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Jin-Hee Han, Junho Jung, Lakkyong Hwang, Il-Gyu Ko, Ok Hyung Nam, Mi Sun Kim, Jung-Woo Lee, Byung-Joon Choi, Deok-Won Lee
Bisphosphonates are generally used as therapeutic agents for bone diseases. However, previous reports on bisphosphonates-related osteonecrosis of the jaw (BRONJ) demonstrated that inflammation triggers and worsens the disease. Recently, polydeoxynucleotide (PDRN), an A2A receptor agonist, has been suggested for the treatment of various diseases and broadly studied for its anti-inflammatory effect. The present study aimed to measure the effect of PDRN on macrophage cells treated with zoledronic acid (ZA) and lipopolysaccharide (LPS)...
July 2018: Experimental and Therapeutic Medicine
Francisco Javier Manzano-Moreno, Javier Ramos-Torrecillas, Elvira de Luna-Bertos, Rebeca Illescas-Montes, Timothy R Arnett, Concepción Ruiz, Olga García-Martínez
OBJECTIVES: The objectives of this study were to analyze the effect of pH on the growth and activity of osteoclasts treated with different doses of two nitrogen-containing BPs, zoledronate and alendronate. MATERIALS AND METHODS: Murine osteoclasts cultured on dentine disks were treated with zoledronate (50 or 500 nM) or alendronate (500 or 5 μM) at two different pH values (7.4 or 7.0). Osteoclasts were counted with transmitted light microscopy, apoptosis/necrosis was studied with flow cytometry and confocal microscopy, and resorption pit number and depth were calculated using reflected light and scanning electron microscopy...
June 6, 2018: Clinical Oral Investigations
Somying Patntirapong, Mahatana Poolgesorn
BACKGROUND: A serious adverse effect of long-term bisphosphonate (BP) administration is bisphosphonate-related osteonecrosis of the jaw (BRONJ). Among different proposed pathogenesis, suppression of immune cells is gaining interest. Because monocytes/macrophages could get access to BP since residing in the blood and bone microenvironment, the aim of this study was to analyze the behaviors of macrophages after bisphosphonate treatments in vitro. METHODS: THP-1 cell, an established human monocytic cell model, was used in this study...
June 5, 2018: Oral Diseases
Elisa Borsani, Veronica Bonazza, Barbara Buffoli, Pier Francesco Nocini, Massimo Albanese, Francesca Zotti, Francesco Inchingolo, Rita Rezzani, Luigi F Rodella
Bisphosphonates are primary pharmacological agents against osteoclast-mediated bone loss and widely used in the clinical practice for prevention and treatment of a variety of skeletal conditions, such as low bone density and osteogenesis imperfecta, and pathologies, such as osteoporosis, malignancies metastatic to bone, Paget disease of bone, multiple myeloma, and hypercalcemia of malignancy. However, long-term bisphosphonate treatment is associated with pathologic conditions including osteonecrosis of the jaw, named BRONJ, which impaired bone regeneration process...
2018: BioMed Research International
Takahiko Shibahara, Takamichi Morikawa, Kaori Yago, Hiromitsu Kishimoto, Yutaka Imai, Kenichi Kurita
PURPOSE: From 2011 to 2013, a nationwide retrospective cohort study was conducted by the Japanese Society of Oral and Maxillofacial Surgeons and the Japanese Society of Dentistry for Medically Compromised Patients to assess the development of bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ) and to elucidate the outcomes and factors associated with remission. MATERIALS AND METHODS: A written questionnaire, including clinical characteristics, management, and outcomes of patients with BRONJ, was sent to 501 institutions...
April 14, 2018: Journal of Oral and Maxillofacial Surgery
Shinichiro Kuroshima, Muneteru Sasaki, Kazunori Nakajima, Saki Tamaki, Hiroki Hayano, Takashi Sawase
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) worsens oral health-related quality of life. Most BRONJ occurs in multiple myeloma or metastatic breast cancer patients treated with bisphosphonate/chemotherapeutic combination therapies. Cyclophosphamide (CY), an alkylating chemotherapeutic drug, is used to treat multiple myeloma, although its use has been recently reduced. The aim of this study was to clarify the effects of CY dose on tooth extraction socket healing when CY is used with or without bisphosphonate in mice...
July 2018: Bone
Dong Wook Kim, Hwiyoung Kim, Woong Nam, Hyung Jun Kim, In-Ho Cha
INTRODUCTION: The aim of this study was to build and validate five types of machine learning models that can predict the occurrence of BRONJ associated with dental extraction in patients taking bisphosphonates for the management of osteoporosis. PATIENTS & METHODS: A retrospective review of the medical records was conducted to obtain cases and controls for the study. Total 125 patients consisting of 41 cases and 84 controls were selected for the study. Five machine learning prediction algorithms including multivariable logistic regression model, decision tree, support vector machine, artificial neural network, and random forest were implemented...
April 23, 2018: Bone
Mirko Ragazzo, Diletta Trojan, Lisa Spagnol, Adolfo Paolin, Luca Guarda Nardini
The use of bisphosphonates has led to a new disease, bisphosphonate-related osteonecrosis of the jaw (BRONJ). There is currently no effective treatment for this disease; the surgical approach is controversial. The widespread use of human amniotic membrane (HAM) in surgery and the results obtained have highlighted its many potential properties, including antimicrobial, anti-inflammatory, antifibrotic and antiapoptotic, as well as its capacity for encouraging epithelialisation and cell differentiation. These properties are believed to encourage the recovery of patients with BRONJ, facilitating the wound healing process after surgical debridement of the bone...
April 2018: Journal of Surgical Case Reports
Francisco Javier Manzano-Moreno, Javier Ramos-Torrecillas, Lucia Melguizo-Rodríguez, Rebeca Illescas-Montes, Concepción Ruiz, Olga García-Martínez
The aim of the present study was to elucidate the role of osteoblasts in bisphosphonates-related osteonecrosis of the jaw (BRONJ). The specific objective was to evaluate the effect on osteoblasts of two nitrogen-containing BPs (zoledronate and alendronate) and one non-nitrogen-containing BP (clodronate) by analyzing modulations in their expression of genes essential for osteoblast physiology. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of zoledronate, alendronate, and clodronate at doses of 10-5 , 10-7 , or 10-9 M on the expression of Runx-2, OSX, ALP, OSC, OPG, RANKL, Col-I, BMP-2, BMP-7, TGF-β1, VEGF, TGF-βR1, TGF-βR2, and TGF-βR3 by primary human osteoblasts (HOBs) and MG-63 osteosarcoma cells...
2018: International Journal of Medical Sciences
Jean-Daniel Kün-Darbois, Hélène Libouban, Guillaume Mabilleau, Florence Pascaretti-Grizon, Daniel Chappard
OBJECTIVES: Pathogenesis of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is not fully explained. An antiangiogenic effect of bisphosphonates (BPs) or an altered bone quality have been advocated. The aims of the present study were to analyze alveolar mandibular vascularization and bone quality in rats with BRONJ. MATERIALS AND METHODS: Thirty-eight Sprague-Dawley rats were randomized into two groups: zoledronic acid (ZA), n = 27, and control (CTRL) n = 11...
February 16, 2018: Clinical Oral Investigations
Francesco Calvani, Antimo Cutone, Maria Stefania Lepanto, Luigi Rosa, Valentino Valentini, Piera Valenti
Osteonecrosis of the jaws is an emerging pathological condition characterized by un-exposure or exposure of the necrotic bone, independently from the etiology. This term is usually referred to medication-related osteonecrosis of the jaws due to severe adverse reaction to certain medicines, as bisphosphonates, used for the treatment of cancer and osteoporosis. The management of patients with Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) remains challenging because surgical and medical interventions may not eradicate this pathology...
February 12, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
J A Coello-Suanzes, V Rollon-Ugalde, A Castaño-Seiquer, E Lledo-Villar, J Herce-Lopez, P Infante-Cossio, A Rollon-Mayordomo
OBJECTIVE: To evaluate the effect of preventive dental management on reducing the incidence and delaying the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients treated with intravenous zoledronic acid (ZA). MATERIAL AND METHODS: This single-center clinical study included 255 cancer patients monitored over a 6-year period. Patients received dental treatment prior (Group A) or after (Group B) the initiation of ZA therapy. Dental treatments performed, incidence proportion (IP) and incidence rate (IR) in both groups were analyzed using significance tests...
February 7, 2018: Oral Diseases
Matias-Ferrán Escobedo, Luis García-Consuegra, Silvia Gay, Lorena Álvarez, Sonsoles Olay, Giuliano Ascani, Luis Junquera
Background: This study aims to evaluate the influence of changes in the teaching contents on medication-related osteonecrosis of the jaw may have on the knowledge and the capacity for practical case resolution about this pathology. Material and Methods: A cross-sectional descriptive study was conducted through a survey divided into four sections: degree of means of knowledge acquisition, habitual practice and ability to solve clinical cases. The total number of respondents (n = 225) was divided into two groups: Group A (Year 2015-2016) and Group B (Year 2016-2017)...
December 2017: Journal of Clinical and Experimental Dentistry
Ranya Elsayed, Pheba Abraham, Mohamed E Awad, Zoya Kurago, Balasudha Baladhandayutham, Gary M Whitford, David H Pashley, Charles E McKenna, Mohammed E Elsalanty
Unlike other antiresorptive medications, bisphosphonate molecules accumulate in the bone matrix. Previous studies of side-effects of anti-resorptive treatment focused mainly on systemic effects. We hypothesize that matrix-bound bisphosphonate molecules contribute to the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this study, we examined the effect of matrix-bound bisphosphonates on osteoclast differentiation in vitro using TRAP staining and resorption assay, with and without pretreatment with EDTA...
May 2018: Bone
Jung-Han Kim, Hae-Mi Kang, Su-Bin Yu, Jae-Min Song, Chul-Hoon Kim, Bok-Joo Kim, Bong-Soo Park, Sang-Hun Shin, In-Ryoung Kim
With rapid economic growth and further developments in medical science, the entry into the aging population is currently increasing, as is the number of patients with metabolic diseases, such as hypertension, hyperlipidemia, heart disease, and diabetes. The current treatments for metabolic bone diseases, which are also on the rise, cause negative side effects. Bisphosphonates, which are used to treat osteoporosis, inhibit the bone resorption ability of osteoclasts and during prolonged administration, cause bisphosphonate-related osteonecrosis of the jaw (BRONJ)...
January 30, 2018: Journal of Cellular Biochemistry
Akira Baba, Tazuko K Goto, Hiroya Ojiri, Mutsumi Takagiwa, Chiho Hiraga, Masahiro Okamura, Sho Hasegawa, Yumi Okuyama, Nobuhiro Ogino, Hideomi Yamauchi, Yuko Kobashi, Shinji Yamazoe, Yohei Munetomo, Takuji Mogami, Takeshi Nomura
OBJECTIVES: Antiresorptive agent-related osteonecrosis of the jaw (ARONJ)/medication-related osteonecrosis of the jaw (MRONJ) include both bisphosphonate-related osteonecrosis of jaw (BRONJ) and denosumab-related osteonecrosis of jaw (DRONJ). The purpose of this study is to study radiological characteristics of ARONJ/MRONJ. These imaging features may serve as one useful aid for assessing ARONJ/MRONJ. METHODS: CT scans of 74 Japanese patients, who were clinically diagnosed by inclusion criteria of ARONJ/MRONJ, obtained between April 1, 2011 and September 30, 2016, were evaluated...
May 2018: Dento Maxillo Facial Radiology
Ji-Su Oh, Su-Gwan Kim
The aim of the present study was to evaluate the possible use of a commercial absorbed collagen sponge and bone morphogenetic protein (BMP) for the prevention of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in rats. Twenty rats received intraperitoneal injections of 0.1-mg/kg of zoledronic acid three times a week for eight weeks before the extraction of both maxillary first molars after eight weeks. A collagen sponge (experimental group 1) and a collagen sponge with recombinant human BMP-2 (experimental group 2) were applied to the right extraction sockets of ten rats each...
December 7, 2017: Brazilian Oral Research
Filip Koneski, Danica Popovic-Monevska, Icko Gjorgoski, Jovanka Krajoska, Mirjana Popovska, Ilijana Muratovska, Boris Velickovski, Gordana Petrushevska, Vladimir Popovski
BACKGROUND: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a complication of the bisphosphonate (BP) treatment and its pathopysiology is still not fully understood. The existing preventive and treatment options require updates and more attention. Geranylgeraniol (GGOH) so far demonstrated an increased activity and viability of the cells previously treated with zoledronic acid (ZA). The aim of this study was to evaluate the in vivo effects of GGOH on the development of BRONJ...
February 2018: Journal of Cranio-maxillo-facial Surgery
Alexandra Johanna Leven, Antony J Preston
Osteonecrosis of the jaw associated with bisphosphonates and other medications is a growing problem facing dentists. It can have a significant and debilitating impact upon patients. Various treatment options ranging from surgical intervention to management with antibiotics and analgesics have been proposed. This article presents one method of conservative treatment and prosthetic rehabilitation in a patient with ongoing BRONJ of the maxilla unsuitable for surgical management. Clinical relevance: Dentists need to be able to identify patients who are at risk of developing BRONJ and have an awareness of the appropriate management as well as potential oral rehabilitation options for these patients...
December 2016: Dental Update
Jie Liu, Nikos Mattheos, Cheng Su, Chuanxi Deng, Nanyu Luo, Zekun Wang, Hua Tang
OBJECTIVE: This study was intended to investigate the effects of icariin on the healing of tooth extraction sites under the systemic administration of zoledronic and dexamethasone. METHOD: Thirty female rats underwent bilateral ovariectomy and were randomly assigned to 5 groups: SS group received a weekly injection of saline, while ZD, ZD + LICA, ZD + MICA, and ZD + HICA groups received zoledronic with dexamethasone for 8 weeks. One week later, mandibular first molars were extracted in all groups...
February 2018: Journal of Oral Pathology & Medicine
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