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Item Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw(Springer, 2017-01) Yoneda, Toshiyuki; Hagino, Hiroshi; Sugimoto, Toshitsugu; Ohta, Hiroaki; Takahashi, Shunji; Soen, Satoshi; Taguchi, Akira; Nagata, Toshihiko; Urade, Masahiro; Shibahara, Takahiko; Toyosawa, Satoru; Department of Medicine, School of MedicineAntiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan.Item Mandible matrix necrosis in beagle dogs After 3-years of daily oral bisphosphonate treatment(2008-05) Allen, Matthew R.; Burr, David B.Purpose An increasing number of reports have implicated bisphosphonates as contributing to osteonecrosis of the jaw. The goal of this study was to evaluate mandible necrosis in beagle dogs treated for 3 years with oral alendronate (ALN). Materials and Methods Skeletally mature female beagles were treated daily for 3 years with oral doses of vehicle (VEH) or ALN (0.20 or 1.0 mg/kg/day). These doses approximate, on a mg/kg basis, those used for postmenopausal osteoporosis and Paget's disease, respectively. At necropsy, the second molar region of the mandible was excised, stained en bloc with basic fuchsin, and assessed for matrix necrosis and intracortical bone turnover rate using histology. Matrix necrosis was defined as a region greater than 500 μm2 that was void of basic fuchsin stain, assessed using both bright-field and confocal microscopy. Results No animals developed exposed bone lesions in the oral cavity during the 3-year study. Matrix necrosis was observed in 25% of ALN0.2 animals, 33% of ALN1.0 animals, and was noticeably absent from all vehicle animals (P < .05 pooled ALN doses vs VEH). These necrotic regions occurred predominately in the alveolar bone and were clearly void of patent canaliculi. Intracortical bone turnover rate of the alveolar mandible bone region was significantly lower (−75%, P < .05) in ALN-treated animals compared with VEH. Conclusions Three years of daily oral bisphosphonate treatment reduces bone turnover significantly and increases the incidence of matrix necrosis within the mandible of dogs.Item Skeletal accumulation of bisphosphonates: implications for osteoporosis treatment(2008-11) Allen, Matthew R.BACKGROUND: Bisphosphonates (BPs), the gold-standard pharmacological treatment for osteoporosis, are unique in that they become physically bound to the bone matrix and therefore accumulate over time. This skeletal accumulation has important physiological implications that are not completely understood. OBJECTIVE: To review concepts related to the biological effects of BP accumulation in the skeleton. METHODS: Articles concerning skeletal accumulation of BP treatment were identified. RESULTS/CONCLUSIONS: Skeletal accumulation of BP, dictated by both chemical and biological factors, is dose-dependent, differs among skeletal sites and likely differs among the various BPs. Bisphosphonate embedded within the skeletal matrix has lasting biological effects, the results of which have both positive and negative implications for bone remodeling. As alternative anti-remodeling agents gain approval for treatment of osteoporosis, the property of skeletal accumulation will likely be unique to BPs and therefore may be the property that determines the future use of this drug class.