain in tooth 33, which presented edema and periapical lesion and association with MRONJ. Patient 2, 61 years old, undergoing treatment for bone metastases due to breast cancer, reported pain symptoms in tooth 47, as well as suppuration in the dental element, grade I mobility, pain on periapical palpation and radiographically an endoperiodontal lesion was evidenced. Patient 3, 56 years old, also undergoing treatment for breast cancer, presented with severe pain in tooth 36. On clinical examination, she presented pain, mobility and suppuration, and radiographs indicated a furcation lesion on tooth 36. The treatment option in the three cases was the extraction of the affected teeth and the use of L-PRF to promote healing. All patients present a favorable outcome in follow-up. The use of L-PRF can be an adjuvant in the prevention of MRONJ; however, further studies are needed to prove its effectiveness.

Rat Calvaria Model Mimicking the Intraoral Lesion of Medication-Related Osteonecrosis in the Jaw: A Preliminary Test.

Numerous preclinical intraoral models have been proposed to study medication-related osteonecrosis of the jaws (MRONJ). However, an extraoral animal model is necessary to investigate the effects of interventions such as grafts or direct therapeutics. This study aimed to establish a MRONJ rat model on the calvaria. Seven rats were allocated to either the control or MRONJ group. The MRONJ group received injections of zoledronic acid and dexamethasone to induce osteonecrosis over 4 weeks. Two weeks after these injections, the maxillary first molar was extracted, and two calvaria defects were created using a 4 mm trephine burr. One defect was left untreated, while the other was filled with harvested calvaria bone. A histological examination of all calvaria in the MRONJ group revealed avascular necrosis and the destruction of cortical bone. An independent t-test and Pearson's correlation coefficient were used for statistical analysis and the evaluation of alveolar and calvaria defects. The total alveolar and calvaria defect volume in the control group was significantly smaller than that in the MRONJ group. A statistically significant correlation was observed between alveolar and calvaria defects (Pearson correlation = 0.6, p = 0.023). The autogenous grafts showed poor results in the MRONJ group since they failed to revascularize and exhibited necrosis. The calvaria in this study successfully mimicked MRONJ lesions with avascular necrosis. This preclinical model could be used to develop treatments that are applicable to MRONJ.

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

INTRODUCTION: 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. MATERIALS AND METHODS: 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 (1.0 mg/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. RESULTS: 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. CONCLUSION: 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 large animal model of periodontal defects in bisphosphonate-related osteonecrosis of the jaw: a comparison of clinical and radiological findings.

PURPOSE: The objective of this study was to demonstrate the suitability of cone-beam computed tomography (CBCT) for in vivo research in periodontology, with implications for oral implantology, facial traumatology, and all disciplines involved in treating patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). METHODS: Halves of the jaws of 9 Swiss mountain sheep, assigned to a control group (n=3), an osteoporosis group (n=3) and a zoledronate-exposed group (n=3), were examined. Clinical and radiological evaluations were conducted using CBCT imaging to assess whether periodontitis and bone defects were observed to a significant extent after surgical tooth extraction. RESULTS: In contrast to the control and osteoporosis groups, the zoledronate group exhibited significant residual bone defects following tooth extraction (P<0.05). CBCT more objectively revealed these effects and enabled a numerical evaluation (in mm3). CONCLUSIONS: Evaluating residual defects in bone blocks from sheep using CBCT analysis was found to be as effective as a clinical examination conducted by specialists in oral and maxillofacial surgery. The strong correlation between radiological findings and clinical conditions suggests that CBCT may become increasingly important in the future, particularly in periodontological research related to BRONJ.

Texture analysis in cone-beam computed tomographic images of medication-related osteonecrosis of the jaw.

Purpose: The aim of this study was to evaluate changes in the trabecular bone through texture analysis and compare the texture analysis characteristics of different areas in patients with medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: Cone-beam computed tomographic images of 16 patients diagnosed with MRONJ were used. In sagittal images, 3 regions were chosen: active osteonecrosis (AO); intermediate tissue (IT), which presented a zone of apparently healthy tissue adjacent to the AO area; and healthy bone tissue (HT) (control area). Texture analysis was performed evaluating 7 parameters: secondary angular momentum, contrast, correlation, sum of squares, inverse moment of difference, sum of entropies, and entropy. Data were analyzed using the Kruskal-Wallis test with a significance level of 5%. Results: Comparing the areas of AO, IT, and HT, significant differences (P<0.05) were observed. The IT and AO area images showed higher values for parameters such as contrast, entropy, and secondary angular momentum than the HT area, indicating greater disorder in these tissues. Conclusion: Through texture analysis, changes in the bone pattern could be observed in areas of osteonecrosis. The texture analysis demonstrated that areas visually identified and classified as IT still had necrotic tissue, thereby increasing the accuracy of delimiting the real extension of MRONJ.

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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The maximum and mean SUVs with SPECT/CT can be useful in the quantitative management of MRONJ patients.

Histopathological assessment of the preventive effect of leukocyte-platelet-rich fibrin on bisphosphonate-related osteonecrosis of the jaw following dental extraction: An animal study.

Background: Leukocyte- and platelet-rich fibrin (L-PRF) could be considered a preventive measure in Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ). The present experiment aimed to assess the preventive effects of L-PRF on osteonecrosis of the jaw in rats. Methods: In this interventional animal study with a split-mouth design, 28 rats were randomly allocated to saline (negative control), bisphosphonate (positive control), and Bis + L-PRF (case) groups. Bilateral extraction of maxillary molar teeth was performed followed by random application of L-PRF to one of the extraction sockets treated with Zoledronic acid for four weeks. Clinical occurrence of BRONJ and histopathologic evaluations were done, and data were subjected to the Kruskal-Wallis test, Mann-Whitney U test and exact Fisher test performed using SPSS 25. The significance level was set at 0.05. Results: The application of L-PRF resulted in a 41.67% reduction in osteonecrosis centers and the number of osteoclast cells. Also, Kruskal Wallis test results showed a significant difference among the three groups regarding the frequency distribution of inflammation severity. However, no significant difference was detected regarding the frequency distribution of the blood vessels (Kruskal Wallis test, P-value = 0.649). Conclusion: It could be inferred that possible preventive effects on the clinical occurrence of osteonecrosis could be expected from the application of L-PRF.

Pulp and periapical disease as a risk factor for osteonecrosis of the jaw: a national cohort-based study in Korea.

PURPOSE: This longitudinal cohort study aimed to evaluate the relationship between osteonecrosis of the jaw and pulp and periapical disease in patients who were administered bisphosphonates. METHODS: Using data from a nationwide cohort, we examined the association among dental caries, pulp and periapical disease, and osteonecrosis of the jaw in women aged >50 years who received bisphosphonates for more than 1 year between 2002 and 2015. Because of ambiguities in the diagnosis of osteonecrosis of the jaw in population-based data, we operationally defined and categorized the condition into established and potential osteonecrosis of the jaw. RESULTS: Pulp and periapical disease significantly increased the development of both established and potential osteonecrosis of the jaw (hazard ratio, 2.21; 95% confidence interval, 1.40-3.48; and hazard ratio, 2.22; 95% confidence interval, 1.65-2.98, respectively). Root canal treatment did not have any influence on the development of osteonecrosis of the jaw. CONCLUSIONS: Pulp and periapical disease may be a major risk factor for osteonecrosis of the jaw. The study findings suggest that patients should undergo regular dental examinations to detect pulp and periapical disease before or during the administration of bisphosphonates and that root canal treatment should be considered to decrease the risk of osteonecrosis of the jaw.

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

Purpose: The 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 Materials: A 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. Results: There 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). Conclusion: The 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.

Treatment outcomes and time to healing of medication-related osteonecrosis of the jaw based on image findings.

OBJECTIVES: This study aimed to evaluate the prognostic treatment outcome of non-operative management of medication-related osteonecrosis of the jaw (MRONJ), particularly regarding the relationship between image findings and treatment outcomes. METHODS: This single-center, retrospective observational study included patients with MRONJ who were conservatively treated between 2010 and 2020. All patients were evaluated in terms of MRONJ treatment outcomes, time to healing, and prognostic factors, including sex, age, underlying disease, antiresorptive drug type, discontinuation of antiresorptive treatment, chemotherapy, corticosteroid treatment, diabetes mellitus, location of MRONJ, clinical stage of MRONJ, and computed tomography image findings. RESULTS: The complete healing rate among the patients was 68.5%. Cox proportional hazards regression analysis revealed that "Sequestrum formation" on the internal texture (hazard ratio = 3.66; 95% confidence interval, 1.30-10.29; P =.014) and chemotherapy (hazard ratio = 0.41; 95% confidence interval, 0.18-0.95; P =.037) were significantly associated with treatment outcome. The median time to healing in patients with "Sequestrum formation" on the internal texture (4.4 months) was significantly shorter than the median time to healing in those marked with "Sclerosis" or "Normal" (35.5 months; P <.001) and "Lytic changes with sclerosis" (14.5 months; P =.015). CONCLUSIONS: The image findings on the internal texture of the lesions at the initial examination and chemotherapy were associated with the treatment outcomes of nonoperative management of MRONJ. The image findings of "Sequestrum formation" were associated with lesions taking a short time to heal and better outcomes, whereas "Sclerosis" and "Normal" were associated with lesions with longer healing times.

Osteonecrosis maxilar inferior asociado a bifosfonatos / Lower jaw osteonecrosis associated with bisphosphonates / Osteonecrose do maxilar inferior associada a bisfosfonatos

Introducción: dada la alta prescripción de bifosfonatos, presentamos sus efectos adversos en la esfera odontológica, siendo una complicación poco frecuente, pero de difícil tratamiento. Sin necesidad de suspender el tratamiento, dado el importante beneficio en cuanto a la prevención de fractura por fragilidad. Estas fracturas causan una alta morbimortalidad en contraposición al bajo riesgo que conlleva la Osteonecrosis mandibular asociada a bifosfonatos. Objetivo: orientar al personal de salud que maneja estos fármacos y quien asiste dichas complicaciones a poseer conocimientos para la prevención de osteonecrosis. Identificar y diferenciar los pacientes con mayor riesgo, de acuerdo con la dosis de bifosfonatos y la frecuencia del tratamiento. Materiales y Método: se realizó una revisión bibliográfica en las siguientes fuentes: Scielo, Google académico, Medline/Pubmed, Biblioteca Virtual en Salud (Brasil), desde el año 2005 a la fecha, idiomas español, portugués e inglés. Los descriptores utilizados son bifosfonatos, mandíbula, maxilar, odontología, osteonecrosis, osteonecrosis de los maxilares asociada a bifosfonatos. Resultados: las últimas pautas de tratamiento fueron modificadas en 2014, por consenso de la Asociación Americana de cirugía Oral y Maxilofacial. La patogénesis de la osteonecrosis maxilar asociada a bifosfonatos no está completamente definida, aunque las publicaciones tratan de explicarla. El riesgo de desarrollarla por terapia oral es menor que por su administración vía intravenosa. Discusión: el médico que prescribe el antirresortivo debe conocer el estado de salud dental de su paciente y, en lo posible, remitirlo a examen con el odontólogo antes de iniciar la terapia con bifosfonatos.

Introduction: Given the high prescription of bisphosphonates, we present their adverse effects in the dental sphere, being an infrequent complication, but difficult to treat. There is no need to suspend treatment, given the important benefit in terms of prevention of fragility fractures. These fractures cause high morbimortality as opposed to the low risk associated with bisphosphonate-associated osteonecrosis of the jaw. Objective: To orient the health personnel who handle these drugs and who assist these complications to have knowledge for the prevention of osteonecrosis. To identify and differentiate patients at higher risk, according to the dose of bisphosphonates and frequency of treatment. Materials and Method: A literature review was performed in the following sources: Scielo, Google academic, Medline/Pubmed, Virtual Health Library (Brazil), from 2005 to date, Spanish, Portuguese and English languages. The descriptors used were bisphosphonates, mandible, maxilla, dentistry, osteonecrosis, osteonecrosis of the jaws associated with bisphosphonates. Results: The latest treatment guidelines were modified in 2014, by consensus of the American Association of Oral and Maxillofacial Surgery. The pathogenesis of bisphosphonate-associated maxillary osteonecrosis is not completely defined, although publications try to explain it. The risk of developing it by oral therapy is lower than by intravenous administration. Discussion: The physician who prescribes the antiresorptive drug should know the dental health status of his patient and, if possible, refer him for examination by a dentist before initiating bisphosphonate therapy.

Introdução: dada a alta prescrição de bisfosfonatos, apresentamos seus efeitos adversos na esfera odontológica, uma complicação rara, mas de difícil tratamento. Sem a necessidade de suspender o tratamento, dado o importante benefício em termos de prevenção de fraturas por fragilidade. Essas fraturas causam alta morbidade e mortalidade, em contraste com o baixo risco associado à osteonecrose da mandíbula associada aos bisfosfonatos. Objetivo: orientar a equipe de saúde que manipula esses medicamentos e que atende a essas complicações para que tenham conhecimento sobre a prevenção da osteonecrose. Identificar e diferenciar os pacientes de maior risco, de acordo com a dose de bisfosfonatos e a frequência do tratamento. Materiais e Método: foi realizada uma revisão da literatura nas seguintes fontes: Scielo, Google acadêmico, Medline/Pubmed, Biblioteca Virtual em Saúde (Brasil), de 2005 até a presente data, idiomas espanhol, português e inglês. Os descritores utilizados foram: bisfosfonatos, mandíbula, maxila, odontologia, osteonecrose, osteonecrose dos maxilares associada a bisfosfonatos. Resultados: as diretrizes de tratamento mais recentes foram modificadas em 2014, por consenso da Associação Americana de Cirurgia Oral e Maxilofacial. A patogênese da osteonecrose da mandíbula associada a bisfosfonatos não está totalmente definida, embora a literatura tente explicá-la. O risco de desenvolvê-la com a terapia oral é menor do que com a administração intravenosa. Discussão: o médico que prescreve o medicamento deve estar ciente do estado de saúde bucal do paciente e, se possível, encaminhar o paciente para ser examinado por um dentista antes de iniciar a terapia com bisfosfonatos.

The effect of drug holiday before tooth extraction on the development of medication-related osteonecrosis of the jaw in cancer patients receiving intravenous bisphosphonates.

Objectives: Drug holidays are suggested to reduce the formation of osteonecrosis in patients under intravenous (IV) bisphosphonates (BPs) therapy. The objectives of this study are to evaluate the incidence of medication-related osteonecrosis of the jaw (MRONJ) following tooth extraction in cancer patients using IV BP, and to assess the effect of drug holiday on the development of MRONJ. Patients and. Methods: A manuel search of the patient folders of Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hacettepe University was undertaken to identify cancer patients who used IV BPs and had at least one tooth extraction between 2012 and 2022. Patents' age, sex, systemic condition, the type of BP used, duration of BP used, number of tooth extraction, duration of drug holiday, localization of tooth extraction and incidence of MRONJ were recorded. Results: One hundred nine teeth were removed from 57 jaws in 51 patients. All tooth extractions were performed under perioperative antibiotic prophylaxis and with primary wound closure. The incidence of MRONJ was 5.3%. Stage 1 MRONJ developed in 3 patients (only one had a drug holiday). The median duration of drug holiday was 2 months. No significant difference between the patients with and without a drug holiday and MRONJ development was found (P=0.315). The mean age of patients developed MRONJ was 40.33±8.08 years. A statistically significant difference was found between age and MRONJ development (P=0.002). Conclusion: The effect of a short-term drug holiday on the development of MRONJ may be limited because BPs remain in bone tissue for a long time. Drug holidays should be applied with the approval of an oncologist with other preventive measurements.

Quantitative indices for cone-beam CT assessment of Medication-Related Osteonecrosis of the Jaw - a scoping review.

Objectives: It is not unusual for Medication-related osteonecrosis of the jaw (MRONJ) lesions that have similar clinical presentation and staging to have dissimilar radiographic extent of disease. The aim of this review was to explore the published scientific literature for quantitative indices that describe the cone-beam computerized tomography (CBCT) radiographic features of MRONJ lesions and assess their clinical utility. Method and Materials: A scoping review of the literature was performed to identify quantitative indices developed to describe the CBCT radiographic features of MRONJ lesions. Five electronic databases were included in the review: PubMed, Scopus, Web of Science, Trip medical database, and Cochrane Library. Articles published from the year 2003 onward were included in the review. Results: 367 articles were initially included in the review. 39 abstracts were screened for full-text assessment. The scoping review yielded 12 full length articles with169 cases reported. The Composite Radiographic Index score (CRI score) was identified as the most meaningful index in published literature that attempted to quantify qualitative radiographic changes (Walton, Grogan et al. 2019). However, lesions with similar CRI scores that corresponded to intermediate severity (3-5) may be very dissimilar radiographically in both nature and extent of radiographic changes, undercutting its clinical value. Conclusion: The CRI index score was the only relevant index for cross-sectional (one-time) assessment of established MRONJ lesions (non-stage 0). This scoping review yielded several critical questions regarding the clinical significance and prognostic implications of various radiographic changes in MRONJ, thereby identifying focus areas for future research.

Evaluation of Jaw Osteonecrosis Following Intra-Ligament Anesthesia in Zoledronate-Treated Rats: a Histological Evaluation.

Statement of the Problem: One of the rare adverse effects in patients who take bisphosphonates is the osteonecrosis of the jaw in the oral cavity following any trauma such as tooth extraction. Purpose: The aim of this study is the histopathological evaluation of the jaw following intra-ligament anesthesia injection in Zoledronate-treated rats. Materials and Method: In this descriptive-experimental study, rats weighing 200-250 g were divided into 2 groups. The first group received a 0.6 mg/kg dose of zoledronate and the second group received normal saline. Five injections with a 28-day interval were performed. At the end of the injection, the animals were sacrificed. Then, five-micrometer histological slides were prepared from the first maxillary molars and the surrounding tissues. Hematoxylin and eosin staining was performed to evaluate osteonecrosis, infiltration of inflammatory cells, fibrosis, and root and bone resorption. Results: There was no difference between the macroscopic and clinical features in both groups and no evidence of osteonecrosis of the jaw was observed in the samples. From the histological point of view, all the samples had normal tissues and none of them showed any evidence of inflammation, tissue fibrosis, disorder, or pathological root resorption. Conclusion: According to the histological findings, the periodontal ligament space, the bone adjacent to the roots, and the dental pulp conditions were similar in both groups. Osteonecrosis of the jaw did not develop in the rats that took bisphosphonates after intraligamental injection.

Significance of bisphosphonates on angiogenesis in vivo and their effect under geranyl-geraniol addition - could it alter the treatment of bisphosphonate-associated necrosis of the jaw?

PURPOSE: The aim of this study was to contribute to the understanding of the inhibitory effects of bisphosphonates on tissues, with a special focus on angiogenesis. Referring to bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ), it should be shown that the local addition of the isoprenoid geranyl-geraniol (GGOH) prevents vascularization processes. METHODS: A mouse model with n = 24 animals which received an injection of a collagen matrix was used. In 4 subgroups (n = 6), we examined the effect of zoledronate on the sprouting of capillary-like structures into the matrix, with and without the presence of geranyl-geraniol, as well as testing against control groups with PBS injections or collagen matrix containing PBS instead of GGOH. This was followed by a histological evaluation of the capillary-like structures. RESULTS: Zoledronate inhibits the sprouting of blood vessels into a collagen matrix in vivo; in the presence of GGOH this effect is significantly weakened by a factor of 3.9 (p = 0.00068). CONCLUSION: This work commits to the investigation of the pathophysiology of BP-ONJ and shows a possible causal therapeutic path via the topical application of GGOH.

Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid-case-control study.

INTRODUCTION: Medication-related osteonecrosis of the jaws (MRONJ) is a complication that develops in patients who use or have used antiresorptive or antiangiogenic medications for the treatment of bone metabolic disease and bone metastases. Clinically, MRONJ is characterized by the appearance of an inflammation in soft tissues and exposure of necrotic bone tissue in mandible or maxilla, for a period of 8 weeks, in patients with no history of head and neck radiotherapy that were being or are being treated with antiresorptive and/or antiangiogenic agents. The fibrin-rich platelets and leukocytes (L-PRF) membrane has been used as an alternative for MRONJ prevention. The aim of this study was to evaluate the use of L-PRF in prevention and treatment of bone necrosis. MATERIAL AND METHODS: The patients included had MRONJ diagnosis confirmed after clinical and radiographic examination and patients whose only therapeutic option was dental extraction. RESULTS: Twenty patients were included in the study and were divided in three groups. Two patients were removed from the study due to previous history of pentoxifylline and tocopherol use. The result of surgical treatment was successful in 57% in group 1 (control/MRONJ prevention), 100% in group 2 (MRONJ prevention), and 80% in group 3 (MRONJ treatment). CONCLUSION: L-PRF is an autologous biomaterial that allows the release of growth factors for a prolonged time, resulting in a better healing, reducing the risk contamination, edema, and postoperative pain, being a great ally in the prevention and treatment of MRONJ because it returns to these patients, mainly quality of life, reducing pain, and recurrent infections commonly seen in the processes of bone necrosis of the jaws.