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Bisphosphonate necrosis

Thomas Mücke, Christian R Krestan, David A Mitchell, Jan S Kirschke, Arno Wutzl
For patients with malignant disease taking bisphosphonates and denosumab, the incidence of medication-related osteonecrosis of the jaw (MRONJ) is up to 15% in contrast to 0.01% in patients with osteoporosis. Clinical presentation of MRONJ extends from asymptomatic exposure of bone in 94% of patients to severe cases of mandibular fractures in a minority of 4.5%. The strongest risk factors for MRONJ are invasive dental procedures and dental infections. Advances in imaging provide more preoperation information compared with panoramic radiograph...
July 2016: Seminars in Musculoskeletal Radiology
M Pedrazzoli, L Autelitano, F Biglioli
Mandibular fracture is usually the clinical end of bisphosphonate-related osteonecrosis of the jaw. This is a painful complication and patients cannot feed as usual, with a worsening of their quality of life. The goal of treatment in bisphosphonate related osteonecrosis of jaw (BRONJ) patients is to slow progression of bone necrosis. We present a novel technique for treatment of severe mandibular BRONJ in stage 3 patients that present with a high risk to develop fracture, since they have a residual unaffected mandibular bone height less than 6 mm...
August 2016: Acta Otorhinolaryngologica Italica
Mohammed Qaisi, Jamie Hargett, Matthew Loeb, Jeffrey Brown, Ronald Caloss
Bisphosphonates have been used for years in the treatment of patients with distant bony metastasis and in the prevention of osteoporosis. One of main side effects of these medications is the development of bisphosphonate related osteonecrosis of the jaw (BRONJ) in a small subset of patients. A new class of medications with a shorter half-life, known as receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, was introduced with the hopes of avoiding this side effect. However, reports of osteonecrosis of the jaw after the use of RANKL inhibitors have also been documented...
2016: Case Reports in Dentistry
Minju Song, Abdullah Alshaikh, Terresa Kim, Sol Kim, Michelle Dang, Shebli Mehrazarin, Ki-Hyuk Shin, Mo Kang, No-Hee Park, Reuben H Kim
INTRODUCTION: Surgical interventions such as tooth extraction increase the chances of developing osteonecrosis of the jaw in patients receiving bisphosphonates (BPs) for the treatment of bone-related diseases. Tooth extraction is often performed to eliminate preexisting pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related osteonecrosis of the jaw (BRONJ) development after tooth extraction is not clearly defined...
September 13, 2016: Journal of Endodontics
Liping Wang, Tian-Zhi Guo, Tzuping Wei, Wen-Wu Li, Xiaoyou Shi, J David Clark, Wade S Kingery
BACKGROUND: Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenesis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that antiresorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain...
October 2016: Anesthesia and Analgesia
Young-Mi Kang, Seong-Hwan Hong, Jae-Ho Yang, Jin-Cheol Oh, Jin-Oh Park, Byung Ho Lee, Sang-Yoon Lee, Hak-Sun Kim, Hwan-Mo Lee, Seong-Hwan Moon
BACKGROUND: N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro...
August 2016: Journal of Bone Metabolism
Thomas Mücke, Herbert Deppe, Jana Hein, Klaus-Dietrich Wolff, David A Mitchell, Marco R Kesting, Margitta Retz, Jürgen E Gschwend, Mark Thalgott
INTRODUCTION: To explore the preventive effect of a prophylactic oral and maxillofacial treatment to reduce bisphosphonate associated necrosis of the jaws (BRONJ) in metastatic prostate cancer (PC) patients treated with zoledronic acid (4.0 mg i.v./months). MATERIALS AND METHOD: 253 PC patients with bone metastases were prospectively randomized. All patients received baseline assessments including a dental panoramic tomogram. Group A was monitored and treated where deemed necessary by the patient's dentist and were re-evaluated once a year...
August 2, 2016: Journal of Cranio-maxillo-facial Surgery
Fei Wang, Yang Wang, Ningning Hu, Xuman Miao
During first year of steroid usage, osteocyte necrosis and blood vessel blockage may occur, which subsequently may produce steroid-induced bone infarction (SIBI) resulting in painful movement of patient. For treatment of SIBI, pharmaceutical strategy is the basic approach. It involves the use of various pharmacologically active compounds including bisphosphonates, hyperbaric oxygen (HBO), coenzyme Q10, erythropoietin, antihyperlipidemics, anticoagulants, antioxidants, and tissue repair protein. Out of these, there is no pharmaceutical agent that may completely treat this disease because many factors are found to be responsible for SIBI development; therefore, there are multiple biomarkers of this disease...
May 2016: Acta Poloniae Pharmaceutica
Tsutomu Nakazawa, Mitsutoshi Nakamura, Ryosuke Matsuda, Fumihiko Nishimura, Young Soo Park, Yasushi Motoyama, Yasuo Hironaka, Ichiro Nakagawa, Hiroshi Yokota, Shuichi Yamada, Kentaro Tamura, Yasuhiro Takeshima, Kouji Omoto, Yoshitaka Tanaka, Yukiteru Ouji, Masahide Yoshikawa, Takahiro Tsujimura, Hiroyuki Nakase
Nitrogen-containing bisphosphonates (N-BPs), which prevent bone resorption, exert direct and γδT cell (GDT)-mediated antitumor effects against several tumor cell types, including glioblastoma (GBM). However, limited information is available regarding the antitumor effects of N-BPs in GBM. Specifically, the antitumor effects of minodronate (MDA), a third-generation N-BP, in GBM are yet unclear. This study aimed to investigate the antitumor effects of MDA in GBM in vitro and in vivo. We performed growth inhibition and apoptosis detection assays using the GBM cell lines U87MG and U138MG...
September 2016: Journal of Neuro-oncology
Yuichiro Takei, Teruyoshi Tanaka, K Craig Kent, Dai Yamanouchi
OBJECTIVE: Arterial calcification is common and contributes to the pathogenesis of occlusive vascular disease. Similar to the dynamics of bone, it is a tightly controlled process that maintains a balance between osteogenesis and osteolysis. However, whether calcium homeostasis plays a role in the development of aneurysms has not been explored. We hypothesized that macrophages differentiate into osteoclasts in aneurysmal arteries and that protease byproducts contribute to aneurysm pathophysiology...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Hiromitsu Morita, Yuko Imai, Masahiro Yoneda, Takao Hirofuji
Bisphosphonates and irradiation are useful medical treatments, but can often cause oral complications such as medication-related oral necrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) during oral surgery, including tooth extraction. Therefore, we should take all risks into consideration carefully before choosing dental treatment for patients with a medical history of such therapies. A 55-year-old woman who underwent cord blood transplantation to treat extranodal natural killer T (NK/T) cell lymphoma (nasal type IVB) had a medical history of bisphosphonate and irradiation treatments...
June 30, 2016: Special Care in Dentistry
P G de Barros Silva, C C de Oliveira, Lac Brizeno, Dvt Wong, Rcp Lima Júnior, R P Gonçalves, F B Sousa, Mrl Mota, R de Albuquerque Ribeiro, Apnn Alves
OBJECTIVES: Characterize the cell profile and immunostaining of proinflammatory markers in an experimental model of bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIALS AND METHODS: Male Wistar rats (n = 6-7) were treated chronically with saline solution or zoledronic acid (ZA) at 0.04, 0.20, and 1.00 mg kg(-1) (1.4 × 10(-7) , 6.9 × 10(-6) , and 3.4 × 10(-5)  mol kg(-1) ), and subsequently, the first left inferior molar was extracted...
October 2016: Oral Diseases
Gustavo Maluf, Milena Correia de Pinho, Sandra Ribeiro de Barros da Cunha, Paulo Sérgio da Silva Santos, Eduardo Rodrigues Fregnani
This paper describes two cases in which the use of leucocyte-rich and platelet-rich fibrin (LPRF) combined with bone resection did not result in complete tissue response in the treatment of medication-related osteonecrosis of the jaw (MRONJ). It has been recently described in patients receiving subcutaneous administration of RANK-inhibitors, such as Denosumab, and anti-angiogenic drugs, such as Bevacizumab, as observed in our cases. Due to promising results in recent studies, more patients will receive these medications in order to avoid skeletal complications due to metastatic bone disease and, therefore, this scenario has a potential to become a comparable challenge to the bisphosphonate- induced jaw necrosis in the area of Oral and Maxillofacial Surgery...
May 2016: Brazilian Dental Journal
Francesco Saverio DE Ponte, Luciano Catalfamo, Gregorio Micali, Michele Runci, Giuseppina Cutroneo, Giovanna Vermiglio, Antonio Centofanti, Giuseppina Rizzo
Osteonecrosis of the jaw (ONJ) is an adverse effect of bisphosphonate treatment that has become the subject of increasing investigations, in particular due to its poorly understood pathogenesis. Several experimental studies on animal models have been conducted; however, the majority of these replicate human ONJ following tooth extraction, and describe alterations in the bone and gingival epithelium when necrosis is manifested. The aim of the present study was to analyze the rat mandibular bone and gingival epithelium during 45 days of zoledronate treatment (which is a bisphosphonate agent), without tooth extraction...
May 2016: Experimental and Therapeutic Medicine
Daniele Rosella, Piero Papi, Rita Giardino, Emauele Cicalini, Luca Piccoli, Giorgio Pompa
Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse drug reaction, consisting of progressive bone destruction in the maxillofacial region of patients. ONJ can be caused by two pharmacological agents: Antiresorptive (including bisphosphonates (BPs) and receptor activator of nuclear factor kappa-B ligand inhibitors) and antiangiogenic. MRONJ pathophysiology is not completely elucidated. There are several suggested hypothesis that could explain its unique localization to the jaws: Inflammation or infection, microtrauma, altered bone remodeling or over suppression of bone resorption, angiogenesis inhibition, soft tissue BPs toxicity, peculiar biofilm of the oral cavity, terminal vascularization of the mandible, suppression of immunity, or Vitamin D deficiency...
March 2016: Journal of International Society of Preventive & Community Dentistry
Stefano Andrea Denes, Riccardo Tieghi, Giovanni Elia
The buccal fat pad (BFP) is a well-established tool in oral and maxillofacial surgery and its use has proved of value for the closure of oroantral communications. Oroantral communication may be a common complication after sequestrectomy in "bisphosphonate-related osteonecrosis of the jaws."The authors report a clinical case of a 70-year-old female patient in bisphosphonate therapy presented with right maxillary sinusitis and oroantral communication after implants insertion.The BFP was used to close the defect...
May 2016: Journal of Craniofacial Surgery
Ilaria Giovannacci, Marco Meleti, Maddalena Manfredi, Carmen Mortellaro, Alberta Greco Lucchina, Mauro Bonanini, Paolo Vescovi
INTRODUCTION: Dentoalveolar surgery including tooth extractions and dental implants placement is considered the major risk factor for developing medication-related osteonecrosis of the jaw (MRONJ).In this study, a patient series of MRONJ around dental implants were carefully analyzed to describe the findings and to assess the possible risk factors. METHODS: Fifteen patients with peri-implant bone osteonecrosis were selected out of a group of 250 patients (6%). Patients were divided into 2 groups according to the temporal relationship...
May 2016: Journal of Craniofacial Surgery
Alia M Daoud, Mack Hudson, Kenneth G Magnus, Fleur Huang, Brita L Danielson, Peter Venner, Ronak Saluja, Bronwen LeGuerrier, Helene Daly, Urban Emmenegger, Alysa Fairchild
Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN. In this case report, we describe a patient with prostate cancer metastatic to bone diagnosed with AVN after receiving single-fraction palliative RT to the left femoral head...
2016: Curēus
A Monegal, P Peris, M Alsina, J Colmenero, N Guañabens
Non-uremic calciphylaxis is a severe rare disorder characterized by ischemic necrosis. Recently, three cases of cutaneous calciphylaxis have been described in the context of teriparatide treatment. We present a 51-year-old woman with alcoholic cirrhosis who developed multiorganic calciphylaxis shortly after starting teriparatide treatment associated with calcium and 25-hydroxyvitamin D supplements for severe osteoporosis. After lengthy care of the infectious complications and treatment with bisphosphonates and sodium thiosulfate progressive improvement was observed over a 3-year period...
August 2016: Osteoporosis International
Louis Tsun Cheung Chow
Defining giant cell-rich osteosarcoma (GCRO) as "an osteosarcoma in which more than 50% of the tumor consists of numerous uniformly distributed osteoclastic giant cells amidst oval or spindle mononuclear cells embedded in a fibrovascular stroma," eight such cases identified among 265 cases of osteosarcoma were analysed. Their age ranges from 11 to 33 years, with peak incidence in the second decade and equal sex distribution. Seventy-five percent presented with pain, commonest in the knee, affecting the metaphysis...
June 2016: Virchows Archiv: An International Journal of Pathology
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