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Perceptions and attitudes of patients towards medication-related osteonecrosis of the jaw (MRONJ): a qualitative study in England.

ABSTRACT: OBJECTIVE:To explore the impact of medication-related osteonecrosis of the jaw (MRONJ) on quality of life and to explore the attitudes and perceptions of patients towards the multidisciplinary approach to the prevention of the condition. DESIGN:Interpretivist methodology using qualitative semistructured interviews. SETTING:Primary care general medical practices and secondary care dental services in England. PARTICIPANTS:23 patients; 6 with MRONJ, 13 prescribed bisphosphonates, 4 with osteoporosis not currently prescribed any medication. RESULTS:Patients felt that MRONJ had a significant negative impact on their quality of life and had poor knowledge of the preventive strategies recommended in the literature. Patients demonstrated positive attitudes towards a multidisciplinary approach to care; however, they perceived prescribers as having the key role in articulating risk. Four salient and inter-related themes emerged from the interviews: (1) perception of knowledge, indicating limited awareness of the condition, risk factors and preventive strategies; (2) quality of life, indicating the lived experiences of patients and the physical, psychological and social impacts of MRONJ; (3) interprofessional management, indicating a perceived organisational hierarchy, professional roles and responsibilities, prioritising aspects of care, articulation of risk and communication and (4) wider context, indicating demands on National Health Service resources and barriers to dental care. CONCLUSIONS:MRONJ has a significant detrimental impact on quality of life, yet appropriate preventative education is not apparent. Effective interprofessional patient education and prevention to mitigate against the risk of developing MRONJ is required.

SUBMITTER: Sturrock A

PROVIDER: S-EPMC6443056 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo explore general dental practitioners' (GDPs') perceptions of, and attitudes towards, the risks of medication-related osteonecrosis of the jaw (MRONJ) and the current/potential multidisciplinary approach(es) to prevention of the condition.DesignInterpretivist methodology using a grounded theory approach and constant comparative analysis to undertake an iterative series of semistructured interviews. Ritchie and Spencer's framework analysis facilitated the identification and prioritisation of salient themes.SettingPrimary care general dental practices in the North East of England.Participants15 GDPs.ResultsGDPs are aware of the risk of MRONJ with commonly implicated medicines; however, they report limited collaboration between professional groups in person-centred avoidance of complications, which is a key requirement of the preventive advice recommended in extant literature. Four salient and inter-related themes emerged: (1) perception of knowledge; indicating the awareness of the risk, limited knowledge of implicated medications and experience of managing the condition; (2) risk; indicating the importance of accurate medication histories, the treatment of low risk patients in primary dental care, counselling of poorly informed patients, the fear of litigation and perceived low priority of oral health in the context of general health and well-being; (3) access and isolation; referring to access to general medical records, professional isolation and somewhat limited and challenging professional collaborative relationships; (4) interprofessional working; indicating oral health education of other professional groups, collaboration and communication, and a focus on preventive care.ConclusionsPatients continue to be at risk of developing MRONJ due to limited preventive interventions and relatively disparate contexts of multidisciplinary team healthcare. Effective collaboration, education and access to shared medical records could potentially improve patient safety and reduce the potential risk of developing MRONJ.

Project description:Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). pARs, including nitrogen-containing bisphosphonates (N-BPs; e.g., zoledronic acid, alendronate) and anti-RANKL antibodies (e.g., denosumab), are used to manage bone metastases in patients with cancer or to prevent fragility fractures in patients with osteoporosis. Though significant advances have been made in understanding MRONJ, its pathophysiology is still not fully elucidated. Multiple species have been used in preclinical MRONJ research, including the rat, mouse, rice rat, rabbit, dog, sheep, and pig. Animal research has contributed immensely to advancing the MRONJ field, particularly, but not limited to, in developing models and investigating risk factors that were first observed in humans. MRONJ models have been developed using clinically relevant doses of systemic risk factors, like N-BPs, anti-RANKL antibodies, or AgIs. Specific local oral risk factors first noted in humans, including tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection, etc.), were then added. Research in rodents, particularly the rat, and, to some extent, the mouse, across multiple laboratories, has contributed to establishing multiple relevant and complementary preclinical models. Models in larger species produced accurate clinical and histopathologic outcomes suggesting a potential role for confirming specific crucial findings from rodent research. We view the current state of animal models for MRONJ as good. The rodent models are now reliable enough to produce large numbers of MRONJ cases that could be applied in experiments testing treatment modalities. The course of MRONJ, including stage 0 MRONJ, is characterized well enough that basic studies of the molecular or enzyme-level findings in different MRONJ stages are possible. This review provides a current overview of the existing models of MRONJ, their more significant features and findings, and important instances of their application in preclinical research.

Project description:BACKGROUND:Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare, yet significant, adverse effect of bisphosphonate therapy. A multidisciplinary approach to the prevention of BRONJ is recommended due to the significant morbidity and difficulty treating the condition. Current evidence suggests that both general practitioners (GPs) and community pharmacists have limited knowledge relating to BRONJ and that preventative strategies are rarely implemented. OBJECTIVE:To explore the attitudes and perceptions of GPs and community pharmacists on the risks and preventative strategies for the development of BRONJ. DESIGN:Interpretivist methodological approach using qualitative semistructured interviews. PARTICIPANTS:9 community pharmacists and 8 GPs. SETTING:Primary Care in North East England and Cumbria, UK. METHODS:Using a Grounded Theory methodology and integrating a process of constant comparison in the iterative enrichment of data sets, semistructured interviews were undertaken, transcribed and analysed using framework analysis. Salient themes were identified and related back to extant literature in the field. RESULTS:Four salient and inter-related themes emerged: (1) uncertain knowledge, indicating limited exposure of respondents to BRONJ, and limited awareness of the implications of its diagnosis, risk factors and preventative strategies; (2) patient specific, referring to the complexity of patients, patient education and prioritising aspects of care; (3) wider context, indicating a lack of interdisciplinary communication and referral processes between professions, workload pressures, access and patient receptivity to dental services; and (4) professional, reflecting professional roles and responsibilities, authority and educational initiatives CONCLUSIONS: Effective communication or collaborative care between GPs and community pharmacists for the prevention of BRONJ is not apparent. Interventions to mitigate against the risk of developing BRONJ and clarity of GP and community pharmacy roles are required.

Project description:Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive or antiangiogenic medications, used in the treatment of bone malignancy or osteoporosis. Bone necrosis, mainly represented by osteocytic death, is always present in MRONJ sites; however, the role of osteocyte death in MRONJ pathogenesis is unknown. High mobility group box 1 (HMGB1) is a non-histone nucleoprotein that in its acetylated form accumulates in the cytoplasm, whereas non-acetylated HMGB1 localizes in the nucleus. SIRT1 deacetylase regulates cellular localization of HMGB1. Interestingly, HMGB1 is released during cell necrosis and promotes inflammation through signaling cascades, including activation of the RAGE receptor. Here, we utilized a well-established mouse MRONJ model that utilizes ligature-induced experimental periodontitis (EP) and treatment with either vehicle or zolendronic acid (ZA). Initially, we evaluated HMGB1-SIRT1 expression in osteocytes at 1, 2, and 4 weeks of treatment. Significantly increased cytoplasmic and perilacunar HMGB1 expression was observed at EP sites of ZA versus vehicle (Veh) animals at all time points. SIRT1 colocalized with cytoplasmic HMGB1 and presented a statistically significant increased expression at the EP sites of ZA animals for all time points. RAGE expression was significantly higher in the submucosal tissues EP sites of ZA animals compared with those in vehicle group. To explore the significance of increased cytoplasmic and extracellular HMGB1 and increased RAGE expression in MRONJ pathogenesis, we used pharmacologic inhibitors of these molecules. Combined HMGB1/RAGE inhibition resulted in lower MRONJ incidence with statistically significant decrease in osteonecrotic areas and bone exposure versus non-inhibitor treated ZA animals. Together, our data point to the role of HMGB1 as a central alarmin, overexpressed at early phase of MRONJ pathogenesis during osteocytic death. Moreover, HMGB1-RAGE pathway may represent a new promising therapeutic target in patients at high risk of MRONJ. © 2022 American Society for Bone and Mineral Research (ASBMR).

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Perceptions and attitudes of patients towards medication-related osteonecrosis of the jaw (MRONJ): a qualitative study in England.

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