ArticleInternational journal of molecular sciences2021
Zoledronate Causes a Systemic Shift of Macrophage Polarization towards M1 In Vivo.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Periodontitis and Glycaemic Dyscontrol Substantially Increase the Risk of Medication-Related Osteonecrosis of the Jaw: A Preclinical Study in Female Rats.Journal of clinical medicine · 2026Article
- New Immunological Insights into Bisphosphonate-Related Osteonecrosis of the Jaw: A Multidimensional Reappraisal from Molecular Switches to Clinical Phenotypes.Current issues in molecular biology · 2026Review
- Myeloid cell reprogramming combined with zoledronic acid effectively suppresses bone metastasis.Cancer biology & medicine · 2026Article
- Combined innate immune cell therapy, tumor-specific antibody, and radiation prompt antitumor response in pancreatic cancer models.Science advances · 2025Article
- Minimal Residual Disease in Breast Cancer: Tumour Microenvironment Interactions, Detection Methods and Therapeutic Approaches.International journal of molecular sciences · 2025Review
- Mitochondrial metabolic regulation of macrophage polarization in osteomyelitis and other orthopedic disorders: mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Prevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK inhibitors.Theranostics · 2025Article
- Advancing oral immunology for improving oral health.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2025Review
- Thoughts on the Etiology of Cherubism.Journal of clinical medicine · 2024Article
- Unexpected chronic lymphocytic leukemia B cell activation by bisphosphonates.Cancer immunology, immunotherapy : CII · 2024Article
- Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions - anFrontiers in immunology · 2023Article
- Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis.Frontiers in immunology · 2023Review
- A Mathematical Model of In Vitro Cellular Uptake of Zoledronic Acid and Isopentenyl Pyrophosphate Accumulation.Pharmaceutics · 2022Article
- A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients.Scientific reports · 2022Article
- Macrophage Polarization and the Osteoimmunology of Periprosthetic Osteolysis.Current osteoporosis reports · 2022Review
- Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundImmunomodulatory properties of bisphosphonates (BP) are suggested to contribute to the development of medication-associated osteonecrosis of the jaw (MRONJ). Furthermore, bisphosphonate-derived immune modulation might contribute to the anti-metastatic effect observed in breast cancer patients. Macrophages are potential candidates for the mediation of immunomodulatory effects of bisphosphonates. The study aimed to investigate the influence of bisphosphonates alone and in combination with surgical trauma on systemic macrophage polarization (M1 vs. M2) using an in vivo rat model.
methodsA total of 120 animals were divided into four groups. Groups 2 and 4 were treated with 8 × 40 μg/kg body weight of the BP Zoledronate i.p. (week 0-7). Groups 3 and 4 were exposed to surgical trauma (week 8, tooth extraction + tibia fracture), whereas in Group 1 neither medication nor surgical trauma was applied. After 8, 10, 12 and 16 weeks, skin, lung and spleen were immunohistochemically examined for macrophage polarization via expression analysis of CD68, CD163 and iNOS using a tissue microarray (TMA).
resultsA significant shift of macrophage polarization towards M1 was observed in skin, spleen and lung tissue of animals, with and without surgical trauma, treated with BP when compared to those without BP application. Surgical trauma did not cause a significant increase towards M1 polarization.
conclusionsBP application leads to a systemic pro-inflammatory situation in vivo, independent of surgical trauma, as evidenced by the shift in macrophage polarization towards M1 in various somatic tissues. This provides a possible explanation for the clinically observed anti-tumor effect of bisphosphonates and might also contribute to pathogenesis of MRONJ.
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