ArticleJournal of bone and mineral metabolism2018
Effect of anti-angiogenesis induced by chemotherapeutic monotherapy, chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on tooth extraction socket healing in mice.
Article in Journal of bone and mineral metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- Anti-VEGF neutralizing antibody delays osteomucosal healing by reducing collagen formation in mice.Scientific reports · 2025Article
- Mild antiresorptive activity of an anti-vascular endothelial growth factor A antibody and sunitinib in a rat model of bone resorption.Bone reports · 2025Article
- Influence of antiresorptive/antiangiogenic therapy on changes in periodontal and oral tissue structures: a histomorphometrical analysis in rats.Clinical oral investigations · 2023Article
- Influence of antiresorptive/antiangiogenic therapy on the surgical treatment outcomes of experimentally induced peri-implantitis lesions.Clinical oral investigations · 2023Article
- Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw.International journal of molecular sciences · 2023Review
- Zoledronate/Anti-VEGF Neutralizing Antibody Combination Administration Increases Osteal Macrophages in a Murine Model of MRONJ Stage 0-like Lesions.Journal of clinical medicine · 2023Article
- Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics.Scientific reports · 2022Article
- Zoledronic Acid Deteriorates Soft and Hard Tissue Healing of Murine Tooth Extraction Sockets in a Dose-Dependent Manner.Calcified tissue international · 2022Article
- Review
- Anti-VEGFR therapy is one of the healing inhibitors of antiresorptive-related osteonecrosis of the jaw.Journal of bone and mineral metabolism · 2021Article
- Combined Pharmacotherapy with Alendronate and Desferoxamine Regulate the Bone Resorption and Bone Regeneration for Preventing Glucocorticoids-Induced Osteonecrosis of the Femoral Head.BioMed research international · 2020Article
- Article
- Systemic administration of quality- and quantity-controlled PBMNCs reduces bisphosphonate-related osteonecrosis of jaw-like lesions in mice.Stem cell research & therapy · 2019Article
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy. The maxillary first molars were extracted 3 weeks after the initiation of drug treatment. Moreover, antivascular endothelial growth factor A (VEGFA) monoclonal antibody (mAb) was administered once every 2 days just after tooth extraction for 2 weeks. Soft and hard tissue wound healing was evaluated 2 and 4 weeks post-extraction using histomorphometry, microcomputed tomography and immunohistochemistry. ZA monotherapy did not induce impaired oral wound healing and ONJ-like lesions 2 and 4 weeks post-extraction, respectively. Tooth extraction socket healing worsened with severe anti-angiogenesis by CY monotherapy and CY/ZA combination therapy 2 weeks post-extraction. However, CY monotherapy rarely induced ONJ-like lesions with severe angiogenesis suppression, whereas CY/ZA combination therapy frequently induced ONJ-like lesions with severe angiogenesis inhibition 4 weeks post-extraction. Interestingly, anti-VEGFA mAb therapy delayed osseous wound healing with normal soft tissue wound healing of tooth extraction sockets, although this therapy significantly suppressed blood vessel formation. Our findings suggest that anti-angiogenesis alone is not the main cause of ONJ-like lesions induced by CY/ZA combination therapy. The combination of suppressed osteoclasts and anti-angiogenesis, in addition to other risk factors such as chemotherapy, may contribute to the development of ONJ.
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