Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesions; however, the role of individual species in the process of disease development remains elusive. A comprehensive PubMed search was conducted to identify relevant studies on the microbiome of BRONJ patients using the terms "microbiome", "osteonecrosis of the jaws", and "bisphosphonates". Studies focusing on symptoms, epidemiology, pathophysiology, risk factors, and treatment options were included. The principal risk factors for BRONJ are tooth extraction, surgical procedures, and the administration of high doses of bisphosphonates. Importantly, the oral microbiome plays a significant role in the progression of the disease. Several studies have identified alterations of microbial composition in BRONJ lesions. However, there is no consensus regarding bacterial species that are associated with BRONJ across studies. The bacterial genera typically found include Actinomyces, Fusobacterium, and Streptococcus. It is postulated that these microbes contribute to the pathogenesis of BRONJ by promoting inflammation and disrupting normal bone remodeling processes. Current therapeutic approaches are disease-stage-specific and the necessity for more effective treatment strategies remains. This review examines the potential causes of and therapeutic approaches to BRONJ, highlighting the link between microbial colonization and BRONJ development. Future research should seek to more thoroughly investigate the interactions between bisphosphonates, the oral microbiome, and the immune system in order to develop targeted therapies.

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.

Addressing Osteonecrosis: A preventable catastrophe - A multi-center study.

Objectives: To assess the knowledge of medical doctors about osteonecrosis who prescribe radiotherapy and bisphosphonates and dentists who receive these patients with such risk factors. Methods: This cross sectional multicenter study was carried out from 15th October 2021 to 20th November 2021 in different set-ups of Pakistan. A validated and piloted questionnaire was sent to dental and non-dental doctors working in different set-ups of Pakistan through email. All data was analyzed in SPSS version 22 with p value <0.05 being significant. Results: A total of 400 completed responses were received. Only 58% and 67% of the participants were actively educating their patients regarding the hazards of bisphosphonate and radiotherapy, respectively whereas only 45% of the medical doctors referred their patients to dentists before prescribing bisphosphonates and/or radiotherapy. Although the medical doctors had a statistically better knowledge of the definition of osteonecrosis, overall both the dental and non-dental doctors performed poorly regarding answering the questions pertaining to definition, clinical features and risk factors. The dental doctors also showed a poor performance for more technical and in depth questions that was statistically related to lesser work experience, working in a tertiary care facility and previous exposure to such patients. Conclusion: The inadequate awareness of dentists and physicians about the prevention and management of osteonecrosis of jaw is alarming. Efforts should be undertaken to raise the knowledge of dentists and physicians in this regard.

Titanium implant alters the effect of zoledronic acid on the behaviour of endothelial cells.

OBJECTIVES: To evaluate the effect of zoledronic acid (ZA) on human umbilical vein endothelial cells (HUVECs) attached to different surfaces. MATERIALS AND METHODS: A total of three groups were evaluated in this study: sandblasting and acid etching (SLA) + HUVECs; mechanically polished (MP) + HUVECs; and plastic cell culture plates + HUVECs. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, surface roughness and water contact angle were tested for titanium surface characterisation. ZA was added at different concentrations (0, 1, 10, 50 and 100 µM). Cell adhesion, proliferation, viability, apoptosis and gene expression were evaluated. RESULTS: Mechanically polished and SLA surfaces showed negative effects on cell adhesion and proliferation and promoted cell apoptosis with 100 µM ZA (p < .05). The highest expression of intercellular adhesion molecule-1 (ICAM-1) and angiopoietin-1 was found on SLA surfaces (p < .01). The lowest expression of platelet-endothelial cell adhesion molecule-1 and ICAM-1 was found on MP surfaces (p < .05). A significant decrease in von Willebrand factor was detected on MP and SLA surfaces (p < .001). CONCLUSIONS: Zoledronic acid has an anti-angiogenic effect on HUVECs attached to titanium implants, while the SLA surface might stimulate HUVECs to express angiogenic and adhesive factor genes despite ZA treatment.

[Bisphosphonate-related osteonecrosis of the jaws]. / Bisfosfonatnye osteonekrozy chelyustei.

The number of patients with metabolic osteopathies and oncological diseases occurring with the formation of bone metastases is constantly growing and requires special attention not only of oncologists, but also maxillofacial surgeons, dental surgeons and periodontists, due to severe complications from the oral cavity, against the background of antiresorptive therapy with bisphosphonates. These drugs are associated with the development of necrotic processes of the jaw bones and surrounding tissues. It is worth noting the fact that the development of complications after taking these drugs leads to a significant increase in the suffering of patients. The importance of an integrated approach to the treatment and prevention of such complications is extremely important, as it reduces the risk of possible complications and improves the quality of life of this group of patients.

Qualitative and quantitative analysis of the CTX in relation to the period of intake of bisphosphonates: A systematic review.

The aim of this systematic review was to determinate the true value of C-terminal crosslinking telopeptide test (CTX) in patient who takes Bisphosphonate. A comprehensive search of studies published up to March 2020 and listed in the PubMed/MEDLINE and Cochrane Library databases, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. The search identified 99 publications; 6 studies were finally deemed eligible for inclusion according to the study criteria. These studies included a total 104 patients and was selected 101. The CTX value in the various study groups is less than 150 pg/ml. There is a difference between the age of the patient and the period of taking the drug. This systematic review indicates that the CTX test has diffent predictive value in determining the risk of osteonecrosis in patients taking bisphosphonate compared to previus standard.

Current knowledge regarding medication-related osteonecrosis of the jaw among different health professionals.

PURPOSE: To assess the current knowledge regarding medication-related osteonecrosis of the jaw (MRONJ); the adverse effects of anti-resorptive (AR) and anti-angiogenic (AA) drugs; strategies for MRONJ prevention and treatment; and perception of the dentist's role in assisting patients who use these drugs among physicians, dentists, and nurses. METHODS: Using questionnaires, the current knowledge of MRONJ was assessed among dentists, physicians, and nurses, who were divided into group I, which included specialties that directly assist cancer patients, and group II, which included other specialties. The questionnaires assessed the characteristics of the health professionals, training time, and specialties; their knowledge of AR and AA drugs; and their knowledge of MRONJ. RESULTS: A total of 1370 health professionals participated in the study, including 1032 dentists, 239 physicians, and 99 nurses. Among dentists and physicians, the training time (p = 0.036 and p < 0.001, respectively) and specialization in group I domains (p < 0.001 and p < 0.001, respectively) had a significant impact on MRONJ knowledge, while nurses showed no significant impact regardless of the training time and specialty. Less than 10% of the physicians and dentists could correlate the signs and symptoms of all stages of MRONJ. CONCLUSION: The findings indicated a notable lack of knowledge regarding MRONJ among dental surgeons and physicians, and especially among nurses. More experienced professionals and specialists in the areas that assist cancer patients usually have a greater understanding of the dentist's role in MRONJ prevention, diagnosis, treatment, and patient care and will introduce or are already using AR and AA drugs.

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.

Circulating microRNA Panel as a Novel Biomarker to Diagnose Bisphosphonate-Related Osteonecrosis of the Jaw.

There is no defined biomarker for BRONJ diagnosis with satisfactory performance in clinic. In this study, we established the BRONJ model and selected 7 microRNAs as candidate for BRONJ diagnosis from microRNA microarray reported by other research. Dysregulated microRNAs during BRONJ were detected and validated in two independent animal experiments using serum samples. In the first part, serum miR-21, miR-23a and miR-145 were significantly altered in between BRONJ and control group. And an Indice was constructed as -0.032+(0.154×miR-21)+(0.145×miR-23a)+(-0.700×miR-145) using logistic regression model to improve diagnostic performance. The performance of Indice to differentiate BRONJ subjects from control group was analyzed as AUC of 0.82 (95% CI, 0.72-0.92) or 0.85 (95% CI, 0.73-0.97) in the first or second part. Moreover, the predictive performance of Indice to discriminate BRONJ-1w and BRONJ-4w from control group was displayed as AUC of 0.65 (95% CI, 0.47-0.84) or 0.75 (95% CI, 0.60-0.91), which was better than individual circulating microRNAs. In addition, the expressions of candidate microRNAs were validated in human samples. Consequently, we investigated a combined Indice constructed with circulating microRNAs for BRONJ diagnosis and prediction.

The Effects of Kaempferol-Inhibited Autophagy on Osteoclast Formation.

Kaempferol, a flavonoid compound, is derived from the rhizome of Kaempferia galanga L., which is used in traditional medicine in Asia. Autophagy has pleiotropic functions that are involved in cell growth, survival, nutrient supply under starvation, defense against pathogens, and antigen presentation. There are many studies dealing with the inhibitory effects of natural flavonoids in bone resorption. However, no studies have explained the relationship between the autophagic and inhibitory processes of osteoclastogenesis by natural flavonoids. The present study was undertaken to investigate the inhibitory effects of osteoclastogenesis through the autophagy inhibition process stimulated by kaempferol in murin macrophage (RAW 264.7) cells. The cytotoxic effect of Kaempferol was investigated by MTT assay. The osteoclast differentiation and autophagic process were confirmed via tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, western blot, and real-time PCR. Kaempferol controlled the expression of autophagy-related factors and in particular, it strongly inhibited the expression of p62/SQSTM1. In the western blot and real time-PCR analysis, when autophagy was suppressed with the application of 3-Methyladenine (3-MA) only, osteoclast and apoptosis related factors were not significantly affected. However, we found that after cells were treated with kaempferol, these factors inhibited autophagy and activated apoptosis. Therefore, we presume that kaempferol-inhibited autophagy activated apoptosis by degradation of p62/SQSTM1. Further study of the p62/SQSTM1 gene as a target in the autophagy mechanism, may help to delineate the potential role of kaempferol in the treatment of bone metabolism disorders.

Current management concepts for bisphosphonate-related osteonecrosis of the jaw: a review.

Bisphosphonate (BP) drugs are used to preserve bony tissue in patients diagnosed with osteoporosis and metastatic bone disease. However, these drugs are associated with rare but serious complications. The most commonly encountered adverse effect is bisphosphonate-related osteonecrosis of the jaw (BRONJ). Diagnosis and treatment of teeth that are likely to cause infection and the replacement or adjustment of dentures or restorations that could lead to trauma are the key steps that can be taken before the initiation of BP therapy in order to prevent the development of BRONJ. To date, the most efficacious management approach for BRONJ has not been clearly established. This article presents current approaches for the treatment of BRONJ, including conservative drug therapy and surgical therapy, and discusses new treatment modalities.

Efficacy of laser therapy in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ): a systematic review.

Bisphosphonate-related osteonecrosis of the jaw is a well-known potential side effect of long-term bisphosphonate therapy; the primary objective of the treatment should be to improve patient quality of life through pain and infection management, to prevent the development of new lesions, and to slow disease progression. In recent years, the use of laser for bisphosphonate-related osteonecrosis of the jaw has become more widespread, due to its use of administration and widely reported beneficial effects on tissue healing. The present systematic review of the literature sought to elucidate whether low-level laser therapy has positive effects on the treatment of bisphosphonate-related osteonecrosis of the jaw. We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library electronic databases, with no restrictions on language or year of publication. Search strategies were formulated using keywords and Boolean operators. The electronic search strategy retrieved 55 records. From 55 articles, 16 were selected for full-text review, and of these, 10 were ultimately included for data analysis in this review. Our findings show that treatment modalities including laser were associated with superior outcomes in terms of cure or improvement of bisphosphonate-related osteonecrosis of the jaw lesions as compared with conventional surgical and/or conservative drug therapy. It can be concluded that combined treatment with antibiotics, minimally invasive surgery (including Er:YAG laser surgery), and low-level laser therapy in the early stages of the disease should be the gold standard for bisphosphonate-related osteonecrosis of the jaw management.

Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model. MATERIALS AND METHODS: Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison. RESULTS: Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 %) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30-80 µm); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05). CONCLUSION: Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ. CLINICAL RELEVANCE: Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.

Altered macrophagic THP-1 cell phagocytosis and migration in bisphosphonate-related osteonecrosis of the jaw (BRONJ).

OBJECTIVES: Local immune dysfunction via macrophages is a proposed aetiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study aimed to clarify the effects of various bisphosphonates on macrophage function using a THP-1 monocytic model to examine migration, phagocytosis, and fibrin structure. MATERIALS AND METHODS: THP-1 cell migration was measured in the presence and absence of zoledronate, ibandronate, risedronate, alendronate, pamidronate (0.5, 5 and 50 µM) and clodronate (125, 250 and 500 µM) using the real-time xCELLigence system. Phagocytosis and actin fibre assays were performed after 72 h with zoledronate, ibandronate, alendronate and clodronate. RESULTS: Time to maximum migration for THP-1 cells was significantly reduced (p < 0.05) for high dosages of zoledronate, ibandronate and alendronate compared to controls. All dosages of clodronate and a low dose of zoledronate exhibited prolonged migrations. Phagocytic capacity was significantly reduced in high dosages of all bisphosphonates and for 5 µM zoledronate and ibandronate (p < 0.05). Low bisphosphonate exposure was accompanied by overcharged phagosoms. Altered appearance in F-actin fibrin structure was observed in bisphosphonate-exposed cells. CONCLUSIONS: All bisphosphonates altered the migration of THP-1 cells dose-dependently. Low doses also prolonged migration and altered cell morphology. These findings support the idea of a disturbed local immune function of macrophages even in jaw bone exposed to low concentrations of bisphosphonate. CLINICAL RELEVANCE: These are the first real-time results for disrupted migration and function of macrophagic THP-1 cells in high doses. Low dosages also demonstrated altered macrophage phagocytosis and cell morphology, suggesting a disturbed local immune function in BRONJ pathogenesis.

The effects of bisphosphonate on the remodeling of different irregular bones in mice.

BACKGROUND: We aimed to compare the effects of bisphosphonate on the remodeling of irregular bones (the jaw and ilium) in mice after trauma. METHODS: To verify the feasibility of modeling osteonecrosis, 20 mice were injected intraperitoneally with zoledronate and dexamethasone (ZOL&DEX group), dexamethasone (DEX group), or phosphate-buffered saline (PBS) [control (CTR) group]. Mice then underwent extraction of the right maxillary first molar and creation of an artificial bony cavity in the ilium. Bone sections were stained with H&E for morphological studies. To further compare differences between the maxilla and the ilium caused by similar traumas, 80 mice were injected intraperitoneally with ZOL&DEX or PBS. Pathological progression at the injury sites was assessed at 1 day and at 1, 3, and 8 weeks after trauma using micro-computed tomography (CT), H&E and immunohistochemistry analyses, high-performance liquid chromatography-mass spectrometry, and enzyme-linked immunosorbent assay. RESULTS: Only the ZOL&DEX model group effectively developed osteonecrosis. Bony sequestra, osseous sclerosis, unhealed mucosa, and radiopaque alveolar bone were found in the maxilla. In the ilium, there was a lower frequency of osteonecrotic disease and osseous sclerosis, and less suppression of bone remodeling than in the maxilla following long-term bisphosphonate administration. Zoledronate levels were higher in the maxilla. ZOL&DEX treatment suppressed the levels of RANKL and IL-17, but induced an upregulation of osteoprotegerin and FAM20C in both bones. CONCLUSION: Accumulation of bisphosphonate may increase the incidence of osteonecrosis. The RANKL/OPG pathway and IL-17 and FAM20C cytokines play key roles in the progression of pathologically abnormal bone remodeling.

An osteonecrosis model induced by oral bisphosphonate in ovariectomised rats.

OBJECTIVE: To develop a model of osteonecrosis using oral bisphosphonate in ovariectomy-induced osteoporotic rats. MATERIALS AND METHODS: Thirty-six rats were subjected to ovariectomy or sham surgery. After 8 weeks, rats received oral alendronate (1.0 mg kg(-1) ) or saline once weekly for 4 weeks; then, serum C-telopeptide cross-linked collagen type I levels were measured to evaluate bone metabolism. Twelve rats from each group were injected with either lipopolysaccharide or saline into the bone marrow of the mandibles and femurs, and the areas of osteonecrosis were evaluated by histomorphometry. RESULTS: Serum C-telopeptide cross-linked collagen type I levels were significantly increased in the ovariectomy group (105.1 ± 2.1 ng ml(-1) ) compared with the sham group (78.9 ± 12.5 ng ml(-1) ); they were significantly reduced following oral alendronate administration in the ovariectomy group (91.0 ± 4.4 ng ml(-1) ). Following alendronate and lipopolysaccharide administration, extensive osteonecrosis was observed in the mandibles and femurs of ovariectomy (0.45 ± 0.08 mm(2) , 1.69 ± 0.72 mm(2) , respectively) and sham (1.12 ± 0.45 mm(2) , 1.84 ± 0.66 mm(2) , respectively) groups. Significantly wider osteonecrosis occurred in the mandibles of sham-operated rats than ovariectomy rats following alendronate or lipopolysaccharide treatment. CONCLUSIONS: We successfully developed a model of osteonecrosis in ovariectomised rats following oral bisphosphonate administration.

Genetic association between VEGF polymorphisms and BRONJ in the Korean population.

OBJECTIVES: The purpose of this study was to evaluate the association between vascular endothelial growth factor (VEGF) polymorphisms and bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the Korean population. SUBJECTS AND METHODS: Forty-five individuals (2 men, 43 women; mean age: 68.7 ± 12.3 years) were recruited for this study. All visited the Yonsei University Dental Hospital for surgical intervention from January 2012 to January 2013 and had a history of bisphosphonate (BP) administration (oral and/or intravenous). Patients were allocated to case (n = 26) or control (n = 19) groups according to the patients' selection criteria. Association between three VEGF single nucleotide polymorphisms (rs699947 (-2578 C>A), rs2010963 (-634 G>C) and rs3025039 (+936 C>T)) and BRONJ were investigated using multiple logistic regression analysis and Fisher's exact test where appropriate (α = 0.05). RESULTS: The CC homozygotes of rs2010963 and rs3025039 of VEGF gene were associated with an increased risk of BRONJ (P = 0.04, 0.03, respectively). In haplotype analysis, no differences in haplotype C-C (-2578/-634) and haplotype C-C-C (-2578/-634/+936) were observed. CONCLUSION: The CC homozygotes of rs2010963 and rs3025039 polymorphisms in the VEGF gene were associated with an increased risk of BRONJ in the Korean population. Further epidemiological cohort studies with a larger sample size would be required to confirm the suggestive correlations.

Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVE: The objective of this study was to identify differentially expressed salivary proteins in bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients that could serve as biomarkers for BRONJ diagnosis. SUBJECTS AND METHODS: Whole saliva obtained from 20 BRONJ patients and 20 controls were pooled within groups. The samples were analyzed using iTRAQ-labeled two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: Overall, 1340 proteins were identified. Of these, biomarker candidates were selected based on P-value (<0.001), changes in protein expression (≥1.5-fold increase or decrease), and unique peptides identified (≥2). Three comparisons made between BRONJ and control patients identified 200 proteins to be differentially expressed in BRONJ patients. A majority of these proteins were predicted to have a role in drug metabolism and immunological and dermatological diseases. Of all the differentially expressed proteins, we selected metalloproteinase-9 and desmoplakin for further validation. Immunoassays confirmed increased expression of metalloproteinase-9 in individual saliva (P = 0.048) and serum samples (P = 0.05) of BRONJ patients. Desmoplakin was undetectable in saliva. However, desmoplakin levels tended to be lower in BRONJ serum than controls (P = 0.157). CONCLUSIONS: Multiple pathological reactions are involved in BRONJ development. One or more proteins identified by this study may prove to be useful biomarkers for BRONJ diagnosis. The role of metalloproteinase-9 and desmoplakin in BRONJ requires further investigation.

Management of bisphosphonate-related osteonecrosis of the jaw: a literature review.

Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non-bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high-dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. As treatment protocols based on randomized controlled trials (RCTs) do not exist, we critically reviewed the existing data concerning the management of bisphosphonate-related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen.

Immediate Implant Placement in a Patient With Osteoporosis Undergoing Bisphosphonate Therapy: 1-Year Preliminary Prospective Study.

The purposes of this preliminary study are to assess the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a patient with osteoporosis using zoledronic acid and to report the results of a 1-year prospective clinical study regarding 5 immediately inserted implants in the anterior mandible. For this comparative prospective study, 24 female patients, aged ≥54 years, were chosen, all with partially edentulous mandibles. Group A consisted of 12 patients with osteoporosis taking zoledronic acid receiving a once-yearly intravenous infusion of zoledronic acid (5 mg). Control group B consisted of 12 other patients without osteoporosis and not taking drugs. In both groups, the remaining teeth were extracted before 120 implants, 3.7-mm wide and 16-mm long, were immediately installed in the interforaminal region of the mandibles. The 1-year implant survival rate was 100%. No apparent necrotic bone was observed among patients receiving zoledronic acid (group A) after implant surgery. Immediate implant osseointegration can be successful in a patient with osteoporosis using bisphosphonates, suggesting the safety of implantology as a treatment modality.