Artikel
The selective norepinephrine reuptake inhibitor reboxetine negatively affects net bone quality but enhances osteogenesis during fracture healing
Suche in Medline nach
Autoren
-
Antonia Donat
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Unfallchirurgie und Orthopädie, Hamburg, Germany
-
Shan Jiang
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Unfallchirurgie und Orthopädie, Hamburg, Germany
-
Weixin Xie
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Unfallchirurgie und Orthopädie, Hamburg, Germany
-
Paul-Richard Knapstein
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Unfallchirurgie und Orthopädie, Hamburg, Germany
-
Lilly Albertsen
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Unfallchirurgie und Orthopädie, Hamburg, Germany
-
Denise Jahn
- Charité – Universitätsmedizin Berlin, Molekulare Unfallchirurgie; Julius Wolff Institut, Centrum für Muskuloskeletale Chirurgie (CMSC), Berlin, Germany
-
Serafeim Tsitsilonis
- Charité – Universitätsmedizin Berlin, Molekulare Unfallchirurgie; Julius Wolff Institut, Centrum für Muskuloskeletale Chirurgie (CMSC), Berlin, Germany
-
Anke Baranowsky
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Unfallchirurgie und Orthopädie, Hamburg, Germany
-
Johannes Keller
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Unfallchirurgie und Orthopädie, Hamburg, Germany
| Veröffentlicht: | 25. Oktober 2022 |
|---|
Gliederung
Text
Objectives: Delayed fracture healing and non-unions remain a challenging task for physicians in the clinical setting. Fractures also frequently occur in trauma patients which are treated with selective norepinephrine reuptake inhibitors (SNRI) due to psychiatric disorders. As increased levels of norepinephrine decreased bone mass in previous studies in experimental and clinical settings [1], [2], we aimed to identify potential negative effects of the SNRI reboxetine on the fracture healing process in a rodent model.
Methods: A standardized osteotomy (Fx) was performed on the femur of female WT mice (C57BL/6J). Following Fx, injections of either reboxetine or vehicle were administered daily until the timepoint of scarification. The intact bone (spine) and the callus were analyzed to assess radiographical and histological characteristics at early, intermediate and late stages of the fracture healing process. Furthermore, biomechanistic properties and gene expression in the callus tissue were investigated and compared using student's t-test.
Results and conclusion: In the treatment group, no significant alterations in structural callus parameters were observed during early and intermediate stages of bone regeneration, while an improved osseous callus bridging was detected at the end of the healing process. Gene expression of osteogenic markers including Runx2, Sp7 and Bglap increased by tendency at the early stages of fracture healing. Biomechanical testing at the late stages of bone repair revealed significantly higher integrity of the callus in mice treated with reboxetine. Simultaneously, a decrease in bone volume and an elevation of osteoclast parameters was observed in spine sections of the same mice.
Our findings support prior reports of reduced bone mass upon treatment with the SNRI reboxetine, which most likely results from increased osteoclast activity. In contrast, the fracture healing process was not negatively affected upon treatment with reboxetine, as the treatment group displayed enhanced osteogenesis on a molecular level as well as improved callus bridging with superior biomechanical stability. Therefore, increased levels of norepinephrine due to SNRI may positively affect union of long-bone fractures.
References
- 1.
- Ma Y, Krueger JJ, Redmon SN, Uppuganti S, Nyman JS, Hahn MK, Elefteriou F. Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis. J Biol Chem. 2013 Oct 18;288(42):30105-13. doi: 10.1074/jbc.M113.481309
- 2.
- Agarwal S, Germosen C, Kil N, Bucovsky M, Colon I, Williams J, Shane E, Walker MD. Current anti-depressant use is associated with cortical bone deficits and reduced physical function in elderly women. Bone. 2020 Nov;140:115552. DOI: 10.1016/j.bone.2020.115552
