title: Effect of antiresorptive drugs on bony turnover in the jaw: denosumab compared with bisphosphonates.
abstract: Osteonecrosis of the jaw as a result of treatment with receptor activators of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab) is a new type of bony necrosis, the exact pathogenesis of which is unknown. Our aim was to find out whether the turnover of bone in the jaw is increased after denosumab has been given compared with other skeletal sites, and if that turnover might have a role in denosumab-related osteonecrosis of the jaw (DRONJ). Bone scintigraphic images of 45 female patients with breast cancer and bone metastases were analysed retrospectively, and divided into 3 groups: those given denosumab, those given a bisphosphonate, and a control group (n=15 in each). All patients had bone scintigraphy before treatment (T0) and during the course of treatment after 12 (T1) and 24 (T2) months. The data were analysed quantitatively using 6 preset bony regions of interest. There was similar turnover of bone in the mandible compared with other skeletal sites (such as the femur), while the maxilla showed significantly higher turnover. None of the bony regions investigated showed any significant changes after the bisphosphonate had been given. There was a tendency to increase bone turnover in those patients taking denosumab. The bone turnover of the jawbone is not overtly changed either by a bisphosphonate or denosumab, so it seems unlikely that oversuppression of bony turnover in the jawbones plays an important part either in the pathogenesis of DRONJ or in the bisphosphonate-related osteonecrosis of the jaw (BRONJ).
authors.affiliation: Ludwig-Maximilians Universität München, Goethestr. 70, D-80336 Munich, Germany; Medizin & Aesthetik, Clinic for Oral and Maxillofacial and Plastic Surgery, Lenbachplatz 2a, D-80333 Munich, Germany. Electronic address: ristow@aesthetik-muenchen.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ristow
authors.affiliation: Technische Universität München, Department of Nuclear Medicine, Ismaninger Straße 22, D-81675 Munich, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gerngroß
authors.affiliation: Technische Universität München, Department of Nuclear Medicine, Ismaninger Straße 22, D-81675 Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Technische Universität München, Department of Oral and Maxillofacial Surgery, Ismaninger Straße 22, D-81675 Munich, Germany; Medizin & Aesthetik, Clinic for Oral and Maxillofacial and Plastic Surgery, Lenbachplatz 2a, D-80333 Munich, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hohlweg-Majert
authors.affiliation: Technische Universität München, Institute of Medical Statistics and Epidemiology, Ismaninger Straße 22, D-81675 Munich, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Kehl
authors.affiliation: Technische Universität München, Department of Obstetrics and Gynecology, Ismaninger Straße 22, D-81675 Munich, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Jansen
authors.affiliation: Ludwig-Maximilians Universität München, Goethestr. 70, D-80336 Munich, Germany; Medizin & Aesthetik, Clinic for Oral and Maxillofacial and Plastic Surgery, Lenbachplatz 2a, D-80333 Munich, Germany.
authors.forename: Lilian
authors.initials: L
authors.lastname: Hahnefeld
authors.affiliation: Ludwig-Maximilians Universität München, Goethestr. 70, D-80336 Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Koerdt
authors.affiliation: Ludwig-Maximilians Universität München, Department of Oral and Maxillofacial Surgery, Lindwurmstr. 2a, D-80336 Munich, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Otto
authors.affiliation: Ludwig-Maximilians Universität München, Department of Oral and Maxillofacial Surgery, Lindwurmstr. 2a, D-80336 Munich, Germany; Medizin & Aesthetik, Clinic for Oral and Maxillofacial and Plastic Surgery, Lenbachplatz 2a, D-80333 Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pautke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D016723:Bone Remodeling / Q000187:drug effects*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000556:secondary; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005624:Frontal Bone / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007093:Imidazoles / Q000627:therapeutic use; D007571:Jaw Diseases / Q000139:chemically induced / Q000378:metabolism; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008437:Maxilla / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010020:Osteonecrosis / Q000139:chemically induced / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D011877:Radionuclide Imaging; D012189:Retrospective Studies; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab; D000077211:Zoledronic Acid
keywords: BRONJ; Bisphosphonate; Bone scan; Bone scintigraphy; Bone turnover; Denosumab; ONJ; Osteonecrosis of the jaw; Pathogenesis; RANKL-inhibitor; Xgeva