25dkou226 10.3205/25dkou226 urn:nbn:de:0183-25dkou2269 Meeting Abstract Menger Menger Maximilian M

BG Klinik Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland

author El Kayali El Kayali Moses Kamal Dieter MKD

Klinisch-Experimentelle Chirurgie, Universität des Saarlandes, Homburg, Deutschland

author Braun Braun Benedikt B

BG Klinik Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland

author Rollmann Rollmann Mika M

BG Klinik Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland

author Herath Herath Steven S

BG Klinik Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland

author Menger Menger Michael M

Klinisch-Experimentelle Chirurgie, Universität des Saarlandes, Homburg, Deutschland

author Hans Hans Sandra S

Klinisch-Experimentelle Chirurgie, Universität des Saarlandes, Homburg, Deutschland

author Histing Histing Tina T

BG Klinik Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland

author Laschke Laschke Matthias M

Klinisch-Experimentelle Chirurgie, Universität des Saarlandes, Homburg, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20251031 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0634 226 Deutsche Gesellschaft für Orthopädie und Unfallchirurgie Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie Deutsche Gesellschaft für Unfallchirurgie Berufsverband für Orthopädie und Unfallchirurgie Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2025) Grundlagenforschung | Cell & Bone 2 Berlin 20251028 20251031 AB32-4217 TextObjectives and questions: Loop diuretics, such as furosemide, are widely used in cardiovascular diseases and disorders with fluid accumulation. By inhibiting the Na+/K+/2Cl− transport system in the loop of Henle, treatment with furosemide is associated with increased renal calcium excretion as well as higher levels of parathyroid hormone and bone-specific alkaline phosphatase, indicating accelerated bone turnover. Consequently, furosemide treatment has been linked to decreased bone mineral density and an increased risk of hip fractures. However, there is little information on whether furosemide also affects the process of fracture healing. Material and methods: The effect of furosemide on fracture healing was studied in a stable closed femur fracture model in mice using intramedullary screw fixation. The animals were treated daily with intraperitoneal injections of furosemide (15 mg/kg, n = 19) or vehicle (control, n = 20). Fracture healing was investigated by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry and Western blotting (WB) at 2 and 5 weeks after fracture. Comparison between the two groups was performed using the unpaired Student’s t-test. All data are given as Mean ± SEM. Statistical significance was accepted for p < 0.05.Results: The biomechanical analysis revealed a significantly reduced bending stiffness in furosemide- treated animals at 2 weeks after fracture when compared to controls (3.1 ± 0.3 vs. 9.6 ± 1.2 N/mm). This was associated with a significantly lower ratio of bone tissue (29.8 ± 2.6 vs. 62.2 ± 5.0%) and a higher ratio of fibrous tissue (52.2 ± 4.0 vs. 30.2 ± 6.1%) within the callus of furosemide-treated animals, indicating impaired fracture healing. Histological analyses revealed a lower number of cathepsin K-positive osteoclasts (1.7 ± 0.2 vs. 3.3 ± 0.4 osteoclasts/high power field), neutrophilic granulocytes and macrophages at 2 weeks after fracture within the callus tissue of furosemide-treated mice. These findings indicate an impaired osteoclast activity and a reduced inflammatory response in furosemide-treated animals when compared to controls. In addition, WB analyses at 2 weeks after fracture revealed a significantly lower expression of NF-κB ligand (RANKL) and the pro-osteogic marker, cysteine-rich angiogenic inducer 61 (Cyr61), within the callus of furosemide-treated animals. Discussion and conclusions: Taken together, these novel findings demonstrate that furosemide treatment impairs fracture healing by suppressing the activity of osteoclasts and the inflammatory response at an early healing time point. Hence, furosemide shoud be used with caution in patients with a high risk of delayed healing and non-union formation. 0 0 0 0