The selective norepinephrine reuptake inhibitor reboxetine promotes late-stage fracture healing in mice
Antonia Donat,
Shan Jiang,
Weixin Xie,
Paul Richard Knapstein,
Lilly-Charlotte Albertsen,
Judith Luisa Kokot,
Jan Sevecke,
Ruben Augustin,
Denise Jahn,
Timur Alexander Yorgan,
Karl-Heinz Frosch,
Serafeim Tsitsilonis,
Anke Baranowsky,
Johannes Keller
Affiliations
Antonia Donat
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Shan Jiang
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Weixin Xie
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Paul Richard Knapstein
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Lilly-Charlotte Albertsen
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Judith Luisa Kokot
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Jan Sevecke
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Ruben Augustin
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Denise Jahn
Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Timur Alexander Yorgan
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Karl-Heinz Frosch
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; Department of Trauma Surgery, Orthopedics and Sports Traumatology, BG Hospital Hamburg, 21033 Hamburg, Germany
Serafeim Tsitsilonis
Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Anke Baranowsky
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Johannes Keller
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; Corresponding author
Summary: Impaired fracture healing is of high clinical relevance, as up to 15% of patients with long-bone fractures display non-unions. Fracture patients also include individuals treated with selective norepinephrine reuptake inhibitors (SNRI). As SNRI were previously shown to negatively affect bone homeostasis, it remained unclear whether patients with SNRI are at risk of impaired bone healing. Here, we show that daily treatment with the SNRI reboxetine reduces trabecular bone mass in the spine but increases cortical thickness and osteoblast numbers in the femoral midshaft. Most importantly, reboxetine does not impair bone regeneration in a standardized murine fracture model, and even improves callus bridging and biomechanical stability at late healing stages. In sum, reboxetine affects bone remodeling in a site-specific manner. Treatment does not interfere with the early and intermediate stages of bone regeneration and improves healing outcomes of the late-stage fracture callus in mice.
