Efficacy and side effects of different regimens of experimental postmenopausal osteoporosis therapy with zoledronic acid and their correction by combination with resveratrol

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.12.1169

Abstract

Introduction: As an age-associated metabolic disease of the skeleton, osteoporosis (OP) causes a significant medical and socio-economic burden. One of the challenges in clinical practice is the adverse effects of widely used bisphosphonates. Therefore, the search for preventive pharmacotherapeutic strategies is needed.

Materials and Methods: Sixty female Wistar rats randomized into 6 equal groups were used to study the effects of a single and prolonged intravenous administration of zoledronic acid (ZA) without and in combination with an endothelioprotective dose of resveratrol (2 mg/kg intraperitoneally daily), compared with sham-operated and osteoporotic animals. X-ray densitometry and histological methods were used.

Results and Discussion: Already at 4 weeks after bilateral ovariectomy (OVx), the typical signs of osteoporotic lesions comparable with OP in humans are present. A single administration of ZA following 4 weeks of OP had a significant corrective effect on bone structure and the fatty component of bone marrow. After a second dose of ZA at 8 weeks after OVx, signs of bone damage were detected by week 12. The addition of 4 weeks of resveratrol therapy after the second dose of ZA (until 12 weeks after OVx) leads to switching of bone marrow precursors to osteoblastic differentiation, reducing the adipocytic component; cytoprotective action on osteocytes with their switching to a synthetic phenotype, reducing the potential activation of osteoclasts and blocking periosteocytic osteolysis; and protection of bone vessels via the endothelioprotective properties of resveratrol.

Conclusion: An endothelioprotective dose of resveratrol exerts multitarget cell- and endothelium-dependent mechanisms of protective action when combined with prolonged zoledronic acid therapy, preventing its adverse effects.

Graphical Abstract

Keywords:

osteoporosis, zoledronic acid, resveratrol

References

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Author Contribution

Olga A. Shevchenko, Belgorod State National Research University, Belgorod, Russia

Senior Lecturer, Department of Microbiology and Virology with a Course in Clinical Immunology, Belgorod State National Research University, Belgorod, Russia; e-mail: shevchenko_olga@bsuedu.ru; ORCID ID: https://orcid.org/0009-0006-9785-9162. The author took part in the planning of the experiment, the conducting of the experimental work, the analysis of the material, and the writing of the manuscript.

Alexander A. Dolzhikov, Belgorod State National Research University, Belgorod, Russia

Doctor Habil. of Medical Sciences, Professor, Professor of the Department of Human Anatomy and Histology, Belgorod State National Research University, Belgorod, Russia; e-mail: anatomda@mail.ru; ORCID ID: https://orcid.org/0000-0001-7425-8416. The author conceived the idea of the study and performed the histological examination.

Oleg S. Gudyrev

Cand. Sci. (Medicine), Associate Professor, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: gudyrev@mail.ru; ORCID ID: https://orcid.org/0000-0003-0097-000X. The supervisor provided overall guidance, participated in the data analysis and interpretation, and reviewed the manuscript.

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Published

26-06-2026

How to Cite

Shevchenko OA, Dolzhikov AA, Gudyrev OS (2026) Efficacy and side effects of different regimens of experimental postmenopausal osteoporosis therapy with zoledronic acid and their correction by combination with resveratrol. Research Results in Pharmacology 12(2): 147–157. https://doi.org/10.18413/rrpharmacology.12.1169

Issue

Vol. 12 No. 2 (2026)

Section

Experimental Pharmacology

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Copyright (c) 2026 Shevchenko OA, Dolzhikov AA, Gudyrev OS

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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