title: Denosumab-associated osteonecrosis of the jaw affects osteoclast formation and differentiation: Pathological features of two cases.
abstract: Medication-related osteonecrosis of the jaw (ONJ) is caused by antiresorptive (bisphosphonates and denosumab) and antiangiogenic agents, with the first report of denosumab-related ONJ emerging in 2010. To date, although certain case reports on denosumab-related ONJ have been published, those of ONJ caused by a single application of the drug are scarce. In addition, only one report described the histopathological features of this condition, although not completely; only the sequestrum resected by conservative surgery was evaluated. Although conservative treatment is recommended, the effectiveness of extensive surgery in the early stages of bisphosphonate-related ONJ has been described in recent years. Here we report the clinical and histopathological features of denosumab-related ONJ caused by single application of the drug, which was treated by extensive surgery in two patients. Histopathological analysis revealed a decreased number of osteoclasts in viable bone around the sequestrum, and these appeared morphologically immature, as indicated by the presence of very few nuclei. These findings are different from those for bisphosphonate-related ONJ and may assist in elucidating the mechanism underlying denosumab-related ONJ. Furthermore, extensive surgery may be effective for the management of this condition.
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Hayashida
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan; Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Yamada
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
keywords: bisphosphonate osteonecrosis; cathepsin K; denosumab; medication-related osteonecrosis of the jaw; osteoclasts; osteocytes