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Joint Diseases and
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Original Article · Open access

Effects of soluble guanylate cyclase activator vericiguat on fracture healing in rats

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Azat Dzhumukov

Department of Orthopedics and Traumatology, Torbalı State Hospital, İzmir, Türkiye

ORCID: 0009-0003-2430-1385

Bilal Karabak

Department of Orthopedics and Traumatology, Erzurum City Hospital, Erzurum, Türkiye

ORCID: 0000-0003-3134-8731

Aziz Demirci

Department of Orthopedics and Traumatology, Erzurum City Hospital, Erzurum, Türkiye

ORCID: 0000-0003-0676-8435

Ferhat Yıldırım Hoyur

Department of Orthopedics and Traumatology, Yavuz Selim Bone Desease and Rehabilitation Hospital, Trabzon, Türkiye

ORCID: 0000-0002-1013-8850

Muhammed Çağatay Engin

Department of Orthopedics and Traumatology, Atatürk University Hospital, Erzurum, Türkiye

ORCID: 0000-0002-9302-9587

Abstract

Objectives: The aim of this study was to assess the healing effects of vericiguat at various concentrations on rat femur fractures through clinical and radiological and biomechanical and histopathological assessments.

Materials and methods: In this study, a total of 60 female Wistar-Albino rats were used. The study comprised of six rat groups with 10 rats in each group: Group 1 (normal controls), Group 2 (positive controls - only fracture), Group 3 (low-dose vericiguat - 3 mg/kg), Group 4 (high-dose vericiguat - 6 mg/kg), Group 5 (fracture + low-dose vericiguat), Group 6 (fracture + high-dose vericiguat). Under general anesthesia, standard closed fractures were created in the right femurs of rats in the fracture groups. Radiological examinations were performed on Days 7, 14, and 28. The Lane-Sandhu scoring system was used for radiological assessment. At the end of Day 28, the rats were sacrificed, and the fracture healing tissues were examined biomechanically and histologically using the Huo scale.

Results: The 28th day biomechanical assessment showed significant differences in maximum load values between the fractured groups (Group 2: 88.75 ± 23.25 N, Group 5: 83.54 ± 23.15 N, Group 6: 39.07 ± 10.38 N; p = 0.003). The stiffness values showed similar patterns (Group 2: 64.71 ± 45.52 N/mm, Group 5: 99.20 ± 43.82 N/mm, Group 6: 40.47 ± 19.27 N/mm; p = 0.088). In the histological evaluation according to the Huo scale, Group 5 showed the highest quality of healing (8.6 ± 1.14) and a significant difference was found between Group 2 and Group 5 (p = 0.009). Group 6 demonstrated necrosis in four out of 10 animals and severe inflammation in eight out of 10 animals. In the radiological evaluation on Days 7, 14, and 28, no statistically significant differences were observed between the groups according to the Lane-Sandhu scoring system (p = 0.811 on Day 14; p = 0.299 on Day 28).

Conclusion: Our study results suggest that soluble guanylate cyclase (sGC) activators show promise for fracture healing treatment when used at specific concentrations, but their therapeutic range remains limited and their toxic effects at high doses need careful consideration.

Declarations

Author Contributions

A.D., B.K.: Idea/concept, design, writing the article, critical review; A.D., M.Ç.E.: Control/ supervision; B.K., F.Y.H.: Data collection and/or processing; M.Ç.E., A.D.: Analysis and/or interpretation; A.D., A.D.: Literature review; M.Ç.E., A.D.: References and fundings; A.D., F.Y.H.: Materials; F.Y.H., A.D.: Other.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This research was supported by Atatürk University Scientific Research Projects as a project code TTU-2023-13018.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

AI Disclosure

The authors declare that artificial intelligence (AI) tools were not used, or were used solely for language editing, and had no role in data analysis, interpretation, or the formulation of conclusions. All scientific content, data interpretation, and conclusions are the sole responsibility of the authors. The authors further confirm that AI tools were not used to generate, fabricate, or ‘hallucinate’ references, and that all references have been carefully verified for accuracy.

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