Bisphosphonate-associated Osteonecrosis Research Articles

Occurrence of bisphosphonate-associated osteonecrosis of the jaws in individuals with rheumatoid arthritis - a systematic review.

To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA). Observational studies that evaluated the occurrence of BAONJ in individuals with RA (BAONJ-RA) were considered for inclusion. Electronic searches were performed up to December 2022 in six databases and in the grey literature. The study selection, data extraction, and quality assessment of the included studies according to the Joanna Briggs Institute Critical Appraisal Checklists was performed. The certainty of evidence was evaluated using the GRADE approach. Five studies were included three cohort and two cross-sectional. The sample size of subjects with RA ranged from 16 to 3201. Together, the studies presented 36 cases of BAONJ-RA. Prevalence of BAONJ-RA ranged from 0.094% to 56.25%. The incidence ranged from 0.4% to 2.21. Women between the 6th and 8th decade of life were the most affected. Alendronate (n=5) and zoledronic acid (n=9), orally and intravenously, respectively, were the most used bisphosphonates. The duration of bisphosphonates use ranged from 2.7 to 8 years. The certainty of evidence was very low. The occurrence of BAONJ-RA is low. However, the certainty of the evidence was very low for this outcome.

Knowledge of Brazilian dentists about bisphosphonate-associated osteonecrosis of the jaw

Knowledge of Brazilian dentists about bisphosphonate-associated osteonecrosis of the jaw

Analysis of the content of mineral elements in connective tissues in patients with bisphosphonate osteonecrosis

BACKGROUND: The presence of a large number of pathological studies and a significant amount of literature on high bone density in patients with bisphosphonate osteonecrosis determined the conduct of this study.
 AIM. To monitor micro- and macronutrients in patients with bisphosphonate osteonecrosis of the jaws, to detail their role in the pathological process.
 MATERIALS AND METHODS. In 184 patients with bisphosphonate necrosis, after sequestrectomy, the micro- and macronutrient composition of bone fragments removed from the lesion was analyzed.
 RESULTS. Deviations from reference values were found in such elements as sulfur (S2-), chlorine (Cl-), potassium (K+), calcium (Ca2+), phosphorus (P3+). The dynamics of micro and macro elements correlated with the clinical picture of the pathological process under study and the number of sessions or courses of adjuvant therapy.
 CONCLUSIONS. It is assumed that violations of cascade physiological reactions that develop as a result of violations of the mineral composition in the connective tissue are due to the pharmacokinetic properties of bisphosphonate preparations. The study of a number of micro and macro elements is predetermined by their role in the life and functional activity of amino acids, enzymatic systems, importance in the structure of cells and tissues.
 Keywords
 Bisphosphonate-Associated Osteonecrosis of the Jaw, micro and macro elements, sequestrations, bone fragments.

Medication-related osteonecrosis of the jaw and the role of the doctor of dental surgery: a literature review

Introduction: Medication-related Osteonecrosis of the Jaw (MRONJ) is a condition that may affect patients undergoing oral surgery procedures that use antiresorptive drugs. It is essential that the Doctor of Dental Surgery (DDS) is familiar with the pathology and how to diagnose, prevent and approach it. Objectives: To perform a literature review on MRONJ and to guide the DDS on how to manage the affected patients. Methodology: a systematized search was conducted on the PubMed virtual database using the terms: "diphosphonates", "dentist's practice pattern", "dentists", "dentist's role" and "Bisphosphonate-Associated Osteonecrosis of the Jaw". 29 articles in English, published in the last 5 years, were included. Results and discussion: MRONJ is characterized by exposed and necrotic bone that persists for more than 8 weeks and happens in patients taking antiresorptive agents. It is multifactorial and its severity depends on the dosage, route of administration, and treatment duration. Its management must be multidisciplinary to improve the patient's quality of life. The DDS must focus on prevention. Every patient should have their oral health evaluated before starting antiresorptive therapy and be informed of its risks and benefits. Most DDSs do not feel confident to adequately manage these cases, even though information on MRONJ is more widespread among younger DDSs and recent graduates. Conclusion: MRONJ is a harmful condition for the patient and it is the DDS's responsibility to know how to treat and prevent it, by having adequate knowledge of this pathology and making decisions based on the latest scientific evidence.

Experimental modeling of mandibular defect and analysis of the functional efficiency of the jaw exoskeleton

Modeling of jaw bone defects after bisphosphonate administration is presently an urgent task of oral surgery. Methods for virtual modeling of pathological processes and ways for their elimination are becoming increasingly popular in experimental studies. However, biomedical research with experimental animals, which is strictly regulated by law, does not lose its relevance. The choice of a model for our study has been based on the assumption that bisphosphonate-associated osteonecrosis and jaw defect in experimental animals are identical to human clinical presentations. In addition, this study considers the development of devices for correcting biomechanical problems and positioning the jaw bone fragments. Simulated subtotal mandibular defects are accompanied by restricted mouth opening, malnutrition and, as a result, inhibited habitual functional activity in the experimental animals. This has served as a guide for incorporating the simultaneous fixation of fragments with a multifunctional device, such as with the mandibular exoskeleton, into the protocol of surgical intervention. Positive changes in the early postoperative period have been characterized by restoration of the biomechanical balance of the dentition. The findings provide evidence that it is necessary to modernize the device and to test the exoskeleton in patients with subtotal mandibular defects.

Organic Bone Matrix Component Type I and V Collagen Are Not Destructed in Bisphosphonate-Associated Osteonecrosis of the Jaws.

Background and objectives: The investigation of the pathophysiology behind medication-related osteonecrosis (MRONJ) of the jaw mostly focuses on alterations in osteoclast and osteoblast cell activity, but changes in the organic and inorganic bone matrix have rarely been studied. The aim of this study was to investigate whether collagen, the main organic component of extracellular bone matrix, is destructed in osteonecrosis of the jaw secondary to antiresorptive medication. Material and methods: Bone samples of patients with MRONJ (n = 15, control group n = 3) were demineralized, and collagen fragments were separated from intact collagen pellets by ultrafiltration. The quantification of mature collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in pellets and ultrafiltrates was performed by high-performance liquid chromatography (HPLC). The detection of hydroxyproline (Hyp) was carried out using a spectrophotometric assay. In addition, collagen chains were analyzed by sodium dodecylsulfate-polyacrylamide gel (SDS-PAGE). Results: The results revealed significantly higher concentrations of HP, LP and Hyp in pellet samples. In addition, there were no significant differences between samples from MRONJ patients and those of the control group. These results were paralleled by SDS- PAGE. Conclusion: These findings suggest that MRONJ does not involve the destruction of type I and V collagen molecules, in contrast to previously reported destruction by osteoradionecrosis.

Patients' Awareness of the Complications of Bisphosphonate Therapy

INTRODUCTION: Bisphosphonate-associated osteonecrosis of the jaws (BAONJ) is a serious complication that has been reported predominantly in cancer patients treated with Bisphosphonate (BP). The level of knowledge of dental and medical practitioners, as well as patients, is crucial for its prevention.OBJECTIVES: To investigate patients’ awareness of BAONJ in order to evaluate some problems of the prevention, prophylaxis and diagnosis. MATERIALS AND METHODS: A prospective epidemiological study of 112 oncology patients diagnosed with Bisphosphonate-associated osteonecrosis of the jaw was conducted in the Clinic of maxillo-facial surgery of university multiprofile hospital for active treatment (UMHAT) “St. George”, Plovdiv, Bulgaria, based on anamnesis, clinical examination, hospital documentation, and imaging studies. SPSS Statistics v.24 was used for statistical analysis, at a significance level p<0.05.RESULTS: Before initiation of therapy, only 17.86% of the patients were consulted by a medical practitioner about the risk of jaw complications associated with the use of Bisphosphonates, 9.82% knew about the need for regular dental check-ups after the initiation of therapy and 4.46% had a dental examination and oral sanation. By the time of diagnosis, 61.61% of the patients remained unaware, with the last dental manipulation being most often extraction (52.68%) and removable dentures (21.42%) considered risky by experts. Diagnosed by a general dental practitioner or oncologist were 6.74% of the respondents – the medical practitioners who usually monitor the condition of these patients. Over 2/3 of the patients were diagnosed at a more advanced stage (II/III).CONCLUSION: The lack of patient awareness leads to omissions and errors in their prophylaxis, and to the diagnosis of BAONJ at a more advanced stage.

Knowledge of dental professionals and Dental students on bisphosphonates and bisphosphonate-associated osteonecrosis of the jaws

Introduction and objective: the present study assessed the knowledge of dentists and dental students about bisphosphonates and bisphosphonate-associated osteonecrosis of the jaws (BAONJ). Methodology: a survey was applied to dentists and dental students during dental meetings in the city of Rio de Janeiro/RJ, Brazil. Results were descriptively and comparatively analyzed using the SPSS program. Results: the final sample (n=308) was composed mostly by young adults, females (n=233; 76%) and 52% (n=159) were dental students. Most participants (n=185; 60%) were derived from private dental schools. From the total, 79% (n=243) of the participants told they had some information about bisphosphonates, 68% (n=209) recognized BAONJ as a possible side effect of their use, and 84% (n=259) considered important to ask about bisphosphonates use during anamnesis. Participants with more access to information, derived from public dental schools and graduate dentists demonstrated a higher understanding about the indications for bisphosphonates use, their action mechanism, BAONJ as an adverse effect, risk factors associated with the drugs, oral risk factors and oral care measures important to BAONJ risk reduction. Conclusions: there are several knowledge gaps on bisphosphonates and BAONJ and understanding these difficulties is important for the establishment of strategies of diffusion of the information and changing teaching models in dental schools, dental meetings and extension activities.

The importance of Cone-Beam computed tomography in diagnosis of associated mandibular osteonecrosis: case report / A importância da TCFC no diagnóstico e prognóstico da osteonecrose mandibular associada aos bisfosfonatos: relato de caso clínico

The Cone-Beam Computed Tomography (CBCT) is very useful in diagnosis and treatment planning, as well as in the prognosis of osteonecrosis of the jaws. This study reports a clinical case of Bisphosphonate-Associated Mandibular Osteonecrosis from the perspective of CBCT. The patient, female, 83 years old, presented painful symptoms in the posterior region of the right mandible and reported Bisphosphonate medication for more than five years to treat osteoporosis and osteopenia. Based on clinical and CBCT imaging characteristics, the patient was diagnosed with Bisphosphonate-Associated Mandibular Osteonecrosis. Initially, the treatment consisted of oral antibiotic therapy, pain control, hyperbaric oxygenation and oral hygiene (mouthwashes). After 11 months of clinical therapy, CBCT revealed bone reconstruction of the buccal cortex, but also a hypodense imaging in the lingual cortex compatible with bone lysis and bone sequestration. The patient was referred for bone debridement and sequestrectomy. The histopathological diagnosis consisted of osteonecrosis with secondary acute osteomyelitis. After 60 days of the surgical procedure and hyperbaric sessions/systemic antibiotic therapy, an oral healthy mucosa in the region of the right mandibular body was evidenced in the intraoral examination. Cortical bone regeneration was observed on CBCT. Concluded that the use of CBCT, in this case report, makes it possible to estimate the extent of the lesion and the post-treatment outcome, assessing bone density, the presence of bone sequestration and the involvement of the involved areas. In fact, early diagnosis is essential for the success of the therapeutic approach.

Does Drug Holiday Affect Jaw Trabeculation in Medication Related Osteonecrosis of the Jaw? - A Pilot Study.

BackgroundThe role of drug holiday in long term antiresorptive drug users to prevent MRONJ is debated for quite some time. We aimed to compare jawbone trabeculation between patients on drug holiday with those not on drug holiday among Medication Related Osteonecrosis of the Jaw (MRONJ) cases using fractal analysis and to estimate the frequency of MRONJ despite being on drug holiday. Material and MethodsThe sample of 18 MRONJ cases were divided into drug holiday, and non-drug holiday groups. Non-drug holiday group was further divided into pre- and post- drug holiday groups. Jawbone trabeculation was assessed utilizing fractal analysis method (ImageJ software) by two observers. ANOVA was used to compare the fractal dimension (FD) values between the groups. A ‘p’ value of less than 0.05 was considered significant. Results8 patients developed MRONJ despite being on drug holiday (44.44%). There was no significant difference in the FD values between drug holiday and pre-drug holiday groups. When pre- and post-drug holiday FD values were compared, the difference was significant only on the right maxilla with observer 2. Also, no significant difference was noted between the two observers. ConclusionsBone trabeculation remained unaltered following drug holiday from anti-resorptive drugs. This study serves as a preliminary proof for the argument against drug holiday which portrays the necessity for a detailed prospective study in this arena. Key words:Osteonecrosis, bisphosphonates, Bisphosphonate-Associated Osteonecrosis of the Jaw, anti-resorptive drugs, osteoporosis, jaw.

Curious Case of Rodent Poison: A Case Report

Osteonecrosis was first described as a consequence of ionizing radiation used in the treatment of malignant tumors but later a variety of causes for osteonecrosis were found which include, Medication induced, radiation induced, chemical induced and infection induced. Terms such as: bisphosphonate osteonecrosis (BON), Bisphosphonate Associated Osteonecrosis of the Jaws (BONJ), Bisphosphonate Related Osteonecrosis of the Jaws (BRONJ), Antiresorptive Osteonecrosis of the Jaw (ARONJ) and Medication Related Osteonecrosis of the Jaw (MRONJ) have all had proponents and all continue to be utilized. However, Migliorati first proposed a designation of the disease as osteochemonecrosis. This case report is about a chemical induced osteonecrosis patient who placed rat poison inside the mouth.

Medication-Related Osteonecrosis of the Jaw, a Hidden Enemy. An Integrative Review

Background: Drug-induced osteonecrosis of the jaw (ONJ) ​​is a serious complication associated with prolonged use of antiresorptive (e.g., bisphosphonates and denosumab) and antiangiogenic drugs (e.g., bevacizumab and sunitinib) in patients with osteoporosis or cancer. With this situation, a progressive infection of the maxillary or mandibular bone and later an avascular necrosis of the bone occurs. The incidence of ONJ is higher in people with cancer who are frequently received high doses of antiresorptive drugs intravenously. Risk factors associated with antiresorptive or antiangiogenic therapy have been identified to possibly contributing to the onset of ONJ. Purpose: To review and analyze the current available therapeutic options to treat at-risk patients or who already have ONJ. Methods: In this integrative review of the literature, publications were searched in the ScienceDirect, PubMed, SciELO, and ResearchGate databases between 2003 and 2020. The search terms were “bisphosphonate-associated maxillary osteonecrosis,” “maxillary osteonecrosis associated with medication,” and “maxillary osteonecrosis.” Results: 64 articles were selected in which extractions are identified as the main risk factor for developing ONJ (52 % to 61 %). A second factor identified was the spontaneous appearance of bone necrosis lesions. Conclusions: It is important to implement preventive measures in medical and dental care before, during, and after antiresorptive and antiangiogenic treatments to minimize the risks of ONJ in patients.

Geranyl-geraniol addition affects potency of bisphosphonates—a comparison in vitro promising a therapeutic approach for bisphosphonate-associated osteonecrosis of the jaw and oral wound healing

PurposeAnalysis of the influence of geranyl-geraniol (GG) addition on four bisphosphonate derivatives regarding their influence on cell viability and migration ability of bone metabolism and endothelial cells in vitro.MethodsClodronate, pamidronate, ibandronate, and zoledronate were observed with and without GG addition, for their effect on human osteoblasts (HOB), normal human dermal fibroblasts (NHDF), human endothelial progenitor cells (EPC), and endothelial cells of the human umbilical cord (HUVEC) using migration-, MTT-, and colony-forming cell assays.ResultsData pointed to a depressing effect of all bisphosphonates on the migration ability of NHDF, EPC, and HOB. MTT assay demonstrated a decreased cell viability of HUVEC of all bisphosphonates in a 50 μM concentration and of NHDF when treated with 50 μM of clodronate, ibandronate, or zoledronate. Tested drugs showed a depressing effect on colony-forming potential of EPC even in a 5 μM concentration. GG addition demonstrated an attenuate impact on bisphosphonate effect on all primary cell cultures, respectively.ConclusionIn vitro comparison showed that the addition of GG weakens the effect of all bisphosphonates examined. It supports investigations that suggest GG to be able to prevent bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) in vivo. Future clinical trials may discover the local therapeutic use of GG for the prevention of BP-ONJ.

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.

RISK FACTORS IN PATIENTS WITH BISPHOSPHONATE - ASSOCIATED OSTEONECROSIS OF THE JAWS

Purpose: To investigate patient diagnosed with BAONJ in order to identify the presence of risk factors. Material/Methods: A prospective epidemiological study of 112 patients diagnosed with Bisphosphonate-associated Osteonecrosis of the jaw in 2016 and 2017 was conducted in the Clinic of maxillo-facial surgery of UMHAT "St. George", Plovdiv, Bulgaria, based on anamnesis, clinical examination, hospital documentation, and imaging studies. SPSS Statistics v.24 was used for statistical analysis, at a significance level p<0.05. Results: Of the patients, 77.89% had a primary oncological diagnosis of breast or prostate cancer; the average duration of bisphosphonate therapy up to the time of the study is 4.5 years; the most common co-morbidities were hypertension (72.73%), anemia (40.00%) and diabetes (23.67%); 65.18% of patients smoke or are former smokers; the time till first oral complaints after initiation of BP treatment was usually 2 years (31.25%, n = 35) and 3 years (24.11%, n = 27) (p> 0.05).; the last dental manipulation before the onset of symptoms was tooth extraction (52.68%), followed by removable dentures (21.42%). Conclusions: The investigation of identified in the literature risk factors with their occurrence in the studied population shows a correlation with the data of leading researchers.

Pušenje i konzumiranje alkohola kao faktori rizika kod 112 onkoloških bolesnika sa dijagnozom bisfosfonatne osteonekroze vilica

Background: Bisphosphonate-associated osteonecrosis of the jaws (BAONJ) is a complication of great medical importance. Some of the most discussed and controversial aspects are the risk factors, some of which are related to patients' smoking and alcohol consumption. The Aim: To study cancer patients with BAONJ and determine their participation in the mentioned above risky health-related habits. Material and methods: A prospective epidemiological study of 112 patients diagnosed with bisphosphonate-associated osteonecrosis of the jaw in 2016 and 2017 was conducted at the Clinic of Maxillofacial surgery of University hospital "St. George", Plovdiv, Bulgaria, based on anamnesis, clinical examination, and hospital documentation. SPSS Statistics v.24 was used for statistical analysis, at a significance level p<0.05. Results: Over 2/3 of the patients were smokers (40.18%) or ex-smokers (25.00%), which linked them with the risk factor of smoking. At the time of the study, patients smoking between 1 and 9 and between 10 and 19 cigarettes a day had equal relative shares of 44.22%. More than half of the patients smoked from the age of 20-39, which we explain by the high average age. The majority of patients studied consumed alcohol, most often once a week or on weekends (28.57%) or only on occasions (26.79%), followed by 24.11% who used alcohol several times per week. Nearly 2/3 drink drinks with both low and high alcohol content. Conclusion: The highest proportion of patients are smokers / ex-smokers and consume alcoholic beverages occasionally, which links them to these risk potential factors.

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.

Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307).

Bisphosphonates reduce bone metastases in postmenopausal women with early-stage breast cancer but carry the risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We describe risk factors for BRONJ and compare BRONJ provoked by infection or trauma with spontaneous lesions, which carry a better prognosis. SWOG 0307 randomized women with stage I-III breast cancer to receive zoledronic acid (ZA), clodronate (CL), or ibandronate (IB) for 3 years, implemented BRONJ prevention guidelines, and collected information about dental health and development of BRONJ. All statistical tests were two-sided. Of 6018 women, 48 developed BRONJ. Infection was present in 21 (43.8%). Median time to BRONJ was 2.1 years for ZA, 2.0 years for IB, and 3.4 years for clodronate (p = 0.04). BRONJ was associated with bisphosphonate type (28/2231 (1.26%) for ZA, 8/2235 (0.36%) for CL, 12/1552 (0.77%) for IB), dental calculus (OR 2.03), gingivitis (OR 2.11), moderate/severe periodontal disease (OR 2.87), and periodontitis > 4 mm (OR 2.20) (p < 0.05). Of 57 lesions, BRONJ occurred spontaneously in 20 (35.1%) and was provoked by dental extraction in 20 (35.1%), periodontal disease in 14 (24.6%), denture trauma in 6 (10.5%), and dental surgery in 2 (3.5%). Spontaneous BRONJ occurred more frequently at the mylohyoid ridge. There were no differences in dental disease, infection, or bisphosphonate type between spontaneous and provoked BRONJ. ZA and worse dental health were associated with increased incidence of BRONJ, with a trend toward additive risk when combined. BRONJ incidence was lower than in similar studies, with prevention strategies likely linked to this. NCT00127205 REGISTRATION DATE: July 2005.

Calcium Phosphate Ceramics Can Prevent Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonate-associated osteonecrosis of the jaw (BRONJ), a post-surgical non-healing wound condition, is one of the most common side effects in patients treated with nitrogen-containing bisphosphonates. Its physiopathology has been related with suppression of bone turnover, of soft tissue healing and infection. Biphasic calcium phosphates (BCP) are used as a drug delivery vehicle and as a bone substitute in surgical wounds. Due to their capacity to adsorb zoledronate, it was hypothesized these compounds might have a protective effect on the soft tissues in BRONJ wounds. To address this hypothesis, a reproducible in vivo model of BRONJ in Wistar rats was used. This model directly relates chronic bisphosphonate administration with the development of osteonecrosis of the jaw after tooth extraction. BCP granules were placed in the alveolus immediately after tooth extraction in the test group. The animals were evaluated through nuclear medicine, radiology, macroscopic observation, and histologic analysis. Encouragingly, calcium phosphate ceramics were able to limit zoledronate toxicity in vivo and to favor healing, which was evidenced by medical imaging (nuclear medicine and radiology), macroscopically, and through histology. The studied therapeutic option presented itself as a potential solution to prevent the development of maxillary osteonecrosis.

Saliva diagnostics in patients suffering from bisphosphonate-associated osteonecrosis of the jaw: Results of an observational study

ObjectiveOne of the severe side effects of bisphosphonate (BP) therapy is bisphosphonate-associated osteonecrosis of the jaw (BONJ). However, there is no information available about its pathogenesis. Hence, the aim of this observational study was to contribute to discerning this pathogenesis by comparing salivary quantity and quality in patients with BONJ and undergoing BP treatment. Materials and methodsThis study included 60 patients divided into three groups. The first group consisted of 20 patients with established BONJ, the second group had 20 patients undergoing BP treatment, and the third group comprised 20 healthy individuals. These groups were analysed for the flow rate of stimulated saliva, buffer capacity, and salivary pH level. ResultsReduced salivation was observed in a significantly high number of patients with established BONJ (n = 8) and those undergoing BP treatment (n = 9) in comparison with the healthy control group (n = 4; p = 0.039). Though the distribution of the mean value of stimulated saliva flow rates in patients undergoing BP treatment was lower than in the control group, the difference was not significant. Moreover, there were no significant differences in the salivary pH level and buffer capacity in patients undergoing BP treatment as compared with the healthy control group. ConclusionsIt is possible that the quantity of human saliva is affected by BP treatment. This reduction in saliva production could have a negative effect on mucosal health and is perhaps a cofactor in the pathogenesis of BONJ.