title: Copper accumulation in the sequestrum of medication-related osteonecrosis of the jaw.
abstract: Bisphosphonates (BPs) have been widely, efficiently, and safely used for the treatment of various bone-related diseases such as osteoporosis. However, concerns about jaw osteonecrosis associated with oral treatment (medication-related osteonecrosis of the jaw [MRONJ]) have been increasing. Although many risk factors for MRONJ have been elucidated, its precise etiology and methods of prevention remain unknown. In this study, we have applied various elemental analysis methods for MRONJ specimens (e.g., X-ray fluorescence with synchrotron radiation [SR-XRF], particle-induced X-ray emission [PIXE], X-ray absorption fine structure [XAFS]) in order to reveal the accumulation and chemical state of trace bone minerals. In four MRONJ sequestra, the characteristic localization of copper (Cu) was observed by SR-XRF. Using micro-PIXE analysis, Cu looked to be localized near the edge of the trabecular bone. The chemical state of the accumulated Cu was estimated using XAFS and the possibility of a Cu-BP complex formation was assumed. Thus, in this study we argue for the feasibility of the trace element analysis to evaluate the potential pathophysiological mechanism of MRONJ.
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Advanced Biomaterials Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Uo
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of Materials and Environmental Science, Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, Japan.
authors.forename: Teruyasu
authors.initials: T
authors.lastname: Mizoguchi
authors.affiliation: Advanced Biomaterials Department, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 131-8310, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Omagari
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 131-8310, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komiyama
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mori
keywords: Medication-related osteonecrosis of the jaw; Particle-induced X-ray emission analysis; Synchrotron radiation X-ray fluorescence analysis; Trace elements; X-ray absorption fine structure analysis