Bisphosphonate Osteonecrosis Research Articles

Clinical Effectiveness of the Method of Sealing a Bone Wound and Accelerating Osteogenesis in Patients with Bisphosphonate Osteonecrosis of the Jaw

Clinical Effectiveness of the Method of Sealing a Bone Wound and Accelerating Osteogenesis in Patients with Bisphosphonate Osteonecrosis of the Jaw

Biomechanics of the Patient with Bisphonate Osteonecrosis According to the Diagnosis Neurophysiological Monitoring

Effective rehabilitation of patients with volumetric jaw defects at the present stage of development of science and technology is impossible without a comprehensive analysis of biomechanical disorders and improvement of technical aspects of operational ways to eliminate them. The aim of the study was to analyze the biomechanical activity of the chewing muscles in patients with bisphosphonate osteonecrosis based on the results of neurophysiological monitoring. 184 patients with bisphosphonate osteonecrosis of the mandibular bone were monitored, 112 of whom were men and 72 women, group 1 included 60 % of patients who had an apparatus for extracellular osteosynthesis of jaw bones fixed, and group 2 – 40 % of patients whose jaw fragments were fixed with bone mini-plates of various profiles and cross-sections. In the preoperative period, all patients underwent general clinical studies, multispiral computed tomography, and monitoring of quality of life criteria using a modified questionnaire "The MOS 36-item Short-From Hervey". Results and discussion. Indicators in the long-term postoperative period in patients of group 1 approached the physiological norm on the healthy side and significantly improved on the affected side, compared with patients from group 2 who did not receive devices for extracellular osteosynthesis in the postoperative period. Conclusions. Ensuring the positioning of jaw bone fragments in three mutually perpendicular planes restores biomechanical balance in the dental and maxillary apparatus, which accelerates the rehabilitation of patients and predicts a favorable outcome of surgery.

Modern understanding of the problem of bisphosphonate osteonecrosis of the jaws

The article is devoted to the concept of osteonecrosis formation in oncological patients with bone metastases taking bisphosphonate preparations. The significance of the problem of bisphosphonate osteonecrosis of the jaws is associated with an increase in the number of such patients over the past few decades, a high frequency of complications and relapses, and a negative prognosis of the disease. The number of inflammatory lesions of the jaws when using bisphosphonate preparations can reach 25% of the total number of patients, the number of abscesses and phlegmon reaches 45%. The article considers risk factors, the frequency of inflammatory lesions of the jaw bones, known approaches to the diagnosis and treatment of drug-associated osteonecrosis of the jaws.

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.

Diagnostic analysis of toxic damage due to a dose of zoledronic acid

Introduction: Comprehensive analysis is necessary to analyze the widespread use of bisphosphonate drugs in the treatment and prevention of various diseases of connective tissue structures. The relevance of the study depends on the impact they have on the patient’s somatic condition, given the number of early and late complications diagnosed by domestic and foreign clinicians.
 Materials and methods: The methodology used was developed on Stavropol Regional Clinical Hospital from 2010 to 2022. A randomized and observational study of the state of connective tissue structures was conducted in 186 patients who had a history of taking zoledronic acid and developed bisphosphonate osteonecrosis of the jawbone. At the diagnostic and treatment stages, patients were tested using laboratory methods to monitor amino acids in biological fluids (blood), as well as bone blocks extracted intraoperatively using highly effective gas-liquid chromatography on AAA 500.
 Results and discussion: Aminograms obtained in the pre-operative period indicate toxic effects of zoledronic acid on neuro, endocrine, and other human systems. The initiation and progression of aseptic inflammatory processes in tissue structures is correlated with the deteriorating general ocular status of patients when amino acids, such as alanine, serine, taurine, phenylalanine, tyrosine, proline, histidine, glycine, and valine, against a background of 90.4±2.1 mmol/L ammonia are reduced critically.
 Conclusion: Zoledronic acid initiates an aseptic chronic inflammatory process in the jaw bones, accompanied by toxic acidosis, which worsens osteoporotic symptoms.

ОСТЕОМОДИФИЦИРУЮЩИЕ АГЕНТЫ И БИФОСФОНАТНЫЙ ОСТЕОНЕКРОЗ ЧЕЛЮСТЕЙ: ЗАРУБЕЖНЫЕ ИССЛЕДОВАНИЯ

Subject. The relevance of this review is related to the increasing number of patients taking osteomodifying agents. Osteomodifying agents are used in the treatment of bone metastases of malignant tumors and osteoporosis. A serious complication associated with the use of osteomodifying agents – bisphosphonates – is bisphosphonate osteonecrosis of the jaw. There are also data on the development of osteonecrosis of the jaw when taking denosumab. However, the pathogenesis of this complication is not fully understood. Study of etiological factors and pathogenetic mechanisms of jaw osteonecrosis development, associated with taking osteomodifying agents will allow to prevent it at early stages and improve quality of life of patients. Objectives – analysis of foreign studies on the impact of osteomodifying agents on the human body and associated osteonecrosis of the jaws. Methodology. The literature review was carried out on the basis of the analysis of the published studies. Using the key words in the electronic resource of the journal "Nature" the foreign scientific studies with the results of the research on the influence of the osteomodifying agents on the human body and the cases of osteonecrosis of the jaws associated with them were selected. Results. OMAs increase bone density through several mechanisms. However, some osteomodifying agents increase the risk of atypical fractures of the femur, forearms, and vertebrae, and increase the incidence of osteonecrosis of the jaw and some cancers. Research continues on risk factors for these complications in patients taking osteomodifying agents. Conclusion. Osteomodifying agents are widely used in oncology and prevention of age-related changes in the human bone system. Therapeutic effects and complications of therapy with osteomodifying agents are studied worldwide.

Comparative analysis of the mineral composition of the
 leukocyte, erythrocyte fraction and PRP plasma in patients with bisphosphonate osteonecrosis of the jaw bones

A complication of the use of bisphosphonate drugs is the development of bisphosphonate osteonecrosis. There is not enough information about the state of the microelement composition of the blood and the dynamics of metabolic processes for various bisphosphonate drugs. There are 184 patients under observation for bisphosphonate osteonecrosis of the jaw bones. The mineral components of three blood fractions were monitored: sulfur (S2-), chlorine (Cl-), potassium (K+), calcium (Ca2+), phosphorus (P3+) at the preoperative and postoperative stages. At the preoperative stage, the negative dynamics of indicators of bone metabolites (Ca2+ and P3+) contributed to the development of osteomalacia, followed by a jaw fracture due to local loads. Hypercalcemia developed against the background of acidosis in the bone tissue (Ca2+ ions were replaced by H+ ions, with partial diffusion into the liquid fraction, due to disorganization of the synthesis of chondroitinsulfuric acid). Hyperphosphatemia is due to the pharmacokinetics of bisphosphonate drugs. Violation of the metabolism of sulfur-containing amino acids leads to the accumulation of S2- in blood fractions. The decrease in Cl- is due to metabolic acidosis against the background of an atrabiliary gas exchange function of erythrocytes, which enhances the pathological focus of tissues with the migration of Cl- to the lesion. A decrease in K+ was noted against the background of severe muscle atony. The dynamics of the studied parameters correlates with the clinical picture of bisphosphonate osteonecrosis. The trace element composition of blood fractions, starting from the 7th day of the postoperative period, was characterized by a trend towards positive dynamics. With further observation at the 3rd and 6th months, the content of the studied trace elements in the reference values. The clinical picture corresponds to the scope and timing of surgery in 100% of patients.

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.

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.

EFFECT OF EXOGENOUS NITRIC MONOXIDE THERAPY ON IMMUNOLOGICAL PARAMETERS IN BISPHOSPHONATE OSTEONECROSIS OF THE JAWS

Bisphosphonate osteonecrosis of the jaw (BONCH) is a drug-induced osteonecrosis in patients with a history of malignancies. It is characterized by progressive destruction of the jawbone with the development of a chronic inflammatory process in the parotid tissues. For the treatment of the disease, the use of exogenous nitrogen monoxide (NO) synthesized using the Plason device is proposed. The study of immunological parameters in patients with BONCH in the main group (n = 26), who received NO-therapy, and in the comparison group (пи = 27), who received traditional sanitation with 0,05 % chlorhexidine bigluconate. The dynamics of indicators in the main group - a decrease in the activity of the cellular link (activity of phago-quoting granulocytes and monocytes) to normal values, an increase in the intensity of local immunity (IgA) and a decrease in the concentration of humoral factors of acute (IgM) and chronic (IgG) inflammation p < 0,05) - confirms the anti-inflammatory and immunomodulatory effect of exogenous NO therapy. In the case of the comparison group, reducing only one indicator (AFM) to normal values does not allow us to prove the effect of traditional sanitation on immunological parameters in General. Thus, the use of exogenous nitrogen monoxide for patients with BONCH is justified both at the stage of preoperative preparation and as a basic conservative therapy if surgical treatment is not possible.

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.

Disorders of microcirculation in the mechanism of bisphosphonate osteonecrosis: preliminary study in rats.

We investigated the possibilities of angioprotection and the reduction of osteonecrosis in rats that had been given bisphosphonates. In our experiment, 27 rats were divided into three groups: Group 1 was injected with saline; Group 2 was given zoledronic acid for six weeks; and Group 3 was given zoledronic acid for six weeks, with added doses of sulodexide after three weeks. After that we constructed a model of how the teeth should be extracted. The velocity of linear blood flow in the periodontal area of an extracted tooth in rats was studied using laser and high-frequency Doppler ultrasound (with the application of the vasoactive substance acetylcholine 3% for 1min). We evaluated changes in the structure of the bony tissues of the head using computed tomography, comparing the control group with the saline group. A rapid reduction in microcirculation was detected during the use of zoledronic acid for six weeks. A smaller reduction in microcirculation was detected after three weeks of treatment with sulodexide and zoledronic acid. There was a reduction in blood flow in the mucous membranes and, to a greater extent, in bony tissue. Zoledronic acid causes significant impairment of the periosteal blood flow to the mucous membranes because of a complex of disorders, which includes both the cellular component (impaired endothelium-dependent vasodilation of the mucous membrane vessels) and by reducing the intensity of microcirculation in the mucous membranes and bony tissues. Sulodexide, however, improves the restoration of blood flow and reduces the severity of osteonecrosis.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) in cancer patients

This literature review focuses on the latest advances in the study of osteonecrosis of the jaw in cancer patients taking bisphosphonates. Prescribing bisphosphonates for the treatment of metastatic bone disease is justifiable and unavoidable measure. The action of bisphosphonates leads to increase in bone tissue strength, but significantly suppressing normal bone remodelling, essential for repair, and becomes vulnerable to mechanical trauma and bacterial invasion. The unique anatomical and physiological features of the jaw bones determine their selective damage. The disease is characterized by progressive jaw necrosis, chronic inflammation of the surrounding tissues complicated by a pathological fracture and persistent oroantral fistula, which aggravates chronic pain and leads to a deterioration in the quality of life of patients. The occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a multifactorial process. Most often, it occurs in patients with long term treatment with zoledronic acid preparations against after tooth extraction. The fact of an increase in the incidence of osteonecrosis is undeniable for objective reasons, the main of which are an increase in cancer, an increase in the life expectancy of cancer patients and their need for bisphosphonate therapy. In the article, it was analyzed the latest scientific reports on the causes of the disease, risk factors and the pathogenesis of the disease. Data on the frequency of jaw osteonecrosis in different countries are presented. It was shown promising developments and summarizes information on existing methods for diagnosing jaw bisphosphonate osteonecrosis. Questions about the key approaches in the treatment of the disease, as well as about new experimental techniques, are examined. The main problems of the prevention of bisphosphonate-related osteonecrosis of the jaws are formulated.

Prevention of bisphosphonate osteonecrosis in dental patient with osteoporosis

The analysis of scientific literature on the use of bisphosphonates in the treatment of osteoporosis. This effective group of drugs was included in the first line of appointments by specialists dealing with the problem of osteoporosis. At the same time, a number of authors associate the appearance of medicinal osteonecrosis of the jaws, called BONJ (bisphosphonate osteonecrosis of the jaws), in patients with the administration of bisphosphonates. One of the triggering mechanisms of the emergence of BONJ are surgical dental interventions performed in patients receiving bisphosphonates. Today, patients may not understand the seriousness of taking these drugs and often do not warn the dentist before manipulation, as well as not all dentists attach importance to the danger of drugs from osteoporosis. In this paper, based on the analysis of scientific literature, the attention of dentists to the problem of possible complications in the treatment of patients with osteoporosis, taking bisphosphonates. A questionnaire included in the questionnaire of a dental patient, taking into account the name of the drug and the duration of its administration, is proposed.

ОПЫТ ПРОВЕДЕНИЯ ПРОФЕССИОНАЛЬНОЙ ГИГИЕНЫ ПОЛОСТИ РТА У ПАЦИЕНТОВ С ХРОНИЧЕСКИМ ПАРОДОНТИТОМ В СОЧЕТАНИИ С МЕДИКАМЕНТОЗНО АССОЦИИРОВАННЫМ ОСТЕОНЕКРОЗОМ ЧЕЛЮСТИ

Thing. The experience of conducting professional oral hygiene in patients with chronic periodontitis in combination with drug-associated jaw osteonecrosis is presented. The goal is to identify the features of the oral cavity status of patients with chronic periodontitis and bisphosphonate osteonecrosis of the jaw (BONCH) on the background of postoperative chemotherapy after using two domestic mouthwashes (OML). Methodology. A clinical examination of the oral cavity of 15 patients aged 50 to 66 years was carried out, which were divided into two groups: the main group (after resection of the jaw segments) and the comparison group (5 and 10 people, respectively). Dental examination included examination of the oral cavity: the condition of periodontal tissues and mucous membrane, determination of the intensity of dental caries and hygiene and bleeding indices. Studies of mixed saliva (SS) were carried out before and after a single and daily course use of two domestic rinses based on chlorhexidine bigluconate and benzidamine and extracts of medicinal plants. Results. The pH value after the course application of OMLPR-1 in patients with BONCH has shifted from weakly acid (6.45 ± 0.4 units) to slightly alkaline (7.15 ± 0.15 units) medium. The structure of the SS before the application of OPLPR-1 was represented by small conglomerates of irregular shape and individual tree crystals of small sizes, and after the double use of OPLPR-1, the properties of the SS improved and medium-sized tree crystals appeared. After the course application of OPLR-2 in these patients, crystal-prismatic structures of a tree form were identified, a tendency to restore the structural properties of SS was determined. Findings. After the course application of LPRS, a tendency to restore the structural properties of SS was revealed. The course use of CPLR stimulates the excretion of SS, cleansing and a feeling of freshness in the mouth. The consecutive use of OPLR-1 and OPLR-2 helps to alleviate the condition of patients, especially against the background of BONCH and chemotherapy.

BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW

Bisphosphonates (BPs) are a class of drug used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. According to modern data, bisphosphonate osteonecrosis of the jaws (BPONJ) is a complication of antiresorptive therapy, characterized by death and exposure of the bone area, which persists for more than 8 weeks, with subsequent progression of the process, provided there is no radiation therapy on the head area in history. BRONJ can adversely affect quality of life, as it may produce significant morbidity. The purpose of this article is to offer a perspective on how dentists should manage patients on BPs, and to present diagnostic aids and treatment s strategies to the condition.

Experience of the interdisciplinary approach to diagnostics and treatment of patients with bisphosphonate osteonecrosis of the upper jaw

The article discusses the issues of diagnosis, the clinical course of osteonecrosis of the upper jaw in patients with oncological diseases. The assessment of radiological indicators of bone pathology of the upper jaw, signs of the development of the inflammatory process of the maxillary sinus and other sinuses of the nose. The experience of conservative tactics and surgical treatment of patients in this group is analyzed with the participation of specialists from otorhinolaryngologists and maxillofacial surgeons.

Лазерная доплеровская флоуметрия - метод определения границ секвестрэктомии при бисфосфонатном остеонекрозе челюсти

osteonecrosis of the is a severe complication that can occur in patients receiving bisphosphonate therapy due to bone metastases. The relevance of research is conditioned by spread use of bisphosphonates in patients with proved bone metastases in myeloma. Despite the active study of the problem, a high percentage of relapses of the disease remains, the direct criteria of sequestrectomy determination lines during surgical treatment. The study was conducted on the basis of the Department of maxillofacial surgery MAI CCCH №23”, where patients with the diagnosis of Bisphosphonate osteonecrosis of the jaw in the period from December 2017 to December 2018 were treated.

Bisphosphonate suspension and osteonecrosis of the jaw

Bisphosphonate suspension and osteonecrosis of the jaw

ASSESSMENT OF BONE METABOLISM IN PATIENTS WITH BISPHOSPHONATE OSTEONECROSIS OF THE JAWS

The aim of the study was to evaluate bone metabolism in cancer patients with bisphosphonate osteonecrosis of the jaws. The study included 45 people of the main group (patients with cancer with osteonecrosis of the jaw in patients receiving bisphosphonates) and 25 in the control group (cancer patients treated with bisphosphonates, but did not have osteonecrosis of the jaw), which had a stabilization of the underlying disease. Bone metabolism was evaluated by the level of osteocalcin (OC), bone-specific alkaline phosphatase (bALP), aminoterminal of propeptide of procollagen type I (P1NP), tartrate-resistant acid phosphatase (TRAP5b), calcium (Cа), phosphorus (P) in blood serum before treatment and after 6 months. Compared to the average levels of marker patients of the main and control groups using the Mann-Whitney test for p < 0,05. A baseline level of СТХ (0,23±0,02 ng/ml) and OС (11,58±0,54 ng/ml) in the treatment group was significantly (p < 0.05) lower than control group (0,43±0,01 ng/ml and 17,94±0,83 ng/ml), and the level of osteocalcin in the main group (11,58±0,54 ng/ml) was on average below normal 2,59 times. Recorded significantly higher (p < 0,05) levels bALP (133,24±14,03 U/l) and TRAP5b (3,54±0,38 U/l) in patients with osteonecrosis compared with a control group (73,32±3,41 U/l and 3,12±0,12 U/l). Reliably detected differences in the levels of P1NP, Ca and P were not detected (p > 0,05). In the main group after 6 months of treatment was observed a tendency of growth of СТХ, TRAP5b, OK, bALP, P1NP, Ca, but only for the markers of resorption and СТХ, TRAP5b these differences were significant. Indicators of patients in the control group were stable and did not differ in the dynamics. The development of bisphosphonate osteonecrosis of the jaws is directly related to bone metabolism and occurs with predominance of the processes of bone resorption and inhibition of bone formation processes.