Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors.
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ABSTRACT:
SUBMITTER: Wan JT
PROVIDER: S-EPMC7064532 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Osteonecrosis of the jaw (ONJ), a rare, but potentially severe side effect of anti-resorptive medications, presents as exposed bone in the maxillofacial region lasting for at least 8 weeks. While clinical experience and animal models concur in finding that systemic antiresorptive treatment in conjunction with local risk factors, such as tooth extraction or dental disease may lead to ONJ development, the subclinical molecular changes that precede bone exposure remain poorly understood. The identification of these changes is not only important in understanding disease pathophysiology, but could provide potential for treatment development. Here, we evaluated the early stages of ONJ utilizing a model of experimental periodontitis (EP) in mice treated with two different types of antiresorptives, targeting potential changes in vasculature, hypoxia, oxidative stress, and apoptosis. Antiresorptive treatment in animals with EP increased levels of empty osteocytic lacunae and increased ONJ prevalence compared to Veh animals. The arteriole and venule network seen around EP areas was diminished in animals treated with antiresorptives. Higher levels of vascular endothelial growth factor A (VEGF-A) and vascular cell adhesion protein-1 (VCAM-1) were observed 1-week following EP in treated animals. Finally, levels of hypoxia, oxidative stress, and apoptosis remained high in antiresorptive treated animals with EP through the duration of the experiment. Together, our data point to subclinical vasculature organizational disturbances that subsequently affect levels of hypoxia, oxidative stress, and apoptosis in the area of developing ONJ.
| S-EPMC6763394 | biostudies-literature
Project description:PurposeThe prevention and early diagnosis of medication-related osteonecrosis of the jaw (MRONJ) is fundamental to reducing the incidence and progression of MRONJ. Many in the field believe that dental hygienists should play an integral role in primary and secondary MRONJ prevention. However, to date, very few publications in the literature have proposed standardised MRONJ protocols, which are dedicated to dental hygienists. The aim of this study was to provide guidance to the health care providers managing MRONJ.MethodsThe expert opinion in this study was developed by dental hygienists from the main Italian technical-scientific associations (Italian Dental Hygienists Association, AIDI and National Union of Dental Hygienists, UNID) and authors of the latest Italian recommendations regarding MRONJ from the field of dentistry and maxillofacial surgery.ResultsThe oral care protocol outlined in this position paper is focused on the role of dental hygienist in patients at risk or affected by MRONJ, and it regards 3 main issues: primary prevention, secondary prevention and supporting the treatment of MRONJ. Each issue contains easy-to-apply indications and procedures, as described by the authors, regarding the role of the dental hygienist.ConclusionReferring to the main issues under consideration (primary prevention, secondary prevention and the treatment of MRONJ), a clinical examination of periodontal tissue is critical in preventing MRONJ. It is the opinion of the authors of this study that the application of a periodontal screening score is fundamental in defining personalised strategies for patients at risk of MRONJ. By means of these basic procedures, a protocol for assisting the health care provider and the presentation of a practical approach for patients at risk or affected by MRONJ are described in this study.
| S-EPMC9213300 | biostudies-literature
Project description:IntroductionOsteonecrosis of the jaw (ONJ) is an adverse event that requires association of both systemic risk factors, such as powerful anti-resorptives (pARs; e.g. zoledronic acid [ZOL]), and local oral risk factors (e.g. tooth extraction, periodontitis). Whereas optimal oral health prior to initiate pARs is recognized as critically important for minimizing ONJ risk, the efficacy of preventive/maintenance measures in patients who are taking pARs is understudied. Rice rats fed a standard diet (STD), rich in insoluble fiber, develop localized periodontitis. STD-rats with localized periodontitis treated with ZOL for 18-24 wk develop ONJ. Hence, we hypothesized that controlling/preventing localized periodontitis in the ZOL-treated rats, reduces ONJ occurrence.MethodsWe used two approaches to attempt reducing periodontitis prevalence: 1) periodontal cleaning (PC); and 2) replacing the STD-diet with a nutritionally-equivalent diet high in soluble fiber (SF). 75 four-week-old male rats were weight-randomized into five groups (n = 15) in a 24-week experiment. Three groups ate the STD-diet and two the high SF-diet. STD-diet groups received intravenous (IV) vehicle (VEH) q4wks (STD + VEH), 80 μg/kg ZOL q4wks IV (STD + ZOL), or ZOL plus PC q2wks (STD + ZOL + PC). The SF-diet groups received VEH (SF + VEH) or ZOL (SF + ZOL). Jaws were processed for histopathology and evaluated for ONJ prevalence and tissue-level periodontitis.Results1) 40% of STD + VEH rats developed maxillary localized periodontitis with no ONJ; 2) 50% of STD + ZOL rats developed ONJ; 3) 7% of STD + ZOL + PC rats developed ONJ (p < 0.01 vs. STD + ZOL); and 4) one SF + ZOL rat developed localized periodontitis, and no SF + VEH or SF + ZOL rats developed ONJ (p < 0.001 vs. STD + ZOL).Conclusions1) Periodontal cleaning in ZOL-treated rats decreases localized periodontitis severity and reduces ONJ prevalence; and 2) feeding a SF-diet to ZOL-treated rats reduces both incidence of localized periodontitis and ONJ. Our data indicates strong oral microbial community shifts according to oral health condition and trends in the shifts associated with diet.
| S-EPMC8265021 | 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
Project description:Objectives: Osteonecrosis of the jaw (ONJ), a necrotic bone disease unique to the craniofacial region, is often observed among cancer patients treated with bisphosphonate (BP)-based chemotherapy and becomes a costly and debilitating source of pain and reduced quality of life. Elucidation of clinicopathological mechanism and biomarkers of ONJ that can indicate probable disease course would allow for better assessment of treatment strategies for individual patients. To address our overall goal of identifying novel diagnostic and prognostic strategies for ONJ, this study specifically aims to understand the alendronate (ALN) treatment-induced perturbation of bone proteome and microenvironmental pathophysiology of ONJ using targeted molecular analyses and computational approaches based on an in vitro cell culture system. This study also focuses on identifying proteome perturbation and potential molecular biomarkers during ONJ development. Methods: To understand the molecular mechanisms underlying ONJ, an unbiased and global proteomics approach combined with big data analysis using bioinformatics was applied. Biochemical and functional analyses were followed to tease out the mechanisms regulated by ALN treatment. Results: The current findings from our global proteomics study and biochemical analyses suggested that the RIPK3/Wnt/GSK3/β-catenin signaling pathway is significantly perturbed upon alendronate treatment, resulting in abnormal angiogenesis/inflammation/bone anabolism/remodeling/bone mineralization in the in vitro cell culture system. Conclusion: This investigation on potential key signaling mechanisms underlying ONJ will provide a rational basis for suppressing BP-induced ONJ and novel therapeutic strategies against ONJ.
2021-09-10 | PXD024585 | Pride
Project description:Purpose of reviewOsteonecrosis of the jaw (ONJ) is an uncommon condition noted to occur in patients with cancer who are receiving intravenous bisphosphonates. The cause of ONJ remains unknown. The leading hypotheses addressing the mechanism of ONJ are reviewed here.Recent findingsThe present clinical data suggest that ONJ may occur in approximately 5% of patients with metastatic bone disease. The ability to predict an individual's risk of developing ONJ remains elusive. It is likely that an altered bone microenvironment and/or host defense mechanisms effected by medications used to treat patients with metastatic bone disease contributes to the development of ONJ. Medications that significantly reduce osteoclastic activity are associated with ONJ. Preclinical models of ONJ are being developed but to establish such an intricate systemic condition in animals is challenging.SummaryThe ONJ field has progressed via knowledge gained by case reports, population-based studies, and emerging animal models. Still, there are myths that need to be resolved and important clues that need to be investigated. Understanding the pathophysiology of this condition will be critical to improve patient care. Communications between oncologists, dentists, basic scientists, and patients are central to effective treatment and research for this condition.
| S-EPMC2962852 | biostudies-literature
Project description:BackgroundA case-control study was performed to define clinical and genetic risk factors associated with osteonecrosis of the jaw in patients with metastatic cancer treated with bisphosphonates.MethodsClinical data and tissues were collected from patients treated with bisphosphonates for metastatic bone disease who were diagnosed with osteonecrosis of the jaw (cases) and matched controls. Clinical data included patient, behavioral, disease, and treatment information. Genetic polymorphisms in CYP2C8 (rs1934951) and other candidate genes were genotyped. Odds ratios from conditional logistic regression models were examined to identify clinical and genetic characteristics associated with case or control status.ResultsThe study population consisted of 76 cases and 126 controls. In the final multivariable clinical model, patients with osteonecrosis of the jaw were less likely to have received pamidronate than zoledronic acid (odds ratio = 0.18, 95% Confidence interval: 0.03-0.97, p = .047) and more likely to have been exposed to bevacizumab (OR = 5.15, 95% CI: 1.67-15.95, p = .005). The exploratory genetic analyses suggested a protective effect for VEGFC rs2333496 and risk effects for VEGFC rs7664413 and PPARG rs1152003.ConclusionsWe observed patients with ONJ were more likely to have been exposed to bevacizumab and zoledronic and identified potential genetic predictors that require validation prior to clinical translation.
| S-EPMC8284838 | biostudies-literature
Project description:BackgroundChildren and adolescents with special health care needs (SHCN) have higher unmet dental needs, but the potential mechanisms by which parental factors can influence dental care use have not been determined. Parenting a child with SHCN can present special demands that affect parents' well-being and, in turn, their caregiving. Hence, the study's overall aim was to apply the stress process model to examine the role of parental psychosocial factors in the association between child SHCN and dental care. Specifically, the study tested hypotheses regarding how (a) children's SHCN status is associated with child dental care (unmet dental needs and lack of preventive dental visits), both directly and indirectly via parental psychosocial factors (parenting stress, instrumental, and emotional social support) and (b) parental social support buffers the association between parenting stress and child dental care.MethodsA secondary data analysis of the 2011-2012 US National Survey of Children's Health was performed for 6- to 11-year-old children (n = 27,874) and 12- to 17-year-old adolescents (n = 31,328). Our age-stratified models estimated associations between child SHCN status and parental psychosocial factors with two child dental care outcomes: parent-reported unmet child dental needs and lack of preventive dental care.ResultsParents of children with (vs without) SHCN reported higher unmet child dental needs, higher parenting stress, and lower social support (instrumental and emotional). Instrumental, but not emotional, parental support was associated with lower odds of their child unmet dental needs in both age groups. The association between parenting stress and child dental care outcomes was modified by parental social support.ConclusionDifferences existed in child unmet dental needs based on SHCN status, even after adjusting for parental psychosocial factors. SHCN status was indirectly associated with unmet dental needs via parental instrumental support among adolescents, and parental instrumental support buffered the negative association between parenting stress and both child dental care outcomes. Hence, parental social support was an important determinant of child dental care and partially explained the dental care disparities in adolescents with SHCN.
| S-EPMC9275152 | biostudies-literature
Project description:ObjectiveTo investigate whether early or regular preventive dental visit (PDV) reduces restorative or emergency dental care and costs for low-income children.Study settingEnrollees during 1998-2012 in the Alabama CHIP program, ALL Kids.Study designRetrospective cohort study using claims data for children continuously enrolled in ALL Kids for at least 4 years. Analyses are conducted separately for children 0-4 years, 4-9 years, and >9 years. For 0-4 years, the intervention of interest is whether they have at least one PDV before age 3. For the other two age groups, interventions of interest are if they have regular PDVs during each of the first 3 years, and if they have claims for a sealant in the first 3 years. Outcomes-namely restorative and emergency dental service and costs-are measured in the fourth year. To account for selection into PDV, a high-dimensional propensity scores approach is utilized.Data extractionClaims data were obtained from ALL Kids.Principal findingsOnly sealants are associated with a reduced likelihood of using restorative and emergency services and costs.ConclusionsWhether PDVs without sealants actually reduce restorative/emergency pediatric dental services is questionable. Further research into benefits of PDV is needed.
| S-EPMC5134206 | biostudies-literature
Project description:Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and in vivo micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology.
| S-EPMC5471352 | biostudies-literature