Interventions for managing medication-related osteonecrosis of the jaw.
Ontology highlight
ABSTRACT:
SUBMITTER: Beth-Tasdogan NH
PROVIDER: S-EPMC9309005 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Interventions for managing medication-related osteonecrosis of the jaw.
Beth-Tasdogan Natalie H NH Mayer Benjamin B Hussein Heba H Zolk Oliver O Peter Jens-Uwe JU
The Cochrane database of systematic reviews 20220712
<h4>Background</h4>Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab, and antiangiogenic agents), and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, this adverse drug reaction may occur rarely (e.g. following the oral administration o ...[more]
Similar Datasets
Project description: Not available
| S-EPMC6485859 | biostudies-literature
Project description:PurposeOsteonecrosis of the jaw (ONJ) is an established side effect of intravenous bisphosphonates and other antiresorptive medications. Although bisphosphonates are frequently prescribed for patients with the skeletal disorder fibrous dysplasia (FD), there are no reports of ONJ in this population. This has led some to conclude that patients with FD are at low risk for the development of bisphosphonate-related ONJ.Patients and methodsPatients were evaluated as part of a longstanding FD natural history study at the National Institutes of Health.ResultsOf 76 patients with FD who were treated with bisphosphonates, 4 developed ONJ (5.4%). Three patients developed ONJ in areas of FD-affected bone and 1 in an area of normal bone. All 4 patients had features known to be associated with ONJ in the general population, including long-term high-dose intravenous bisphosphonate treatment, periodontal and endodontic infections, and dentoalveolar surgical procedures.ConclusionsThese cases establish ONJ as a potential complication of bisphosphonate treatment in patients with FD. The presence of established risk factors for ONJ in this group of patients with FD suggests that high-risk patients could be identified before the development of ONJ. Clinicians should use caution in prescribing bisphosphonates to patients with FD and should do so only for established indications.
| S-EPMC5039058 | biostudies-literature
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.
| S-EPMC8743993 | biostudies-literature
Project description:BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but potentially serious, adverse event that can occur after exposure to bone-modifying agents (BMAs; e.g., bisphosphonates, denosumab, and antiangiogenic therapies). BMAs are typically used at higher doses to prevent skeletal-related events in cancer patients and at lower doses for osteoporosis/bone loss. MRONJ can cause significant pain, reduce quality of life, and can be difficult to treat, requiring a multiprofessional approach to care.MethodsWe reviewed the literature and guidelines to summarize a practical guide on MRONJ for nurses and other allied healthcare professionals.ResultsWhile there is a risk of MRONJ with BMAs, this should be considered in relation to the benefits of treatment. Nurses and other allied healthcare professionals can play a key role alongside physicians and dentists in assessing MRONJ risk, identifying MRONJ, counseling the patient on the benefit-risk of BMA treatment, preventing MRONJ, and managing the care pathway of these patients. Assessing patients for MRONJ risk factors before starting BMA treatment can guide preventative measures to reduce the risk of MRONJ. Nurses can play a pivotal role in facilitating multiprofessional management of MRONJ by communicating with patients to ensure compliance with preventative measures, and with patients' physicians and dentists to ensure early detection and referral for prompt treatment of MRONJ.ConclusionsThis review summarizes current evidence on MRONJ and provides practical guidance for nurses, from before BMA treatment is started through to approaches that can be taken to prevent and manage MRONJ in patients receiving BMAs.
| S-EPMC7378104 | biostudies-literature
Project description:Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-?1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.
| S-EPMC7578793 | biostudies-literature
Project description:Medication-related osteonecrosis of the jaw (MRONJ) is a severe devastating complication for which the exact pathogenesis is not completely understood. Multiple systemic and local factors may contribute to the development of MRONJ. A growing body of evidence supports diabetes mellitus (DM) as an important risk factor for this complication; however, the exact mechanism by which DM may promote MRONJ has yet to be determined. The current review elucidates the role of DM in the pathogenesis of MRONJ and the mechanisms by which DM may increase the risk for MRONJ. Factors related to DM pathogenesis and treatment may contribute to poor bone quality through multiple damaged pathways, including microvascular ischemia, endothelial cell dysfunction, reduced remodeling of bone, and increased apoptosis of osteoblasts and osteocytes. In addition, DM induces changes in immune cell function and promotes inflammation. This increases the risk for chronic infection in the settings of cancer and its treatment, as well as antiresorptive medication exposure, thus raising the risk of developing MRONJ. A genetic predisposition for MRONJ, coupled with CYP 450 gene alterations, has been suggested to affect the degradation of medications for DM such as thiazolidinediones and may further increase the risk for MRONJ.
| S-EPMC4438733 | biostudies-literature
Project description:Bisphosphonates (BPs) have been widely, efficiently, and safely used for the treatment of various bone-related diseases such as osteoporosis. However, concerns about jaw osteonecrosis associated with oral treatment (medication-related osteonecrosis of the jaw [MRONJ]) have been increasing. Although many risk factors for MRONJ have been elucidated, its precise etiology and methods of prevention remain unknown. In this study, we have applied various elemental analysis methods for MRONJ specimens (e.g., X-ray fluorescence with synchrotron radiation [SR-XRF], particle-induced X-ray emission [PIXE], X-ray absorption fine structure [XAFS]) in order to reveal the accumulation and chemical state of trace bone minerals. In four MRONJ sequestra, the characteristic localization of copper (Cu) was observed by SR-XRF. Using micro-PIXE analysis, Cu looked to be localized near the edge of the trabecular bone. The chemical state of the accumulated Cu was estimated using XAFS and the possibility of a Cu-BP complex formation was assumed. Thus, in this study we argue for the feasibility of the trace element analysis to evaluate the potential pathophysiological mechanism of MRONJ.
| S-EPMC5365207 | biostudies-literature
Project description:Osteoporosis is a major, growing healthcare issue. This is especially of concern in an ageing population like that of Singapore. Osteoporotic patients are at risk of fractures, which can result in increased morbidity and mortality. The use of antiresorptive therapy with bisphosphonates or denosumab has been proven to reduce fracture risk. However, the use of these medications has rarely been associated with the development of osteonecrosis of the jaw, a potentially debilitating condition affecting one or both jaws. Appropriate understanding of the patient's antiresorptive therapy regime, as well as early institution of preventive dental measures, can play an important role in preventing medication-related osteonecrosis of the jaw (MRONJ). Regular monitoring and prompt referral to specialist care is warranted for patients with established MRONJ.
| S-EPMC6119741 | biostudies-literature
Project description:Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug reaction. Our previous whole-exome sequencing study found SIRT1 intronic region single-nucleotide polymorphism (SNP) rs7896005 to be associated with MRONJ in cancer patients treated with intravenous (iv) bisphosphonates (BPs). This study aimed to identify causal variants for this association. In silico analyses identified three SNPs (rs3758391, rs932658, and rs2394443) in the SIRT1 promoter region that are in high linkage disequilibrium (r2 > 0.8) with rs7896005. To validate the association between these SNPs and MRONJ, we genotyped these three SNPs on the germline DNA from 104 cancer patients of European ancestry treated with iv BPs (46 cases and 58 controls). Multivariable logistic regression analysis showed the minor alleles of these three SNPs were associated with lower odds for MRONJ. The odds ratios (95% confidence interval) and p values were 0.351 (0.164-0.751; p = 0.007) for rs3758391, 0.351 (0.164-0.751; p = 0.007) for rs932658, and 0.331 (0.157-0.697; p = 0.0036) for rs2394443, respectively. In the reporter gene assays, constructs containing rs932658 with variant allele A had higher luciferase activity than the reference allele, whereas constructs containing SNP rs3758391 and/or rs2394443 did not significantly affect activity. These results indicate that the promoter SNP rs932658 regulates the expression of SIRT1 and presumably lowers the risk of MRONJ by increasing SIRT1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).
| S-EPMC8733933 | biostudies-literature
Project description:This study aimed to investigate the preventive effect of teriparatide (TPD) administration on medication-related osteonecrosis of the jaw (MRONJ) before tooth extraction due to periodontal lesions in bilaterally ovariectomized female rats treated with zoledronic acid. Thirty skeletally mature Sprague-Dawley rats were randomly divided into three groups: control (CONT, n = 10), zoledronic acid (ZA, n = 10), and zoledronic acid and teriparatide (ZA-TPD, n = 10). The rats were sacrificed 8 weeks after tooth extraction. Micro-computed tomography analysis of the tibia showed that bone mineral density was highest in the CONT, followed by that in the ZA and ZA-TPD groups (CONT/ZA, p = 0.009; CONT/ZA-TPD, p < 0.001; ZA/ZA-TPD, p < 0.001). In the trabecular bone analysis of the extraction site, significant differences in specific bone surface (CONT/ZA, p = 0.010; CONT/ZA-TPD, p = 0.007; ZA/ZA-TPD, p = 0.002) and trabecular thickness (CONT/ZA-TPD, p = 0.002; ZA/ZA-TPD, p = 0.002) were observed. Histological analyses of the extraction sites revealed characteristic MRONJ lesions in the ZA group. Osteonecrosis, inflammatory cells, and sequestrum were less frequently observed in the ZA-TPD group than in the ZA group. In conclusion, TPD administration before tooth extraction helped reduce the occurrence of MRONJ in rats treated with zoledronic acid, confirming its preventative effects.
| S-EPMC10509150 | biostudies-literature