Treatment Of Bisphosphonate-related Osteonecrosis Of The Jaw Research Articles

Major aspects of the use of bisphosphonates and the formation of osteonecrosis in the involvement of dental implants: a systematic review

Introduction: Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. Dental patients receiving bisphosphonate treatment are at higher risk of bisphosphonate-related osteonecrosis of the jaws (BRONJ), necessitating dentists' awareness of these risks. Objective: It was to highlight the main aspects of the use of bisphosphonates and the formation of osteonecrosis in the involvement of dental implants, as well as possible treatments. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from April to July 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 120 articles were found, 40 articles were evaluated in full and 15 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 14 studies with a high risk of bias and 21 studies that did not meet GRADE and AMSTAR-2. Most studies did not show homogeneity in their results, with X2=89.5%>50%. Therefore, the present study suggests that patients undergoing treatment with BFs should be informed about the potential risk of BRONJ. Furthermore, it would be advisable for providers responsible for BF therapy to refer patients for dental check-ups before starting treatment, allowing for patient monitoring by a multidisciplinary team. Although the morbidity rate of this pathology is not high, prevention should be mandatory, thus avoiding mutilating and painful processes. However, if surgery is necessary, the use of these new adjuvant therapies, such as lowlevel laser therapy and magnetotherapy, can be proposed in the treatment of BRONJ. It is essential to increase our caseload and also involve other institutions in the use of these new effective and safe therapies in 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.

Identification of Potential Biomarkers and Small Molecule Drugs for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ): An Integrated Bioinformatics Study Using Big Data.

This study aimed to identify potential molecular mechanisms and therapeutic targets for bisphosphonate-related osteonecrosis of the jaw (BRONJ), a rare but serious side effect of bisphosphonate therapy. This study analyzed a microarray dataset (GSE7116) of multiple myeloma patients with BRONJ (n = 11) and controls (n = 10), and performed gene ontology, a pathway enrichment analysis, and a protein-protein interaction network analysis. A total of 1481 differentially expressed genes were identified, including 381 upregulated and 1100 downregulated genes, with enriched functions and pathways related to apoptosis, RNA splicing, signaling pathways, and lipid metabolism. Seven hub genes (FN1, TNF, JUN, STAT3, ACTB, GAPDH, and PTPRC) were also identified using the cytoHubba plugin in Cytoscape. This study further screened small-molecule drugs using CMap and verified the results using molecular docking methods. This study identified 3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl) methoxy) phenyl) propanoic acid as a potential drug treatment and prognostic marker for BRONJ. The findings of this study provide reliable molecular insight for biomarker validation and potential drug development for the screening, diagnosis, and treatment of BRONJ. Further research is needed to validate these findings and develop an effective biomarker for BRONJ.

A multifunctional composite hydrogel promotes treatment of bisphosphonate-related osteonecrosis of the jaws

The growing use of bisphosphonates (BPs) is a great challenge to the treatment of bisphosphonate-related osteonecrosis of the jaws (BRONJ), however effective treatment methods are currently lacking. Here, modified citraconic amide-functionalized chitosan (CAS) was selected to encapsulate the zeolite imidazolate framework 8 (ZIF-8) loaded with gold nanoparticles (Au NPs) to prepare Au@ZIF-8/CAS. Characterizations confirmed the successful synthesis of Au@ZIF-8/CAS. Mass spectrometry-based metabolomics detected the effects of Au@ZIF-8/CAS on significant metabolic pathways of macrophages in the presence of zoledronic acid (ZA). Twenty-three candidate key metabolites were identified, mainly focusing on the phenylalanine/tyrosine/tryptophan biosynthetic metabolic pathway in the amino acid metabolic pathway. In vitro experiments further confirmed that Au@ZIF-8/CAS could promote the polarization of macrophages from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype, so as to produce a good immune microenvironment. In the co-culture system, Au@ZIF-8/CAS could also promote the expression of alkaline phosphatase (ALP), Osteocalcin (OCN), and Runt-related transcription factor 2 (Runx2), and synergistically increased the osteogenic differentiation ability of MC3T3-E1 cells through immunomodulatory effects and direct osteogenic stimulation. Furthermore, the antibacterial properties of Au@ZIF-8/CAS were also investigated. In vivo experiments further verified the potential role of Au@ZIF-8/CAS in treatment of BRONJ. These results will provide new directions and ideas for the treatment of inflammatory diseases.

Treatment of Apical Periodontitis Induced BRONJ with Endodontic Treatment

Bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is one of the serious side effects of bisphosphonates, has an increasing clinical importance due to the widespread use of bisphosphonates in the treatment of many diseases such as osteoporosis, osteopenia, Paget's disease, osteogenesis imperfecta, and multiple myeloma. BRONJ can spontaneously develop in the jawbones. In addition, many factors such as tooth extraction, periodontal diseases, and local trauma can trigger BRONJ. In our case, it was detected that the lesion appearing like BRONJ in the left lower jaw of the 67-year-old female patient with a history of oral bisphosphonate use developed due to apical periodontitis resulting from the tooth numbered 34. Root canal treatment was administered to the relevant tooth of the patient, the fistula tract was closed after this treatment, and as a result of the CBCT examination, it was observed that the enlargement in the necrotic bone area stopped. In addition, the patient's complaints about the relevant tooth disappeared. As a result, endodontic treatment is an effective treatment approach in the treatment of BRONJ developing due to apical periodontitis. In order to avoid the risk of BRONJ, a detailed oral examination should be performed before starting the bisphosphonate treatment, and necessary endodontic, restorative and periodontal treatments should be followed.

Geranylgeraniol Restores Zoledronic Acid-Induced Efferocytosis Inhibition in Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe side effect of long-term administration of bisphosphonates such as zoledronic acid (ZA), but its pathogenesis remains unclear. Impairment of the clearance of apoptotic cells (termed “efferocytosis”) by ZA may be associated with the pathogenesis of BRONJ. The aim of this study was to investigate whether ZA might inhibit macrophage efferocytosis and promote osteocytic apoptosis, and the underlying mechanisms responsible for the disturbing balance between clean and generation of osteocytic apoptosis. We found that ZA significantly promoted the apoptosis of osteocyte and pre-osteoblast via BRONJ mouse models and in vitro MC3T3-E1 but also inhibited the efferocytosis of macrophage on apoptotic cells. Moreover, supplement with geranylgeraniol (GGOH), a substrate analog for geranylgeranylation of Rac1, could restore Rac1 homeostasis and rescue macrophage efferocytosis. GGOH partially inhibits MC3T3-E1 apoptosis induced by ZA via downregulation of Rac1/JNK pathway. We also examined the Rac1 distribution and activation conditions in bone marrow-derived macrophages (BMDMs) and MC3T3-E1 under ZA treatment, and we found that ZA impaired Rac1 migration to BMDM membrane, leading to round appearance with less pseudopodia and efferocytosis inhibition. Moreover, ZA simultaneously activated Rac1, causing overexpression of P-JNK and cleaved caspase 3 in MC3T3-E1. Finally, the systemic administration of GGOH decreased the osteocytic apoptosis and improved the bone healing of the extraction sockets in BRONJ mouse models. Taken together, our findings provided a new insight and experimental basis for the application of GGOH in the treatment of BRONJ.

Osteoradionecrosis and bisphosphonate-related osteonecrosis of the jaw: a review of the pathogenesis and treatment

Osteoradionecrosis of the jaw (ORNJ) and bisphosphonate-related osteonecrosis of the jaw (BRONJ) are usually caused by head and neck radio-therapy and by the usage of bisphosphonate, respectively. These diseases can lead to facial deformity and dysfunction of the mandible, and may cause severe chronic facial pain. The pathogenesis of ORNJ and BRONJ are complex, and the therapy of which is still challenged. The present article reviewed the latest literature about the pathogenesis and treatment of ORNJ and BRONJ were reviewed for update. The irradiation may damage the endothelia cells and microvessels in jaw bone, which leads to the termination of the bone remodeling 15 days after irradiation. Mesenchymal stem cells based bio-therapy can assist the recovery of mandibular circulation and the reconstruction of the bone, showing therapeutic potential for ORNJ clinical treatment. Bisphosphonate can induce the dysfunction of bone marrow mesenchymal stem cells and the immune imbalance of the body. Allogeneic mesenchymal stem cells transplantation can rebuild the jaw bone and rebalance the immune of the recipient, demonstrating the ideally potential for the treatment of BRONJ. Taking together, although it would be complicated and winding, the improvement of biotech and the usage of mesenchymal stem cells shed a light on the way of ORNJ and BRONJ treatments.

Application of a collagen scaffold saturated with platelet-rich plasma in prevention of bisphosphonate-related osteonecrosis of the jaw in the rat animal model

BackgroundAmong the myriad adverse events of drugs in the oral cavity, Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most detrimental drug reactions that have ever been known. ObjectiveThis study was aimed to investigate the success of applying collagen scaffold alone and platelet-rich plasma (PRP)+collagen scaffold in prevention of zoledronic acid-induced BRONJ in the rat. MethodsA total of 17 male Wistar-rats were treated with 4 weekly doses of zoledronic acid. All rats were undergone bilateral tooth extraction of mandibular first molars and divided into three groups of scaffold + PRP + suture, scaffold + suture, and suture only. All rats were scarified and clinical, radiological, histological and histomorphomerical evaluations were made on week 8 post-treatment. The soft tissue healing, bone mineralized density (BMD), number of osteoclasts and osteoblasts, necrotic bone (NB), intensity of inflammation and new bone formation (NBF) were analyzed. ResultsBMD, number of osteoblasts and NBF variables proved to be statistically were higher in the treatment groups than the control group. In addition, the PRP + scaffold group showed the better results in terms of BMD, number of osteoblasts and NBF than that of the scaffold alone group. Number of osteoclasts, inflammation intensity and osteonecrosis were also significantly different in the PRP + scaffold group compared to the scaffold alone and the control groups. ConclusionApplication of a PRP-enriched collagen scaffold appeared to be a successful preventive treatment for BRONJ by effecting of the number of osteoblasts and osteoclasts, BMD, NBF, inflammation, and osteonecrosis.

Bisphosphonate-associated osteonecrosis of the jaw.

The purpose of this systematic review was to determine the possible risk factors related to pathophysiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and identify adequate treatment strategies available and success rates. We performed a search for publications about the treatment of BRONJ, published between 2003 and 2018 in the PubMed/Medline data base using the key words: "Bisphosphonate-Associated Osteonecrosis of the Jaw" OR "Bisphosphonate Osteonecrosis" OR "BRONJ", based on the list of MeSH and DeCS. According to pre-established criteria for data collection concerning the treatment of BRONJ, we found 19 articles covering a total of 400 patients. Treatments that showed good outcomes were Ozone, PRF, PRP/Debridement/Laser bio-stimulation, Laser surgery and Laser surgery/Laser bio-stimulation. HBO did not achieve good results and was used in only 10 patients. BRONJ is a rare condition in patients with osteoporosis/other pathologies using BP orally. These patients had long exposure time and cumulative doses of BPs until onset of the lesion. The oncological patients were exposed to more potent intravenously administered BPs such as pamidronate and zoledronate. These patients had a shorter exposure time until onset of the lesion. The treatment of BRONJ is still under debate and there are promising treatments that need randomized trials with larger numbers of patients to confirm their results. Patients receiving BPs or those who will start treatment should be encouraged to perform preventive dental treatment and maintain good oral hygiene.

Interdisciplinary Management of Bisphosphonate-Related Osteonecrosis of the Jaw

Bisphosphonate (BP) Related Osteonecrosis of the Jaw (BRONJ) is one of the frequently occurring adverse reaction of BP intake, which is indicated in management of osteoporosis, Paget disease, multiple myeloma, and hypercalcemia in malignancies. The risk of osteonecrosis of the jaw relates to dose and duration of the therapy and the route of administration (i.e. more often BRONJ occurs in patients undergoing intravenous BPs therapy). At present, the management of BRONJ is a dilemma. No effective treatment has yet been developed. There is currently no gold standard of treatment for BRONJ. However, nowadays new alternative methods appear to be a promising modality of BRONJ treatment in early stages of the disease, while being safe and welltolerated, i.e. hyperbaric therapy, ozone therapy, use of platelet rich fibrine and platelet rich plasma, photodynamic therapy, low level laser therapy.

Soft Tissue Coverage with Submental Flap in Massive Medication-Related Osteonecrosis of the Mandible

Intravenous Bisphosphonates (BPs) are used to treat cancer-related conditions, including hyperkalemia of malignancy, Skeletal-Related Events (SREs) associated with bone, and for management of lytic lesions in the setting of multiple myeloma. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is a severe complication of BPs, which affects the patient's quality of life. In the treatment of BRONJ, soft tissue coverage for coverage of the debrided bone is essential. In severe soft tissue deficiency, the use of local or distant soft tissue flap is necessary this case report; a massive BRONJ was described in which a submental flap was used to cover the mandibular bone.

Bisphosphonate-associated osteonecrosis of the jaw: systematic review

Objective The purpose of this systematic review was to determine the possible risk factors related to pathophysiology of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) and identify adequate treatment strategies available and success rates. Evidence acquisition We performed a search for publications about the treatment of BRONJ, published between 2003 and 2018 in the PubMed/Medline data base using the key words: 'Bisphosphonate-Associated Osteonecrosis of the Jaw' OR 'Bisphosphonate Osteonecrosis' OR 'BRONJ', based on the list of MeSH and DeCS. Evidence synthesis According to preestablished criteria for data collection concerning the treatment of BRONJ, we found 19 articles covering a total of 400 patients. Treatments that showed good outcomes were Ozone, PRF, PRP/Debridement/Laser bio-stimulation, Laser surgery and Laser surgery/Laser bio-stimulation. HBO did not achieve good results and was used in only 10 patients. BRONJ is a rare condition in patients with osteoporosis/other pathologies using BP orally. These patients had long exposure time and cumulative doses of BPs until onset of the lesion. The oncological patients were exposed to more potent intravenously administered BPs such as pamidronate and zoledronate. These patients had a shorter exposure time until onset of the lesion. Conclusions The treatment of BRONJ is still under debate and there are promising treatments that need randomized trials with larger numbers of patients to confirm their results. Patients receiving BPs or those who will start treatment should be encouraged to perform preventive dental treatment and maintain good oral hygiene.

Tetrahedral Framework Nucleic Acid Promotes the Treatment of Bisphosphonate-Related Osteonecrosis of the Jaws by Promoting Angiogenesis and M2 Polarization.

Bisphosphonates are often used to treat osteoporosis, malignant bone metastases, and hypercalcemia. However, it can cause serious adverse reactions, bisphosphonate-related osteonecrosis of the jaw (BRONJ), which seriously affects the quality of life of patients. At present, the treatment of BRONJ is still difficult to reach an agreement, and there is no effective treatment. Therefore, it is very important to find effective treatments. Many studies have shown that the occurrence of BRONJ may be due to unbalanced bone turnover, anti-angiogenesis, bacterial infection, direct tissue toxicity, and abnormal immune function. The previous research results show that tetrahedral framework nucleic acids (tFNAs), a new type of nanomaterial, can promote various biological activities of cells, such as cell proliferation, migration, anti-inflammation and anti-oxidation, and angiogenesis. Therefore, we intend to explore the potential of tFNAs in the treatment of BRONJ through this study. The results show that tFNAs can promote the treatment of BRONJ by promoting angiogenesis and promoting M2 polarization in macrophages and inhibiting M1 polarization both in vitro and in vivo. These results provide a theoretical basis for the application of tFNAs in the treatment of BRONJ and also provide new ideas and methods for the treatment of other diseases based on ischemia and immune disorders.

Treatment of BRONJ with ozone/oxygen therapy and debridement with piezoelectric surgery.

Bisphosphonate related osteonecrosis of the jaw (BRONJ) is progressive bone destruction in the maxillofacial region of patients under current or previous treatment with Bisphosphonates. The present case series study aimed to evaluate if ozone/oxygen therapy and debridement with piezoelectric surgery may improve the treatment of BRONJ. The treatment modality of the patients included ozone/oxygen mixture from medical oxygen. The protocol for ozone/oxygen mixture therapy appointments was set as twice a week for 10 weeks, for a total of 20 applications for each patient. The evaluation of the lesions was based on the clinical and radiologic parameters. The primary outcome was the necrotic lesion reduction during ozone/oxygen therapy sessions and up to the end of follow up periods. The healing of the lesion was taken as a positive result. The level of significance was taken as p <0.05. A total of 14 patients affected by osteonecrosis were included. The mean follow-up of the patients was 14.3 months. The overall success rate after treatment was 64.2%. According to the results, ozone/oxygen therapy and debridement with Piezoelectric surgery for BRONJ treatment is a safe procedure with successful outcomes.

Zoledronic acid regulates the synthesis and secretion of IL-1\u03b2 through Histone methylation in macrophages

Long-term administration of nitrogen-containing bisphosphonates increases the risk of detrimental side effects, such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). BRONJ development is associated with inflammation, but its pathophysiology remains unknown. Here, we examined whether histone methylation is responsible for zoledronic acid (Zol)-induced inflammatory responses. We found that Kdm6a and Kdm6b markedly increased interleukin 1β expression and Gasdermin D cleavage, which are both activated by Caspase 1, in macrophages. Inhibitors of Kdm6a and Kdm6b robustly abolished Zol-enhanced interleukin 1β synthesis and secretion from macrophages. When Kdm6a and Kdm6b were pharmacologically inhibited in vivo, poor healing of the alveolar socket and inflammatory responses were ameliorated in Zol-treated mice. Taken together, we showed the pathologic role of Kdm6a and Kdm6b in Zol-promoted inflammatory responses and demonstrated that Kdm6a and Kdm6b are potential therapeutic targets for the treatment of BRONJ.

Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate treatment. Zoledronic acid (ZA) is a commonly used bisphosphonate due to its effectiveness in increasing bone density and reducing skeletal events, with evidence that it alters angiogenesis. Replacement of the mevalonate pathway using geranylgeraniol (GGOH) was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts. Osteoclast cultures were generated from peripheral blood mononuclear cells of three patients using the peripheral blood mononuclear cell isolation. These cells were phenotyped by phase-contrast microscopy, tartrate-resistant acid phosphatase staining, and pit assays. Primary osteoclasts were found to express a number of key angiogenic molecules at very high levels. Gene expression levels for 84 human angiogenic factors were determined using PCR arrays. Three genes with significant fold regulation (FR) in response to ZA were as follows: tumor necrosis factor (FR = +2.57, P = 0.050), CXCL9 (FR = +39.48, P = 0.028), and CXCL10 (FR = +18.52, P = 0.0009). The co-addition of geranylgeraniol with ZA resulted in the significant down-regulation of these three genes along with CCL2, TGFBR1, ENG, and CXCL1. GGOH reversed the gene changes induced by ZA and may offer a promising treatment for BRONJ.

Adipose-derived stem cells prevent the onset of bisphosphonate-related osteonecrosis of the jaw through transforming growth factor \u03b2-1-mediated gingival wound healing

BackgroundDue to its complex pathogenesis and low clinical cure rate, bisphosphonate-related osteonecrosis of the jaw (BRONJ) poses a substantial challenge for oral and maxillofacial surgeons. Therefore, the treatment of BRONJ should focus on prevention. In clinical studies, primary wound closure can significantly reduce the incidence of BRONJ. Whether local stem cell transplantation can promote primary gingival healing in patients with a medication history and prevent BRONJ has not been reported.MethodsIn this study, animals were divided into a healthy group (non-drug treatment), a BP group, a hydroxyapatite (HA) group, and an adipose-derived stem cell (ADSC) group. All groups except the healthy group were treated with BPs and immunosuppressive drugs once per week for 8 weeks, simulating clinical use for the treatment of cancer patients with bone metastasis, to induce BRONJ-like animals. After the sixth drug treatment, the bilateral premolars were extracted in all groups. In contrast to the healthy and BP groups, the extraction sockets in the HA and ADSC groups were filled with HA or HA + ADSCs simultaneously post extraction to observe the preventive effect of ADSCs on the occurrence of BRONJ. At 2 and 8 weeks post extraction, animals from all groups were sacrificed.ResultsAt 8 weeks post transplantation, ADSCs prevented the occurrence of BRONJ, mainly through accelerating healing of the gingival epithelium at 2 weeks post extraction. We also found that ADSCs could upregulate the expression of transforming growth factor β1 (TGF-β1) and fibronectin in tissue from animals with a medication history by accelerating gingival healing of the extraction socket. A rescue assay further demonstrated that TGF-β1 and fibronectin expression decreased in TGF-β1-deficient ADSC-treated animals, which partially abolished the preventive effect of ADSCs on the onset of BRONJ.ConclusionADSCs prevent the onset of BRONJ, mainly by upregulating the expression of TGF-β1 and fibronectin to promote primary gingival healing, ultimately leading to bone regeneration in the tooth extraction socket. Our new findings provide a novel stem cell treatment for the prevention of BRONJ.

Novel insight into the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

SummaryBisphosphonate-related osteonecrosis of the jaw (BRONJ), characterized by refractory bone exposure, has recently emerged as a serious side effect of bisphosphonate (BPs) treatment. We discuss novel insights that may help to improve the efficacy of BRONJ treatment and prevention. Our report highlights the following: (1) The presence of exposed bone in patients taking BPs does not necessarily reflect BRONJ, and diagnoses of oral ulceration with bone sequestration and malignancy must be excluded. (2) Osteonecrosis type of BRONJ is difficult to avoid using preventive dental measures alone. However, as with osteomyelitis type of BRONJ, preventive dental measures are indispensable for reducing the risk of secondary infection and disease progression. (3) The importance of tooth extraction as a risk factor for BRONJ among patients taking BPs has been overstated, particularly when they are administered at low doses. Delaying tooth extraction may increase the risk for the onset and progression of osteomyelitic BRONJ. (4) In patients taking low doses of BPs, dental implant surgery is not necessarily contraindicated if there are no other risk factors, such as combined use of corticosteroids or concomitant diabetes. However, the risk of BRONJ due to peri-implantitis must be explained when obtaining patient consent.

The Effect of Polydeoxyribonucleotide Extracted from Salmon Sperm on the Restoration of Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonates (BPs) used for treating skeletal diseases can induce bisphosphonate-related osteonecrosis of the jaw (BRONJ). Despite much effort, effective remedies are yet to be established. In the present study, we investigated the feasibility of polydeoxyribonucleotide (PDRN) extracted from salmon sperm for the treatment of BRONJ, in a BRONJ-induced rat model. Compared with BRONJ-induced samples, PDRN-treated samples exhibited lower necrotic bone percentages and increased numbers of blood vessels and attached osteoclast production. Moreover, local administration of PDRN at a high concentration (8 mg/kg) remarkably resolved the osteonecrosis. Findings from this study suggest that local administration of PDRN at a specific concentration may be considered clinically for the management of BRONJ.

Photochemical-Associated Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw: a Case Report

Laser therapy and photochemical treatment variations in bisphosphonate-related osteonecrosis of the jaw (BRONJ) management are more widespread, considering the possibility of generating oxidative stress and biomodulation of inflammatory factors. Unfortunately, there is no gold standard treatment for BRONJ. To suggest alternative treatment, we describe the case of a 79-year-old man presenting with a lower jaw bone exposure for 3 months, owing to a tooth extraction, and previous medical history of prostate cancer treated with goserelin acetate (Zoladex LA 10.8 mg) and zoledronic acid (Zometa 4 mg), 2 years ago. Methylene blue (0.05%) with red laser (660 nm, 90 J/cm2) were applied on the necrotic areas; the necrotic bone fragments were removed, and low-level laser therapy protocol (780 nm, 7.5 J/cm2 and 660 nm, 7.5 J/cm2) was applied once a week. Satisfactory clinical aspect after 2 sessions and no signs of relapse were observed within the 6 months of patient monitoring.