ArticleBone2018
Removal of matrix-bound zoledronate prevents post-extraction osteonecrosis of the jaw by rescuing osteoclast function.
Article in Bone, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Serum C-terminal cross-linking telopeptide level as a predictive biomarker of osteonecrosis after dentoalveolar surgery in patients receiving bisphosphonate therapy: Systematic review and meta-analysis.Journal of the American Dental Association (1939) · 2019Pooled it
- Clinical Characteristics and Serum Vitamin D Levels in Patients with MRONJ Associated with Antiresorptive Therapy: A Retrospective Study.Medicina (Kaunas, Lithuania) · 2026Article
- Effects of Zoledronate on Alveolar Bone and Teeth in Rats: Relationship Between Root Resorption and Occlusion.International journal of dentistry · 2026Article
- Does Sex Matter in Obesity-Induced Periodontal Inflammation in the SSDentistry journal · 2024Article
- Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway.Bone reports · 2024Article
- Effect of active oxygen gel on the clinical parameters of MRONJ.The Saudi dental journal · 2024Article
- Rodents as an animal model for studying tooth extraction-related medication-related osteonecrosis of the jaw: assessment of outcomes.Archives of oral biology · 2024Review
- Functional and analytical recapitulation of osteoclast biology on demineralized bone paper.Nature communications · 2023Article
- Dietary nitrate improves jaw bone remodelling in zoledronate-treated mice.Cell proliferation · 2023Article
- Medication-Related Osteonecrosis: Why the Jawbone?Dentistry journal · 2023Review
- Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing RANKL‑mediated NF‑κB and JNK and their downstream signalling pathways.Molecular medicine reports · 2022Article
- Review
- Matrix-Bound Zolzoledronate Enhances the Biofilm Colonization of Hydroxyapatite: Effects on Osteonecrosis.Antibiotics (Basel, Switzerland) · 2021Article
- Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review.BMC cancer · 2020Review
- Stress response in periodontal ligament stem cells may contribute to bisphosphonate‑associated osteonecrosis of the jaw: A gene expression array analysis.Molecular medicine reports · 2020Article
- Dendritic cell derived exosomes loaded with immunoregulatory cargo reprogram local immune responses and inhibit degenerative bone diseaseJournal of extracellular vesicles · 2020Article
- Synthetic Hydroxyapatite Inhibits Bisphosphonate Toxicity to the Oral Mucosa In Vitro.Materials (Basel, Switzerland) · 2020Article
- Role of dendritic cell-mediated immune response in oral homeostasis: A new mechanism of osteonecrosis of the jaw.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors.Bone research · 2020Review
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Unlike other antiresorptive medications, bisphosphonate molecules accumulate in the bone matrix. Previous studies of side-effects of anti-resorptive treatment focused mainly on systemic effects. We hypothesize that matrix-bound bisphosphonate molecules contribute to the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this study, we examined the effect of matrix-bound bisphosphonates on osteoclast differentiation in vitro using TRAP staining and resorption assay, with and without pretreatment with EDTA. We also tested the effect of zoledronate chelation on the healing of post-extraction defect in rats. Our results confirmed that bisphosphonates bind to, and can be chelated from, mineralized matrix in vitro in a dose-dependent manner. Matrix-bound bisphosphonates impaired the differentiation of osteoclasts, evidenced by TRAP activity and resorption assay. Zoledronate-treated rats that underwent bilateral dental extraction with unilateral EDTA treatment showed significant improvement in mucosal healing and micro-CT analysis on the chelated sides. The results suggest that matrix-bound bisphosphonates are accessible to osteoclasts and chelating agents and contribute to the pathogenesis of BRONJ. The use of topical chelating agents is a promising strategy for the prevention of BRONJ following dental procedures in bisphosphonate-treated patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.