ArticleeLife2022
Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate.
Article in eLife, 2022. 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, 31 citations in OpenAlex.
- Effect of S1P/S1PR on bone metabolism in bisphosphonate-related osteonecrosis of the jaws.Medical molecular morphology · 2026Article
- Pharmacotherapy of Kienböck Disease and the Carpal Avascular Necrosis Family: A Narrative Review with a Four-Axis Translation Framework.Medicines (Basel, Switzerland) · 2026Review
- Mechanism-Oriented Biomaterial Strategies for Bone Regeneration in BRONJ: From Pathological Barriers to Evidence-Matched Repair.Biomolecules · 2026Review
- 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
- Soluble Sema4D From γδ T Cells Exerts Osteoblast Inhibition via Plexin-B/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws.Cell proliferation · 2026Article
- Rescuing Mitochondrial Dysfunction in Macrophages Prevents Osteonecrosis of the Jaw in Anti-Resorptive Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Zoledronate enhances lipopolysaccharide-induced inflammation via toll-like receptor 4 upregulation.Journal of dental sciences · 2026Article
- Unraveling Ginsenoside Rg1's osteoprotective pathways in zebrafish models of glucocorticoid induced osteoporosis via transcriptomics.Scientific reports · 2025Article
- Direct and indirect effects of transforming growth factor-beta on osteoclast-mediated bone remodeling using a new in vitro bone matrix model.JBMR plus · 2025Article
- Recent Stem-Cell-Based and Stem-Cell-Free Possibilities for the Therapeutic Management of the Osteonecrosis of the Jaw.Biomolecules · 2025Review
- Siglec-15 as a potential molecule involved in osteoclast differentiation and bone metabolism.Heliyon · 2024Review
- Targeting endoplasmic reticulum stress-induced lymphatic dysfunction for mitigating bisphosphonate-related osteonecrosis.Clinical and translational medicine · 2024Article
- Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing.Frontiers in bioengineering and biotechnology · 2024Article
- Article
- Correlations between Immune Response and Etiopathogenic Factors of Medication-Related Osteonecrosis of the Jaw in Cancer Patients Treated with Zoledronic Acid.International journal of molecular sciences · 2023Article
- Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.BMC oral health · 2023Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) presents as a morbid jawbone lesion in patients exposed to a nitrogen-containing bisphosphonate (N-BP). Although it is rare, BRONJ has caused apprehension among patients and healthcare providers and decreased acceptance of this antiresorptive drug class to treat osteoporosis and metastatic osteolysis. We report here a novel method to elucidate the pathological mechanism of BRONJ by the selective removal of legacy N-BP from the jawbone using an intra-oral application of hydroxymethylene diphosphonate (HMDP) formulated in liposome-based deformable nanoscale vesicles (DNV). After maxillary tooth extraction, zoledronate-treated mice developed delayed gingival wound closure, delayed tooth extraction socket healing and increased jawbone osteonecrosis consistent with human BRONJ lesions. Single cell RNA sequencing of mouse gingival cells revealed oral barrier immune dysregulation and unresolved proinflammatory reaction. HMDP-DNV topical applications to nascent mouse BRONJ lesions resulted in accelerated gingival wound closure and bone socket healing as well as attenuation of osteonecrosis development. The gingival single cell RNA sequencing demonstrated resolution of chronic inflammation by increased anti-inflammatory signature gene expression of lymphocytes and myeloid-derived suppressor cells. This study suggests that BRONJ pathology is related to N-BP levels in jawbones and demonstrates the potential of HMDP-DNV as an effective BRONJ therapy.
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