Bisphosphonate-related Osteonecrosis Research Articles

Mitigating jaw osteonecrosis: bioactive glass and pericardial membrane combination in a rat model

ObjectivesBisphosphonates (BFs) show clinical effectiveness in managing osteoporosis and bone metastases but pose risks of bisphosphonate-related jaw osteonecrosis (BRONJ). With no established gold standard for BRONJ treatment, our focus is on symptom severity reduction. We aimed to assess the preventive effects of bioactive glass and/or pericardial membrane in a preclinical BRONJ model, evaluating their potential to prevent osteonecrosis and bone loss post-tooth extractions in zoledronic acid (ZA)-treated animals.MethodsRats, receiving ZA or saline biweekly for four weeks, underwent 1st and 2nd lower left molar extractions. Pericardial membrane alone or with F18 bioglass was applied post-extractions. Microarchitecture analysis and bone loss assessment utilized computerized microtomography (CT) and positron emission tomography (PET) with 18F-FDG and 18F-NaF tracers. Histological analysis evaluated bone injury.ResultsExclusive alveolar bone loss occurred post-extraction in the continuous ZA group, inducing osteonecrosis, osteolysis, osteomyelitis, and abscess formation. Concurrent pericardial membrane with F18 bioglass application prevented these outcomes. Baseline PET/CT scans showed no discernible uptake differences, but post-extraction 18F-FDG tracer imaging revealed heightened glucose metabolism at the extraction site in the ZA-treated group with membrane, contrasting the control group.ConclusionThese findings suggest pericardial membrane with F18 bioglass effectively prevents BRONJ in the preclinical model.

Beta-adrenergic receptor antagonist propranolol prevents bisphosphonate-related osteonecrosis of the jaw by promoting osteogenesis

Background/purposeBisphosphonate-related osteonecrosis of the jaw (BRONJ), a complication arising from the use of bisphosphonates (BPs), inflicts long-term suffering on patients. Currently, there is still a lack of effective treatments. This study aimed to explore the preventive effects of propranolol (PRO) on BRONJ in vitro and in vivo, given PRO's potential in bone health enhancement. Materials and methodsIn vitro, effect of PRO on zoledronic acid (ZA)-pretreated bone marrow mesenchymal stem cells (BMSCs) was detected by cell counting kit-8, alkaline phosphatase (ALP) staining, alizarin red staining, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In vivo, forty mice were divided into four groups: control, ZA, PRO, and ZA-PRO. The maxillary extraction sockets sides were analyzed with micro-CT and histomorphometry. Hematoxylin-eosin (H&E), Masson staining, immunofluorescence staining of ALP, bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2) and TUNEL staining were performed. ResultsPRO increased proliferation and osteogenic differentiation of BMSCs. PRO stimulated bone formation and facilitated the healing process in zoledronic acid-induced osteonecrosis of jaw in mouse model. Compared with ZA group, control and PRO group showed more BMP2+, RUNX2+, and ALP+ cells (P < 0.05). However, PRO rescued the decreased expression of ALP, RUNX2, BMP2 due to ZA and decreased the expression of TUNEL (P < 0.05). ConclusionThe findings suggest that propranolol may offer a promising preventive strategy against BRONJ by enhancing bone regeneration. This research contributes to the understanding of the pathogenesis of BRONJ and opens avenues for potential treatments of BRONJ focusing on β-adrenergic signaling.

Polysacharide of Agaricusblazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.

Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.

Zoledronic Acid Accelerates ER Stress-Mediated Inflammation by Increasing PDE4B Expression in Bisphosphonate-Related Osteonecrosis of the Jaw.

Long-term administration of bisphosphonates can lead to a significant side effect known as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Although macrophage-mediated inflammation has been established as an important factor in BRONJ, the underlying mechanism remains elusive. In the current study, the roles of endoplasmic reticulum (ER) stress in zoledronic acid (ZOL)-induced inflammation were analyzed in macrophages, and the regulatory mechanism of ER stress activation was next investigated. An in vitro model of BRONJ was established by treating RAW264.7 cells with ZOL. The activation of ER stress was analyzed by western blotting and transmission electron microscopy, and inflammation was assessed by quantitative real-time PCR and enzyme-linked immunosorbent assay. ER stress was significantly activated in ZOL-treated macrophages, and inhibition of ER stress by TUDCA, an ER stress inhibitor, suppressed ZOL-induced inflammation in macrophages. Mechanistically, phosphodiesterase 4B (PDE4B) was significantly increased in ZOL-treated macrophages. Forced expression of PDE4B promoted ER stress and inflammation, whereas PDE4B knockdown decreased ZOL-induced ER stress and inflammation in macrophages. More importantly, PDE4B inhibitor could improve ZOL-induced BRONJ in vivo. These data suggest that ZOL accelerates ER stress-mediated inflammation in BRONJ by increasing PDE4B expression. PDE4B inhibition may represent a potential therapeutic strategy for BRONJ. Subsequent research should concentrate on formulating medications that selectively target PDE4B, thereby mitigating the risk of BRONJ in patients undergoing bisphosphonate treatment.

Impact of Bisphosphonate Therapy on Oral Health in Patients with Breast and Prostate Cancer and Bone Metastases: A Comprehensive Study.

This study investigates the impact of bisphosphonate therapy on the stomatognathic system in 80 patients with cancer of the breast and prostate with bone metastases. Bisphosphonates are integral for managing skeletal complications in these malignancies but are associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ), affecting 0.8-18.5% of patients. BRONJ manifests with pain, neuropathy, tissue swelling, mucosal ulceration, tooth mobility, and abscesses, yet its pathogenesis remains elusive, complicating risk prediction. The research employed comprehensive dental and radiological evaluations. Dental status was assessed using DMFT and OHI-S indices, Eichner's classification, and clinical periodontal measurements like the pocket depth (PD), clinical attachment loss (CAL), and modified Sulcus Bleeding Index (mSBI). A radiological analysis included panoramic X-rays for radiomorphometric measurements and TMJ lateral radiographs. Results indicated a significant decline in oral hygiene in patients with cancer after bisphosphonate therapy, marked by increased DMFT and OHI-S scores. Periodontal health also showed deterioration, with increased PD and CAL readings. The incidence of BRONJ symptoms was noted, although exact figures are not quantified in this abstract. The study also revealed changes in radiomorphometric parameters, suggesting bisphosphonates' impact on bone density and structure. No substantial alterations were observed in TMJ function, indicating a need for extended observation to understand bisphosphonates' long-term effects on the stomatognathic system. These findings highlight the importance of continuous dental monitoring and prophylaxis in patients undergoing bisphosphonate therapy. Implementing meticulous oral care protocols is essential for mitigating BRONJ risk and managing the complex oral health challenges in patients with cancer.

Bisphosphonate-related Osteonecrosis of The Jaw : Is the Medication Duration Related to Advanced Disease Stage?

Abstract Objectives Osteonecrosis of the jaw (ONJ) is a serious adverse effect of therapy with bisphosphonates (BP) and other antiresorptive agents. The aim of the study was to report thirteen bisphosphonates related osteonecrosis of the jaw (BRONJ) patient cases at Kaohsiung Veterans General Hospital (VGHKS), Taiwan and their medical history and disease outcomes. Methods Thirteen symptomatic patients with BRONJ were reviewed between 1985 and 2021 at VGHKS. We included symptomatic patients who were in advanced BRONJ stage two and three. Four multiple myeloma, three bone metastatic breast cancer and six advanced osteoporosis patients. Results Seven patients were AAOMS MRONJ stage three and six were stage two. The average anti-resorptive medication duration was 25.83 ± 31.45 months in BRONJ stage two patients and 53.71 ± 31.25 months in BRONJ stage three patients respectively. No correlation was found between the anti-resorptive agent duration and BRONJ stage (p value = 0.098; Mann-Whitney U test) among cancer (p value = 0.157; Mann-Whitney U test) and osteoporosis patients (p value = 0.184; Mann-Whitney U test). Conclusion Most of them died of terminal stage cancer disease or complications of being bedridden. The correlation between the duration of anti-resorptive agents and BRONJ stage needs larger patient data to confirm the result.

Treatment of Bisphosphonate-related Osteonecrosis of Jaw (BRONJ) in Rabbit Model: A Proof-of-concept Animal Study Comparing Angiogenesis Factor Versus Autologous Bone Marrow-derived Osteoblasts (ABMDO)

Objective We created Bisphosphonate-related Osteonecrosis of Jaw (BRONJ) in rabbits and treated them with an angiogenesis factor or autologous bone marrow derived osteoblasts (ABMDO) to assess the efficacy of the treatment by Micro-computerized Tomography (M-CT) and histopathology. Materials and Methods Thirty female New Zealand rabbits were procured and were divided into three groups of 10 animals each. The number of animals to achieve statistical significance was based on the reported studies. Group I was control group (C), Group II was Osteoblast group (O), and Group III was angiogenesis group (P). In all Groups, BRONJ was produced. At 8 weeks of tooth extraction, BRONJ was confirmed histologically and radiologically in two rabbits from each group of animals. Group I received 0.5 of normal saline, Group II received a single dose of 5 million osteoblasts suspended in 0.5 ml, and Group III received 5 mg of angiogenesis factor thrice weekly for three weeks. The healing of BRONJ was assessed using M-CT and histopathology. Results In O and P groups, the extraction sockets healed and closed with normal-looking tissue, whereas in the C (control) group, suppuration with an area of necrosis was observed. Micro-CT analysis of socket revealed an exaggeration on non-mineralized soft tissue volume in the C group, whereas most of the bone promotion parameters were improved in the O and P groups with statistical difference (P&lt;0.001) for the parameters bone volume, bone surface area, trabecular number and trabecular thickness. Histologically, the element of healing was represented by reactive bone formation and fibrosis, which were more prominent in groups O and P as compared to the control group. Conclusion Our study shows that ABMDO and angiogenesis factor have a robust potential to heal BRONJ. Clinical Relevance The study shows angiogenesis factor and osteoblasts heals BRONJ and warrant sincere human trials to tackle this unrelenting complication of bisphosphonates use.

Medical and Dental Professions' Varying Levels of Awareness Regarding Medication-related Osteonecrosis of the Jaw in Saudi Arabia? A Cross-sectional Study.

This study aimed to assess the awareness of the risk of medication-related osteonecrosis of the jaw (MRONJ) among general dental practitioners (GDPs) and primary care physicians (PCPs), focusing on the clinical implications and coordination of treating or identifying high-risk patients. Two Google Forms electronic questionnaires were distributed to 724 GDPs and 617 PCPs in primary care settings. One for PCPs with eight multiple choice questions and the other for GDPs with 10 multiple choice questions. A clinical case scenario and a section on open-ended comments were included in both questionnaires. The data obtained from each group were statistically analyzed and compared. A total of 239 GDPs and 220 PCPs participated in the study, with a response rate of 34.23%. The mean age of participants was 29.5 years and 54.35% were females (51.2% and 57.5% in the GDPs and PCPs group, respectively). Most participants had graduated from Saudi Arabia. Almost all dentists were aware of osteonecrosis of the jaw (95.1%), 68.3% of them were aware of the guidelines regarding bisphosphonate-related osteonecrosis of the jaw (BRONJ) and MRONJ, 60.5% rated their general knowledge about MRONJ as very poor to poor, and 91.8% did not know any guidelines regarding BRONJ or MRONJ. Among the participants, 75.3% did not know how MRONJ was present in the oral cavity. A total of 69.9% of participants were unaware of other factors associated with an increased risk of MRONJ. MRONJ risk awareness varies greatly between dentists who diagnose and manage patients in dental clinics and physicians who write about medicines and therapies. Counseling sessions and greater coordination between dental and medical specialists are strongly suggested while prescribing antiresorptive drugs to prevent the consequent development of MRONJ. This study shows a significant lack of knowledge regarding MRONJ among GDPs and PCPs, which may affect the prevention and treatment of patients. Therefore, we urge GDPS and PCPs to take more information from scientific sources on this topic and more cooperation from specialties for the benefit of patients. How to cite this article: Aljohani MH, Aljohani AS, Aljohani RM, et al. Medical and Dental Professions' Varying Levels of Awareness Regarding Medication-related Osteonecrosis of the Jaw in Saudi Arabia? A Cross-sectional Study. J Contemp Dent Pract 2024;25(1):62-67.

Photodynamic therapy repairs medication-related osteonecrosis of the jaw by reducing NF-kB protein in rats.

To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model. Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson's trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey's post-test (p<0.05). Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05). PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions.

Similarities and Differences between Osteoclast-Mediated Functional Activation of NK, CD3+ T, and γδ T Cells from Humans, Humanized-BLT Mice, and WT Mice.

This study is focused on assessing the activation in NK, CD3+ T, and γδ T cells when they interact with osteoclasts (OCs) and monocytes in the presence or absence of zoledronate (ZOL), both in humans and WT mice. OCs resulted in increased IFN-γ secretion in NK, CD3+ T, and γδ T cells, however, the significantly highest increase was seen when cells were co-cultured with ZOL-treated OCs. Our previous studies have demonstrated increased IFN-γ secretion in the peripheral blood-derived immune cells of bisphosphonate-related osteonecrosis of the jaw (BRONJ) mice model. This could be due to increased OCs-induced activation of immune cells with ZOL treatment. We also observed increased IFN-γ secretion in humanized-BLT (hu-BLT) mice NK cells when were co-cultured with OCs or monocytes, and higher IFN-γ secretion levels were seen in the presence of OCs or ZOL-treated OCs. In addition, similar effects on IFN-γ secretion levels of NK, CD3+ T, and γδ T cells were seen whether cells were co-cultured with allogeneic OCs or autologous OCs.

Assessment Results of Dental Students' Knowledge about Bisphosphonates and Bisphosphonate-Related Osteonecrosis of the Jaw.

The aim of this cross-sectional study is to evaluate Lithuanian fourth- and fifth-year dental students' knowledge about bisphosphonates and bisphosphonate-related osteonecrosis of the jaw. The anonymous survey using a questionnaire was conducted from February to March 2022. The survey was sent to 173 students at Lithuanian University of Health Sciences (LSMU) and 107 of them were completed. It consisted of student data, questions about the main properties of bisphosphonates, bisphosphonate-related osteonecrosis of the jaw (BRONJ), and the necessity of additional studies for students. Chi-square test and Cramér's V coefficient were used for the analysis of variables. Most of the fifth-year students knew the main properties of bisphosphonates and what diseases they are used to treat. Twenty fifth-year students (33.9%) knew the accurate definition of BRONJ, while only 11 fourth-year students (22.9%) chose the same correct answer. Statistically significant (P < 0.05) data were found about the knowledge of main properties of bisphosphonates. The vast majority of fourth- and fifth-year students (39 [81.3%] and 45 [76.3%]), agreed that the University should provide more information about bisphosphonates. The study revealed that fifth-year students demonstrated better knowledge about bisphosphonates compared to fourth-year students and this was due to a curriculum supplemented with information about this pathology. The overall findings of this research suggest that Universities need to expand their student curricula by providing more knowledge about bisphosphonates and its relation to bisphosphonate-related osteonecrosis of the jaw.

Awareness of Oral and Medical Healthcare Professionals in the Prevention, Diagnosis, and Management of Bisphosphonate-related Osteonecrosis of the Jaw

Awareness of Oral and Medical Healthcare Professionals in the Prevention, Diagnosis, and Management of Bisphosphonate-related Osteonecrosis of the Jaw

Dental implants in breast cancer patients receiving bisphosphonate therapy

This review article aims to assess the success of dental implants in breast cancer patients receiving bisphosphonate therapy, and to evaluate the risk of developing bisphosphonate related osteonecrosis of the jaw following dental implant surgery.Breast cancer patients undergoing bisphosphonate therapy may receive dental implants. However, the risk of developing BRONJ and implant failure is quite high. Risk factors such as the type of BP received, the route of administration, and the length of treatment prior to surgery should be considered.

Depletion of macrophages deteriorates bisphosphonate-related osteonecrosis of the jaw-like lesions in mice.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a potentially intractable disease with no definitive pathophysiology and no treatment and prevention strategies. This study aimed to investigate whether time-selective depletion of macrophages worsens BRONJ-like lesions in mice. A murine model of high-prevalence BRONJ-like lesions in combination with zoledronate/chemotherapeutic drug administration and tooth extraction was created according to the methods of our previous studies. Daily intra-oral submucosal administration of clodronate-loaded liposomes, which temporarily depletes systemic macrophages, was performed immediately after tooth extraction. Spleens, femora, tibiae, and maxillae were dissected 2weeks after extraction to evaluate BRONJ-like lesions and systemic conditions by micro-computed tomography analysis, histomorphometric and immunofluorescent analyses, and serum chemistry with ELISA. Depletion of macrophages significantly decreased the numbers of local and systemic macrophages and osteoclasts on the bone surface, which markedly worsened osseous healing, with increased necrotic bone and empty lacunae in the existing alveolar bone and newly formed bone in the extraction sockets, and soft tissue healing, with decreased collagen production and increased infiltration of polymorphonuclear cells. Interestingly, the depletion of macrophages significantly shifted macrophage polarization to M1 macrophages through an increase in F4/80+CD38+ M1 macrophages and a decrease in F4/80+CD163+ M2 macrophages, with decreases in the total number of F4/80+ macrophages. These data demonstrated that severe inhibition of osteoclasts in bone tissue and polarization shifting of macrophages in soft tissue are essential factors associated with BRONJ.

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

Electron microscopic analysis of necrotic bone and failed implant surface in a patient with medication-related osteonecrosis of the jaw

BackgroundBisphosphonates (BP), a commonly used medication for various bone diseases, have been known to have severe complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Failure of dental implants has also been found in patients with medication-related osteonecrosis of the jaw (MRONJ). In this study, we analyzed the necrotic bone tissues and the surface of the failed implants removed from the jaw in patients treated with BPs and antiresorptive agents.ResultsChronic inflammatory cells with collagen and fibrous tissues and bone sequestrum were shown at 5.0 × , 10.0 × , 20.0 × , and 40.0 × magnified histologic sections in the bone and fibrotic scar tissues removed from patients with MRONJ due to osteonecrosis. Hardened bone tissues with microcracked bony resorbed lacunae were observed in SEM. Unlike the previously published comparative data where immune cells, such as dendritic cells, were found in the failed implant surface, these immune cells were not identified in the BRONJ-related peri-implantitis tissues through the TEM investigations. Furthermore, EDS revealed that in addition to the main titanium element, gold, carbon, oxygen, calcium, phosphorus, silicon, and sulfur elements were found.ConclusionHardened bone tissues with microcracked bony resorbed lacunae were observed in the SEM findings, which were considered as the main characteristic of the osteonecrosis of the jaw. Immune cells, such as dendritic cells were not identified in the TEM. EDS showed that in addition to the main titanium element, gold, carbon, oxygen, calcium, phosphorus, and silicon elements were found. Furthermore, it was revealed that sulfur was found, which was considered to be one of the complicated causes of implant failure in patients with BRONJ.

Impact of beta-tricalcium phosphate on preventing tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaw in rats

Antiresorptive or antiangiogenic drugs can cause medication-related osteonecrosis of the jaw that is refractory. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) may be caused by procedures such as tooth extraction damage the alveolar bone, release bisphosphonates (BPs) and impede healing. This study investigated strategies for BRONJ prevention and molecular mechanisms of its onset. We assessed the effectiveness of filling extraction sockets with beta-tricalcium phosphate (β-TCP). Rats were administered zoledronic acid (ZA) 1.2 mg/kg once per week for 2 weeks, and a molar was extracted. They were randomly assigned to the β-TCP group (bone defects filled with 0.01 g of β-TCP) or control group. Tissue content measurements indicated 2.2 ng of ZA per socket in the β-TCP group and 4.9 ng in the control group, confirming BP distribution and BP adsorption by β-TCP in vivo. At 4 weeks after extraction, the β-TCP group had normal mucosal coverage without inflammation. Moreover, at 8 weeks after extraction, enhanced bone healing, socket coverage, and new bone formation were observed in the β-TCP group. Connective tissue in the extraction sockets suggested that local increases in BP concentrations may suppress the local autophagy mechanisms involved in BRONJ. Filling extraction sockets with β-TCP may prevent BRONJ.

Effectiveness of acidified electrolyzed water in the prevention of bronj after exodonts: experimental study in wistars rats

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a complication associated with dental intervention and prolonged use of bisphosphonates (BF). Acidified Electrolyzed Water (AEA) is a substance that seems to improve tissue regeneration. To evaluate the effectiveness of (AEA) as an adjuvant in the treatment of BRONJ after lower molar extractions in Wistar rats. A split-mouth study was carried out in twelve Wistar rats (6 females and 6 males) received weekly intravenous injection of 0.3 mL of zoledronate (80 μg/kg in PBS) for 9 weeks and underwent tooth extraction. mandibular first and second molars in the eighth and ninth week, respectively. The Acidified Electrolyzed Water (AAG) group (right side of the mandible) was irrigated with AEA every three days while the control group (CG) (right side of the mandible) received no treatment after extractions. The animals were euthanized 6 weeks after the second extraction, the mandibles were dissected for clinical analysis with the data obtained submitted to statistical analysis with a significance level of 0.05. (Fischer's test). Two males were lost during AEA therapy, leaving 10 animals, 6 females and 4 males. Inflammation was absent in all alveoli; bone sequestration was noted in all alveoli; suppuration was present in 3 sites of the GC group, epithelialization present in 5 GAEA alveoli and 2 GC. Comparison of bone exposure did not show statistically significant results. The results obtained were slightly favorable to the use of AEA, however, without statistical significance.