ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2012
Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 132 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
- Infectious/Inflammatory Oral Diseases and Medication-Related Osteonecrosis of the Jaw (MRONJ).Advances in experimental medicine and biology · 2026Review
- Unraveling Jawbone Susceptibility: Distinctive Features Underlying Medication-Related Osteonecrosis.Dentistry journal · 2026Review
- Dose-, duration- and age-dependent effects of zoledronic acid on bone structure and mechanical properties in growing rice rats.Frontiers in endocrinology · 2026Article
- Mild antiresorptive activity of an anti-vascular endothelial growth factor A antibody and sunitinib in a rat model of bone resorption.Bone reports · 2025Article
- Development and validation of a clinical prediction model for osteonecrosis of the jaw in patients receiving zoledronic acid using FAERS and canadian databases.Frontiers in pharmacology · 2024Article
- Bisphosphonate-incorporated coatings for orthopedic implants functionalization.Materials today. Bio · 2023Review
- Preventive effect of teriparatide on medication-related osteonecrosis of the jaw in rats.Scientific reports · 2023Article
- Review
- Intermittent parathyroid hormone enhances the healing of medication-related osteonecrosis of the jaw lesions in rice rats.Frontiers in medicine · 2023Article
- Bone structural, biomechanical, and histomorphometric characteristics of the hindlimb skeleton in the marsh rice rat (Oryzomys palustris).Anatomical record (Hoboken, N.J. : 2007) · 2022Article
- Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw (MRONJ).International journal of oral science · 2022Review
- Nonexposed antiresorptive agent-related osteomyelitis of the jaw: a single-center cohort study.Journal of bone and mineral metabolism · 2022Article
- Long-Term Ligature-Induced Periodontitis Exacerbates Development of Bisphosphonate-Related Osteonecrosis of the Jaw in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: a nationwide population-based study.Clinical oral investigations · 2022Article
- Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS.The Journal of clinical endocrinology and metabolism · 2022Review
- Indigenous microbiota protects development of medication-related osteonecrosis induced by periapical disease in mice.International journal of oral science · 2022Article
- Customized Titanium Mesh for Guided Bone Regeneration in the Posterior Mandible in a Patient Previously Treated with Bisphosphonates.Case reports in dentistry · 2022Article
- Review
- Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Though osteonecrosis of the jaw (ONJ) is temporally-associated with the use of nitrogen-containing bisphosphonates (N-BPs), a cause-and-effect relationship has not yet been established. We hypothesize that ONJ is a two-stage process in which: (1) risk factors initiate pathologic processes in the oral cavity that lead to a supranormal rate of hard tissue necrosis; and (2) powerful antiresorptives reduce the rate of removal of necrotic bone sufficiently to allow its net accumulation in the jaw. To test this hypothesis, we used the rice rat model of periodontitis. At age 28 days, rats (n = 15/group) were placed on a high-sucrose and casein diet to exacerbate the development of periodontitis. Animals were injected subcutaneously (SC) biweekly with vehicle or alendronate (ALN, 15 µg/kg), or IV once monthly with vehicle, a low dose (LD) of zoledronic acid (ZOL), or a high dose (HD) of ZOL and sacrificed after 6, 12, 18, and 24 weeks. Mandibles and maxillae were analyzed to determine the effects on the: (1) progression of periodontitis; (2) integrity of alveolar bone; (3) status of bone resorption and formation; (4) vascularity; and (5) osteocyte viability. We found that only HD-ZOL induced ONJ-like lesions in mandibles of rice rats after 18 and 24 weeks of treatment. These lesions were characterized by areas of exposed necrotic alveolar bone, osteolysis, a honeycomb-like appearance of the alveolar bone, presence of bacterial colonies, and periodontal tissue destruction. In addition, inhibition of bone formation, a paradoxical abolition of the antiresorptive effect of only HD-ZOL, increased osteocyte necrosis/apoptosis, and decreased blood vessel number were found after 18 and/or 24 weeks. Our study suggests that only HD-ZOL exacerbates the inflammatory response and periodontal tissue damage in rice rats, inducing bone lesions that resemble ONJ.
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