Novel use of bisphosphonates to improve surgical outcomes in experimental bone tuberculosis

doi:10.5312/wjo.v17.i1.112262

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World Journal of Orthopedics

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2218-5836

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Orthop. Jan 18, 2026; 17(1): 112262
Published online Jan 18, 2026. doi: 10.5312/wjo.v17.i1.112262

Novel use of bisphosphonates to improve surgical outcomes in experimental bone tuberculosis

Veronika V Petukhova, Alexander Yu Mushkin, Alexey S Maletin, Marine Z Dogonadze, Natalia V Zabolotnykh, Marina E Dyakova, Dilyara S Esmedlyaeva, Tatiana I Vinogradova, Mikhail M Kostik

Veronika V Petukhova, Alexander Yu Mushkin, Alexey S Maletin, Department of Pediatric Orthopedics and Surgery, Saint-Petersburg Research Institute of Phthisiopulmonology, Saint Petersburg 191036, Russia

Alexander Yu Mushkin, Department of Traumatology and Orthopedic, First Saint Petersburg State Medical University, Saint Petersburg 197022, Russia

Marine Z Dogonadze, Marina E Dyakova, Dilyara S Esmedlyaeva, Research Laboratory of Microbiology, Biochemistry and Immunogenetics, Saint-Petersburg Research Institute of Phthisiopulmonology, Saint Petersburg 191036, Russia

Natalia V Zabolotnykh, Tatiana I Vinogradova, Research Laboratory of Experimental Medicine, Saint-Petersburg Research Institute of Phthisiopulmonology, Saint Petersburg 191036, Russia

Mikhail M Kostik, Hospital Pediatrics, Saint Petersburg State Pediatric Medical University, Saint Petersburg 194100, Russia

Author contributions: Petukhova VV contributed to the literature search and writing original draft; Petukhova VV and Mushkin AY contributed to conceptualization, writing review, and editing; Petukhova VV, Mushkin AY, and Vinogradova TI contributed to design and methodology; Petukhova VV, Mushkin AY, and Kostik MM contributed to formal analysis and interpretation; Petukhova VV, Dogonadze MZ, Zabolotnykh NV, Dyakova ME, and Esmedlyaeva DS contributed to the investigation; Petukhova VV and Kostik MM contributed to validation; Maletin AS contributed to software, resources, and data curation; Mushkin AY and Kostik MM contributed to funding, supervision, project administration, and critical review of the manuscript. All authors have read and agreed to the published version of the manuscript.

Supported by Russian Science Foundation Grant, No. 24-15-00185.

Institutional animal care and use committee statement: The study was approved by the Independent Ethical Committee of the Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health, Russian Federation (Approval No. 74). All animals enrolled in the study completed it according to the protocol, and no deviations or dropouts were recorded. Ethical considerations were thoroughly addressed, including adherence to European Commission guidelines for animal care (2007/526/EC) and national standards (GOST 33215-2014), ensuring humane treatment throughout the experiment. The confirmation certificate regarding animal care and use was issued by the government authority on 10 April 2021, in accordance with national law.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Mikhail M Kostik, MD, PhD, Professor, Hospital Pediatrics, Saint Petersburg State Pediatric Medical University, Lytovskaya 2, Saint Petersburg 194100, Russia. kost-mikhail@yandex.ru

Received: July 23, 2025
Revised: September 4, 2025
Accepted: November 14, 2025
Published online: January 18, 2026
Processing time: 170 Days and 20.4 Hours

Abstract

BACKGROUND

Tuberculous osteitis is a chronic, granulomatous bone infection that frequently results in impaired bone healing following surgery. Despite surgical intervention and prolonged anti-tuberculous therapy, complete bone regeneration often remains unachieved, contributing to subsequent orthopedic complications.

AIM

To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.

METHODS

A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups: (1) Bisphosphonates alone; (2) Bisphosphonates combined with anti-tuberculous therapy; and (3) Anti-tuberculous therapy alone. The control group consisted of animals that received no surgical or medical treatment. Clinical evaluations, biochemical markers, micro-computed tomography imaging, and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.

RESULTS

Pamidronate treatment significantly reduced early implant resorption, increased osteoblastic activity, improved trabecular bone regeneration, and maintained graft integrity compared to the anti-tuberculous therapy-only group. Histologically, pamidronate led to enhanced vascular remodeling and increased bone matrix formation. Crucially, bisphosphonate therapy demonstrated safety, compatibility with anti-tuberculous medications, and did not exacerbate tuberculous inflammation. Furthermore, micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups, underscoring the anabolic effects of bisphosphonates. Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces. These combined radiological, histological, and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.

CONCLUSION

A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis. The following prospective studies are needed.

Keywords: Tuberculosis; Bone and joint tuberculosis; Pamidronate; Bisphosphonates; Bone regeneration; Bone grafting; Bone resorption

Core Tip: A single intravenous dose of pamidronate significantly enhances bone regeneration after surgical treatment of experimental tuberculous osteitis. Pamidronate effectively inhibits early implant resorption, increases osteoblastic activity, and promotes prolonged osteogenesis, showing compatibility and safety when combined with antituberculosis therapy. This finding suggests that bisphosphonates may be a promising adjunctive therapeutic strategy for enhancing clinical outcomes in patients undergoing skeletal tuberculosis surgery.